Tissue Bath & Pe rfusion Systems Selection Guide

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r h r t a s t u s . c u o m e 1 Isolated Organ & Tissue Spysetemrsf &u Asppiliocatnion s& Ove rtviiews sue bath perfusion & tissue bath Perfusion and Tissue Bath Systems Overview

organs systems for organs tissues systems for tissues applications

Smooth Muscle Gastro-intestinal Tract > Moist Chamber, Perfusion System for Liver, etc. • Ileum > Schuler Vertical Tissue Bath for Frequently Used for • Esophagus > UP-100, perfusion of isolated liver... in-situ or ex-vivo • Stomach > Graz Vertical Tissue Bath Studying • Stomach > PBTO, Intestine perfusion • Duodenum > Mayflower Horizontal Tissue Bath • Spasm • Liver/Pancreas > Servo Controlled Perfusion System, Perfusion of • Telia Coli > Modular Organ Bath for Isolated Tissues • Spasmolysis • Intestine Isolated Liver: In-Situ or Ex-Vivo > Compact Organ Bath for Isolated Tissues • Vascular tone > IPR, Perfusion Bath for Ileum Peristaltic Reflex Studies > M Series Myograph • Edema

Vascular Musculature > IH-SR, HA-PL, UP-100, IH-5, IH-9 Isolated Heart System for • Aorta > Schuler Vertical Tissue Bath > Compact Organ Bath p Small Rodents, Rabbit, Small Pig for Isolated Tissues h e • Hind Quarter > Graz Vertical Tissue Bath

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u > M Series Myograph

> Moist Chamber With Edema Balance b

> Mayflower Horizontal Tissue Bath s • Mesenteric Bed • Vein e i o > PBTO, Blood Vessel Perfusion u n > Modular Organ Bath for Isolated Tissues • Coronary Vasculature s

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u > IPL-4, IPL-2, IPL-4, IPL-16 Isolated Perfused Lung of Mouse, • Trachea > Schuler Vertical Tissue Bath > Modular Organ Bath o i e s • Lung Rat and Guinea Pig, Rabbit, Pig for Isolated Tissues b

• Lung > Graz Vertical Tissue Bath u f t a r x t > Compact Organ Bath e h > PBTO, Intraluminal Trachea Perfusion

> Mayflower Horizontal Tissue Bath e • Bronchi for Isolated Tissues t p > PCLS, Precision Cut Lung Slice Chamber

I > Coleman Superfusion Bath s

> M Series Myograph e o u l s a s t i e T d

Uro-Genital Tract O > PS-1, Moist Chamber, Perfusion System for Kidney, etc. • Bladder > Schuler Vertical Tissue Bath & r n g

• Kidney > Graz Vertical Tissue Bath a a > PBTO, Intraluminal Vas Deferens Perfusion • Ureter g n r

> Mayflower Horizontal Tissue Bath & • Placenta • Vas-deferens O

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> Coleman Superfusion Bath e i

• Uterus t s a s l u > Superfusion Cascade Bath • Placenta o e s > M Series Myograph I

Cardiac Heart > IH-SR, BL-IH, HA-PL, BL-UP, UP-100, IH-5, IH-9 Isolated Heart System • S-A node • Purkinjie > Schuler Vertical Tissue Bath Frequently Used for for Small Rodents, Rabbit, Small Pig • Langendorff • A-V node Fiber > Graz Vertical Tissue Bath Studying: • Working heart • Atrium > Mayflower Horizontal Tissue Bath • Inotropism • Heart-Lung Preparation • Cardiac Muscle > Steiert Tissue Bath for Cardiac AP and Force Measurement • Chronotropism • Trabecula • Dromotropism • Papillary Muscle • Refractory State

Skeletal Muscle • Intact Limb/Hindquarter > UP-100 • Sartorious > Schuler Vertical Tissue Bath for Strips or Rings Frequently Used for • Gastrocnemius > Graz Vertical Tissue Bath for Strips or Rings Studying: • Nerve-muscle > Mayflower Horizontal Tissue Bath for Strips or Rings • Metabolism Preparations • Neromuscular Transmission

Nerve Bundle • Brain • Nerve > Marsh Ganglion Bath for Whole Nerve and Ganglion Frequently Used for • Spinal Cord • Ganglion > Schuler Vertical Tissue Bath for Nerve-Muscle Preparation Studying: • Ganglion • Neuro-Neuronal Transmission • Neuromuscular Transmission

2 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com 3 Tihse Hoarlvardt Aeppdara tous r3 gTiear Anppr o&ach tto iRsesesaruch e Our 3 Tier System is Organized in the Following Manner:

advanced research

Harvard Apparatus HSE Advanced Research This tier offers cutting edge research systems with advanced features for ultimate physiological stability and experimental flexibility. Guided by 3

Isolated Heart for t i decades of in-the-field research and development, Harvard Apparatus HSE e Small Rodents r

Advanced Research solutions are the engines of breakthrough research. a p p With more capability packages and measurement possibilities than any r o We recommend that researchers contact us directly to discuss specific a comparable system, Harvard Apparatus HSE Advanced Research systems c applications so that we may custom configure a system tailored to your h allow physiological recording to be more integrated than ever before. In

research goals. This proven approach allows us to construct a system t o with the tools to achieve immediate research goals and the upgradeability addition, modular engineering and construction allows options and r e to achieve those which are not yet apparent. These systems will grow s capabilities to be added at any time as the goals and demands of your e with your research needs. a research change. r c h I s o l a t e d

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T i s s u Harvard Apparatus Research e This tier is designed for functionality and ease of use, Harvard Apparatus Research systems are fully configured with necessary components and accessories already included. It offers precision systems for the routine or standard measurements in any lab. Harvard Apparatus Research systems are also perfect for compound screening or rapid-throughput experimentation.

To make these systems easy to order, each complete system is represented by a single Ordering # and option packages are clearly marked.

teaching

Harvard Apparatus Teaching This third tier of equipment was designed for the teaching labs needs. The products are constructed to meet a special set of demands, especially where usage is high and regular maintenance is a challenge. Harvard Apparatus Teaching systems are exceptionally rugged, reliable and accurate, while representing an excellent value.

4 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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Graz Tissue Bath System Order # Product 73-2369 Basic Unit for 4-Position Tissue Bath, Model GRAZ The Graz Organ Bath can be used for many standard pharmacological experiments. This apparatus was originally developed for experiments on small isolated 73-0559 Mounting Material for Tissue Vessel and Holder vascular rings (1 to 2 mm dia.) with special attention to a low incubation 73-0560 Holder for 10 or 20ml GRAZ Glass Tissue Bath volume of the medium. The smallest tissue vessel available has a volume of 2 73-2271 Glass Tissue Bath, 10ml for GRAZ Tissue Bath ml. The muscle contractions produced in these experiments can be measured 73-2276 Glass Tissue Bath, 20ml for GRAZ Tissue Bath either as forces (isometrically) or as displacements (isotonically). 73-0561 Holder for 2 or 5ml GRAZ Glass Tissue Bath The organ bath is also available in variable versions. Larger tissue vessels of 73-2273 Glass Tissue Bath, 2ml for GRAZ Tissue Bath 5, 10 or 20 ml are available for larger vessels and other muscle preparations. 73-2275 Glass Tissue Bath, 5ml for GRAZ Tissue Bath These baths can also be used for experiments on papillary muscle or isolated 73-3531 Core Tissue Holder Without Electrical Stimulation atria (e.g. guinea-pig), with provision for electrical stimulation. 73-3533 Core Tissue Holder With Field Stimulation Electrodes The recommended F30 isometric transducer can easily be replaced by other for 10 or 20 ml GRAZ Tissue Vessel t i s

s types of transducers without any modification of the apparatus. 73-3532 Core Tissue Holder With Field Stimulation Electrodes u

e for 2 or 5 ml GRAZ Tissue Vessel

The main consideration in designing the bath has been a simple and clear b a 73-3535 Support Set for Rings 0.5mm Wire

t arrangement, without neglecting the necessary stability. A rigid construction h (Large Version only 10 and 20 ml Vessels)

s is an essential requirement for measuring small contraction forces. A rigid y

s 73-3537 Support Set for Rings 0.3 mm Wire

t Plexiglas baseplate carriers 4 vertical rods on which the individual components e m are mounted. Tissue vessels and suitable holders are available in 4 different 73-3534 Support Set for Strips 0.5 mm Wire s sizes. The perfusion solution is aerated by glass frits fused into the vessel 73-2117 Gas Distribution Block for Aerating I s bottom. A needle valve is provided for each tissue vessel to permit accurate o l adjustment of the gas flow. a t e For a system description according your requirements please use: d The tissue supports consist of a core holder and support sets.

www.hugo-sachs.de/timail.html O r Two types of core holder are available with or without field stimulation g or contact our technical experts at: a

n electrodes. The field stimulation electrodes are two parallel Platinum plates [email protected]

& of 15 x 5 mm separated by 11 mm for the 10 or 20 ml tissue vessels or 12 x 5 For a custom configuration and full system quotation.

