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Biomedical subjects

L Schmetterer

Publications and source records attributed to L Schmetterer.

At least 55 records · Page 3Linked to original sources
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

Endothelin-1 contributes to hyperoxia-induced vasoconstriction in the human retina.

PURPOSE: There is evidence that ocular blood flow strongly depends on arterial oxygen tension. Results from recent animal studies indicate that the vasoconstrictor response to hyperoxia may be mediated in part by an increased production of endothelin (ET)-1. In an effort to answer the question whether the retinal vasoconstrictive response to hyperoxia in humans is mediated through ET-1, changes in ocular hemodynamics induced by 100% O2 breathing were studied in the absence and presence of an ET(A) receptor antagonist (BQ-123). METHODS: The study was a randomized, placebo-controlled, double-masked, balanced, three-way crossover design. On separate study days 15 healthy male subjects received infusions of BQ-123 (either 60 microg/min or 120 microg/min) or placebo. The effects of BQ-123 or placebo on hyperoxia-induced (100% O2 breathing) changes in retinal and pulsatile choroidal blood flow were assessed with the blue-field entoptic technique and with laser interferometric measurement of fundus pulsation, respectively. RESULTS: During baseline conditions, hyperoxia caused a decrease in retinal blood flow between -29% and -34% (P<0.001) and a decrease in fundus pulsation amplitude between -7% and -8% (P<0.001). BQ-123 dose dependently blunted the response to hyperoxia in the retina (60 microg/min: -25%, 120 microg/min: -20%; P = 0.003), but not in the choroid. CONCLUSIONS: These results indicate that ET-1 contributes to hyperoxia-induced retinal vasoconstriction in the human retina.

Adult↗
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↗
PubMed2000

Response of choroidal blood flow in the foveal region to hyperoxia and hyperoxia-hypercapnia.

PURPOSE: Arterial carbon dioxide tension and arterial oxygen tension are important determinants of retinal and cerebral blood flow. In the present study the hypothesis that changes in arterial blood gases also influence choroidal blood flow was tested. METHODS: The effect of breathing different mixtures of oxygen (O(2)) and carbon dioxide (CO(2)) on choroidal blood flow in the foveal region was investigated in healthy subjects. The study was performed in a randomized, double-masked four way cross-over design in 16 subjects. Using a compact laser Doppler flowmeter, red blood cell velocity (ChBVel), volume (ChBVol), and flow (ChBF) in the choroidal vasculature were measured during the breathing of various mixtures of O(2)and CO(2) (hyperoxia-hypercapnia): 100% O(2), 97%O(2)+3%CO(2), 95%O(2)+5%CO(2) (carbogen) and 92%O(2)+8%CO( 2). Arterial oxygen tension (pO(2)) and carbon dioxide tension (pCO(2)) were measured from arterialized blood samples from the earlobe. RESULTS: Breathing 100% O(2) had no significant effect on ChBVel (-3.7%), ChBVol (+1.7%) and ChBF (-4.3%). Addition of 3% CO(2) to O(2) also produced no significant change on these blood flow parameters. In contrast, carbogen significantly increased ChBVel (10.0 +/- 4.4%, 95% CI, p < 0.001) and ChBF (12.5 +/- 11.7%, p = 0.002). The effect of 92% O(2) + 8% CO(2) was more pronounced since it significantly increased ChBVel and ChBF by 15.5 +/- 7.5% (p < 0.001) and 16.2 +/- 11.0% (p < 0.001), respectively. None of the gas mixtures induced a significant change in ChBVol. The increase in ChBF was approximately 1.5% per 1 mmHg increase in pCO(2). CONCLUSIONS: This study demonstrates that, in healthy subjects, pCO(2) is an important determinant of foveal choroidal blood flow, whereas pO(2) has little impact on it.

Administration, Inhalation↗
PubMed1999

Systemic NO synthase inhibition blunts the chronotropic, but not the inotropic response to isoprenaline in man.

