Biomedical subjects

Michaela Bayerle-Eder

Publications and source records attributed to Michaela Bayerle-Eder.

8 recordsLinked to original sources

PubMed2006

C-peptide does not affect ocular blood flow in patients with type 1 diabetes.

OBJECTIVE: The aim of the present study was to investigate the effect of intravenous C-peptide infusion on ocular blood flow in patients with type 1 diabetes under euglycemic conditions. RESEARCH DESIGN AND METHODS: The study was performed in a randomized, placebo-controlled, double-masked, two-way, crossover design in 10 type 1 diabetic patients. C-peptide was intravenously administered at two different dosages (dosage 1: 25 pmol . kg(-1) . min(-1) bolus followed by 5 pmol . kg(-1) . min(-1) continuous infusion; dosage 2: six times higher than dosage 1), each for 60 min. Physiologic saline solution was used as a control for C-peptide on a different study day. On both study days, euglycemic clamps were performed. To assess retinal blood flow, laser Doppler velocimetry (blood flow velocities) and retinal vessel analyzer (vessels diameters) measurements were performed. Laser interferometric measurements of fundus pulsation were used to assess pulsatile choroidal blood flow. Blood velocities in the ophthalmic artery were measured using color Doppler imaging. RESULTS: Eight patients (two female and six male) completed the study according to the protocol and without adverse events. One patient developed an anaphylactic reaction to C-peptide, which resolved without sequelae. The following results originate from the remaining eight subjects. Systemic hemodynamic parameters remained stable during both study days. Infusion of C-peptide did not affect any ocular hemodynamic parameter. CONCLUSIONS: The data of the present study indicate that exogenous C-peptide exerts no effect on ocular hemodynamic parameters in type 1 diabetic patients under euglycemic conditions. The maximum detectable change in these parameters was <25%.

Adult↗

PubMed2003

The ocular hemodynamic response to nitric oxide synthase inhibition is unaltered in patients with early type I diabetes.

BACKGROUND: An impaired ocular hemodynamic response to systemic nitric oxide synthesis inhibition has been demonstrated in patients with long-standing insulin-dependent diabetes mellitus. It is unclear whether this altered responsiveness is already detectable in early uncomplicated type I diabetes. METHODS: The effect of the nitric oxide synthase inhibitor N(G)-monomethyl- l-arginine (L-NMMA) was studied in 10 male patients with early type I diabetes under euglycemic conditions and 10 healthy matched control subjects in a single (analyst) blinded cohort study design. Changes in ocular hemodynamics (fundus pulsation amplitude, mean flow velocity in the ophthalmic artery) and in pulse rate and mean blood pressure were measured in response to systemic intravenous doses of 1.5, 3, and 6 mg/kg L-NMMA. RESULTS: L-NMMA dose-dependently and significantly decreased fundus pulsation amplitude (-21.0% vs -23.3% in diabetics and controls, respectively), mean flow velocity in the ophthalmic artery (-12.3% vs -10.8%) and pulse rate (-15.4% vs -16.6%) and increased mean arterial pressure (+19.5% vs +14.7%). The ocular and systemic hemodynamic effects of L-NMMA were not different between patients with diabetes and controls. CONCLUSION: The responsiveness of the choroidal vasculature and the ophthalmic artery to L-NMMA is not altered in early type 1 diabetes. An impaired hemodynamic response to nitric oxide synthesis inhibition in diabetes is therefore not caused by a primary defect but rather due to altered vascular responsiveness secondary to long-standing disease.

Adult↗

PubMed2003

C-peptide has no effect on forearm blood flow during local hyperinsulinaemia in healthy humans.