T i mm and separated by 6 mm for the 2 and 5 ml glassware. s s u Four types of support sets are available. A support set consists of the anchor e for the tissue, mounted on the core holder and the connecting wire to the transducer. The anchors can be easily interchanged to adapt to the current experiment. – Support set for muscle strips (see Fig. 1) wire diameter 0.5 mm – Support set for rings (see Fig 2) exist in two versions wire diameter 0.5 mm fixed pin lenght 6 mm and wire diameter 0.3 mm fixed pin length 6 mm for very small vessels. – Support set for rings with 0.5 mm diameter fixed pin length 11 mm can only be used with 10 or 20 ml vessels. Additional items required are a thermociculator, a reservoir for the solution, transducers, monitoring system setup using the PLUGSYS Amplifier System. Recording and Evaluation of the signals using ACAD software, in case of electrical stimulation a multiple output stimulator is required.

6 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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Muscle strips Tissue Rings With Without With Without Volume Tissue Vessel Stimulation Stimulation Stimulation Stimulation

50 ml

50 ml

73-2259 t i s s u e b a 73-2201 73-0400 73-0400 73-2277 t h s y s t e m s I s o 20 ml l 20ml a t e d

O

r 73-2259 g a n

&

T i s s 73-2256 0.3mm wire u 73-2200 73-0397 73-2203 73-0397 e 73-3102 0.2mm wire

20ml 10 ml 73-2257 73-2249 73-2258

PY2 PY2 73-2200 73-0404 73-0364 73-2206 73-0404 73-2207

5 ml

73-0364 73-2259

73-2202 73-2206 73-0364 73-0393 73-0364

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8-Channel Compact Organ Bath t i s s u e b a t h s y s t e m s I s o l a t e d

O Key Features Components Included r g a • Compact design reduces space requirements • Compact organ bath unit n

& • Complete accessibility to all components • Micropositioners (one per chamber)

T i facilitates maintenance s • Thermo regulation unit s u • Independent perfusate inputs allow use of e • Tissue holder different physiological solutions in the • Oxygen outlet for petri chambers same chamber • Set of spare fuses • All the input-output connections are accessible on the rear panel of the device • Instruction manual • Two modes for solution replacement: overflow/ • Calibration certificate emptying and filling • 2 year warranty • Turbulence-free water circulation Options • Use of safety sensors for both water level and • Tissue chambers water temperature (cut-off at 50°C) • Stimulation electrodes • Electronic heating resistance control system prevents thermal shock • Stimulators • Available accessories for continuous perfusion • Isometric or isotonic transducers • Ensures optimal heat stability • Signal amplifiers • PROTOWIN Software Parameters Measured • Parameters given by the associated software (see PROTOWIN) Use of totally inert materials, Viton, Teflon, Delrin, Silicone and other materials that are not degraded by acids or salt

10 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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Research Double Tissue Bath Set • Temp. automatically held within 0.5°C • Dial graduated from 15° to 45°C in 5° increments • Large 11.2 L water bath capacity for stable temp. in coils and tissue vessels • Magnetic stirrer ensures uniform temp. • 250 watts of heating power for fast heat-up time • Warming coils lie flat against sides of tank, leaving center free for procedures • 400 ml capacity flat perfusate warming coils Basic Double Tissue Bath Set ensure sufficient supply of temp. controlled t

i with 50-0652 Complete Simple

s perfusate for lengthy assays s Lever Assembly* u

e • Detachable stem tissue vessel, for increased b convenience when changing tissue vessels a t h (tissue chamber can be removed without s y disturbing stem or disconnecting tubing for s t e warmed perfusate and drainage m s Basic Double/Basic Single Tissue Bath Sets I s

o • Temperature automatically held within 0.5°C l a

t • Dial graduated from 15° to 45°C in 5° increments e d

• Fixed stem tissue vessels supplied as standard O r g a Student Single Tissue Bath Set n

& • Manual temperature control

T i s • Offers superior visibility and access for student s u Basic Single Tissue Bath Set Student Single Tissue Bath Set e • Side limb of the special fixed stem student tissue with 50-0652 Complete Simple with 50-0652 Complete Simple vessel is curved upward making it easy to Lever Assembly* Lever Assembly connect to the spiral perfusate warming coil

Specifications and Ordering Information for Harvard Apparatus Tissue Bath Sets Research Double Basic Double Basic Single Student Single Tissue Bath Set Tissue Bath Set Tissue Bath Set Tissue Bath Set 115 VAC, 60 Hz/230 VAC, 50 Hz 115 VAC, 60 Hz/230 VAC, 50 Hz 115 VAC, 60 Hz/230 VAC, 50 Hz 115 VAC, 60 Hz/230 VAC, 50 Hz Heated Water Bath Heater Power 250 W 80 W 80 W 50 W Temperature Control Automatic within 0.5°C Automatic within 0.5°C Automatic within 0.5°C Manual Magnetic Stirrer Yes No No No Capacity 11.2 L 4.7 L 3.6 L 0.8 L Dimensions, H x W x D 18 x 29 x 21.5 cm 15.5 x 21.5 x14 cm 15.5 x 16.5 x 14 cm 12.5 x 10 cm (H x D) (7.25 x 11.5 x 8.5 in) (6.25 x 8.5 x 5.5 in) (6.25 x 6.5 x 5.5 in) (5 x 4 in) Tissue Vessel(s) Quantity per Set 2 2 1 1 Type Supplied Detachable Stem Fixed Stem Fixed Stem Student Fixed Stem Perfusate Warming Coils Type Flat Coil Spiral Coil Spiral Coil Spiral Coil Capacity per Vessel 200 ml 35 ml 35 ml 35 ml Thermometer Length 15 cm 10 cm 10 cm 10 cm Order # 50-2146 / 50-2153 50-2120 / 50-2138 50-2104 / 50-2112 50-0306 / 50-0314

12 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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Mayflower Tissue Bath System 73-2155 Mayflower Tissue Bath Configured as a flow- through system t i s s u e b a t h s y s t e t e m x

s • Horizontal tissue bath for isometric contraction t Incubation System (73-3600) measurements using a F10 or F30 force transducer The tissue chamber is jacketed. The bottom of the chamber is made of a I s o • Two versions are available: teflon coated stainless steel plate to optimize the temperature stability of l a

t – Flow-through superfusion system the solution. A additional small stainless steel heat exchanger is also built e d – Incubation system in to avoid temperature fluctuation.

O r g • Possibility of electrical stimulation The incubation chamber can also be used as a flow-through superfusion a n • Exchangeable holders depending on tissue used chamber. The superfusion chamber cannot be used for incubation.

&

(for vascular or tracheal rings, for strips) T Additional Equipment: i s

s – A multi-channel roller pump for the perfusate circuit u e – A thermocirculator for keeping the perfusate solution The Mayflower tissue bath is a horizontal tissue chamber with an integral at constant temperature contraction force measurement. It is completely open at the top and has a small bath volume of 3 - 5 ml. The compact and modular construction pro - The modular concept of this apparatus offers a wide range of different vides ideal conditions for investigations on small muscle preparations arrangements to meet individual requirements regarding bath geometry, (urethra, papillary muscle, cavernous body), vascular rings, or tracheal tissue holders and stimulation electrodes. The horizontal arrangement of rings. the tissue and the open top provide ideal conditions during preparation and experiment. Basic Equipment: – Acrylate support with a movable mounting platform for preload The various parts of the apparatus are made mainly from Plexiglas or adjustment through a micrometer screw. This platform receive stainless steel and are therefore inert and corrosion-resistant. The solution the tissue chamber and acts as holder for the force transducer. flows in from a roller pump and passes through a heat exchanger, the The acrylate support also includes a glass heat exchanger for outflow is under suction through a suction tube with height adjustment by the pre-heating of the perfusate solution. the same pump. A frit for aeration is located in the tissue chamber. Two – The tissue chamber differentiates the two versions. connection sockets for the stimulation electrodes are located on either side of the tissue chamber. Flow Through System (73-2155) The tissue chamber is carved out of an acrylate block and placed on the support stand. This chamber includes the tissue holder, the connections for electrical stimulation electrodes, a frit for aeration and a draw-off tube with height adjustment to set the bath volume. As it is not jacketed, continuous flow through the chamber is required.

