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.