Biomedical subjects

K Polak

Publications and source records attributed to K Polak.

At least 19 recordsLinked to original sources

PubMed2004

Twelve hour reproducibility of choroidal blood flow parameters in healthy subjects.

AIMS/BACKGROUND: To investigate the reproducibility and potential diurnal variation of choroidal blood flow parameters in healthy subjects over a period of 12 hours. METHODS: The choroidal blood flow parameters of 16 healthy non-smoking subjects were measured at five time points during the day (8:00, 11:00, 14:00, 17:00, and 20:00). Outcome parameters were pulsatile ocular blood flow as assessed by pneumotonometry, fundus pulsation amplitude as assessed by laser interferometry, blood velocities in the opthalmic and posterior ciliary arteries as assessed by colour Doppler imaging, and choroidal blood flow, volume, and velocity as assessed by fundus camera based laser Doppler flowmetry. The coefficient of variation and the maximum change from baseline in an individual were calculated for each outcome parameter. RESULTS: None of the techniques used found a diurnal variation in choroidal blood flow. Coefficients of variation were within 2.9% and 13.6% for all outcome parameters. The maximum change from baseline in an individual was much higher, ranging from 11.2% to 58.8%. CONCLUSIONS: These data indicate that in healthy subjects the selected techniques provide adequate reproducibility to be used in clinical studies. Variability may, however, be considerably higher in older subjects or subjects with ocular disease. The higher individual differences in flow parameter readings limit the use of the techniques in clinical practice. To overcome problems with measurement validity, a clinical trial should include as many choroidal blood flow outcome parameters as possible to check for consistency.

Adult↗

PubMed2004

Response of choroidal blood flow to carbogen breathing in smokers and non-smokers.

AIM: To investigate a potential difference in ocular vascular reactivity during carbogen breathing in optic nerve head, choroid, and retina between healthy smokers and non-smokers. METHODS: 25 (13 smokers and 12 non-smokers) healthy male volunteers participated in this observer masked, two cohort study. During inhalation of carbogen (5% CO(2) and 95% O(2)) over 10 minutes measurements were taken using laser Doppler flowmetry to assess submacular choroidal and optic nerve head blood flow, laser interferometry to assess fundus pulsation amplitudes, and retinal vessel analyser (RVA) to assess retinal vessel diameters. RESULTS: At baseline choroidal blood flow was higher (p = 0.018, ANOVA) in smokers than in non-smokers. During administration of carbogen the response in choroidal blood flow was significantly different between the two groups: there was an increase in non-smokers after carbogen breathing (p = 0.048) compared with relatively stable blood flow in smokers (p = 0.049 between groups, ANOVA). A similar response pattern was seen for fundus pulsation amplitude, which increased notably after carbogen breathing in non-smokers but not in smokers (p<0.001 between groups, ANOVA). Optic nerve head blood flow and retinal vessel diameters were reduced in both groups to a comparable degree during carbogen breathing. CONCLUSION: The study indicated abnormal choroidal vascular reactivity in chronic smokers. These early haemodynamic changes may be related to the increased risk to smokers of developing ocular vascular diseases. The specific mechanisms underlying abnormal choroidal vascular reactivity in chronic smokers remain to be characterised.

Adult↗

PubMed2003

Choroidal blood flow and arterial blood pressure.

PURPOSE: Untreated hypertension is associated with ocular complications and is a risk factor for the development and progression of vascular ocular pathologies. We set out to investigate the association between systemic blood pressure and choroidal blood flow. METHODS: All subjects were male non-smokers, who did not receive any medication and had normal or slightly elevated blood pressure (systolic blood pressure < or = 160 mmHg; diastolic blood pressure < or = 100 mmHg). The association between systemic blood pressure and fundus pulsation amplitude, a measure of pulsatile choroidal blood flow, was investigated in 318 volunteers. In addition, the association between systemic blood pressure and blood flow velocities in the posterior ciliary arteries supplying the choroid was investigated in these subjects. RESULTS: Ocular fundus pulsation amplitude (r = 0.252; P < 0.001) and mean flow velocity in the posterior ciliary arteries (r = 0.346, P < 0.001) were significantly associated with mean arterial pressure. The correlation of ocular haemodynamic variables with systolic and diastolic blood pressure was in the same range. CONCLUSIONS: Our data indicate a small, but significant increase in choroidal blood flow with increasing blood pressure.

