Effect of Isoproterenol, Phenylephrine, and Sodium Nitroprusside on Fundus Pulsations in Healthy Volunteers

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British Journal of Ophthalmology 1996; 80: 217-223 217 Effect of isoproterenol, phenylephrine, and sodium nitroprusside on fundus pulsations in Br J Ophthalmol: first published as 10.1136/bjo.80.3.217 on 1 March 1996. Downloaded from healthy volunteers

Leopold Schmetterer, Michael Wolzt, Alex Salomon, Alexander Rheinberger, Christian Unfried, Gabriele Zanaschka, Adolf Friedrich Fercher

Abstract have not yet been carried out and quantitative Aims/Background-Recently a laser inter- pressure flow relations in human choroidal ferometric method for topical measure- vessels are as yet unknown. Linear choroidal ment of fundus pulsations has been pressure flow relations have been obtained in developed. Fundus pulsations in the macu- animal experiments in different species.5-8 In lar region are caused by the inflow and out- the rabbit, the choroidal blood flow has been flow ofblood into the choroid. The purpose shown to be pressure independent when IOP ofthis work was to study the influence of a was less than 20-25 mm Hg.9 peripheral vasoconstricting (the a,x adreno- Blood vessels can be considered as cylin- ceptor agonist phenylephrine), a predomi- ders filled with fluid at a pressure greater than nantly positive inotropic (the non-specific that outside the cylinders. The pressure dif- I adrenoceptor agonist isoproterenol), and ference between the inside and the outside of a non-specific vasodilating (sodium nitro- a vessel is called the transmural pressure P. prusside) model drug on ocular fundus The corresponding tension T in the vessel pulsations to determine reproducibility wall can be calculated by Laplace's law and sensitivity ofthe method. P=T/R, where R is the radius of the cylinder. Methods-In a double masked ran- Any variation of the transmural pressure domised crossover study the drugs were alters the tension of the vessel wall. Thus, administered in stepwise increasing doses pressure oscillations of cardiac pulse pressure to 10 male and nine female healthy output lead to a pulsation of the vessel wall. volunteers. Systemic haemodynamic As blood is pumped into an artery, the systolic variables and fundus pulsations were pressure increases and dilates the vessel wall. measured at all infusion steps. When cardiac ejection decreases, the pressure Results-Fundus pulsation increased falls and the vessel wall returns to its equilib- during infusion of isoproterenol with rium position, the diastolic pressure.10 The http://bjo.bmj.com/ statistical significance versus baseline at arterial pressure contour becomes progres- the lowest dose of 0-1 uwg/min. Neither sively more distorted as the wave is transmit- peripheral vasoconstriction nor peripheral ted down the arterial system. The elastic vasodilatation affected the ocular fundus properties of an artery are described by the pulsations. arterial compliance, the change in diameter of fundus over the in Conclusions-Measurements change pressure. The non-linear on September 27, 2021 by guest. Protected copyright. pulsations is a highly reproducible method elastic response of arteries implies that their in healthy subjects with low ametropy. mechanical properties depend on the mean Changes oflocal pulsatile ocular blood flow arterial pressure.11 were detectable with our method following In retinal and choroidal vessels the mean the infusion of isoproterenol. As systemic transmural pressure at the arteries entering the pharmacological vasodilatation or vaso- eye nearly equals the mean perfusion pressure, constriction did not change fundus pulsa- defined as the pressure in the arteries entering tions, further experimental work has to be the eye (Pa) minus the pressure in the veins Institute ofMedical done to evaluate the sensitivity of the laser (Pv) leaving the eye. Pf=Pa-Pv. The pressure Physics L Schmetterer interferometric fundus pulsation measure- in the veins, Pv, is significantly higher than the C Unfried ment in various eye diseases. intraocular pressure (IOP) in the retinal ves- A F Fercher (BrJ Ophthalmol 1996; 80: 217-223) sels'2 whereas the difference in the choroidal Department of Clinical vessels is small.'3 Therefore, the transmural Pharmacology pressure in the veins is rather small or even L Schmetterer Although 85% of the blood volume in the eye zero. Changes in transmural pressure and the M Wolzt G Zanaschka circulates in the choroid,' choroidal circulation consecutive change in vessel diameter lead to is far less investigated than the retinal blood pulsations of the surrounding tissue. Department of flow. The outer layers of the retina are Our work is concerned with local tissue Ophthalmology B nourished the A Salomon by choroid, and animal experi- pulsations at the foveola. This area of highest A Rheinberger ments suggest that 90% of the oxygenation of visual acuity is approximately 350 ,um in dia- the photoreceptors are supplied by choroidal meter.'4 This is a little smaller than the retinal Correspondence to: L Schmetterer, Institut fMr circulation.2 The introduction of fluorescein avascular zone measuring approximately Medizinische Physik, angiography,3 particularly of video fluorescein 500-600 ,um in diameter. In our study, where Wahringer Strasse 13, A-1090 Wien, Austria. angiography,4 has increased the understanding the area involved in the measurement is 20-50 Accepted for publication of choroidal circulation. However, systematic ,um, the effect of tissue pulsations is only influ- 9 November 1995 investigations of choroidal haemodynamics enced by the blood flow in choroidal vessels. 218 Schmetterer, Wolzt, Salomon, Rheinberger, Unfried, Zanaschka, Fercher

