Pulsatile Flow in Pulmonary Artery, Capillary, and Vein in the Dog'

Cardiovascular Research, 1974, 8, 330-337.

Pulsatile flow in pulmonary artery, capillary, and vein in the dog' Downloaded from https://academic.oup.com/cardiovascres/article/8/3/330/298317 by guest on 25 September 2021

WARREN G. GUNTHEROTH, RICHARD GOULD, JOHN BUTLER, and EDWIN KINNEN~ With the technical assistance of Donald Breazeale, George McGough, and John Mendenhall From the Departments of Pediatrics and Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA

AUTHORS' SYNoPsis The temporal relationship of flow pulses in the pulmonary artery, capillaries, and veins was investigated in 10 chronic dog preparations with pulsed ultrasonic flowmeters and a nitrous oxide-body plethysmograph for capillary flow. Implanted pressure transducers in the left atrium provided reference to the conventional atrial pulses: A, C, X-descent, V, and Y-descent. Left atrial contraction produced an A-wave pressure transient followed by retrograde flow up the veins. The C-pressure pulse occasionally produced a minimal trough in the venous flow pattern. Early in ventricular systole, X-descent in left atrial pressure preceded a venous flow pulse of modest amplitude, which began prior to the onset of the pulse of capillary flow. On average, right ventricular ejection was followed in 37 msec by the major flow pulse in the capillaries, which in turn was followed 68 msec later by the onset of venous flow. This venous flow pulse was simultaneous with a rise in left atrial pressure, the V-wave. With the onset of diastole, the Y-descent in atrial pressure preceded a major venous flow pulse. With accelerated heart rate, separation of the V and Y venous flow pulses was lost, and a monophasic pulse was found.

Pulsatile flow patterns in the main pulmonary or to reflect left ventricular dynamics (Morgan artery have been reported for the past decade et al, 1966b), or a combination of both right and from ultrasonic and electromagnetic flow re- left heart activity (Kinnen and Stankus, 1968). cordings (Franklin et al, 1962; Hoffman et al, An analysis of the temporal sequence of the flow 1965; Morgan et al, 1966a). Pulmonary capillary patterns in the pulmonary artery, capillary, and flow is also pulsatile, as has been shown by Lee vein and the downstream pressure pulses in the and Du Bois (1955), with a nitrous oxide-body left atrium would be of considerable assistance in plethysmograph technique (Wasserman et al, resolving the origin of the pulsatile flow pattern 1966). Similarly, pulmonary vein flow is pulsatile, in the pulmonary vein. and the pulse has been regarded as transmitted We have combined the use of pulsed ultrasonic from the pulmonary artery (Morkin et al, 1965) flowmeters, nitrous oxide-body plethysmograph, and implanted pressure transducers, providing Supported by Public Health Service Grants HE 03998. HE 13517. and HE 10289. E.K. was a Special Fellow of the Public Health Service the first simultaneous measurement of pulmonary (HE 48675). artery, capillary and vein flow, and left atrial Reprint requests to: Warren 0.Guntheroth, Department of Pedia- trics (RD-20). University of Washington School of Medicine, Seattle, pressure. We conclude that the forward flow Washington 98195, USA. pulses in the pulmonary vein cannot be ascribed a Present address: Department of Electrical Engineering, University of Rochester, Rochester, New York. entirely to transmitted pulses from the right 331 Flow pulses in pulmonary artery, capillary, and vein heart, but represent a variable interaction between absorption of nitrous oxide was recorded from the vis a tergo and uis a fronte. airflow into the plethysmograph after the lungs had been inflated with an 80% N20:20%O2 mixture. Methods Brief apnoea is induced by hyperventilating just The dogs, weighing 16 to 24 kg, were anaesthetized before the absorption recording. The record of the with pentobarbital (30 mg/kg iv). Respiration was absorption after a similar inflation with air, which supported by a Palmer respirator and a left gives the zero flow level, was subtracted point by