Adult↗

PubMed2002

Effect of inhalation of different mixtures of O(2) and CO(2) on retinal blood flow.

AIM: To determine the effects of various mixtures of O(2) and CO(2) on retinal blood flow in healthy subjects. METHODS: A randomised, double masked, four way crossover trial was carried out in 12 healthy male non-smoking subjects. Gas mixtures (100% O(2), 97.5% O(2) + 2.5% CO(2), 95% O(2) + 5% CO(2), and 92% O(2) + 8% CO(2)) were administered for 10 minutes each. Two non-invasive methods were used: laser Doppler velocimetry (LDV) for measurement of retinal blood velocity and fundus imaging with the Zeiss retinal vessel analyser (RVA) for the assessment of retinal vessel diameters. Arterial pH, pCO(2), and pO(2) were determined with an automatic blood gas analysis system. Retinal blood flow through a major temporal vein was calculated. RESULTS: Retinal blood velocity, retinal vessel diameter, and retinal blood flow decreased during all breathing periods (p <0.001 each). Administration of 92% O(2) + 8% CO(2) significantly increased SBP, MAP, and PR (p <0.001 each, versus baseline), whereas the other gas mixtures had little effect on systemic haemodynamics. Addition of 2.5%, 5%, and 8% CO(2) to oxygen caused a marked decrease in pH and an increase in pCO(2) (p <0.001 versus pure oxygen). CONCLUSIONS: Breathing of pure oxygen and oxygen in combination with carbon dioxide significantly decreases retinal blood flow. Based on these data the authors speculate that hyperoxia induced vasoconstriction is not due to changes in intravascular pH and cannot be counteracted by an intravascular increase in pCO(2).

Adult↗

PubMed2001

Ocular hemodynamics during isometric exercise.

The autoregulatory capacity of the human retina is well documented, but the pressure-flow relationship of the human choroid is still a matter of controversy. Recent data, using laser Doppler flowmetry to measure choroidal blood flow, indicate that the choroid has some autoregulatory potential, whereas most data using other techniques for the assessment of choroidal hemodynamics indicate that the choroidal pressure-flow curve is linear. We used a new laser interferometric technique to characterize choroidal blood flow during isometric exercise. Twenty healthy subjects performed squatting for 6 min during normocapnia and during inhalation of 5% CO2 and 95% air. Ocular fundus pulsation amplitude, flow velocities in the ophthalmic artery, intraocular pressure, and systemic hemodynamics were measured in 2-min intervals. To gain information on choroidal blood flow fundus pulsation amplitude was corrected for changes in flow pulsatility using data from the ophthalmic artery and for changes in pulse rate. Ocular perfusion pressure was calculated from mean arterial pressure and intraocular pressure. The ocular pressure-flow relationship was calculated by sorting data according to ascending ocular perfusion pressure values. In a pilot study in 6 healthy subjects comparable ocular pressure flow relationships were obtained when choroidal blood flow was assessed with the method described above and with laser Doppler flowmetry. In the main study isometric exercise caused a significant increase in mean arterial pressure (56%, P < 0.001), pulse rate (84%, P < 0.001), and intraocular pressure (37%, P 0.004), but decreased fundus pulsation amplitude (-36%, P < 0.001). Significant deviations from baseline choroidal blood flow were observed only at ocular perfusion pressures >69% during normocapnia and 70% during hypercapnia. Our data indicate that during isometric exercise the choroid has a high capacity to keep blood flow constant despite changes in perfusion pressure and that this pressure-flow relationship is not altered by moderate changes in arterial carbon dioxide levels.

Adult↗

PubMed2001

Glucose and insulin exert additive ocular and renal vasodilator effects on healthy humans.