14 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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applications (0 to 30 mmHg) and the second for high pressure applications Standard PBTO Bath (0 to 300 mmHg). The unit comes with four different interchangeable cannulae with the following diameters: 1.5, 2.5, 3 and 4 mm. For smaller vessels customized stainless steel cannulae can be made on request. For micro-vessels, glass capillary pipettes pulled to the required diameter can be connected to the adapter cannulae using a silicone tube collar. A special sliding block for testing stent (e.g. drug diluting stent) has been developed. An additional port allows insertion of a stent into a cannulated isolated vessel. Additional equipment required: thermocirculator, reservoir, peristaltic i s o pump, transducer, monitoring system setup using the PLUGSYS Amplifier l a

t System. Recording and Evaluation of the signals using BDAS software. e d o r g a Order # Product n s

y 73-2158 Horizontal Tissue Bath PBTO, Type 813/6 s t e 73-2044 Device for Afterload Pressure of 0-30 cmH20 m

s 73-2333 Device for Afterload Pressure of 0-300 mmHg I s o l a Applications t e d • Basic test in gastro-intestinal research

O r g • Peristaltic reflex in guinea pig ileum a n

• For studying emptying phase of peristaltic reflex &

T i s IPR s Benefits and Features u

e The IPR (Ileum Peristaltic Reflex) is a version of the PBTO that has been • Perfusion of tubular organs (trachea, blood designed for studying the peristaltic reflex in the guinea-pig ileum. The circular vessels, intestines) muscle contraction which propels the contents of the ileum from aboral to • Individual solutions for intraluminal perfusions anal direction is induced by the increase of the intraluminal pressure up to a and extraluminal superfusion threshold point. • Controlled perfusion pressure The tissue bath is a jacketed Plexiglas bath. The holder for the cannulae can Applications be removed from the main bath during the preparation. The oral and aboral ends of a 4 to 5 cm long segment of guinea pig ileum is cannulated. Three • Intraluminal perfusion of tubular organs (trachea, different sizes of cannulae are available. The cannulae are fixed on sliding blood vessels, intestines) holders to adapt the distance between the cannulae to the individual length of • Testing circular-action musculature, vascular tone the ileum. The inflow is controlled by means of a peristaltic pump with a and stents in isolated vessels flowrate of about 0.5 ml/min. The direction of the perfusion flow must meet the physiological way. The outflow can be switched using a stopcock from a PBTO level equivalent to the level of the bath to a level of about 3 cm above the The PBTO has been designed for the studying of perfused tubular organs level of the fluid in the bath. The peristaltic reflex is induced by this procedure. such as trachea, blood vessels, intestines and vas deferens. Individual In the ‘peristalsis’ position, the pressure increases slowly resulting in a solutions can be used for intraluminal perfusion and extraluminal distention of the ileum until the pressure threshold level is reached. At this superfusion. Two peristaltic pumps are required, one for intraluminal time the emptying phase is started as a visible contraction of the circular constant flow perfusion and the second for extraluminal superfusion. The muscle moving from the oral to the aboral side.The intraluminal pressure is intraluminal perfusion pressure is generated by an adjustable afterload then recorded from the oral side. control system. A differential pressure transducer is used to measure the Additional equipment required: thermocirculator, reservoir, peristaltic pump, intraluminal pressure difference at the proximal and distal end of the organ. transducer, monitoring system setup using the PLUGSYS Amplifier System. The tissue bath is a jacketed Plexiglas bath. The holder for the cannulae Recording and Evaluation of the signals using BDAS can be removed from the main bath for the cannulation of the segment of software. tubular organs. The cannulae are fixed on sliding holders to adjust to organs of different length, up to 50mm. The intraluminal pressure is Order # Product controlled by one of two afterload systems available. One for low pressure 73-3013 Horizontal Tissue Bath IPR, Type 813/2

16 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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Coleman Vernier preparation. The lower part is funnel- Superfusion Control shaped to allow the collection of the Bath efluate for reperfusing, perfusing the next tissue or bioassay analysis. The isometric force transducer is fixed on Force the rod using a Vernier control. Transducer The tissue holder is a separate part that is installed in the main superfusion chamber. The holder can easily be Superfusion removed to simplify the preparation. Lines The holder consists of the body, the hook for fixing the tissue, the stainless steel cannulas for superfusion and the t i s Stimulation

s stimulation electrodes. The tissue is u Electrodes e attached using a thread to the tissue b a hook. The thread at the other end of the t h

tissue must be attached to the s Tissue y Benefits and Features s Hook transducer. A slide in the holder body t e

m • Suitable for virtually any tissue sample allows easy positioning of the thread in s • Compact, allows the study of up to four tissue the central hole. The superfusion

I cannulae can be rotated in the main s preparations in parallel o body to optimize the superfusion after the holder is in place into the chamber l a • Rapid removal of potentially toxic metabolites t and the thread fixed to the transducer. The stimulation electrodes are made of e d • Obviates the necessity of repeated washing

platinum and must be buckled to be close to the tissue. The electrodes do not O r procedures touch the tissue but must be parallel and close enough to the tissue so that the g a n • Simple reclaimation of perfusate for recirculation superfusing solution makes electrical contact.

& or collection The dual heat exchanger consists of Tygon tubing loops inside a jacket T i s tube connected to a thermocirculator. s Applications u e • Evaluation of the potency of labile substances In the Flow through mode each tissue is superfused individually with fresh solution or solution containing the test compound. The outcoming solution is • Determining the rates of onset and offset of collected and goes to waste or is stored for later bioassay analysis. drug action • Evaluation of spasmogenic and spasmolitic agents In the Recirculating mode each tissue is superfused individually. The outcoming solution after superfusion is collected and used for superfusing again in the same tissue. The Coleman superfusion system is suitable for a variety of applications involving the study of contraction and relaxation of smooth muscle In the Cascade mode the first tissue is superfused with fresh solution and preparations, the effect of drugs that interfere with these actions, as well as all the subsequent tissues are superfused with the outcoming solution of those that interfere with autonomic neurotransmission. The system consists the preceding chamber. of a main stand that can receive up to eight single superfusion chambers. Additional equipement required: peristaltic pump, force transducer with Each chamber is equipped with electrical stimulation capability, a rod for Vernier control, bridge amplifier for the force transducer, Data acquisition fixing the force transducer and an optional two channel heat exchanger. The ACAD, electrical stimulator, thermocirculator if heat exchangers are used. lower end of the tissue is held by a stainless steel hook. The thread attached to the top of the tissue passes through the opening directly to the force Order # Product transducer. The superfusion solution is fed by a peristaltic pump through a 73-2221 Basic Unit for Superfusion Bath according to stainless steel cannula to the thread; it runs down the thread and superfuses COLEMAN (stand for 4-Baths) Type 840 the tissue. Two separate solution paths are available for superfusion with 73-2222 Superfusion Bath according to COLEMAN and without test substance. Two platinum wires are placed parallel to the 73-2917 Heat Exchanger to Superfusion Bath COLEMAN tissue to form stimulation electrodes. The solution running down provides electrical contact between the electrodes and the tissue.

The superfusion chambers are made of Plexiglas and do not require For a system description according your requirements please use: thermostating owing to the low thermal conductivity of the material. The www.hugo-sachs.de/timail.html chamber is fixed on the frame in the horizontal position. All additional parts or contact our technical experts at: (tissue holder, dual heat exchanger, road for mounting the transducer) are [email protected] fixed on the chamber. The upper part of the chamber receives the tissue For a custom configuration and full system quotation. holder. The lower part can be swung away to simplify access to the

18 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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l l i e l e e n e . s 1 9 Isolated Organ & Tissue tissue bath systems ad vanced i s o PClLaS Ptrecisdion lCuut nLungg S lsicey Cshatmeberms research

Incubation Cells Platinum Wire with Nylon Threads

Inlet From Waterbath Vacuum Pipes Return to waterbath Vacuum Pipes

Gas Inlet Filling Pipes i s o Incubation Chamber Top View l a t e d l u n The incubation chamber was developed to allow incubation and observation of g

s slices by an inverted microscope. The chamber is made of Polycarbonate. It is y s connected to a water bath to maintain constant temperature conditions. Two t e m incubation cells are positioned in the center of the chamber. The bottom of the s cells is sealed by glass, the cover is made of acrylic glass. The slices are fixed in I

s the incubation cells by positioning them under nylon strings fixed to a bent o l platinum wire. The incubation cells can be filled with buffer, medium or drug a t e solutions through the filling pipe. Buffer solution can be removed from the cells d

O over a vacuum pipe. In addition, it is possible to gas the incubation cells in order r g to use bicarbonate buffered media. a n Figure 1. Exposure of a PCLS to increasing concentrations of endothelin-1.

