July 2011
Volume 52, Issue 8
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Clinical Trials  |   July 2011
Role of Adenosine in the Control of Choroidal Blood Flow during Changes in Ocular Perfusion Pressure
Author Affiliations & Notes
  • Doreen Schmidl
    From the Departments of Clinical Pharmacology and
  • Guenther Weigert
    Ophthalmology and
  • Guido T. Dorner
    Ophthalmology and
  • Hemma Resch
    Ophthalmology and
  • Julia Kolodjaschna
    From the Departments of Clinical Pharmacology and
  • Michael Wolzt
    From the Departments of Clinical Pharmacology and
  • Gerhard Garhofer
    From the Departments of Clinical Pharmacology and
  • Leopold Schmetterer
    From the Departments of Clinical Pharmacology and
    the Center of Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria.
  • Corresponding author: Leopold Schmetterer, Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; leopold.schmetterer@meduniwien.ac.at
Investigative Ophthalmology & Visual Science July 2011, Vol.52, 6035-6039. doi:10.1167/iovs.11-7491
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      Doreen Schmidl, Guenther Weigert, Guido T. Dorner, Hemma Resch, Julia Kolodjaschna, Michael Wolzt, Gerhard Garhofer, Leopold Schmetterer; Role of Adenosine in the Control of Choroidal Blood Flow during Changes in Ocular Perfusion Pressure. Invest. Ophthalmol. Vis. Sci. 2011;52(8):6035-6039. doi: 10.1167/iovs.11-7491.

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Abstract

Purpose.: The purpose of the present study was to investigate whether the nucleoside adenosine is involved in the regulatory processes of choroidal blood flow (ChBF) during an experimental decrease in ocular perfusion pressure (OPP).

Methods.: In this randomized, double-masked, placebo-controlled, two-way crossover study, 14 subjects received either intravenous adenosine or placebo on two different study days. The suction cup method was used for a stepwise increase in intraocular pressure (IOP). Subfoveal ChBF was measured by laser Doppler flowmetry. Mean arterial pressure (MAP) and IOP were measured noninvasively. Ocular perfusion pressure was calculated as OPP = ⅔MAP − IOP.

Results.: Adenosine increased ChBF significantly versus placebo before application of the suction cup (P < 0.05). When the suction cup was applied, a significant decrease in OPP was observed. This effect was comparable on all study days. The decrease in OPP was paralleled by a significant decrease in ChBF (maximum between −43% and −52%) which was less pronounced than the decrease in OPP (maximum between −62% and −64%). Neither placebo nor adenosine influenced the ChBF increase during suction cup–induced changes in OPP.

Conclusions.: The data of the present study confirm that the human choroid shows some regulatory capacity during a decrease in OPP. Adenosine influences basal vascular tone in the choroid but is not involved in the regulatory mechanisms during an increase in IOP. (ClinicalTrials.gov number, NCT00712764.)