AIMS/HYPOTHESIS: There is evidence that insulin and glucose cause renal and ocular vasodilation. There is, however, currently no data on the effect of combined hyperglycaemia and hyperinsulinaemia on the renal and ocular blood flow seen in diabetic patients on insulin therapy. METHODS: We carried out two different 3-way crossover studies in healthy subjects (each, n = 9). In study one, hyperglycaemic clamps (5.6 mmol/l, 11.1 mmol/ 1, 16.7 mmol/l) were carried out during placebo or insulin (dose 1: 1 mU/kg/min; dose 2: 2 mU/kg/min) infusion. The second study was identical but endogenous insulin secretion was blocked with somatostatin. The renal plasma flow, glomerular filtration rate and pulsatile choroidal blood flow were measured using the paraaminohippurate method, the inulin method and a laser interferometric measurement of fundus pulsation amplitude, respectively. RESULTS: Insulin increased renal plasma flow and fundus pulsation amplitude but not the glomerular filtration rate. Hyperglycaemia increased all the renal and ocular parameters studied. Haemodynamic effects of glucose and insulin were additive when somatostatin was co-administered but not under basal conditions. CONCLUSIONS/INTERPRETATION: Glucose and insulin can exert additive vasodilator properties on renal and ocular circulation. To find out whether this observation is related to the increased regional perfusion in diabetes longitudinal studies on patients with Type I (insulin-dependent) diabetes mellitus are needed.

Adult↗

PubMed2001

Retinal blood flow and systemic blood pressure in healthy young subjects.

BACKGROUND: The aim of the present study was to investigate the association between systemic blood pressure and retinal blood flow in healthy young subjects. METHODS: Three independent study cohorts were included. A cross-sectional study was performed in 420 young male subjects with systolic blood pressure < 160 mmHg and diastolic blood pressure <100 mmHg. Retinal white blood cell flux (n=210) and blood velocity in the central retinal artery (n=210) were measured. In addition, a longitudinal study was performed in 40 young male subjects in whom retinal and systemic haemodynamic parameters were measured thrice within 6 weeks. Retinal white blood cell flux was measured with the blue-field entoptic technique. Blood flow velocity in the central retinal artery was measured by means of colour Doppler imaging. RESULTS: Retinal white blood cell flux (r=0.262; P<0.001) and mean flow velocity in the central retinal artery (r=0.174, P=0.010) were significantly associated with mean arterial pressure in the cross-sectional study. In the longitudinal study retinal white blood cell flux and mean flow velocity in the central retinal artery were also correlated with systemic blood pressure. CONCLUSIONS: Our data indicate a slight but significant increase in retinal blood flow with blood pressure. Whether this is of clinical relevance in eye diseases with altered retinal perfusion, such as diabetic retinopathy, remains to be established.

Adult↗

PubMed2001

Role of nitric oxide in the control of ocular blood flow.

In the recent years it has been recognized that nitric oxide is an important regulator of ocular blood flow. Nitric oxide is involved in the control of basal blood flow in the choroid, optic nerve and the retina. In addition, nitric oxide mediates a number of vasodilator responses in ocular vessels to agonists such as acetylcholine, bradykinin, histamine, substance P and insulin. Nitric oxide also plays a role in hypercapnia-induced vasodilation in the choroid and is a modulator of pressure autoregulation in this vascular bed. Abnormalities of the L-arginine/nitric oxide system have been observed in a variety of ocular diseases including glaucoma, diabetic retinopathy and retinopathy of prematurity. This makes the L-arginine/nitric oxide pathway an attractive target for therapeutic interventions. Additional research is required, particularly in characterizing the role of the three nitric oxide synthase isoforms in the control of ocular perfusion, to implement this concept into the clinical management of ocular diseases.

Animals↗

PubMed2001

A double masked placebo controlled study on the effect of nifedipine on optic nerve blood flow and visual field function in patients with open angle glaucoma.