thoracotomy was performed under surgical asepsis. point, manually, to obtain the true capillary blood Downloaded from https://academic.oup.com/cardiovascres/article/8/3/330/298317 by guest on 25 September 2021 Light-weight, bivalved flow transducers for a flow. The frequency response of the plethysmo- pulsed ultrasonic flowmeter (Franklin et al, 1959; graphic apparatus is flat to 13 Hz. Zero flow levels Mullins et al, 1962) were placed around the for the ultrasonic flowmeter were obtained by root of the main pulmonary artery and the left temporary cardiac arrest with intravenous actyl- lower lobe pulmonary vein. The flow probes were choline. Calibration was not performed since timing large enough to cause no compression of the of events was our primary concern in this study. artery or vein with the chest open. Silastic cannulae. Records of pulmonary vein flow were used only were inserted through purse-string sutures into the from those animals in the first two or three weeks main pulmonary artery and left atrium in the first after operation to minimize the risk of fibrosis five animals and solid-state pressure transducers causing obstructed pulmonary vein flow. Moreover, were implanted in the last five. the presence of fibrosis, confirmed by necropsy The animals were allowed to recover for one after several weeks, could easily be predicted by week. Records were obtained under light anaes- the diminished and dampened flow signal during thesia using morphine (2 mg/kg im) and pento- the cardiac cycle. The internal diameter of the barbital (15 mg/kg iv). The animal was intubated venous flow probe was 6 mm, which was one third and placed in a dog-sized, whole-body plethys- of the diameter of the probe for the pulmonary mograph of 47.5 1. (Fig. 1). The technique has been artery, and consequently one ninth of the cross- previously described (Cheney et al, 1969); pulsatile sectional area. With identical amplification of the

FIG. I Dog plethysmograph. Flow into the box through the flowmeter (3) reflects instantaneous N20 absorption in the pulmonary capillaries from the previously inflated lung, during apnoea. Other flow transients due to gas absorption and the mechanical activity of the heart are recorded afrer an exactly similar air inflation (air bag) and subtracted from the experimental record after inflation with N20(N20 bag). FA= femoral artery catheter, Ppa=pulmonary artery pressure, PLA=left atrial pressure, V =flowmeter in wall of plethysmograph, QPa =pulmonary artery pow, QPV =pulmonary venous flow, Jug vein =jug venous catheter. 332 Guntheroth, Gould, Butler, and Kinnen flow signal for the two vessels, it was possible to (Linderholm et al, 1962). We tested this with our estimate the relationship of flow in the pulmonary apparatus by injecting a small bolus (about 0.5 ml.) vein to the cardiac output (root of the pulmonary of saline into a small pulmonary vein of an acutely artery). Since there are usually five pulmonary veins, prepared dog in the plethysmograph. A very thin a damped flow record would result if the flow in the (0.6 mm ID; 1.5 mm OD) polyethylene catheter was pulmonary vein was substantially reduced below threaded retrogradely up the pulmonary vein from one fifth of the cardiac output. For the actual the left atrium to pierce the wall of a small vein and recording, the amplifier gain for the pulmonary then the lung surface. It was drawn through until a Downloaded from https://academic.oup.com/cardiovascres/article/8/3/330/298317 by guest on 25 September 2021 vein was increased, relative to the pulmonary bell-shaped expansion on its inner end wedged in a artery, for better identification of the component venous bifurcation. The catheter was cut as short pulses. as possible and connected to a thick walled T-tube, The plethysmograph record has been assumed to one limb of which went toa strain gauge manometer lag the capillary flow events by between 5 msec and the other to a 5 ml. syringe. The system was ( Wasserman and Comroe, 1962) and 20 msec filled with saline. Striking the plunger caused a