There is evidence that nitric oxide (NO) is involved in the chronotropic, the inotropic, and the vasodilator response to beta-adrenoceptor agonists. In the present study we hypothesized that inhibition of NO synthase may modulate the systemic vascular and cardiac effects of isoprenaline, a beta-adrenoceptor agonist, in healthy subjects. Subjects received stepwise increasing doses of isoprenaline (0.1-0.8 microg/min) in the absence or presence of systemic NO-synthase inhibition using two intravenous doses of N-monomethyl-L-arginine (L-NMMA; dosage 1, 3.0 mg/kg over 5 min, followed by 30 microg/kg/min over 75 min; dosage 2, 6.0 mg/kg over 5 min, followed by 60 microg/kg/min over 75 min) or peripheral vasoconstriction using exogenous endothelin-1 (ET-1; 5.0 ng/kg/min for 80 min). The chronotropic (RR interval) and the inotropic (QS2c) responses were assessed by noninvasive measurement of systolic time intervals. L-NMMA alone did not influence QS2c, but did increase the RR interval (P < 0.001) and the mean arterial blood pressure (P = 0.003). L-NMMA did not attenuate the blood pressure and the QS2c responses to isoprenaline, but significantly and dose-dependently blunted the heart rate response to beta-adrenoceptor stimulation (P = 0.029). ET-1 decreased the RR interval (P < 0.001) and increased the mean arterial blood pressure (P = 0.028). Our results indicate that beta-adrenoceptor mediated effects on the heart rate are much more susceptible to NOS inhibition than inotropic responses. This indicates that NO has an important role in heart rate control during beta-adrenoceptor stimulation.

Adult↗
PubMed1999

Effects of peribulbar anesthesia on ocular blood flow in patients undergoing cataract surgery.

PURPOSE: The effects of extraconal, peribulbar anesthesia on ocular blood flow may be caused by concomitant elevations in intraocular pressure or direct pharmacologic alteration of vascular tone. We quantified the effect on ocular circulation with a new technique for assessment of ocular hemodynamics. METHODS: In a prospective study, ocular hemodynamics were measured before and 1 and 5 minutes after peribulbar anesthesia in 22 eyes with age-related cataract. Measurements included fundus pulsation amplitude with a laser interferometric method assessing the pulsatile choroidal blood flow and mean blood flow velocity as well as resistive index in the ophthalmic and central retinal artery with Doppler sonography. Systemic blood pressure and pulse were monitored throughout the period of ocular hemodynamic measurements. RESULTS: Fundus pulsation amplitude decreased significantly after peribulbar anesthesia (after 1 minute and 5 minutes: -13% and -8%; P < .001). In the central retinal artery, mean blood flow velocity dropped (-15%; P < .001) and resistive index increased (+3%; P = .02) 1 minute after peribulbar anesthesia compared with baseline. There were no changes in ophthalmic artery hemodynamics. Intraocular pressure was elevated 1 minute after peribulbar anesthesia (+29%; P = .003) but reached baseline values after 5 minutes. CONCLUSION: Pulsatile choroidal blood flow and retinal blood flow velocities were reduced after peribulbar anesthesia. These reductions were still present 5 minutes after peribulbar anesthesia, when intraocular pressure had returned to baseline values. This supports the theory of drug-induced vasoconstriction after peribulbar anesthesia. A loss of vision may be a risk of peribulbar anesthesia in patients who have compromised ocular blood flow before surgery.

Adult↗
PubMed1999

Effect of small incision cataract surgery on ocular blood flow in cataract patients.

PURPOSE: To evaluate the effect of small incision cataract surgery using peribulbar anesthesia on ocular blood flow in patients with senile cataract. SETTING: Department of Ophthalmology, University of Vienna, Vienna, Austria. METHODS: In 33 eyes of 33 consecutive patients scheduled for cataract surgery, ocular hemodynamics were measured preoperatively and 1 day, 1 week, and 1 month postoperatively. Measurements included fundus pulsation amplitude (FPA) with a laser interferometric method that assessed the pulsatile choroidal blood flow, mean blood flow velocity (MFV), and resistive index (RI) in the ophthalmic artery (OA) and the central retinal artery (CRA) with Doppler sonography. Systemic hemodynamics and intraocular pressure (IOP) also were measured. RESULTS: The FPA, MFV, and RI in the OA and the CRA did not change postoperatively from baseline values. Systemic hemodynamics, IOP, and as a consequence ocular perfusion pressure, also remained unchanged. CONCLUSION: Uneventful small incision cataract surgery using peribulbar anesthesia did not affect ocular blood flow in patients with senile cataract between 1 day and 1 month postoperatively.