AIMS: To investigate whether nifedipine affects ocular perfusion or visual fields in open angle glaucoma patients. METHODS: In a parallel group study nifedipine or placebo was administered for 3 months (n = 30). Ocular fundus pulsation amplitude (FPA), cup blood flow (Flowcup) and visual field mean deviation (MD) were measured. RESULTS: Five patients receiving nifedipine discontinued due to adverse events. Nifedipine did not affect FPA [difference: 0.3 microm (95% CI -0.3,0.9); P = 0.70], Flowcup: [difference: -9 rel.units (95% CI -133,114); P = 0.99], or MD [difference: 0.2dB (95% CI -2.2,2.7); P = 0.51] vs placebo. CONCLUSIONS: Systemic nifedipine is not well tolerated in glaucoma patients and exerts no effect on visual fields or ocular perfusion.

Administration, Oral↗

PubMed2001

Free fatty acids/triglycerides increase ocular and subcutaneous blood flow.

Elevated plasma free fatty acids (FFA) induce skeletal muscle insulin resistance and impair endothelial function. The aim of this study was to characterize the acute hemodynamic effects of FFA in the eye and skin. A triglyceride (Intralipid 20%, 1.5 ml/min)/heparin (bolus: 200 IU; constant infusion rate: 0.2 IU. kg(-1). min(-1)) emulsion or placebo was administered to 10 healthy subjects. Measurements of pulsatile choroidal blood flow with laser interferometry, retinal blood flow with the blue field entoptic technique, peak systolic and end diastolic blood velocity (PSV, EDV) in the ophthalmic artery with Doppler sonography, and subcutaneous blood flow with laser Doppler flowmetry were performed during an euglycemic somatostatin-insulin clamp over 405 min. Plasma FFA/triglyceride elevation induced a rise in pulsatile choroidal blood flow by 25 +/- 3% (P < 0.001) and in retinal blood flow by 60 +/- 23% (P = 0.0125). PSV increased by 27 +/- 8% (P = 0.001), whereas EDV was not affected. Skin blood flow increased by 149 +/- 38% (P = 0.001). Mean blood pressure and pulse rate remained unchanged, whereas pulse pressure amplitude increased by 17 +/- 5% (P = 0.019). Infusion of heparin alone had no hemodynamic effect in the eye or skin. In conclusion, FFA/triglyceride elevation increases subcutaneous and ocular blood flow with a more pronounced effect in the retina than in the choroid, which may play a role for early changes of ocular perfusion in the insulin resistance syndrome.

Adult↗

PubMed2001

Effect of endothelin and BQ123 on ocular blood flow parameters in healthy subjects.

PURPOSE: To characterize the role of the endothelin system in the blood flow control of the optic nerve head and of the choroid in humans. METHODS: Two studies were performed in healthy subjects. Study 1 was a randomized, placebo-controlled, double-masked, balanced, two-way crossover design and study 2 a three way-way crossover design. In study 1 twelve healthy male subjects received endothelin (ET)-1 in stepwise increasing doses of 1.25, 2.5, and 5 ng/kg x min (each infusion step occurred over 20 minutes) coinfused with BQ123 (60 microg/kg x min) or placebo on two different study days. In study 2 twelve healthy male subjects received two doses of BQ123 (60 or 120 microg/kg x min over 60 minutes) or placebo on three different study days. Measurements of optic nerve head blood flow (ONHBF) and choroidal blood flow (ChBF) were performed with laser Doppler flowmetry in both studies. In study 2 mean flow velocity (MFV) of the ophthalmic artery was assessed with Doppler sonography. RESULTS: In study 1, ET-1 significantly decreased ONHBF (-22.8% +/- 4.3% at 5 ng/kg x min, P = 0.003 versus baseline) and ChBF (-21.7% +/- 3.2% at 5 ng/kg x min, P = 0.0001 versus baseline). The effect of the highest administered dose of exogenous ET-1 on ONHBF was significantly attenuated (P = 0.04, ANOVA) by coinfusion of BQ123. Effects of exogenous ET-1 on blood flow (2.5 ng/kg x min ET-1 or higher) also were attenuated in the choroid by coinfusion of BQ123 (ChBF: P = 0.03, ANOVA). In study 2, both dosages of BQ123 significantly increased MFV in the ophthalmic artery (60 microg/kg x min, 12.5% +/- 7.3%; 120 microg/kg x min, 17.2% +/- 9.2%, versus baseline; P = 0.001), but did not change blood flow in the ONH or the choroid. CONCLUSIONS: BQ123 antagonizes the effects of exogenously administered ET-1 on blood flow in the ONH and the choroid. The data indicate, however, that ET-1 does not substantially contribute to the regulation of basal vascular tone in these tissues.