Hence the inflow and outflow ofblood into the to participate in this study according to choroid leads to pulsaltile movements ofthe eye procedures approved by the ethics committee fundus. of Vienna University School of Medicine. All Br J Ophthalmol: first published as 10.1136/bjo.80.3.217 on 1 March 1996. Downloaded from These fundus pulsaitions are measured with subjects were drug-free, non-smokers and a recently describedL laser interferometer,15 judged to have no evidence of any relevant which measures the dlistance changes between physical disorder. All had normal laboratory cornea and retina. TIhe purpose of this study evaluations, normal results from ultrasound was to evaluate the sihort term variability, the examinations of carotid arterial blood flow, day to day variability, the intersubject variabil- and normal findings from ophthalmic exami- ity, and the sensitivity of the method to detect nations with ametropy of less than 2-5 dioptres changes in ocular blood flow in healthy and intraocular pressure in the range of 11 to volunteers. We have! therefore studied the 16 mm Hg. The testing of the women was effects of well characterised cardiovascular scheduled between the third and eighth day of model drugs on fundias pulsations in a double menstrual cycles; pregnancy was excluded by masked randomiseci placebo controlled urine pregnancy test (hCG Urine+Plus, crossover study. Abbott, Wiesbaden, Germany). All subjects were asked to refrain from alcohol and caffeine for at least 12 hours before Materials and methiiods study days. Initially, a 20 gauge plastic cannula In a double maske i randomised crossover (Venflon, Viggo-Spectramed, Helsingborg, study design, subjects were assigned to receive Sweden) was inserted into a suitable antecubital infusions of stepwise increasing doses of a vein, and a continuous infusion (1 ml/min) of peripheral vasocons-tricting, a peripheral physiological saline was started for baseline vasodilating, a predoniinately positive inotropic measurements to the comfortably sitting drug, and of placebo ((physiological saline solu- subjects. Each stepwise infusion period lasted tion) on different stiudy days. From the 24 10 minutes unless there was an increase of possible sequences of: administration in the four >40 mm Hg or decrease of >20 mm Hg in way crossover design we randomly chose 19. mean arterial pressure, or until an increase of >40 per minute or decrease of >20 per minute in heart rate versus baseline infusion period, or DRUGS ADMINISTERED until any systemic effects - for example, palpita- These were phenylephrine (Neosynephrine, tion, headache, or diz.ziness occurred. Measure- Winthrop Breon Laaboratories, NY, USA; ments of fundus pulsations were performed in dose 0-5, 1, 2, 4, 8, 16,ug/kg/min), sodium the last 5 minutes of each infusion step. nitroprusside (Nipruiss-Trockensubstanz zur In addition, we conducted measurements Infusionsbereitung, SCanol-Schwarz, Monheim, to assess the influence of isoproterenol and Germany; dose 0 5, 1[,23 4, 8, 16,ug/kg/min), phenylephrine on IOP of eight male volun- isoproterenol (Isupirel, Winthrop Breon teers in our study group. Baseline measure- http://bjo.bmj.com/ Laboratories, NY, UJSA; dose 0O1, 0-2, 0 4, ments of IOP and fundus pulsations were 0-8,1P6, 3-2,g/min), physiological saline solu- performed during a 10 minute infusion of tion. The drugs were diluted with saline or physiological saline solution. The drug effect glucose (for sodium nitroprusside) to yield was calculated from measurements of 10 appropriate concentra itions. minute infusions of 0-8,ug/min isoproterenol and of 2 jig/kg/min phenylephrine, respec- tively. Two measurements ofIOP and fundus on September 27, 2021 by guest. Protected copyright. PATIENTS pulsation measurements were performed Ten men (aged 20-313 years, mean 25X6 (SD during the last 5 minutes of each infusion step 3 7) and nine wom ien (aged 20-30 years, with a Goldmann applanation tonometer. No mean 25-0 (3 6) gave written informed consent measurements of the effect of sodium nitroprusside on IOP were performed, since previous studies indicate that the influence LCCD of systemic administration of sodium nitro- E prusside16 on IOP is small. In contrast, C topical administration has been represented co vc BSC to lowerIOP effectively.17 Systolic and diastolic blood pressures were L measured by an automated oscillometric device (HP CMS patient monitor, Hewlett Packard, Palo Alto, CA, USA). Mean arterial PBSC2 nL 670 nm pressure was calculated as two thirds diastolic u pressure plus one third systolic pressure; pulse L/2 pressure amplitude was calculated as systolic L4 = PBSC1PBSblood pressure minus diastolic blood pressure. Pulse rate was registered automatically from a finger pulse oximetric device (HP CMS patient monitor). Eye Measurements of fundus pulsations were