Adult↗
PubMed1999

Pharmacokinetic-pharmacodynamic profile of systemic nitric oxide-synthase inhibition with L-NMMA in humans.

AIMS: It has been demonstrated that inhibition of endothelium derived nitric oxide with NG-monomethyl-L-arginine (L-NMMA) results in a different cardiac and peripheral vascular response. The purpose of this study was to investigate the pharmacokinetic-pharmacodynamic profile of L-NMMA and pharmacokinetic interactions with L-arginine in healthy subjects. METHODS: Plasma pharmacokinetics were analysed from two different studies: In study 1, 3 mg kg-1 L-NMMA was administered i.v. over 5 min and systemic haemodynamics, cardiac output (CO), fundus pulsation amplitude (FPA), and NO-exhalation (exhNO) were measured at baseline and 15, 65, 95, 155, and 305 min after start of drug administration (n=7). In study 2, 17 mg kg-1 min-1 of the physiologic substrate for nitric oxide synthase, L-arginine, was coinfused i.v. over 30 min with a primed constant infusion of 50 microg kg-1 min-1 L-NMMA (n=8). RESULTS: Bolus infusion of L-NMMA resulted in a maximum plasma concentration of 12. 9+/-3.4 microg ml-1 (mean+/-s.d.) with elimination half-life of 63. 5+/-14.5 min and clearance of 12.2+/-3.5 ml min-1 kg-1 and caused a small hypertensive response, decreased CO by 13%, FPA by 26%, exhNO by 46% and increased systemic vascular resistance by 16% (P<0.05 each) 15 min after start of drug administration. Although only limited data points were available in the L-NMMA plasma concentration range between 0 and 4 microg ml-1, drug effects over time were in good agreement with an Emax model (r2>0.98 each), which also suggested that concentrations producing half-maximum effects were higher for FPA than for CO and exhNO. The coinfusion with L-arginine caused a nearly two-fold increase in plasma L-NMMA levels, indicating a pharmacokinetic interaction. CONCLUSIONS: In the absence of a systemic hypertensive response, L-NMMA significantly decreased CO, exhNO, and FPA. The concentration calculated to produce a half maximal effect was equivalent for exhNO and CO, but markedly higher for FPA. Furthermore, measurement of FPA is susceptible to changes in L-NMMA levels at small plasma concentrations.

Adult↗
PubMed1999

Renal hemodynamic effects of L-arginine and sodium nitroprusside in heart transplant recipients.

BACKGROUND: Long-term treatment with cyclosporine A (CsA) induces vasoconstriction in the kidney and causes renal impairment. An altered L-arginine (L-Arg)/nitric oxide (NO) pathway may play a key role in CsA nephrotoxicity. METHODS: We studied the effect of L-Arg (dosage, 17 mg/kg/min over 30 min), the precursor of NO synthesis, and sodium nitroprusside (SNP; dosage, 1.0 microgram/kg/min over 30 min) on renal hemodynamics in a double-blind, placebo-controlled, randomized, three-way cross-over study comprising 12 stable cardiac transplant recipients on long-term CsA treatment, 10 patients with chronic nephropathy not receiving CsA, and 13 healthy controls. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured by paraaminohippurate (PAH) and the inulin clearance method, respectively. RESULTS: In healthy subjects, L-Arg induced an increase in RPF (P = 0.009) and GFR (P = 0.001). By contrast, L-Arg did not induce renal hemodynamic effects in heart transplant patients or patients with chronic nephropathy. SNP reduced RPF (P = 0.050) and GFR (P = 0.005) in patients with chronic nephropathy but did not affect renal hemodynamics in heart transplant recipients or in healthy subjects. CONCLUSIONS: These data indicate that L-Arg cannot be used to reverse CsA-induced renal vasoconstriction in heart transplant recipients under long-term CsA treatment, although these patients have a normal renal response to SNP.