PULMONARY ARTERY FLO\

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LEFT ATRIAL

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E LEC TROCAR DyIy"Ytlt 10 GRAM FIG. 2 Photographic recording of simultaneous pulsatile pulmonary flows in an intact chronic animal preparation with left atrial pressure and the electrocardiogram. The left atrial pressure was obtained with an implanted, solid-state device. Pulmonary artery and vein flow were recorded with pulsed ultrasonic flowmeters. The pulmonary capillary flow record is that obtained with nitrous oxide, and for quantitative data the curves obtained with air must be subtracted point by point. However, in this animal the upstroke of the major pulse is not afected for purpose of timing, except for the instrumental time lag of 16 msec (roughly three quarters of a division). Component waves of pulmonary vein flow and left atrial pressure are labelled according to conventional alphabetic usage. 333 Flow pulses in pulmonary artery, capillary, and vein

pressure transient via the T-tube and a flow jet into recorded on photographic paper. In the figures used the small veins and capillaries. In six studies, the here selection was dictated primarily by the clarity resulting transient in the capillary blood flow from of wave form of the pulmonary vein flow. (With the plethysmographic record lagged the pressure primary variables of three flows and three pressures transient an average of 16 msec (range 15.3 to records of one or two of these would occasionally 17.3 msec). This 16-msec delay was used in calcu- be less than optimal.) However, the numerical data lating transit time. on transmission time and the conclusions as to the

Although it is not possible to obtain pulmonary relationships of the pressure and flow wave com- Downloaded from https://academic.oup.com/cardiovascres/article/8/3/330/298317 by guest on 25 September 2021 capillary flow records in unanaesthetized dogs, it is ponents rest on analysis of literally thousands of possible to record flows with the ultrasonic flow- feet of analog recordings from all 10 animals. meters and pressure transducers. This permitted evaluation of the effects of spontaneous variations Results in rate. Additional perturbations for relating The flow pulse in the main pulmonary artery pressure and flow waves were performed with acetylcholine (2 mg) and phenylephrine (0.3 mg) rises sharply to a single peak, and falls more intravenously. gradually in late systole, ending in a reverse flow Polygraph recordings were made initially on a pattern coincident with closure of the pulmonary direct-writing Sanborn 350 and simultaneously on valve (Fig. 2). The pulmonary capillary flow FM magnetic tape. The tape was replayed and pulse often showed a diastolic notch, but there

-One Second- I '~

PULMONARY ARTERY dFLOh

N20 PLETHYSMOGRAPH

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FIG. 3 Photographic recording from the same animal presented in Fig. 2 showing the efects of a pure alpha-adrenergic agonist, phenylephrine. Amplification for the variables hus been arbitrarily set to emphasize the relative changes in lefi atrial pressure, and pulmonary vein flow, and to some extent, pulmonary capillary pow. The V-flow pulses are greatly attenuated in the pulmonary vein and even in the capillaries whereas, with the Y-descent in left atrial pressure there is a marked accentuation of flow in the vein and capillary. 334 Guntheroth, Could, Butler, and Kinnen Downloaded from https://academic.oup.com/cardiovascres/article/8/3/330/298317 by guest on 25 September 2021