Figure 1 Optical scheme of the laser interferometer. (PBSC==polarising beam splitter cube, performed with a laser interferometric tech- BSC= beam splitter cube, I12=halfwave plate,L/4= quartrer wave plate, L=lens, nique, which has been described in detail else- VC=video camera, LCCD=linear charge coupled device a?rray). where.15 The interferometer, schematically Effect ofisoproterenol, phenylephrine, and sodium nitroprusside onfundus pulsations in healthy volunteers 219

Coefficients of varieation (%) The detecting unit comprises a linear charge coupled device (CCD) array and a video cam- Short term variability Day to day variability era. Owing to the high spatial coherence of the Br J Ophthalmol: first published as 10.1136/bjo.80.3.217 on 1 March 1996. Downloaded from illuminating laser beam, the interferences of 10 20 30 40 0 10 20 30 40 the two re-emitted beams are not localised. I' II II Optimal visibility can only be achieved in a plane approximately 40 mm in front ofthe eye. SBP +° D 10 This plane is imaged by the lens onto the CCD array and via a beam splitter cube (BSC) onto the photo cathode of the video camera (VC). DBP -CJ-HO {t The video camera is used to supervise the measurement procedure on a video monitor. The readout of the CCD array is a spatio- MAP temporal display of the fundus pulsations. of{< >ID Counting the number of fringes moving inwards and outwards the fundus pulsation Pulse pressure amplitude (FPA), which is the maximum distance change between cornea and retina during the cardiac cycle, can be calculated. The FPA represents the difference of blood volume Pulse rate H-EE a' during the systole and diastole at one particu- lar point of the fundus. A headrest is used to fix the subject's head. Amplitude The whole instrument is mounted on two translation stages and can be moved in x and y direction perpendicular to the optical axis of Figure 2 Short term (leftpanel) and day to day (right panel) variability of our the subject's eye by computer controlled measurements in 19 healthy subjects. In the right panel coefficients ofvariation were stepper motors. The observation of the visible calculatedfor any subjectfrom thefour baseline recordings ofthe 4 study days. In the left panel they were calculatedfrom the seven recordings ofsaline infusion study day. The laser beam reflected at the outer surfaces ofthe bottom ofthe vertical box line marks 25%, the median 50%o, and the top ofthe box 75%. eye and the eyelid facilitates the gross adjust- Whiskers represent 5% and 95%. Mean (square symbols), minimum (triangles), and ment of the instrument. maximum values (circles) are presented. (SBP=systolic blood pressure, DBP=diastolic blood pressure, MAP= mean arterial pressure, pulse pressure=pulse pressure amplitude calculatedfrom SBP-DBP, amplitude=fundus pulsation amplitude. STATISTICAL ANALYSIS shown in Figure 1, is a simplified version ofthe Statistical analysis was done with Statistica soft- instrument described by Schmetterer"5 based ware package (StatSoft Inc, Tulsa, OK, USA). on the same principle. A single mode laser Day to day reproducibility was calculated from diode (Sharp LT 023 MDO; X=783 nm) emits the baseline registrations of the 4 study days. http://bjo.bmj.com/ the beam used for the measurement. The Using the seven measurements of the 10 beam of a second laser diode (Toshiba TOLD minute saline infusion periods we calculated the 9211; X=670 nm) is used to adjust the beam short term variability. For each subject the into the patient's eye and is switched offduring the measurement. The polarising beam splitter PBSC1 combines these two beams to a single on September 27, 2021 by guest. Protected copyright. beam of approximately 1 mm diameter illumi- 6 nating the subject's eye. The beam passes a half wave plate which defines the polarising state. Then the polarising beam splitter PBSC2 deviates the beam towards the subject's eye. This beam splitter is used together with a quarter wave plate to reduce reflective losses in the light re-emitted from the eye when 4 a1) it passes towards the detecting unit. The beam Ce