Adult↗

PubMed2000

Effects of insulin on retinal and pulsatile choroidal blood flow in humans.

BACKGROUND: Insulin induces vasodilation in several tissues, including skeletal muscle and kidneys. OBJECTIVE: To investigate whether insulin may contribute to ocular blood flow regulation. METHODS: The study was performed in a balanced, randomized, placebo-controlled, single-masked, 3-way, crossover design in 9 healthy male subjects. Each subject received 2 doses of insulin (1.5 or 3 mU/kg per minute) or placebo on 3 different study days. Measurements of fundus pulsation amplitude with laser interferometry to assess pulsatile choroidal blood flow, of retinal blood flow with the blue-field entoptic technique, and of mean blood flow velocity in the ophthalmic artery with Doppler sonography were performed under euglycemic clamp conditions over 120 minutes. RESULTS: Hyperinsulinemia significantly increased fundus pulsation amplitude (1.5 mU/kg per minute: 8.7% +/- 1.1% vs baseline; 3 mU/kg per minute: 13.2% +/- 2.3% vs baseline; P<.001 vs placebo [analysis of variance]) and mean blood flow velocity (1.5 mU/kg per minute: 10.0% +/- 4.3% vs baseline; 3 mU/kg per minute: 6.6% +/- 3.5% vs baseline; P = .03 vs placebo). Retinal blood flow did not increase during administration of insulin (1.5 mU/kg per minute: 6.4% +/- 8.0% vs baseline; 3 mU/kg per minute: 8.0% +/- 5.1% vs baseline; P = .99 vs placebo). Neither the effect in the choroid nor that in the ophthalmic artery was dose-dependent. CONCLUSION: Hyperinsulinemia significantly increases choroidal blood flow and mean blood flow velocity in the ophthalmic artery. By contrast, retinal blood flow was not influenced by hyperinsulinemia. The maximum effective dose of insulin for ocular hemodynamics is likely to be within the physiological range.

Adult↗

PubMed2000

Assessment of optic disk blood flow in patients with open-angle glaucoma.

PURPOSE: To characterize optic disk blood flow in patients with open-angle glaucoma compared with age-matched healthy control subjects. METHODS: In this prospective cross-sectional study, 90 eyes of 90 patients with open-angle glaucoma and 61 eyes of 61 age-matched healthy control subjects were evaluated. Flow in the optic disk cup and the neuroretinal rim were assessed with scanning laser Doppler flowmetry. Fundus pulsation amplitude in the cup and the macula were assessed with laser interferometry. Visual field mean deviation was measured with the Humphrey 30 to 2 program. RESULTS: Flow in the neuroretinal rim (-18%, P =.002), and in the cup (-46%, P <.001) and fundus pulsation amplitude in the cup (-33%, P <.001) and in the macula (-24%, P <.001) were significantly lower in patients with open-angle glaucoma compared with healthy control subjects. A significant association between blood flow measurements in the cup and fundus pulsation amplitudes in the cup was observed in both study cohorts. A significant association was also observed between the mean defect from visual field testing and ocular hemodynamic parameters. CONCLUSIONS: Reduced optic disk perfusion in patients with open-angle glaucoma is evidenced from two independent methods in the present study. Moreover, our data indicate that reduced ocular blood flow in these patients is linked to visual field changes. It remains to be established whether compromised optic disk and choroidal blood flow contributes to optic disk damage in glaucomatous eyes or is a secondary functional phenomenon.

Aged↗

PubMed2000

Age dependence of perimacular white blood cell flux during isometric exercise.