FIG. 4 Recording from a resting, unanaesthetized animal demonstrating the eflects of varying heart rate (sinus arrhythmia) on the pulmonary vein flow. Left atrial and carotid artery pressures were obtained with solid-state transducers. The electrocardiogram and phonocardiogram are included for timing. After a long filling interval, a large retrograde flowpulse (due to A-wave) is observed, and two major antegrade flow pulses, V and Y, the first of which is associuted with a rise in left atrial pressure, the V-wave, and the second a decrease in pressure, the Y-descent. A third antegrade flow pulse of small magnitude, the X-pulse, also follows the X-descent in left atrial pressure. As the rate accelerates, the pulses merge into a monophasic wave. 335 Flow pulses in pulmonary artery, capillary, and vein was no other consistent pattern except for a The effects of spontaneous changes in heart fairly wide pulse with a slow rising leading edge rate on the morphology of the venous flow pulse and a prolonged diastolic decline. The foot of this is best seen with sinus arrhythmia. Fig. 4 is from capillary pulse occurred 37 k 4 msec (mean and an awake animal, demonstrating the relationship standard error for all animals) after the foot of of left atrial pressure and pulmonary vein flow the arterial flow. Alpha adrenergic stimulation with marked interval variability. Inspiration with phenylephrine markedly attenuated the occurs twice in this record; at the start and with systolic portion of the capillary flow and en- the fourth beat. After very long beat-to-beat Downloaded from https://academic.oup.com/cardiovascres/article/8/3/330/298317 by guest on 25 September 2021 hanced the diastolic flow so that the dominant intervals, atrial contraction produces large flow in the pulmonary capillaries occurred just regurgitant A-waves, which are progressively after the Y-descent of the left atrial pressure and reduced to slight troughs in the flow record, the pulmonary venous flow labelled Y (Fig. 3). without actual reversal. With the longer intervals, The pulsatile patterns of pulmonary venous three components of forward flow can be flow were the most variable of the three flow recognized : a small X-wave, a dominant V-wave, sites. In half of the records with normal, rela- and a large Y-wave. As the heart rate accelerates, tively slow heart rates, multiple waves could be these waves merge to form a monophasic flow identified in the pulmonary vein, with the pulse. Tachycardia following arrest induced by characteristic patterns seen in Fig. 2. The inter- intravenous acetylcholine produces similar, relationships of the flow pulses in the three sites, monophasic waves, due to apparent overlapping and the relationship of the venous flow pulse to of the components identifiable at slower rates. the left atrial pressure pulses, were studied to try to elucidate the origin of the components of the venous flow. Discussion Atrial contraction (A) produces a positive The present data are in reasonable agreement pressure pulse which leads a negative flow pulse with past reports, except for details of pulmonary in the pulmonary vein. The left atrial C wave venous flow. Some of the differences can be in the pressure recording is followed by a attributed to methodology. Cinegraphic tech- minimal trough in the flow recording. The X- niques (Ferrario et al, 1968) are generally not descent of pressure is followed by a venous flow capable of sufficient resolution and frequency pulse of modest magnitude which clearly pre- response to separate multiple flow pulses. cedes the major flow pulse in the capillaries. Although the authors of that report concluded In Fig. 2, the largest venous flow pulse is that this forward pulmonary venous flow pulse coincident with the V-wave in the pressure was due to the transmitted right ventricular record. The foot of this V-flow pulse follows the ejection pulse, their published figures show that foot of the major pulse in the pulmonary capil- the foot of the venous flow pulse follows the right lary flow by only 40 msec in this animal, allowing ventricular ejection by only 20 to 30 msec. This for the delay of 16 msec in the nitrous oxide is less than the transmission time which we method. For all animals, the mean delay was observed to the capillaries, let alone the time to longer, 68 rt 4 msec. Finally, the Y-descent in veins. Other workers have used acute prepara- left atrial pressure leads the second large flow tions (Pinkerson, 1967), some with open chest. pulse of the pulmonary vein and capillaries. As the prevailing heart rate is relatively rapid The effects of phenylephrine given ‘intra- under such circumstances, the task of separating venously add evidence of the relationships overlapping pulses is difficult (Fig. 4). Morkin et between pulmonary vein flow and capillary flow a1 (1965), using a chronic preparation, measured and left atrial pressure. The V-wave in left atrial flow with electromagnetic flow probes, and pressure is relatively increased, whereas the obtained successful records in six of 33 operated corresponding flow pulse in the vein is attenuated. dogs. They concluded that the major determinant The Y-descent is very steep and is followed by of