The incubation chamber is placed on the stage of an inverted microscope and & Shown is one lung slice containing a small airway (B), a pulmonary artery (PA)

T and a pulmonary vein (PV). The slice was imaged before (C) and after exposure to warmed to 37°C. The slices are screened for airways and transferred to the i s increasing concentrations of endothelin-1, ranging from 10-10 M to 10-6 M. s incubation chamber. Lung slices are selected for study using predefined criteria u e (Martin et al. 1996). Airways and vessels are focused, and finally the images are • Assessment of lung functions under cell culture analyzed by image analysis software (e.g., Optimas or Metamorph). conditions Example of an Application • From any species (murine, rat, human) As an example Figure 1 shows exposure of a slice to increasing • Study of airways of different sizes concentrations of endothelin-1. Shown is a lung slice containing an airway (B), a pulmonary artery (PA) and a pulmonary vein (PV). The pulmonary artery and • Allows quantification of the responsiveness of the airway contracted almost completely, while the pulmonary vein area simple airway passages and simple vessels decreased to only 50% of its initial area. These responses are now easily • Analyzing ciliary beating frequency quantified by digital imaging technique. It is a distinct advantage of this technique that in many ways precision-cut Lung Functions Under the Microscope slices can be treated like a cell culture. Thus, the slices can be incubated Precision-cut lung slices (PCLS) offer a novel and unique way to assess lung under various conditions and gene as well as protein expression or mediator functions under cell culture conditions. They can be prepared from nearly any release be determined. In contrast to cell culture models, in slices the species including mouse, rat and human lungs. The method allows the study of anatomical structure of the lung is largely maintained, so that the functional the response of airways of different size (down to the terminal bronchioles) and consequences of gene expression and mediator release can be evaluated. to relate these changes in lung functions to gene expression and mediator release. Slices are viable for at least three days. They can be placed under an Order # Product inverted microscope, where digital image techniques allow quantification not only of the responsiveness of single airways, but also of single vessels. In 73-2370 Precision Cut Lung Slice Chamber addition, it is possible to analyze the ciliary beating frequency. More than 20 Accessories slices can be obtained from one lung, thus this method is very economical in 73-0125 Thermostatic Circulator E 103, 230 VAC, terms of experimental costs and animal use. Tissue cores are prepared from the 73-2802 Thermostatic Circulator E 103, 115 VAC lungs filled with agarose solution, after cooling to 4°C. From the cores, slices 73-0113 Roller Pump Reglo Analogue ISM 827, | (220 ± 20µm) are cut using a tissue slicer 4 Channels, 0.002 to 30 ml/min

20 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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- s i e n 2 - s 2 1 Isolated Organ & Tissue tissue bath systems ad vanced Moist Chmamboer iTyspet 8 3c4/8 hambers research

Moist Chamber 73-2901

Mini ball joint holders support Moist chamber equiped for isolated arterial and venous cannulae for rat liver perfusion under constant rat liver perfusion flow conditions

Mesentric Bed Per - fusion System m o i s t c h a

m Benefits and Features b e • Excellent temperature control for perfusate and organ r s • Precise positioning of cannulae and measurement I s probes o l a • Straight forward operation and compact dimensions pump and appropriate cannulae are used to complete the perfusion circuit, t e d while a thermocirculator feeds the water-jacketed components to maintain

• A large choice of cannulae, bubble traps and other O r acessories makes the moist chamber suitable for a the thermostating circuit. The Moist Chamber Type 834/8 can also be used to g a form the core of our UP-100 or Perfusion Control system to permit perfusion at

n huge range of perfusion applications

& constant pressure as well as constant flow.

• Provides a complete perfusion system in combination T i The basic Moist Chamber Type 834/8 is configured as shown above and s with the UP-100 or Perfusion Control System s u consists of the chamber, cover and silicon plate only. Contact Harvard e Applications Apparatus for configuration of a complete perfusion system for specific • For perfusion of organs from rodents like liver, applications. kidney, pancreas and mesenteric bed Additional equipment required: thermocirculator, bubble trap, cannulae, • For investigating the tone of small blood vessels holders, peristaltic pump, transducers, monitoring system setup using the under the effect of vasoactive substances PLUGSYS Amplifier System. Recording and Evaluation of the signals using • Biochemistry, studying metabolic processes BDAS software. Special Application: The Rat Mesenteric Bed The popular Moist Chamber Type 834/8 is an exceptionally flexible and The key part of the perfusion system for the rat mesenteric bed is the moist useful tool for perfusion of most “simple” organs from typical rodent chamber. The mesenteric tissue is placed into the moist chamber on a models. In its most basic configuration, the Moist Chamber consists of a stainless steel mesh (replaces the silicone plate) which also acts as anode suitably deep (110x40x35mm) organ chamber and tight-fitting cover. Both during electrical stimulation. components are double-walled and water-jacketed to provide a stable temperature controlled environment within the organ chamber. Perfusate Order # Product is warmed by passage through a built-in heat exchanger and bubble trap 73-2901 Moist Chamber Type 834/8 with Metal Tube immediately before contact with the organ. Heat Exchanger Inside the chamber, a flexible silicon platform acts as a rest for fixation 73-3692 Bubble Trap for Flow Rate up to 50 ml/min (usually with standard fixing pins) of the organ. Anchors for our Mini Ball 73-3094 Stainless Steel Mesh Electrode Joint positioning system and precision arterial and venous cannulae are pre-drilled on both sides of the organ. In addition, several measurement and sample ports are provided for easy access to the inner chamber, even For a system description according your requirements please use: www.hugo-sachs.de/orgmail.html with the cover in place, making the chamber suitable for collecting a wide or contact our technical experts at: range of physiological data. [email protected] The Moist Chamber Type 834/8 can be part of a simple constant flow For a custom configuration and full system quotation. perfusion system. Used as such, a water-jacketed buffer reservoir, peristaltic

22 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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3 f t w o e 2 r m • w a w w . h m a r v a r d a p b p a r a t u e s . c o m r s 2 3 Isolated Organ & Tissue moist chambers ad vanced Moist Chammboer wiistht E dcemha Baalamnce bers research Moist Chamber for Microvascular Permeability Studies

• Compact arrangement 73-3685 Cannulating block • Dual Perfusion System, vascular & intraluminal intestinal • Built-in balance for edema evaluation/organ weight measurement • Vascular bed is in warm and moist environment Weighing during perfusion Transducer • Optimized temperature control of perfusate and organ m Cannulation block removed • Controlled perfusion o

i from chamber for surgery s conditions t c Vascular h Intraluminal • Cannulation block simplifies surgery a Cannulae m Cannulae b Applications e r s • To study simultanuously vascular, luminal and

I lymphatic flows, arterial, venous and intraluminal s o pressures and bowel weight. l a t e • Septic multi-organ failure study in gastro intestinal area d

O r g The system is based on a moist chamber with a built-in organ weighing Additional equipment required: thermocirculator, peristaltic pump, syringe a n system. The jacketed chamber maintains a warm and moist environment for pump, transducer for perfusion pressure, servo controller (SCP), monitoring

&

the organ. The chamber has been configured for studying the edema evolution system setup using the PLUGSYS Amplifier System. Recording and Evaluation T i s in a perfused intestine with attached mesenteric bed with two separate of the signals using BDAS software. s u perfusion lines for simultaneous vascular and intraluminal perfusion. e The chamber can be used for any other organ that requires continuous The chamber is supplied with a movable cannulation block including all the weighing during perfusion. required heating coils and bubble traps. This block acts also as holder for the The interchangeable adapter block holding the perfusion lines and cannulae tubing and cannulae, it can be placed near the animal for easy in-situ can be customized for other types of organ to be perfused. preparation. After surgery, the block with the preparation is moved and fixed on the chamber. This ensures continuous perfusion during the entire duration Developed in cooperation with the Forschungszentrum Borstel, 23845, Borstel of surgery and reduced risk of embolism or ischemia. and Universitätsklinikum, Chirurgie, 24105 Kiel. The chamber provides a number of ports for connecting the measurement Order # Product system and perfusate collection. Measurement of perfusion pressures and 73-3685 Moist Chamber with Edema Balance Type 802 (MCWEB) flows are also available. A peristaltic pump is used for vascular perfusion. A constant pressure is maintained by controlling the pump speed with an electronic controller (SCP) via pressure measurement. For the intraluminal Ileum perfusion, a syringe pump is used.