Autoregulation is defined as the ability of a vascular bed to maintain its blood flow despite changes in perfusion pressure. It is well documented that retinal blood flow is autoregulated in response to changes in perfusion pressure. 1 6 In the past 20 years, evidence has accumulated that the choroid also shows some regulatory capacity. 7 13 Most of these data come from experiments using laser Doppler flowmetry (LDF). Before that era, the choroid was assumed to be a strictly passive vascular bed. 14 17 Choroidal blood flow (ChBF) seems to be better regulated in response to an experimental increase in mean arterial pressure (MAP) than an increase in intraocular pressure (IOP). 11,18 22  
The mechanisms behind ChBF regulation during changes in perfusion pressure have yet to be investigated. Since the pressure–flow relationship in the choroid appears to be unaltered during moderate hypercapnia and hyperoxia, a metabolic mechanism seems unlikely. 18 The choroid, however, shows rich neuronal innervation, indicating that neurogenic mechanisms are involved in ChBF regulation. 12 As such, blood flow regulation in the choroid cannot be considered autoregulation in its strict sense, because the term refers to an isolated vascular bed. A myogenic mechanism may also play a role in ChBF adaptation during changes in ocular perfusion pressure (OPP). 7  
The purine adenosine is a breakdown product of cellular adenosine triphosphate (ATP). P1 receptors, which are selective for adenosine, can further be divided into A1, A2A, A2B, and A3 receptors. 23 In the eye, two of these receptors have been localized in the retina: A1 and A2A. 24 In general, activation of adenosine receptors leads to changes in adenylyl cyclase activity, and whereas activation of A1 receptors results in attenuation of intracellular cyclic adenosine 3,5′-mono-phosphate (cAMP) levels and therefore in vasoconstriction, activation of A2A receptors is associated with elevation of intracellular cAMP levels leading to vasodilatation. 25 The role of adenosine in the eye is still controversial. Adenosine receptor stimulation seems to protect the retina against ischemia–reperfusion damage. 26 Further, there is evidence from several animal studies and recent human studies that adenosine causes choroidal and retinal vasodilatation. 27 29 Gidday and Parks 30 suggested that adenosine is a key participant in mediating regulatory adjustments in retinal blood flow. They demonstrated that arterioles of the newborn piglet retina dilate dose dependently in response to a pharmacologically induced increase in endogenous, interstitial adenosine concentration. Potentiation or inhibition of endogenous adenosine affects the retinal arteriolar dilatative response to hypoxia and hypotension. 30 Adenosine also seems to control ocular blood flow in humans. In a dose–response study, adenosine induced significant effects on choroidal and optic nerve head blood flow. 27 The aim of the present study was to investigate whether adenosine plays a role in ChBF regulation during a decrease in OPP. 
Material and Methods
Subjects
The present study was performed in compliance with the Declaration of Helsinki and the Good Clinical Practice (GCP) guidelines of the European Union. The study protocol was approved by the Ethics Committee of the Medical University of Vienna. After written informed consent was obtained, 14 healthy male subjects participated (age, 26.3 ± 4.3 years, mean ± SD). The number of subjects was based on a sample size calculation using data from a previous study investigating the pressure–flow relationship during an increase in IOP measured with LDF. 12 Sample size was calculated using a double-sided α error of 0.05 and a β error of 0.20, to detect a 15% difference between the active drug and placebo. During the 4 weeks before the first study day, each subject had to pass a pretreatment screening that included recording of medical history and a physical examination, Twelve-lead electrocardiogram, complete blood count, activated partial thromboplastin time, thrombin time, clinical chemistry, urine analysis, and an ophthalmic examination. If any abnormality was found as part of the pretreatment screening the subject was not included unless the investigators considered an abnormality to be clinically irrelevant. In addition, only subjects with ametropia of less than 3 D and no evidence of eye disease that might interfere with the purpose of the study were recruited to participate in the trial. During the last week after completion of the study, a follow-up safety investigation was scheduled. This follow-up investigation was similar to the pretreatment examination. 
Drugs and Drug Administration
The study drugs were administered by intravenous infusion. The following drugs and doses were administered: adenosine sodium chloride solution (3-mg/mL vials Ebewe Pharma GmbH; Unterach am Attersee, Austria; infusion period, 30 minutes; dosage, 40 μg/kg/min) 27 and physiologic saline solution (as a control substance; infusion period 30 minutes). 
Methods
Noninvasive Measurement of Systemic Hemodynamics.
Systolic (SBP), diastolic (DBP), and MAP were measured on the upper arm with an automated oscillometric device. Pulse rate (PR) was automatically recorded with a finger pulse-oximetric device (HP-CMS patient monitor; Hewlett Packard, Palo Alto, CA). 
Laser Doppler Flowmetry.
Measurement of ChBF was performed by LDF 31,32 with a compact instrument. 33 For this purpose, the vascularized tissue is illuminated by coherent laser light. Scattering on moving red blood cells (RBCs) leads to a frequency shift in the scattered light. In contrast, static scatterers in tissue do not change light frequency but lead to randomization of light directions impinging on RBCs. From the Doppler shift power spectrum, the mean RBC velocity (VEL), the blood volume (VOL), and the blood flow (FLOW) can be calculated in relative units. In the present study, LDF was performed in the fovea to assess ChBF. 
IOP, OPP, and Vascular Resistance.
A slit-lamp–mounted Goldmann applanation tonometer was used to measure IOP. Before each measurement, one drop of 0.4% benoxinate hydrochloride combined with 0.25% sodium fluorescein was used for local anesthesia of the cornea. OPP was calculated as ⅔(MAP − IOP). 4  
Suction Cup Method.
IOP was increased using the episcleral suction-cup technique, which has been described previously by Ulrich and Ulrich. 34 While the eye was topically anesthetized, a rigid, standardized, 11-mm diameter plastic suction cup was placed on the temporal sclera with the anterior edge at least 1 mm from the limbus. Through plastic tubing, the suction cup was connected to an automatic suction pump, which was used to increase the vacuum from 50 to 125 mm Hg to produce an IOP increase. 
Study Design
The study was performed in a randomized, double-masked, placebo-controlled, two-way crossover design. Subjects were assigned to receive intravenous infusions of either adenosine or physiologic saline solution on two different study days. The minimum washout-period between the two study days was 4 days. 
On the trial days, baseline measurements of ChBF and systemic hemodynamics were performed after a 20-minute resting period. Thereafter, the suction cup was applied with a suction of 50 mm Hg. The suction was increased in three consecutive steps to 75, 100, and 125 mm Hg. Each suction level was maintained for 2 minutes, and ChBF was measured continuously. The procedure was repeated after a 30-minute resting period. Again, each suction level was maintained for 2 minutes and, instead of ChBF, IOP was measured at each incremental step. Thereafter, another resting period of at least 30 minutes was scheduled. Afterward, adenosine or placebo was administered intravenously for 30 minutes. During the last 11 minutes of drug administration, measurement of ChBF with stepwise increase of IOP was performed again. During all procedures, systemic hemodynamic parameters were assessed every 2 minutes, and heart rate was monitored continuously. 
Data Analysis
Since subjects showed unstable reference signals (direct current, DC) during the measurements, the polynomial correction approach was applied, which was first introduced by Gugleta et al. 35 Briefly, the parameter “yield” was calculated as DC/gain. A regression model applying a third-order polynomial equation was used on the logarithmic values of yield and the respective LDF parameters, to calculate the corrected LDF data. 
An ANOVA model for repeated measurements was used to analyze the data. Statistical significance was analyzed by studying the interaction between time and treatment. In addition, the effect of the drugs under study on basal ChBF was assessed. Data are presented as the mean ± SD. P < 0.05 was set as the level of significance. 
Results
Fourteen subjects completed the study according to the protocol. The baseline characteristics of the study population are presented in Table 1. There were no significant differences between the baseline values on the two study days. Application of the suction cup at different suction levels caused a significant increase in IOP (to average: +13 ± 2, +17 ± 3, +21 ± 2, and +25 ± 3 mm Hg, P < 0.001 versus baseline). This effect was comparable on all study days. Under basal conditions, neither adenosine nor placebo influenced IOP (P = 0.20 between groups). Likewise, arterial blood pressure did not change after administration of placebo (−1.9 ± 6.7 mm Hg) or adenosine (−1.9 ± 4.3 mm Hg; P = 1.0 between groups). Placebo had no significant effect on ChBF compared with the baseline values. Adenosine induced a significant increase in ChBF before application of the suction cup (+15% ± 15%, P = 0.00045; Fig. 1). 
Table 1.
 