Aged↗
PubMed1999

Acetazolamide-induced cerebral and ocular vasodilation in humans is independent of nitric oxide.

Acetazolamide, a carbonic anhydrase inhibitor, is used orally in the treatment of primary and secondary open-angle glaucoma and induces ocular and cerebral vasodilation. Several in vitro studies have shown that carbonic anhydrase pharmacology and the L-arginine-nitric oxide (NO) pathway are closely related. We investigated the role of NO in acetazolamide-induced vasodilation on cerebral and ocular vessels in 12 healthy subjects in the presence or absence of NG-monomethyl-L-arginine (L-NMMA), a NO synthase inhibitor, and in the presence or absence of L-arginine, the precursor of NO. Acetazolamide was administered after pretreatment with either L-NMMA or placebo and either L-arginine or placebo. Pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation. In addition, mean blood flow velocity (MFV) in the middle cerebral artery (MCA) and ophthalmic artery (OA) was measured with Doppler sonography. Acetazolamide increased ocular fundus pulsation amplitude (FPA; +27%, P < 0.001) and MFV in the MCA (+38%, P < 0.001) and in the OA (+19%, P = 0.003). Administration of L-NMMA alone reduced FPA (-21%, P < 0.001) and MFV in the MCA (-11%, P = 0. 030) but did not change MFV in the OA. All hemodynamic effects of L-NMMA were reversed by L-arginine. However, neither L-NMMA nor L-arginine altered acetazolamide-induced changes in cerebral or ocular hemodynamic parameters. The present data indicate that acetazolamide-induced hemodynamic changes are not mediated by NO. Which mediators other than NO are involved in the hemodynamic effects as induced by carbonic anhydrase inhibitors remains to be elucidated.

Acetazolamide↗
PubMed1998

Effect of pituitary adenylate cyclase activating polypeptide 1-27 on ocular, cerebral and skin blood flow in humans.

The aim of the study was to assess the effects of a neuropeptide, pituitary adenylate cyclase activating polypeptide 1-27 (PACAP), on ocular, cerebral and skin blood flow in man. PACAP (0.01-10 pmol kg(-1) min(-1)) was administered intravenously to eight healthy male subjects in a placebo-controlled, double-blind dose escalation trial. Fundus pulsation amplitude was measured by laser interferometry, mean blood flow velocity in the ophthalmic artery and the middle cerebral artery measured by Doppler sonography, and regional blood flow of the skin was estimated by laser Doppler flowmetry. Infusion of PACAP at the highest dose of 10 pmol kg(-1) min(-1) induced a significant increase in fundus pulsation amplitude (+83.4%), mean flow velocity in the ophthalmic artery (+91.9%) and regional skin blood flow (+260.3%, P<0.01, ANOVA; each parameter). In contrast, PACAP did not cause any change in middle cerebral artery blood flow velocity or systemic hemodynamics. Our findings indicate that the vasculatures of the eye and the skin are particularly sensitive to PACAP and may implicate a potential role for this peptide in the regulation of blood flow in these vascular beds.

Adult↗
PubMed1998

Topical fundus pulsation measurements in age-related macular degeneration.

BACKGROUND: The purpose of the present study was to investigate regional fundus pulsations in age-related macular degeneration (AMD) patients with subretinal neovascular membranes. METHODS: Local fundus pulsation amplitudes (FPAs) were measured in 12 patients with AMD with classic neovascular membranes. Measurements were performed directly on the membrane and adjacent to the membrane. FPAs were assessed with a recently developed laser interferometric method. FPA measurements were performed in 12 healthy subjects at similar posterior pole locations. RESULTS: In AMD patients FPAs were consistently lower when measured directly on the neovascular membrane ("inside") than at measurement sites around the membrane ("outside"). The difference in FPA was 26 +/- 3% (mean +/- SEM, range 13-40%, P < 0.0001). In healthy subjects, however, FPAs were significantly higher at the measurement points corresponding to "inside" points (15 +/- 4%, P < 0.0006). CONCLUSIONS: We have shown that FPAs are reduced at classic neovascular membranes in patients with AMD. The mechanism behind this finding remains unclear. Hence, future studies have to ascertain whether this observation is associated with changes in fundus layers or with local choroidal perfusion abnormalities.