is reflected both at the front of the cornea and C.) at 0 the retina. o These two reflected non- a) beams generate .0 localised concentric circular interference E fringes. As the path difference between the two z interfering beams is twice the optical length L 2 of the eye, the interference order N=2xL/AX is a very large number. Distance variations between cornea and retina lead to a corresponding variation AN(t) of the interference order. AN(t) equals the number of fringes that have moved up to the moment t through a o I fixed point in the interferogram. The time 2 4 8 10 12 14 16 course of ihe optical distance variation AL(t) Amplitude

is: - - - I Figure 3 Results offfundus pulsation measurements in 19 healthy subjects under baseline conditions. The amplitude AL(t) =AN(t) x X/2 (1) denotes thefundus pulsation amplitude in units ofA/2. 220 Schmetterer, Wolzt, Salomon, Rheinberger, Unfried, Zanaschka, Fercher

Systolic blood pressure Pulse rate 15 10 Br J Ophthalmol: first published as 10.1136/bjo.80.3.217 on 1 March 1996. Downloaded from 10 5 0 L T T- 0 = t -XT -10 -5 -10 a) -20 C -15 al) Diastolic blood pressure Fundus pulsation amplitude .0 E 15 20 10 I_ 20 5 0) 0 10 - -c -5 -r, ...... L 0a) -10 0 0) CD -15 co C.) Pulse pressure Mean arterial pressure 0~ 10 10 0 5 t =... .IT -10 i... 1 0

0 0.5 1.0 2.0 0.5 1.0 2.0 7 Phenylephrine (p.g/kg/min) Figure 4 Dose-response relation (solid~~~~...... line) ofchanges (%o) from baseline measurements ofsystemic haemodynamics and of fundus pulsations during saline (0) and stepwise infusion ofphenylephrine at doses of 0 5, 1 0, and 2-0 ug/kg/min. The broken line presents the results from the placebo study day. The asterisks indicate significant treatment effects versus placebo as cakulated by repeated measure ANOVA (p<0 05). Results are presented as means (SEM).

coefficient of variation of measurements was dependently (p<0.005 versus placebo and calculated. baseline). The amplitude of fundus pulsations Results of fundus pulsation measurements showed a small increase, which did not reach http://bjo.bmj.com/ were expressed as percentage change from the statistical significance (Fig 4). baseline. Significance was calculated versus baseline by repeated measure ANOVA, and versus placebo by two way repeated measure ISOPROTERENOL ANOVA. For these purposes only infusion The infusion was stopped at 1 6 ,ug/min in steps with less than 20% drop outs were taken eight subjects and at 3-2 ,ug/min in seven into consideration. The significance level was subjects. In the remaining four subjects all on September 27, 2021 by guest. Protected copyright. set to p=0 05. Significances are presented as seven infusion steps were administered. The p<0 05 or p<0O005. systolic blood pressure (p<0005 versus placebo and baseline) and the pulse pressure amplitude (p<0 005 versus placebo and base- Results line) increased significantly. The mean arterial Results for day to day and short term variabil- pressure and the diastolic blood pressure did ity are shown in Figure 2. Interindividual not change. The pulse rate increased signifi- differences are shown in Figure 3. cantly (p<0-005 versus placebo and baseline). The fundus pulsation amplitude increased dose dependently (p<0 005 versus baseline PHYSIOLOGICAL SALINE SOLUTION and placebo, Fig 5). No time dependence of the seven short term readouts was detected. SODIUM NITROPRUSSIDE At 4 pug/kg/min the infusion was stopped in six PHENYLEPHRINE subjects, at 8 ,ug/kg/min in eight subjects, and In three subjects the infusion was stopped at 2 at 16 ,ug/kg/min in five subjects. Blood ,ug/kg/min, in 10 at 4 ,ug/kg/min, in four at 8 pressure decreased during the infusion of ,ug/kg/min, and in two at 16 ,ug/kg/min. There sodium nitroprusside: systolic pressure was a small increase in systolic (p<0.05 versus (p<0 05 versus placebo and p<0 005 versus placebo and baseline), diastolic (NS versus baseline), diastolic pressure (p<0.005 versus placebo, p<005 versus baseline), and mean baseline and placebo), and mean arterial pres- arterial blood pressure (NS versus placebo, sure (p<0005 versus baseline and placebo). p<0 05 versus baseline). The pulse pressure Pulse rate increased significantly (NS versus amplitude was nearly constant during the placebo, p<0 05 versus baseline), whereas infusion steps. The pulse rate decreased dose pulse pressure amplitude decreased only Effect ofisoproterenol, phenylephrine, and sodium nitroprusside onfundus pulsations in healthy volunteers 221