Baseline Data on Each Study Day
Table 1.
 
Baseline Data on Each Study Day
Placebo Day Adenosine Day
MAP, mm Hg 79 ± 6 80 ± 8
PR, beats per minute 68 ± 12 67 ± 7
IOP, mm Hg 12 ± 2 12 ± 2
OPP, mm Hg 41 ± 4 42 ± 5
ChBF, arbitrary units 20 ± 9 20 ± 7
Figure 1.
 
The effects of drug administration on ChBF before suction cup administration. Left column: the value of ChBF in arbitrary units before infusion of placebo (▨) or adenosine (■). BL, ChBF before administration of adenosine or placebo; DA, ChBF during drug administration. Data are presented as the mean ± SD (n = 14).
Figure 1.
 
The effects of drug administration on ChBF before suction cup administration. Left column: the value of ChBF in arbitrary units before infusion of placebo (▨) or adenosine (■). BL, ChBF before administration of adenosine or placebo; DA, ChBF during drug administration. Data are presented as the mean ± SD (n = 14).
The effects of suction cup application on OPP are shown in Figure 2. A pronounced reduction in OPP was observed when suction was applied (P < 0.001 versus baseline). The experimentally induced changes in OPP were comparable during the pretreatment periods on all study days (P = 0.20 between groups). There was no change in the responding pattern of OPP to suction cup application during infusion of placebo or adenosine, compared with pretreatment values (P = 0.30 between groups). 
Figure 2.
 
The effects of suction cup application on OPP (A) in the pretreatment periods and (B) during infusion of placebo or adenosine. Data are presented as the mean ± SD (n = 14).
Figure 2.
 