PURPOSE: To investigate the age dependence of perimacular white blood cell flux (WBCF) during isometric exercise. METHODS: Fourteen healthy young (age range: 21-29 years; 24 +/- 3 years, mean +/- SD, 12 male and 2 female) and 15 healthy middle-aged (age range: 45-57 years; 53 +/- 4 years, mean +/- SD; 5 male and 10 female) volunteers were studied. Subjects performed isometric handgrip for 10 minutes and squatting for 6 minutes. WBCF was assessed with the blue field entoptic technique, mean arterial pressure (MAP) was measured with an automated oscillometric device, intraocular pressure (IOP) was measured by Goldmann applanation tonometry and ocular perfusion pressure (OPP) was calculated as 2/3 MAP - IOP. RESULTS: Baseline WBCF was significantly higher in young subjects than in middle-aged subjects (191 +/- 28 vs 142 +/- 23; p = 0.001). Isometric handgrip induced a significant increase in WBCF in the middle-aged subjects (23 +/- 24%; p = 0.005), but not in the young subjects. Squatting significantly increased WBCF in both groups (young: 42 +/- 23%; p = 0.004 and middle aged: 51 +/- 27%; p < 0.001). A significant deviation from baseline WBCF was observed when OPP increased by 42 +/- 4% (p = 0.003) and 35 +/- 4% (p < 0.001) for the young and middle-aged subjects, respectively. The OPP-WBCF relationship was not different between the two study groups. CONCLUSION: Altered retinal autoregulation as observed in vascular ocular disease appears to be unrelated to the normal physiological aging process.

Adult↗

PubMed2000

Evaluation of the Zeiss retinal vessel analyser.

AIM: To investigate the reproducibility and sensitivity of the Zeiss retinal vessel analyser, a new method for the online determination of retinal vessel diameters in healthy subjects. METHODS: Two model drugs were administered, a peripheral vasoconstrictor (the alpha receptor agonist phenylephrine) and a peripheral vasodilator (the nitric oxide donor sodium nitroprusside) in stepwise increasing doses. Nine healthy young subjects were studied in a placebo controlled double masked three way crossover design. Subjects received intravenous infusions of either placebo or stepwise increasing doses of phenylephrine (0.5, 1, or 2 microg/kg/min) or sodium nitroprusside (0.5, 1, or 2 microg/kg/min). Retinal vessel diameters were measured with the new Zeiss retinal vessel analyser. Retinal leucocyte velocity, flow, and density were measured with the blue field entoptic technique. The reproducibility of measurements was assessed with coefficients of variation and intraclass correlation coefficients. RESULTS: Placebo and phenylephrine did not influence retinal haemodynamics, although the alpha receptor antagonist significantly increased blood pressure. Sodium nitroprusside induced a significant increase in retinal venous and arterial diameters (p<0.001 each), leucocyte density (p=0.001), and leucocyte flow (p=0.024) despite lowering blood pressure to a significant degree. For venous and arterial vessel size measurements short term coefficients of variation were 1.3% and 2.6% and intraclass correlation coefficients were 0.98 and 0.96, respectively. The sensitivity was between 3% and 5% for retinal veins and 5% and 7% for retinal arteries. CONCLUSIONS: These data indicate that the Zeiss retinal vessel analyser is an accurate system for the assessment of retinal diameters in healthy subjects. In addition, nitric oxide appears to have a strong influence on retinal vascular tone.

Adrenergic alpha-Agonists↗

PubMed2000

Ocular haemodynamics and colour contrast sensitivity in patients with type 1 diabetes.

BACKGROUND: There is evidence that altered ocular blood flow is involved in the development and progression of diabetic retinopathy. However, the nature of these perfusion abnormalities is still a matter of controversy. Ocular haemodynamics were characterised with two recently introduced methods. METHODS: The cross sectional study was performed in 59 patients with type 1 diabetes with a diabetes duration between 12 and 17 years and an age less than 32 years and a group of 25 age matched healthy controls. Scanning laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude were used to assess retinal and pulsatile choroidal blood flow, respectively. In addition, colour contrast sensitivity along the tritan axis was determined. RESULTS: Fundus pulsation amplitude, but not retinal blood flow, increased with the progression of diabetic retinopathy. Retinal blood flow was influenced by plasma glucose levels (r = 0.32), whereas fundus pulsation amplitude was associated with HbA(1c) (r = 0.30). In addition, a negative correlation between the colour contrast sensitivity along the tritan axis and retinal blood flow was observed. CONCLUSIONS: The present study indicates that pulsatile choroidal blood flow increases with the progression of diabetic retinopathy. Increased retinal blood flow appears to be related to loss of colour sensitivity in patents with type 1 diabetes.