Citations designed to perfuse isolated intestines through the mesenteric artery and the gut lumen. Steroids A Model of the Isolated Perfused Rat Small Intestine or oxygen carriers were not needed. Functional and morphological integrity of the tissue was pre - Ingmar Lautenschläger,1 Heike Dombrowsky,2 Inez Frerichs,3 Solveig-Carolin Kuchenbecker,3 Stef - served for several hours as confirmed by oxygen consumption, venous lactate-to-pyruvate ratio, fen Bade,2 Holger Schultz,2 Peter Zabel,2 Jens Scholz,3 Norbert Weiler,3,* and Stefan Uhlig2 arterial and venous pH, lactose digestion and galactose uptake, intravascular and luminal pres - 1University Medical Centre Schleswig-Holstein, Campus Kiel 2Research Center Borstel 3University sures, maintained fluid homeostasis, gut motility, and by quantitative light microscopic analysis. Hospital Schleswig-Holstein, Campus Kiel Administration of PAF caused typical effects such as vasoconstriction, gut atony, and loss of galactose uptake. PAF also elicited a transient loss of 20% of the perfusate liquid from the mesen - Submitted 31 July 2009 ; revision received 8 October 2009 ; accepted in final form 8 November 2009 teric vascular bed, two thirds of which were transferred to the lumen. All these responses were en - tirely reversible. This new model provides detailed insights into the physiology of the small ABSTRACT intestine, and will allow to study fundamental processes such as fluid homeostasis, barrier func - Intestinal edema remains a serious clinical problem and novel approaches to study its pathophysiology tions, transport mechanisms and immune responses in this organ. Using this model, here we are needed. It was our aim to develop a long term stable isolated perfused rat small bowel prepara - show a dramatic and yet reversible response of the rat small bowel to PAF suggesting luminal tion permitting analysis of vascular, luminal, interstitial and lymphatic compartments and to demon - water clearance as a novel safety factor in the intestine that may be of clinical relevance. Intes - strate the utility of this model by studying the effects of the pro-inflammatory mediator tine physiology; fluid balance; platelet activating factor. platelet-activating factor (PAF). A temperature-controlled chamber with an integrated balance was

24 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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i ad svanced o l Paertfuesiodn S yostermg foar Isnola tsedy Pisg Ltiveer ms rese arch or Pig Kidney

HSE Perfusion System for Isolated Pig Liver or Pig Kidney i s o l a t e d o r g a n s y s t e m s

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T • For use in physiological or pharmacological i s research for the perfusion of a pig liver or kidney s • Thermostated moist chamber for pig u

e with blood or erythrocyte containing perfusate liver or pig kidney • For liver or kidney transplantation studies The following additional items are required for operating the apparatus: • For liver or kidney xenotransplantation studies • Thermocirculator • Pump with electrical control. For blood we Basic System recommend a Pump Drive BVP-ZX with centrifugal pump head, see the Pump Section A The pig liver to be perfused is placed in a moist, thermostated chamber (inside dimensions: 400 x 300 x 180 mm) and perfused with blood or • SCP, Servo Controlled Perfusion System erythrocyte containing perfusate under constant-flow conditions via the • Measurement system for Flow and Pressure portal vein. A centrifugal pump with a gentle action on blood is employed to • Oxygenator with heat exchanger, e.g. Terumo Capiox reduce hemolysis. As this type of pump does not supply a constant flow or SX10 ® or Medtronic Minimax Plus PRF ® pressure, the constant flow is maintained by an electronic controller (SCP). Additional monitoring equipment can be added to the system as required to For the kidney instead of the liver chamber, a smaller chamber (inside create a custom, application specific, system for your unique research needs. dimensions 260 x 200 x 210 mm) is used. The kidney is mainly perfused at constant pressure, which is also controlled by the SCP. Monitoring System is set up using the PLUGSYS Amplifier System. Recording and Evaluation of the signals using BDAS software.

For a system description according your requirements please use: www.hugo-sachs.de/orgmail.html Order # Product or contact our technical experts at: [email protected] 73-2804 Moist Chamber for Isolated Pig Liver Type 69/2 For a custom configuration and full system quotation. 73-2994 Moist Chamber for Isolated Pig Kidney

26 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com c o y H D B H M S M S M P L A F A P M C I P C C M T F A H S O G W C C H P L U I • •

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Isoilsateod Hleaartt Seysdtem sh Oeveravierw t systems

Perfusion Modes

Langendorff Perfusion Ejecting Working Mode Heart

Constant Pressure Perfusion Constant Flow Perfusion i s o l a t e d h e a r t s y s t e m s

I ADVANTAGES ADVANTAGES ADVANTAGES s o l

a • Physiological mode • Lower cost • Heart produces pressure t e volume work

d • No risk of damaging heart by • Simple methodology

O unintentionally high usually employed in • Ultimate physiological mode r g pressure compound screening a • No risk of isolated heart n

• Most commonly use damaging by unintentionally &

method, facilitates high pressure T i s comparison w/large body

s • Allows study of cardiac u of literature

e function and metabolism

DISADVANTAGES DISADVANTAGES DISADVANTAGES • Heart does only • Non physiological mode • Usually higher cost Isovolumetric work • Heart does only • Since flow is not constant, ef - • Can involve higher cost Isovolumetric work fective dose is difficult to cal - • Since flow is not constant • Risk of massive pressure culate effective dose is difficult to may cause heart damage calculate

TYPICAL APPLICATIONS TYPICAL APPLICATIONS TYPICAL APPLICATIONS • Cardiology • Cardiology • Cardiology • Physiology • Physiology • Physiology • Pharmacology • Pharmacology • Pharmacology • Biochemistery • Biochemistery • Biochemistery • Testing vasoactive • Testing vasoactive • Cardiac preload and afterload substances substances dependent studies • Ischemia / Reperfusion • Testing cardiac rhythm • Low-flow/ischemia studies studies • Ischemia/Reperfusion • Metabolic studies • Testing cardiac rhythm studies • Cardiolplegia recovery • Dispersion of ventricular • Dispersion of ventricular • Hypoxic studies repolarization repolarization • Cardiovascular screening • Cardiovascular screening • Hypoxic studies • Hypoxic studies

28 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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ad i vanced s o IlHa-SRt Iesoldate dh Heearta forr tSm sally Rosdetnets ms research Mouse, Rat and Guinea Pig (continued)

The modular nature of the IH-SR allows for initial integration or later upgrade with the Working Heart perfusion pathway. This enables orthograde perfusion: entering the left atrium, flowing through the left ventricle and exiting the aorta. In this way, more physiological assay of ventricular contractility is possible as the left ventricle is now fully-ejecting and performing pressure volume work. In order to fully exploit this advantage, the IH-SR includes a specialized pathway which easily allows introduction of a Pressure or Pressure Volume catheter directly into the left ventricle via the aorta.

Specifications Operating Modes: i s o Version LH Only Langendorff Mode at constant pressure or l a constant flow t e d Version WH Working Heart Mode (after Neely) h e Limiting Data: a r t Aorta, ID 0.8 to 2.5 mm s y s Position of the Left Atrial Block and Pulmonary Artery, ID 0.8 to 2.5 mm t e Aortic Block in a Working Heart System, m Aortic Flow (WH) Up to 100 ml/min

s shown with optional MAP Electrode. Aortic Pressure Up to 300 mmHg I

s Atrial Pressure Up to 10 mmHg approx. with special option o up to 30 mmHg l Working Heart Extension a t e d Benefits On the Langendorff Preparation Following Signals O r g • Assessment of External Heart Work Under Can Be Measured: a n Adjustable Load (Preload and Afterload) LVP Isovolumetric LVP or Contraction Force

&

PP Perfusion Pressure (Aortic Pressure)

T • Optional Continuous Measurement of Metabolic i s Parameters, i.e. pH, pO , pCO CF Coronary Flow s 2 2 u e • Compact Design, Optimized for Each Species: ECG Electrocardiogram Mouse, Hamster, Rat, Guinea Pig MAP Monophasic Action Potential

• Modular Design to Integrate More Applications pO 2a / e Oxygen Partial Pressure in the Affluent /Effluent in the Future pH pH in the Effluent • Unsurpassed Physiological Environment T Temperature • Unique Aortic Block for Precision Preload and On the Working Heart Preparation Following Signals Afterload Control Can Be Measured: • Small Flow Resistance and Low Dead Space Volume PrP Preload Pressure for Highly Reproducible and Accurate Results AoP Aortic Pressure (Afterload) • Low Volume Drug Injection Pathway LVP Left Ventricular Pressure • Solid State Physiological Circuit Mimics In-vivo PV Loops LV Pressure-Volume Loops Perfusion and Prevents Measurement Artifact AF Aortic Flow • Provides a valuable tool for the researcher who CO Cardiac Output (Flow into Left Atrium) wants to study cardiac function and metabolism ECG Electrocardiogram • Combines the advantages of an isolated organ MAP Monophasic Action Potential pO a / e Oxygen Partial Pressure in the Affluent/Effluent preparation with in situ-like perfusion features 2 • Allows a more comprehensive monitoring of pH pH in the Effluent functional parameters, the calculation of the ex - T Temperature ternal heart work and mechanical efficiency, and a considerably higher sensitivity for various For a system description according your requirements please use: experimental manipulations www.hugo-sachs.de/ihmail.html or contact our technical experts at: The Working Heart model is the ultimate Ex-Vivo physiological model. The [email protected] IH-SR Working Heart allows the researcher to take full advantage of this For a custom configuration and full system quotation. model with physiological simulation that cannot be matched.