Systolic blood pressure Pulse rate 15

* 20 Br J Ophthalmol: first published as 10.1136/bjo.80.3.217 on 1 March 1996. Downloaded from 10 * 5 10 0 .,T,,,,, T .. -5 0 .T.:1.' -10 a) -10 c -15 C,, a) Diastolic blood pressure Fundus pulsation amplitude .0 E 15 60

0 10 ...... I I .T I ..i 'v.... * a) 5 40 CD0)t- 0

4- -5 20 -10 0C 0 a) -15 a) Pulse pressure Mean arterial pressure 0~ 45 45 30 30- 15 15 H 0 L' . .T .. T ... I -i- -15 - 0i - 0- 0 0.1 0.2 0.4 0.8 0 0.1 0.2 0.4 0.8 Isoproterenol (,ug/min) Figure 5 Dose-response relation (solid line) ofchanges (%) from baseline measurements ofsystemic haemodynamics and of fundus pulsations during saline (0) and stepwise infusion of isoproterenol at doses of 0-1, 0-2, 0 4, and 0-8 ,ig/min. The broken line presents the results from the placebo study day. The asterisks indicate significant treatment effects versus placebo as calculated by repeated measure ANOVA (p<0 05). Results are presented as means (SEM).

slightly during the infusion steps. Fundus In our measurements the influence of bulbus pulsations did not show significant changes length is probably low owing to the small during the infusion steps (Fig 6). refractive errors of our study group. Moreover, the axial eye length mainly influences the propagation of the pulse wave through the eye. http://bjo.bmj.com/ IOP MEASUREMENTS Intersubject differences in the angioarchitec- The results of our IOP measurements during ture of the choroid, especially the organisation isoproterenol and phenylephrine infusion are of the vessels in the submacular region, as summarised in Table 1. No changes in IOP reported by Fryczowski et al,19 may have an during administration of isoproterenol and important effect on our measurements. A phenylephrine were observed. decrease of the ocular pulse with an increasing on September 27, 2021 by guest. Protected copyright. heart rate was reported for patients with pace- makers.20 These findings suggest that, at an Discussion increase of the heart rate, there may be a shift Our results show that fundus pulsations in from pulsatile to non-pulsatile blood flow in normal volunteers with ametropy of less than the ocular circulation.20 plus or minus 2-5 dioptres are dose dependently During isoproterenol infusion the positive increased during infusion of isoproterenol but inotropic effect was responsible for both the not during infusion of phenylephrine or sodium dose dependent increase in pulse pressure nitroprusside. Even at higher doses of the amplitude and fundus pulsation amplitude. A peripheral vasoconstrictor and the vasodilator direct comparison of the two variables is not the changes in the amplitude of fundus possible as we do not know the relation pulsations are small. between changes in systemic blood pressure The intrasubject variability of this novel and the perfusion pressure in the ocular ves- method is generally small. The within day vari- sels. Although the presence of 0 adrenergic ability, calculated from the saline infusion study receptors in choroidal vessels was recently day, was slightly smaller than the day to day assumed by showing an increased choroidal variability, calculated from the baseline registra- vascular tone after systemic administration of tions of the 4 study days. This finding was also timolol maleate,21 it is obvious that our obser- observed for the haemodynamic variables and vations mainly depend on the cardiovascular argues for slightly different cardiovascular reac- effects than on the confounding vasoconstrict- tivity on different study days. ing or vasodilating vascular responses. The intersubject variability of our measure- The mean arterial pressure was significantly ments is much wider and may be caused by changed following administration of phenyl- several ocular variables. James et a118 observed ephrine and sodium nitroprusside, whereas a significant change of the ocular pulse with both drugs did not affect pulse pressure ampli- axial eye length and refractive state of the eye. tude. When considering the results after the 222 Schmetterer, Wolzt, Salomon, Rheinberger, Unfried, Zanaschka, Fercher