Adolescent↗

PubMed2000

Hypercapnia-induced cerebral and ocular vasodilation is not altered by glibenclamide in humans.

Carbon dioxide is an important regulator of vascular tone. Glibenclamide, an inhibitor of ATP-sensitive potassium channel (K(ATP)) activation, significantly blunts vasodilation in response to hypercapnic acidosis in animals. We investigated whether glibenclamide also alters the cerebral and ocular vasodilator response to hypercapnia in humans. Ten healthy male subjects were studied in a controlled, randomized, double-blind two-way crossover study under normoxic and hypercapnic conditions. Glibenclamide (5 mg po) or insulin (0.3 mU. kg(-1). min(-1) iv) were administered with glucose to achieve comparable plasma insulin levels. In control experiments, five healthy volunteers received glibenclamide (5 mg) or nicorandil (40 mg) or glibenclamide and nicorandil in a randomized, three-way crossover study. Mean blood flow velocity and resistive index in the middle cerebral artery (MCA) and in the ophthalmic artery (OA) were measured with Doppler sonography. Pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation. Forearm blood flow was measured with venous occlusion plethysmography. Hypercapnia increased ocular fundus pulsation amplitude by +18.2-22.3% (P < 0. 001) and mean flow velocity in the MCA by +27.4-33.3% (P < 0.001), but not in the OA (2.1-6.5%, P = 0.2). Forearm blood flow increased by 78.2% vs. baseline (P = 0.041) after nicorandil administration. Glibenclamide did not alter hypercapnia-induced changes in cerebral or ocular hemodynamics and did not affect systemic hemodynamics or forearm blood flow but significantly increased glucose utilization and blunted the nicorandil-induced vasodilation in the forearm. This suggests that hypercapnia-induced changes in the vascular beds under study are not mediated by activation of K(ATP) channels in humans.

Adenosine Triphosphate↗

PubMed2000

Effects of systemic NO synthase inhibition on choroidal and optic nerve head blood flow in healthy subjects.

PURPOSE: There is evidence from animal studies that nitric oxide (NO) is a major determinant of ocular blood flow. In humans NO synthase inhibition reduces pulsatile choroidal blood flow, but no data on optic nerve head (ONH) vasculature are available yet. The goal of this study was to investigate the effects of NO synthase inhibition on human choroidal and ONH blood flow using laser Doppler flowmetry. METHODS: The study design was a randomized, placebo-controlled, double-masked, balanced three-way crossover. On separate study days 12 healthy male subjects received infusions of N:(G)-nitro-L-arginine (L-NMMA; either 3 mg/kg over 5 minutes followed by 30 microg/kg per minute over 55 minutes or 6 mg/kg over 5 minutes followed by 60 microg/kg per minute over 55 minutes) or placebo. The effects of L-NMMA or placebo on choroidal and ONH blood flow were measured with laser Doppler flowmetry. In addition, laser interferometric measurement of fundus pulsation was performed in the macula to assess pulsatile choroidal blood flow. RESULTS: L-NMMA reduced all outcome parameters in the choroid and the ONH. The higher dose of L-NMMA caused a significant decrease in blood flow in the choroid (-26% +/- 9%; P: < 0.001) and the ONH (-20% +/- 16%; P: < 0.001) as evidenced from laser Doppler flowmetry and a significant decrease in fundus pulsation amplitude (-26% +/- 5%; P: < 0.001). CONCLUSIONS: These results indicate that NO is continuously released in human choroidal and ONH vessels.

Adult↗