30 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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A L a t ) H a r R u t b e T s s a m . r c t s o m s 3 1 Isolated Organ & Tissue isolated heart systems ad i vanced s o IlHa-5 tIseoladted Hheaert aSizre 5t systems research Rat, Guinea Pig and Rabbit

Isolated Heart Size 5

Aortic Block and Heart Chamber Arranged for Langendorff perfusion i s o l a t e d h e a r t s Features and Benefits

y Applications (continued) s t e • Langendorff and Optional Working Heart Perfusion • Ischemia and Reperfusion m s in a Single System • Cardiac Preconditioning • Compact Design, Optimized Individually for: I

s • Cardiovascular Screening Performance o Rabbit, Rat or Guinea Pig l a • Phenotyping of Transgenic Animals t e • Constant Pressure or Constant Flow Perfusion in d • Compound Screening

O One Unit, Easily Switch Between the Two Modes r g • Compact, Doesn’t Require Wall Installed High a In either Langendorrf or Working Heart configuration, the IH-5 can be n

Water Columns, Suitable for Hearts from & outfitted as a complete Cardiac Physiology Workstation with a range of

T Hypertensive animals (Perfusion Pressures up

i measurement devices, signal conditioning equipment and acquisition & s to 300 mmHg are Possible) s

u analysis software to provide a superior solution for virtually any study. e • Unique Integrated Small Volume Aortic Block with To get started, select the basic system then add specific options to suit the Built-in Bubble Trap and Windkessel particular needs of your study. If any questions arise, our expert technical • Unique Cannulae Design team of scientists and engineers is always ready to assist with system – Cannula Resistance is Optimized According configuration, application support or custom design requests. to Hagen-Poiseuilles Physical Law – Different Cannulae Sizes Available, All Metal, Langendorff Heart System No Weak Glass Cannulae (Retrograde Perfusion) • Proprietary Mini Holders Allow Easy and Stress Free Access to Hold Electrodes and Catheters in Position The IH-5 utilizes the proven architecture of our ground-breaking IH-SR to • Drug injection pathway built directly into aortic set the standard for isolated heart perfusion in rabbits, adult guinea pigs perfusate stream and adult rats. Engineered for the increased flow produced by these species, the IH-5 offers ultimate perfusion stability and real physiological • Can easily be upgraded to a working heart system conditions for longer, more relevant recordings with fewer artifacts. Applications Both Langendorff and Working Heart versions allow a choice of • Electrophysiology studies Monophasic Action measurement capabilities unmatched by any existing system, with Potential (MAP) single and multiple ECG measurements dedicated capability packages available for specialized applications. • Dispersion of ventricular repolarization Perfusion of larger hearts creates the opportunity for detailed study of • In-depth hemodynamic applications including study cardiac electrophysiology. With dedicated electrodes, positioners, of cardiac flow, LVP and pressure-volume relationships amplifiers and software for a complete cardiac electrophysiology • Treatment with Inotropic and Vasoactive Substances workstation, the IH-5 is the only choice for measurement and analysis of multiple ECG and MAP signals. • Cardiac Rhythm

32 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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s 3 3 Isolated Organ & Tissue isolated heart systems ad i vanced s o IlHa-5 Itseoladted Hheaert Saizre 5t systems research Rat, Guinea Pig and Rabbit (contined)

Multi-Lead ECG Recording The heart is immersed in the heart chamber. The ECG-electrodes are mounted on an insert placed into the heart chamber. The ECG-signals are picked up from the heart surface using the conductivity of the perfusate. The three electrodes are arranged on the insert to mimic an ‘Einthoven’ derivation with the reference electrode located beneath the heart. The additional six electrodes are mounted around the heart on a special ring to record unipolar Wilson leads V1 to V6. The electrodes are connected to the input box located on top of the unit (on the same box as the MAP electrodes). The box is connected to the PLUGSYS EGM (Einthoven Goldberger Module) and the PLUGSYS WLA (Wilson Lead Amplifier). The twelve leads recorded are I, II, III, aVL, aVR, aVF, V1 to V6. i s o If only a single ECG derivation (II) is required two single elctrodes are simply l a t

e mounted with ball joint holders on the aortic block. In this case the insert is d

not required. h e a r Multiple MAP Recording t s y A special holder for up to 8 MAP-electrodes has been designed. On this holder s t e are located eight evenly spaced cantilever arms holding spring-loaded m

s monophasic action potential electrodes. The spring-force (pressure of the electrodes against the epicardium) can be adjusted individually for each I s

o electrode. Even the position of the electrode on the heart can be adjusted l a Circular Holder for Placement of MAP Electrodes and Multi Lead ECG individually. The electrodes are connected to the main input box type 701/1 t e d fixed on the top of the unit. This input box is connected to the MAPM

O System Description

r (Monophasic action potential module) type 703 an especially designed PLUGSYS g a module. One MAPM can handle six electrodes, two modules are requested.

n The IH-5 is very compact, improved for low volume and high environment

& stability. A special electrode for endocardial MAP is also available. This electrode is

T i All of the components are mounted on a basic Plexiglas stand except for the mounted with ball joint holders on the aortic block s s u thermocirculator, and the PLUGSYS amplifier system. Special attention has e been made to ensure that all critical connecting tubing are maintained short, thus avoiding any cooling through a temperature gradient to ambient Specifications temperature. Perfusion Kit The key part of the system is the unique aortic block which is the interface Body Weight Up to 2.5 kg between the heart and the IH-5. The bubble trap, compliance chamber, Heart Diameter 25 mm patented flow resistance membrane, infusion and measurement ports are all Heart Length (Base - Apex) 30 mm integrated into this single specialized component. In addition, the aortic block Aorta, ID Up to 5 mm features adjustable attachment points for our proprietary Mini Ball Joint Holder Aortic Flow (in WH Mode) Up to 500 ml/min positioning system. This permits precise placement of measurement probes for ultra-stable recordings. Perfusion Pressure (Afterload) Up to 300 mmHg The modular nature of the IH-5 allows the system to evolve along with your Order # Product research. A Langendorff system can easily be upgraded to full Working Heart; and any IH-5 can be upgraded with special purpose capabilies like multi- 73-3604 Basic Unit for Isolated Heart Size 5 Type 843/1 channel ECG and MAP for a complete cardiac electrophysiology workstation. 73-2916 Heart Chamber for IH5 D=135/100 mm H=115 mm 73-3072 Aortic Cannulae Set to IH-5 for Rat/Guinea Pig Hearts The connection to the heart is made through interchangeable aortic cannulae and atrial cannulae in working heart extension. The perfusate is aerated by 73-0719 Aortic Cannulae Set to IH-5 for Rabbit Hearts bubbling in the reservoir. When the perfusate contains erythrocytes or albumine, 73-3064 Working Heart Option to IH-5 Basic Unit a special membrane oxygenator to prevent foaming can equip the unit. In the 73-3066 Left Atrium Cannula for IH-5 for Rat/Guinea Pig Heart, Langendorff mode, heart contractility is measured using a balloon inserted OD=2.3 mm into the left ventricle and connected to a pressure transducer. 73-2880 Left Atrium Cannula for IH-5 for Rabbit Heart, OD=6.0 mm Additional equipment required: thermocirculator, peristaltic pumps, transducers, monitoring system setup using the PLUGSYS Amplifier System. Data acquisition and Evaluation using ISOHEART software.