Systolic blood pressure Pulse rate 15 20 Br J Ophthalmol: first published as 10.1136/bjo.80.3.217 on 1 March 1996. Downloaded from 10 5 10 *~~~~~ 0 -r t 1,:...... -5 0 ..... -10 * a) -10 c -15 CO)C', Diastolic blood pressure Fundus pulsation amplitude .0 E 15 60 0 10 TT e 5 I 40k- 0) 0 cu 20 4J -5 0 -10 0) *~~~~ 0 Ti. CD -15 Pulse pressure Mean arterial pressure C.)0 0~ 15 5 10 I.------'-'-'I---...... -1 5 0 0 -5 T...... -5 -10 1.... -10 -15

0 0.5 1.0 2.0 0 0.5 1.0 2.0 Sodium nitroprusside (,ug/kg/min) Figure 6 Dose-response relation (solid line) ofchanges (%o) from baseline measurements ofsystemic haemodynamics and of fundus pulsations during saline (0) and stepwise infusion ofsodium nitroprusside at doses of 0 5, 1 0, and 2-0 ,ug/kg/min. The broken line presents the results from the placebo study day. The asterisks indicate significant treatment effects versus placebo as calculated by repeated measure ANOVA (p<0 05). Results are presented as means (SEM). administration of phenylephrine, the slight Phenylephrine, but not sodium nitroprus- reduction of cardiac output and stroke volume side,16 slightly decreased IOP. Reduced IOP as reported by several authors must be taken causes a reduced venous pressure and there- into account.22 23 Hence the lack of effect on fore an increased perfusion pressure in ocular fundus pulsation amplitude may be caused by vessels. Yet the transmural pressure changes in http://bjo.bmj.com/ an increase of pulsatile blood flow compared choroidal arteries are not relevantly influenced with the total flow or by a local reaction by this mechanism. The small reduction of in ocular vessels. The first assumption is IOP during infusion of isoproterenol, leading supported by the unchanged pulse pressure to a decreased venous pressure, is negligible in amplitude in spite of the increased mean comparison with the increase in pulse pressure arterial pressure during infusion of phenyl- amplitude. ephrine. Local autoregulative reactions in the Whether absolute measurements of pul- on September 27, 2021 by guest. Protected copyright. choroid are unlikely,9 whereas the observation satile ocular blood flow are feasible with our that posterior ciliary arteries spontaneously instrument requires further investigation. It develop tone24 indicates an autoregulatory is well known that, as a result of injection of capacity in these prechoroidal arteries. Finally, blood flow in the choroid, the ocular volume our results could depend on the change in as well as the IOP changes.27 This fact is used arterial compliance compared with increased for the measurement of ocular blood flow arterial pressure. In the radial artery there is with a pneumatic tonometer.28 Hence, it is experimental evidence that the higher the likely that the comea, which we use as a refer- arterial pressure, the smaller is the arterial ence surface, shows small pulsatile move- cross section change due to a defined change ments as well. Estimation of these movements in blood pressure.25 However, the stretch from the Friedenwald equation29 is difficult behaviour of a vessel as large as the radial owing to the different elastic behaviour of the artery will be somewhat different from that of cornea and the sclera.30 We can only assume the much smaller choroidal vessels.6 that the influence of cornea pulsations is Following the administration of sodium small, as we observed big differences in nitroprusside no change in stroke volume has fundus pulsation amplitudes at various been observed in healthy subjects.26 However, retinal measurement points, when the corneal limited changes in arterial compliance as well as autoregulation in the posterior ciliary Table 1 Effect of0-8 ,ug/min isoproterenol (Iso) and of2 arteries again cannot be excluded in our Agl/kg/min phenylephrine (Phe) onfundus pulsation ampli- experimental setup. Owing to the increased tude (FPA in units ofA/2) and IOP (mm Hg) in eight volunteers. mean arterial pressure the transmural pressure healthy Results are presented as mean (SD). is high and the smooth muscles relaxed. Hence Saline Iso Saline Phe the elastic behaviour and the tension should lOP 13-1 (2-2) 12-6 (2-5) 12-6 (2-7) 12-0 (2-8) rely largely on the passive components of the FPA 8-8 (2-1) 13-4 (3-2) 8-9 (2-7) 8-8 (2-3) vessel wall. Effect ofisoproterenol, phenylephrine, and sodium nitroprusside onfiundus pulsations in healthy volunteers 223

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