The effects of suction cup application on OPP (A) in the pretreatment periods and (B) during infusion of placebo or adenosine. Data are presented as the mean ± SD (n = 14).
The decrease in OPP during suction cup application was paralleled by a significant decrease in ChBF in the pretreatment periods (maximum reduction of ChBF between 41.8 and 42.3%, P < 0.001 versus baseline, Fig. 3). Similar changes in ChBF were observed during infusion of placebo (−43.1% at maximum; P < 0.001 versus baseline) and adenosine (−1.9% at maximum, P < 0.001 versus baseline). However, the decrease in ChBF was less pronounced than the decrease in OPP during all stimulation periods. There was no difference in the ChBF response on the two study days (P = 0.09 between groups). 
Figure 3.
 
Relative change in ChBF plotted against the relative change in OPP during suction cup application (A) before and (B) during administration of placebo or adenosine. Data are presented as the mean ± SD (n = 14).
Figure 3.
 
Relative change in ChBF plotted against the relative change in OPP during suction cup application (A) before and (B) during administration of placebo or adenosine. Data are presented as the mean ± SD (n = 14).
Discussion
The data from the present study indicate that adenosine is not involved in the regulatory mechanisms of the choroid during a decrease in OPP. However, the results are in concordance with previous experiments in humans showing that a decrease in OPP is paralleled by a decrease in ChBF, which is less pronounced than the decrease in OPP, 10,11 indicating some degree of ChBF regulation in response to a decrease in OPP. 
The resting ChBF was significantly increased after administration of adenosine. This is in accordance with findings from several other studies. Adenosine injected intravitreally increased choroidal and retinal blood flow in rabbits. 28 Intravenous adenosine administration in the cat led to a significant increase in choroidal, but not in optic nerve head or retinal, blood flow. 11 In humans, it has been demonstrated that intravenous administration of this nucleoside increases both choroidal and optic nerve head blood flow dose dependently. 27 This vasodilatation is probably mediated via A2A receptors, since enhanced intracellular cAMP levels relax vascular smooth muscle. 36  
Although adenosine influences basal choroidal vascular tone, the findings of the present study suggest that it does not contribute to the regulatory mechanisms during an experimental decrease in OPP in humans since administration of adenosine did not alter the ChBF response during a decrease in OPP. In a study conducted in newborn piglets hemorrhagic hypotension was induced to lower OPP for investigation of retinal arteriolar blood flow regulation. Local interstitial adenosine potentiation significantly increased the dilatative response to hemorrhagic hypotension. The authors therefore concluded that adenosine is a key participant in mediating regulatory adjustments in retinal blood flow. 30 For the human choroid, this does not seem to be true. 
Some limitations of the present study design in humans have to be mentioned. One problem is that subjects start at different baseline OPPs and that there is a wide variety in suction-cup–induced changes in IOP. In a crossover study, this problem is minimized, however, because each subject served as his own control and the ChBF response to changes in IOP shows good reproducibility. There are also some limitations in human studies of ChBF using LDF, which have been discussed in detail elsewhere. 37 Briefly, this device measures only in the subfoveal choroid, and the depth of measurements is unknown. Therefore, the findings of the present study may not be applicable for peripheral parts of the choroid. 
The use of an adenosine receptor antagonist would have been interesting because it would have given clearer insight into the role of adenosine in ChBF during an experimental decrease in OPP. However, to date there is no commercially available adenosine receptor antagonist for use in humans. 
In conclusion, the data of the present study confirm that the human choroid shows some regulatory capacity during a decrease in OPP. Adenosine influences basal vascular tone in the choroid but is not involved in the regulatory mechanisms during an increase in IOP. 
Footnotes
 Supported by Austrian Science Fund (FWF) projects P15970 and P21406.
Footnotes
 Disclosure: D. Schmidl, None; G. Weigert, None; G.T. Dorner, None; H. Resch, None; J. Kolodjaschna, None; M. Wolzt, None; G. Garhofer, None; L. Schmetterer, None
References
Pournaras CJ Rungger-Brandle E Riva CE Hardarson SH Stefansson E . Regulation of retinal blood flow in health and disease. Prog Retin Eye Res. 2008;27:284–330. [CrossRef] [PubMed]
Dumskyj MJ Eriksen JE Dore CJ Kohner EM . Autoregulation in the human retinal circulation: assessment using isometric exercise, laser Doppler velocimetry, and computer-assisted image analysis. Microvasc Res. 1996;51:378–392. [CrossRef] [PubMed]
Rassam SM Patel V Kohner EM . The effect of experimental hypertension on retinal vascular autoregulation in humans: a mechanism for the progression of diabetic retinopathy. Exp Physiol. 1995;80:53–68. [CrossRef] [PubMed]
Robinson F Riva CE Grunwald JE Petrig BL Sinclair SH . Retinal blood flow autoregulation in response to an acute increase in blood pressure. Invest Ophthalmol Vis Sci. 1986;27:722–726. [PubMed]
Riva CE Grunwald JE Petrig BL . Autoregulation of human retinal blood flow: an investigation with laser Doppler velocimetry. Invest Ophthalmol Vis Sci. 1986;27:1706–1712. [PubMed]