34 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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• For the perfusion of two indicator lights. One illuminates when the bath is plugged into the AC line. This System includes the the excised The second illuminates whenever the heating circuit is energized. A screw-in components mammalian heart fuse holder is also mounted on the front panel for easy access. A drain hole with below • Large capacity tubing, a plug and a tapered plastic cone are located in the bottom of the water warming bath with tank. The soft rubber bung that carries the stem of the warming coil fits into the temperature cone making a leakproof joint. The glass warming coil for the perfusing fluid is 5 controlled to 0.5°C cm (2 in) diameter by 9 cm (3-1/2 in) long. It has a capacity of approximately 35 ml. The stem of the warming coil connects to the heart cannula with tubing and • Free-standing a pinch clamp controls the flow of the warmed perfusate. A clamp and grooved apparatus uses rod are supplied for securing the bottom of the excised mammalian heart. minimal bench space The heart cannula has openings to accommodate both a manometer and thermometer. The manometer has a fixed clamp for mounting directly to a i s o crossbar and is connected to the cannula by tubing. The scale reads 0 to l a t 250 mmHg and is free to move up and down behind the tubing to facilitate e d

zero adjustment. The glass thermometer is straight, 10 cm (4 in) long and h The ‘Langendorff’ preparation offers extreme flexibility for handling the e a perfusing fluids: graduated from 0° to 50°C by 0.1°C increments. It is mounted in a rubber r t

bung and fits into the side arm of the heart cannula. All of the clamps, s y • The perfusing fluid reservoir serves as a Mariotte ™ s stands and rods supplied with this apparatus are from our Stronghold line. t flask that maintains a constant perfusion pressure e m as the reservoir empties Two light pulleys are supplied and carry a thread from the heart to a s transducer (not supplied) or writing point. • The perfusion pressure can be varied easily and rap - I s idly by varying the height of the reservoir above the o

l perfused heart. The height of the reservoir can be a t

e varied through 62.5 cm (24 in) d Order # Product Order # Product

O • To rapidly change perfusing fluids a second reser - r g voir (offered as an accessory) can be added to the System Components System Components a n second frame upright and a ‘Y’ connector can con - 50-0496 Constant Head 1 L 53-2522 Rod, 250 mm (10 in)

& nect it to the glass warming coil Reservoir 53-2530 Rod, 500 mm (20 in) T i s 50-0488 Reservoir Holder 53-2550 Rods, 750 mm s u The 1 liter reservoir supplies a constant head of perfusate. The perfusate flow 50-0587 Aeration Reservoir (29 in), qty. of 3 e rate is controlled by one of two methods. If the Reservoir cap is off, the flow 50-0595 Aeration Stone 53-2336 Extra Weight rate is controlled directly by a pinch clamp on the outlet tubing. If the reservoir with Tubing Rectangular cap is tightly sealed, a Mariotte flask is created and the flow rate is set by the 50-0537 Bath Assembly Laboratory Stand perfusion pressure. The height of the reservoir determines this pressure which Base, qty. of 2 50-2898 Tubing 1 m (3-1/4 ft) in turn sets the rate of air allowed to enter the reservoir. As air enters, the 53-2102 Small Clamp with 50-0554 Warming Coil perfusate flows out. This reservoir is placed in the three-prong, spring clip Extension Stem 50-2369 Rubber Bung reservoir holder that has a 20 cm (8 in) long tube that slips on the top of a rod 53-2012 Closed Connectors, and locks in place by a knurled set screw. Using this set screw the height of the 50-2914 Screwclips, 2 qty. of 5 Reservoir can be varied from 15 cm (6 in) above the top of the rod down to the 50-0562 Red Rubber Bung 53-2032 ‘T’ Connectors, top of the rod. If it is necessary to lower the reservoir even more, the holder has 50-0563 Cannula qty. of 3 a clamp mounted on one side that can locate the holder at any point on the rod. 50-6287 Thermometer 53-2062 Large 360° Rotation Connector The total vertical movement of the reservoir is 62.5 cm (24 in) above the top of 50-0588 Manometer 53-2244 Male-Female the fluid warming coil. The aeration reservoir is mounted to the side of the 50-7624 Plug Hinged Adapter reservoir holder. The perfusing fluid is led from the main reservoir to the 50-0596 Tying Rod 50-0686 Ink Pen with Lever aeration reservoir by tubing provided. The aeration stone is mounted on the end 53-2262 Pulleys, qty. of 2 50-7681 Replacement of 2 m (6.6 ft) tubing. This aeration stone fits inside the aeration reservoir and 53-2512 Rod, 150 mm (6 in) Ink Pen provides a high level of oxygenation to the perfusant. 50-0678 Brodie Lever The transparent, heavy plastic water bath which warms the perfusant measures, H x W x D, 15.5 x 16.5 x 14 cm (6-1/4 x 6-1/2 x 5-1/2 in) and has a capacity of 3.6 Order # Product liters. The bath is heated by two simple sturdy cartridge elements that are mounted through the front of the tank near the bottom and extend 5 cm (2 in) into 50-2864 Student Isolated Heart Perfusion Apparatus, 115 VAC, 60 Hz it. These heating elements have a combined rating of 80 watts. The temperature 50-2872 Student Isolated Heart Perfusion Apparatus, of the water is controlled by a front panel dial graduated from 15° to 45°C by 5°C 230 VAC, 50 Hz graduations. A metal tube mounted inside the bath carries a sensitive thermistor 50-2880 Second Reservoir Set Includes Reservoir Holder, sensing bead. Once stabilized, this system maintains the water temperature 1 L Reservoir, glass Aeration Reservoir and Aeration within 0.5°C of the desired temperature. The front panel of the water bath has Stone. Set comes complete with tubing and connectors for mounting on second rod of Perfusion Apparatus

36 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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Perfusion System This system is simple to setup, operate and maintain. Its compact design for Cell Isolation minimizes the bench space required for the system. The wetted components of the perfusion circuit can be flushed with a 70% ethanol solution or autoclaved for sterilization purposes. Additional equipment required: thermocirculator, peristaltic pumps, magnetic stirrer, reservoir, cannulae, operating table and others depending on verison selected, eventualy transducers, monitoring system setup using the PLUGSYS Amplifier System.

Order # Product 73-3756 Easy Setup for Cell Extraction by Organ Disintegration Type 803 73-3761 Heart Chamber to Easy Cell Extraction System c e l l

i For a system description according your requirements please use: s o www.hugo-sachs.de/ihmail.html l a

t or contact our technical experts at: i o

n [email protected] For a custom configuration and full system quotation. I s o l a t e d

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T i s s u e

Easy Setup for Cell Extraction by Constant Flow Perfusion • Cell isolation from mouse, rat, guinea pig organs by disintegration using protease solution • Designed for cardiomyocyte isolation • Can be used for other organs In Situ or Ex Vivo

This perfusion system has been specifically created to meet the needs of individuals who wish to isolate primary cells from organs of species in the size range of mouse to guinea pigs. The system can be configured for either In Situ or Ex Vivo organ perfusion. The system is first used with perfusate for the blanching and than with the protease solution for tissue disintegration. The perfusate for blanching is warmed and oxygenated in separate buffer reservoir and supplied via the peristaltic pump and warming coil. The protease solution is in a separate reservoir oxygenated and stirred. For In Situ perfusion an operating table can be placed just below the warming coil, for Ex Vivo application (heart, liver...) the system can be equipped with a jacketed chamber. We offer a complete line of custom perfusion cannula (Aortic, In Situ and Ex Vivo) to accommodate vessels from 1.0 to 3.5 mm ID. The In Situ and Ex Vivo cannulae feature our unique tip basket to prevent vessel occlusion.