Aged↗
PubMed1998

Reversal of endothelin-1-induced ocular hemodynamic effects by low-dose nifedipine in humans.

BACKGROUND AND PURPOSE: There is evidence that calcium channel blockers may be useful in patients with normal tension glaucoma and vasospastic reactions. We therefore hypothesized that calcium channel blockers may increase ocular blood flow and that there may be a functional antagonism between endothelin-1 (ET-1) and calcium channel blockers in the ocular vasculature. METHODS: This was a randomized, double-blind, three-way crossover study with respect to ET-1 infusions (placebo, 2 ng/kg/min ET-1, and 4 ng/kg/min ET-1) and a randomized double-blind study in two parallel groups with respect to nifedipine (placebo or 5 mg nifedipine). Ocular hemodynamics in the 12 healthy subjects participating in the study was assessed by laser interferometric measurement of fundus pulsation amplitude (FPA) in the optic disc and two-dimensional scanning laser Doppler flowmetry in the optic disc. RESULTS: ET-1 caused a dose-dependent decrease in FPA and flow. With a dose of 4 ng/kg/min a decrease of -18% +/- 5% (p < 0.001) and -17% +/- 5% (p = 0.023) on FPA and flow, respectively, were observed. This effect was completely reversed by nifedipine compared with placebo (FPA, p < 0.001; flow, p = 0.011). However, nifedipine did not affect ocular hemodynamics after placebo infusion. CONCLUSIONS: These results show that nifedipine does not increase optic nerve head blood flow during baseline conditions but reverses ET-1-induced constriction in ocular vasculature at doses that do not affect systemic hemodynamics. This supports the close relation of the therapeutic effect of calcium channel blockers in patients with normal tension glaucoma to the endothelin system. Moreover, the present study provides a strong rationale for a study of low dose nifedipine as a supplementary medication in glaucoma patients.

Adult↗
PubMed1998

Hemodynamic effects of continuous urodilatin infusion: a dose-finding study.

OBJECTIVE: To evaluate the effects of urodilatin (INN, ularitide) on systemic and renal hemodynamic parameters. METHODS: Twenty healthy male subjects were included in this double-blind, randomized placebo-controlled trial and assigned to receive either continuous intravenous infusion of different doses of 7.5, 15, or 22.5 ng/kg body weight/min urodilatin or placebo over 300 minutes. Cardiac performance, systolic time intervals, and airway function were measured noninvasively. The effects on renal hemodynamic values were assessed with para-aminohippurate and inulin clearance techniques. RESULTS: Urodilatin was well tolerated by all subjects at doses of 7.5 and 15 ng/kg/min. Infusion was stopped prematurely for the group that received 22.5 ng/kg/min urodilatin group because of systemic hypotensive responses with nausea and dizziness. Infusion of 15 ng/kg/min urodilatin significantly increased urine flow by a maximum of 165%, filtration fraction by 46%, renal resistance by 49%, and systemic vascular resistance by 45%. It decreased renal plasma flow by a maximum of 31% from baseline value. No change in cardiac inotropic function was detectable, but cardiac output decreased in all dose groups. Effects on glomerular filtration rate, forced expiratory volume, blood pressure, and pulse were not different from those with placebo. CONCLUSION: Continuous infusion of 7.5 ng/kg/min and 15 ng/kg/min urodilatin exerts a significant increase in systemic and renal vascular resistance. Results of our experiments suggested that the therapeutic window for continuous urodilatin infusion is small and that doses higher than approximately 20 ng/kg/min urodilatin carry high risk for adverse drug reactions.

Adult↗