pulmonary vein flow was ejection from the the only major flow pulse, labelled Y. This venous right ventricle. flow pulse follows closely the major N20uptake The timing and origin of venous flow pulses pulse, which is entirely diastolic in timing. were established for the vena cava with the 336 Guntheroth, Could, Butler, and Kinnen pioneering work of Brecher (1956). The pulsatile drop in pressure during early ventricular systole, nature of the flow in the cava is entirely due to the X-descent (Fig. 2). The corresponding the events of the downstream (right) atrium and venous flow pulse is coincidental with, or prior ventricle, since the left ventricular pulse is to the capillary flow pulse and could not then be virtually eliminated by the multiple systemic attributed to a transmitted pulse. We feel that vascular beds of varying lengths and resistances. this flow, the X-wave, is due to ‘suction’ pro- Brecher predicted that the pulmonary vein flow duced by apical displacement of the mitral valve would have similar patterns and origins. Indeed, as the left ventricle contracts (Brecher, 1956). Downloaded from https://academic.oup.com/cardiovascres/article/8/3/330/298317 by guest on 25 September 2021 the first published patterns of the caval and Although the amplitude of the X-pulse is not as pulmonary venous flows in intact animals with striking as in the cavae, its recognition is slow heart rates were strikingly similar (Morgan particularly important when analysing trans- et al, 1966a). There were usually at least two mission times. forward flow pulses per beat, as well as a retro- It must not be stated that allof these wave forms grade pulse with atrial systole. A priori, only one are not seen regularly, and that in many circum- of the two forward pulses in the pulmonary vein stances - approximately half of our records in could be transmitted from the right ventricle (vis this study - the flow pulses run together and only a tergo) and the other should be attributed to a single flow pulse may be recognizable. In our left heart activity (ois afronte). combined experience with pulmonary vein flow We agree with the evidence that one major recordings from over 100 chronic animal pre- forward flow pulse in the vein, the V-wave, is parations, the V-pulse is the most persistent, transmitted from the right heart (vis a tergo) followed by the A-pulse and the Y-pulse. An (Morkin et al, 1965). The evidence is based on X-pulse of substantial magnitude occurs in the findings of a major flow pulse in the capillaries 25-30% of the observations. (Karatzas et al, 1970) which precedes the V-wave We conclude that in most physiological con- in the vein. Additional evidence for transmission ditions the right ventricular flow pulse is trans- from the right heart includes pulsatile flow from mitted through the pulmonary vascular bed and pulmonary veins detached from the left atrium may be identified in the pulmonary capillary (Pinkerson, 1967; Szidon et al, 1968), and flow, in the pulmonary vein flow, and in left atrial recently, pulsatile flow from pulmonary veins pressure as V-waves. With vasoconstriction, into a reservoir with variable compliance however, the V-waves are markedly attenuated (Kinnen et al, 1974). This venous flow pulse is even in the pulmonary capillary flow. TheX-wave approximately coincident, with rising pressure in precedes and the Y-wave follows the V-wave the left atrium (V-wave) as seen in Figs. 2,3, and and both are associated with descending 4. It would be difficult to explain a rising pressure pressure waves in the left atrium, and must be wave in the left atrium, associated with an attributed to vis a.fionte rather thantransmission. increase in vein flow, except as secondary to that With vasoconstriction, the Y-pulse becomes the flow wave. Atrial contraction, for example, dominant flow, not only in the pulmonary vein, produces an increase in pressure (A-wave) but a but in the capillaries. Since flow in the pul- retrograde flow pulse in the pulmonary vein. monary vein is directed into a pump with limited The other major flow pulse in the pulmonary compliance and intermittent ejection, the effects veins occurs during ventricular diastole. It of left heart events on pulmonary vein flow are follows and is distinct from the V-wave and hardly surprising. cannot logically be attributed to transmission from the right ventricle. This flow pulse follows References the Y-descent in the left atrium and may be Brecher, G. A. (1956). Venous Return. Grune and Stratton: presumed to result from filling of the left New York. ventricle. Under certain circumstances, such as Cheney, F. W., Takahashi, S., and Butler, J. (1969). Corn- parison of two methods of measuring pulmonary capillary the administration of a vasoconstrictor (Fig. 3), blood flow in dogs. Journal of Applied Physiology, 27, 127- the Y-wave may be seen in the pulmonary 131. Ferrario, C. M., Nordenstrom, B., and Paulin, S. (1968). capillary flow as the dominant pulse. Flow velocity variations in the pulmonary veins of the dog. Left atrial pressure records usually reveal a Inuestigatiue Radiology, 3, 73-80. 337 Flow pulses in pulmonary artery, capillary, and vein

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