38 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com H I C • • • • • • • • • • s a o r B I P r P E d L H N m A m S D

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– Hypoxic vasoconstriction analysis (pO 2, pCO 2, pH) • Pharmacology • Deoxygenation using membrane oxygenator of – Action of histamine, arachidonic acid metabolites blood or erythrocyte containing perfusion – Immunopharmacology (cytokines...) • Large choice of accessories: thermocirculator, jacketed reservoir, holders etc • Inhalation toxicology – Environmental toxins (ozone, sulphur dioxine...) • Biochemistery – Metabolic activity (biogenic amines, prostacyclin, angiotensin..) – Surfactant biochemistry

40 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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u . s s m e . c : o m s 4 1 Isolated Organ & Tissue tiesoxlt ated lung systems ad vanced i s o IPLl-a2 Istoelatded Plerufusnedg Lu nsg fyor stems rese arch Rat & Guinea Pig

Isolated Perfused Lung System i s o l a t e d l u n g s y s t e t e m x s t I s o Benefits and Features • Biochemistery l a t • Optimized temperature conditions for the isolated e – Metabolic activity (biogenic amines, d

lung, unique jacketed thoracic chamber prostacyclin, angiotensin..) O r g • Optional operating table for non-damaging in-situ – Surfactant biochemistry a n preparation

& Additional Options Include:

T • Negative-pressure ventilation similar to in-vivo i s condition or positive pressure ventilation available • Dedicated PLUGSYS ventilator module for s u negative or positive pressure ventilation VCM e • Low flow resistance and dead space volume, mini mize perfusion artifacts • Dedicated PLUGSYS module for regular induction of hyperinflation of the lung TCM (sigh, • Unique built-in pneumotachometer and air augmented breath) humidifier with small dead volume • Transducers and amplifiers for respiratory • Drug injection pathway built directly into pulmonary mechanics measurement: airflow, tracheal perfusate stream pressure, thoracic chamber pressure • Unique compensation system for vascular • Transducers and amplifiers for perfusion transmural pressure changes measurement: realtime flow, perfusion pressure, • Dedicated option for continuous measurement venous pressure, temperature etc... of lung weight (Edema) • Dedicated software PULMODYN for data • More measurement parameters than any other acquisition and analysis of respiratory mechanics system and perfusion Applications • Optional connection for external ventilator (see • Studies on combined respiratory and vascular section F) for testing barotraumatic ventilation effects • Optional connection for supplying alternative gas • Physiology: mixtures and/or aerosols – Hypoxic vasoconstriction • Sensor and amplifier for continuous perfusate analysis (pO , pCO , pH) – Edema formation 2 2 • Deoxygenation using membrane oxygenator of • Pharmacology blood or erythrocyte containing perfusion – Action of histamine, arachinodic acid • Large choice of accessories: thermocirculator, metabolites jacketed reservoir, holders etc... • Inhalation toxicology – Environmental toxins (ozone, sulphur dioxine)

42 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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n o n m r t - s 4 3 Isolated Organ & Tissue tiesoxlt ated lung systems ad vanced i s o IPLl-a4 Istoelatded Plerufusnedg Lu nsg fyor sRatbebit ms research

Additional Options Include: Isolated Perfused Rabbit Lung System • Dedicated PLUGSYS ventilator module for negative or positive pressure ventilation VCM • Dedicated PLUGSYS module for regular induction of hyperinflation of the lung TCM (sigh, augmented breath) • Transducers and amplifiers for respiratory mechanics measurement: airflow, tracheal pressure, thoracic chamber pressure • Transducers and amplifiers for perfusion me asurement: realtime flow, perfusion pressure, i s venous pressure, temperature etc... (see section I) o l a • Dedicated software PULMODYN for data t e d acquisition and analysis of respiratory mechanics l u and perfusion n g

Benefits and Features

s • Optional connection for external ventilator (see y s • Optimized temperature conditions for the isolated page section F) for testing barotraumatic ventilation t e t e m lung, unique jacketed thoracic chamber x • Optional connection for supplying alternative gas s t • Optional operating table for non-damaging in-situ mixtures and/or aerosols I s preparation o • Sensor and amplifier for continuous perfusate l a • Negative-pressure ventilation similar to in-vivo analysis (pO , pCO , pH) t 2 2 e d condition or positive pressure ventilation available • Deoxygenation using membrane oxygenator of

O r • Low flow resistance and dead space volume, blood or erythrocyte containing perfusion g a n mini mize perfusion artifacts • Large choice of accessories: thermocirculator,

& jacketed reservoir, holders etc

• Drug injection pathway built directly into pul monary T i s perfusate stream s u The Following Signals Can be Measured: e • Unique compensation system for vascular trans- mural pressure changes FL Respiratory Airflow • System dedicated option for continuous TCP Thoracal Chamber Pressure (intrapleural pressure) measurement of lung weight (edema) TP Tracheal Pressure • More measurement parameters than any other PP Perfusion Pressure system VP Venous Outflow Pressure Applications W Lung Weight Changes pO a/e Oxygen Partial Pressure in the Affluent/Effluent • Studies on combined respiratory and vascular effects 2 pCO a/e CO Partial Pressure in the Affluent/Effluent • Physiology: 2 2 pH a/e pH in the Affluent/Effluent – Hypoxic vasoconstriction T Temperature – Edema formation The Following Parameters Can be Evaluated • Pharmacology Using PULMODYN: – Action of histamine, arachinodic acid metabolites Peak Inspiratory and Expiratory Airflow • Inhalation toxicology Tidal Volume, Minute Volume – Environmental toxins (ozone, sulphur dioxine...) Lung Resistance, Dynamic Compliance Vascular Resistance • Biochemistery Precapillary and Postcapillary Resistance – Metabolic activity (biogenic amines, prostacyclin, Filtration Coefficient angiotensin..) O , CO Exchange – Surfactant biochemistry 2 2

44 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com

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e e u t c e s t : e o r e o i d p n m g s 4 5 Isolated Organ & Tissue isolated lung systems advancedisoIPLl-1a6 tIseoladted Pleurfunsegd L usngy fosr tems research Pigs and Large Animals

Description The apparatus consists essentially of a jacketed Plexiglass thoracic chamber (inside dimensions 400 x 500 x 300 mm) and a jacketed cover. The size has been chosen so that a complete pig lung (both lobes) can be mounted inside it. The lung is placed on a platform. The platform can be moved out of the chamber to facilitate the surgery. All connections for perfusion and ventilation are mounted on the plattform. This arrangement offers the advantage that connecting tubing and cannulae can be kept short, resulting in a very small dead volume and ensuring optimum thermal stability. Perfusion

i Constant flow perfusion may mimic the in vivo situation more closely, s o

l however, it has the disadvantage that hydrostatic edema becomes a t e inevitable during vasoconstriction. Constant pressure perfusion permits d

l higher perfusate flow rates since vasoconstriction decreases perfusate u Benefits and Features n flow and hydrostatic edema is less likely to occur. The chamber is the g

• Optimized temperature and humidity conditions for s perfusate reservoir (whole blood or erythrocyte containing perfusate). y

s the isolated lung, unique jacketed thoracic chamber t Perfusion takes place at constant flow. The perfusate is taken from the e m • Continuous measurement of lung weight to reservoir and is passed by means of a peristaltic pump at constant flow s monitor edema formation through the deoxygenator and primary heat exchanger, through a second I s • Very low flow resistance and minimal dead space heat exchanger and a bubble trap to the pulmonary artery and finally into o l a volume virtually eliminate perfusion artifacts the lung vascular bed. The venous discharge returns to the reservoir. For t e d • Drug injection pathway built directly into ventilation, a large animal ventilator Model 665 or 663 or a human

O pulmonary perfusate stream for precision ventilator is used. r g a compound dosing and screening The chamber also includes our exclusive lung weight measurement system n

& • Removable platform to facilitate surgery for continuous monitoring of edema formation.

T i s • Standard connection for ventilator Extensions s u • More measurement parameters with greater e Aerosol nebulizer for inhaled compound challenge Controller for constant precision than any other system pressure perfusion Applications Additional Options Include • Respiratory mechanics • Transducers and amplifiers for respiratory mechanics measurement: airflow, tracheal pressure, thoracic – Airway Flow, Tidal Volume, dynamic chamber pressure resistance and compliance • Transducers and amplifiers for perfusion measure - • Vascular permeability studies ment: realtime flow, perfusion pressure, venous – Arterial and venous resistance calculations pressure, temperature etc. – Inflammation (?) and Tissue Edema • Dedicated software PULMODYN for data acquisi - monitoring tion and analysis of respiratory mechanics and perfusion • Pharmacology • Sensor and amplifier for continuous perfusate – Compound screening, e.g. action of analysis (pO 2, pH) histamine, arachinodic acid metabolites • Deoxygenation using membrane oxygenator of • Inhalation toxicology whole blood or erythrocyte containing perfusion – Environmental toxins, e.g. Ultrafine • Large choice of accessories: ventilators, thermocir - particles, ozone, sulphur dioxin... culator, peristaltic pumps, holders etc... • Biochemistery – Metabolic activity, e.g of biogenic amines, prostacyclin, angiotensin.. Order # Product – Surfactant bioactivity 73-4302 IPL-16 Core System, 115 V • Therapy studies 73-4301 IPL-16 Core System, 230 V – Study of chemotherapy applications using a human lung lobe after lobectomy of the lung is performed in lung cancer patient

46 Harvard Apparatus • phone 508.893.8999 • toll free U.S. 800.272.2775 • fax 508.429.5732 • www.harvardapparatus.com