Grunwald JE Sinclair SH Riva CE . Autoregulation of the retinal circulation in response to decrease of intraocular pressure below normal. Invest Ophthalmol Vis Sci. 1982;23:124–127. [PubMed]
Kiel JW . Choroidal myogenic autoregulation and intraocular pressure. Exp Eye Res. 1994;58:529–543. [CrossRef] [PubMed]
Kiel JW Shepherd AP . Autoregulation of choroidal blood flow in the rabbit. Invest Ophthalmol Vis Sci. 1992;33:2399–2410. [PubMed]
Kiel JW van Heuven WA . Ocular perfusion pressure and choroidal blood flow in the rabbit. Invest Ophthalmol Vis Sci. 1995;36:579–585. [PubMed]
Simader C Lung S Weigert G . Role of NO in the control of choroidal blood flow during a decrease in ocular perfusion pressure. Invest Ophthalmol Vis Sci. 2009;50:372–377. [CrossRef] [PubMed]
Polska E Simader C Weigert G . Regulation of choroidal blood flow during combined changes in intraocular pressure and arterial blood pressure. Invest Ophthalmol Vis Sci. 2007;48:3768–3774. [CrossRef] [PubMed]
Riva CE Titze P Hero M Petrig BL . Effect of acute decreases of perfusion pressure on choroidal blood flow in humans. Invest Ophthalmol Vis Sci. 1997;38:1752–1760. [PubMed]
Findl O Strenn K Wolzt M . Effects of changes in intraocular pressure on human ocular haemodynamics. Curr Eye Res. 1997;16:1024–1029. [CrossRef] [PubMed]
Alm A Bill A . Ocular and optic nerve blood flow at normal and increased intraocular pressures in monkeys (Macaca irus): a study with radioactively labelled microspheres including flow determinations in brain and some other tissues. Exp Eye Res. 1973;15:15–29. [CrossRef] [PubMed]
Alm A Bill A . Blood flow and oxygen extraction in the cat uvea at normal and high intraocular pressures. Acta Physiol Scand. 1970;80:19–28. [CrossRef] [PubMed]
Armaly MF Araki M . Effect of ocular pressure on choroidal circulation in the cat and Rhesus monkey. Invest Ophthalmol. 1975;14:584–591. [PubMed]
Gherezghiher T Okubo H Koss MC . Choroidal and ciliary body blood flow analysis: application of laser Doppler flowmetry in experimental animals. Exp Eye Res. 1991;53:151–156. [CrossRef] [PubMed]
Kiss B Dallinger S Polak K Findl O Eichler HG Schmetterer L . Ocular hemodynamics during isometric exercise. Microvasc Res. 2001;61:1–13. [CrossRef] [PubMed]
Riva CE Titze P Hero M Movaffaghy A Petrig BL . Choroidal blood flow during isometric exercises. Invest Ophthalmol Vis Sci. 1997;38:2338–2343. [PubMed]
Luksch A Polska E Imhof A . Role of NO in choroidal blood flow regulation during isometric exercise in healthy humans. Invest Ophthalmol Vis Sci. 2003;44:734–739. [CrossRef] [PubMed]
Fuchsjager-Mayrl G Luksch A Malec M Polska E Wolzt M Schmetterer L . Role of endothelin-1 in choroidal blood flow regulation during isometric exercise in healthy humans. Invest Ophthalmol Vis Sci. 2003;44:728–733. [CrossRef] [PubMed]
Schmidl D Garhofer G Schmetterer L . The complex interaction between ocular perfusion pressure and ocular blood flow: relevance for glaucoma. Exp Eye Res. Published online September 22, 2010.
Ralevic V Burnstock G . Receptors for purines and pyrimidines. Pharmacol Rev. 1998;50:413–492. [PubMed]
Ghiardi GJ Gidday JM Roth S . The purine nucleoside adenosine in retinal ischemia-reperfusion injury. Vision Res. 1999;39:2519–2535. [CrossRef] [PubMed]
Eltzschig HK . Adenosine: an old drug newly discovered. Anesthesiology. 2009;111:904–915. [CrossRef] [PubMed]
Lutty GA McLeod DS . Retinal vascular development and oxygen-induced retinopathy: a role for adenosine. Prog Retin Eye Res. 2003;22:95–111. [CrossRef] [PubMed]
Polska E Ehrlich P Luksch A Fuchsjager-Mayrl G Schmetterer L . Effects of adenosine on intraocular pressure, optic nerve head blood flow, and choroidal blood flow in healthy humans. Invest Ophthalmol Vis Sci. 2003;44:3110–3114. [CrossRef] [PubMed]
Braunagel SC Xiao JG Chiou GC . The potential role of adenosine in regulating blood flow in the eye. J Ocul Pharmacol. 1988;4:61–73. [CrossRef] [PubMed]
Gidday JM Park TS . Microcirculatory responses to adenosine in the newborn pig retina. Pediatr Res. 1993;33:620–627. [CrossRef] [PubMed]
Gidday JM Park TS . Adenosine-mediated autoregulation of retinal arteriolar tone in the piglet. Invest Ophthalmol Vis Sci. 1993;34:2713–2719. [PubMed]
Riva CE Cranstoun SD Grunwald JE Petrig BL . Choroidal blood flow in the foveal region of the human ocular fundus. Invest Ophthalmol Vis Sci. 1994;35:4273–4281. [PubMed]
Riva CE Geiser M Petrig BL . Ocular blood flow assessment using continuous laser Doppler flowmetry (review). Acta Ophthalmol. 2010;88:622–629. [CrossRef] [PubMed]
Geiser M Diermann U Riva CE . Compact instrument for laser Doppler flowmetry in the foveal region of the choroid. J Biomed Opt. 1999;4:459–464. [CrossRef] [PubMed]
Ulrich WD Ulrich C . Oculo-oscillo-dynamography: a diagnostic procedure for recording ocular pulses and measuring retinal and ciliary arterial blood pressures. Ophthalmic Res. 1985;17:308–317. [CrossRef] [PubMed]
Gugleta K Orgul S Flammer I Gherghel D Flammer J . Reliability of confocal choroidal laser Doppler flowmetry. Invest Ophthalmol Vis Sci. 2002;43:723–728. [PubMed]
Campochiaro PA Sen HA . Adenosine and its agonists cause retinal vasodilation and hemorrhages: implications for ischemic retinopathies. Arch Ophthalmol. 1989;107:412–416. [CrossRef] [PubMed]
Polska E Luksch A Ehrlich P Sieder A Schmetterer L . Measurements in the peripheral retina using LDF and laser interferometry are mainly influenced by the choroidal circulation. Curr Eye Res. 2002;24:318–323. [CrossRef] [PubMed]
Figure 1.
 
The effects of drug administration on ChBF before suction cup administration. Left column: the value of ChBF in arbitrary units before infusion of placebo (▨) or adenosine (■). BL, ChBF before administration of adenosine or placebo; DA, ChBF during drug administration. Data are presented as the mean ± SD (n = 14).
Figure 1.
 
The effects of drug administration on ChBF before suction cup administration. Left column: the value of ChBF in arbitrary units before infusion of placebo (▨) or adenosine (■). BL, ChBF before administration of adenosine or placebo; DA, ChBF during drug administration. Data are presented as the mean ± SD (n = 14).
Figure 2.
 
The effects of suction cup application on OPP (A) in the pretreatment periods and (B) during infusion of placebo or adenosine. Data are presented as the mean ± SD (n = 14).
Figure 2.
 
The effects of suction cup application on OPP (A) in the pretreatment periods and (B) during infusion of placebo or adenosine. Data are presented as the mean ± SD (n = 14).
Figure 3.
 
Relative change in ChBF plotted against the relative change in OPP during suction cup application (A) before and (B) during administration of placebo or adenosine. Data are presented as the mean ± SD (n = 14).
Figure 3.
 
Relative change in ChBF plotted against the relative change in OPP during suction cup application (A) before and (B) during administration of placebo or adenosine. Data are presented as the mean ± SD (n = 14).
Table 1.
 
Baseline Data on Each Study Day
Table 1.
 
Baseline Data on Each Study Day
Placebo Day Adenosine Day
MAP, mm Hg 79 ± 6 80 ± 8
PR, beats per minute 68 ± 12 67 ± 7
IOP, mm Hg 12 ± 2 12 ± 2
OPP, mm Hg 41 ± 4 42 ± 5
ChBF, arbitrary units 20 ± 9 20 ± 7
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