BACKGROUND: C-peptide increases forearm blood flow (FBF) in patients with Type 1 diabetes, probably by interaction with insulin, but not in healthy subjects. It is unclear if the vasodilating effect is sealed at normal fasting insulin concentrations. METHODS: The effects of C-peptide alone and during local hyperinsulinaemia were studied in healthy young men. Subjects received intra-arterial insulin at 6 pmol min-1 (low dose) or placebo for 60 min with subsequent coinfusion of C-peptide at increasing doses of 2-60 pmol min-1 in a double-blind crossover study (n = 8). In control experiments insulin at 30 pmol min-1 (high dose) was coinfused with C-peptide (n = 3). FBF was measured by strain-gauge plethysmography. RESULTS: Placebo had no effect on FBF (mean percentage change from baseline at 50 min -3.1%, 95% confidence interval [CI]-14.9, + 8.7). Insulin infusion slightly enhanced FBF by + 10.2% (95% CI -6.8, + 27.2; low dose) and + 17.6% (95% CI -38.8, + 74.0; high dose), respectively. The mean individual difference of the change in FBF between low-dose insulin and placebo was + 13.3% (95% CI -6.0, + 32.7; P = NS). Infusion of C-peptide increased local C-peptide concentrations from 1.8 +/- 0.1 ng ml-1 to 6.1 +/- 2.8 ng ml-1, but had no effect on FBF during placebo or hyperinsulinaemia (mean difference vs low dose insulin -16.0%, 95% CI -38.9, + 6.9). CONCLUSION: The vasodilating effect of C-peptide seen in Type 1 diabetes is not detectable during fasting or hyperinsulinaemia in the forearm vasculature of healthy subjects. This suggests saturation of its vasodilating potency at insulin concentrations within the normal or in the supraphysiological range.

Adult↗

PubMed2003

Vasodilator effects of L-arginine are stereospecific and augmented by insulin in humans.

The amino acid l-arginine, the precursor of nitric oxide (NO) synthesis, induces vasodilation in vivo, but the mechanism behind this effect is unclear. There is, however, some evidence to assume that the l-arginine membrane transport capacity is dependent on insulin plasma levels. We hypothesized that vasodilator effects of l-arginine may be dependent on insulin plasma levels. Accordingly, we performed two randomized, double-blind crossover studies in healthy male subjects. In protocol 1 (n = 15), subjects received an infusion of insulin (6 mU x kg(-1) x min(-1) for 120 min) or placebo and, during the last 30 min, l-arginine or d-arginine (1 g/min for 30 min) x In protocol 2 (n = 8), subjects received l-arginine in stepwise increasing doses in the presence (1.5 mU x kg(-1) x min(-1)) or absence of insulin. Renal plasma flow and glomerular filtration rate were assessed by the para-aminohippurate and inulin plasma clearance methods, respectively. Pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation, and mean flow velocity in the ophthalmic artery was measured with Doppler sonography. l-arginine, but not d-arginine, significantly increased renal and ocular hemodynamic parameters. Coinfusion of l-arginine with insulin caused a dose-dependent leftward shift of the vasodilator effect of l-arginine. This stereospecific renal and ocular vasodilator potency of l-arginine is enhanced by insulin, which may result from facilitated l-arginine membrane transport, enhanced intracellular NO formation, or increased NO bioavailability.

Adult↗

PubMed2002

Effect of pravastatin on responsiveness to N-monomethyl-L-arginine in patients with hypercholesterolaemia.

Improvement of endothelial function in hypercholesterolaemia is attributed to lipid lowering and to pleiotropic effects of statin therapy. We investigated whether responsiveness to inhibition of constitutive NO formation with N-monomethyl-L-arginine (L-NMMA) is improved after 7 and 28 days of pravastatin. Twelve female and four male subjects with mild or moderate primary hypercholesterolaemia were randomized to pravastatin (20 mg per oral (p.o.) n=8) or placebo (n=8) in a double blind parallel group design. Vascular responsiveness was studied by intravenous bolus infusions of L-NMMA (cumulative doses of 3 and 6 mg/kg). Mean arterial blood pressure (MAP) and pulse rate (PR) were measured noninvasively, pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation amplitudes (FPA) and renal plasma flow (RPF) was measured by the PAH clearance method. Pravastatin lowered plasma cholesterol levels by 16 and 24% after 7 and 28 days of treatment, respectively (P<0.01). L-NMMA caused comparable changes in MAP, PR and RPF between groups. L-NMMA reduced FPA to a similar extent in both groups before and after 7 days of treatment, but the response to L-NMMA was significantly enhanced after 28 days of pravastatin (21%; P<0.001 vs baseline) and greater than after placebo (15%; P<0.01 vs pravastatin). Pravastatin enhances responsiveness to L-NMMA in the ocular microvasculature. Improved responsiveness is associated with changes in total cholesterol levels.

Australia↗

PubMed2002

Regular physical exercise improves endothelial function in heart transplant recipients.

BACKGROUND: Impaired endothelial function is detectable in heart transplant (HTX) recipients and regarded as risk factor for coronary artery disease. We have studied whether endothelial function can be improved in HTX patients participating in a regular physical training program as demonstrated in patients with chronic heart failure, hypertension and coronary artery disease. METHODS: Male HTX patients and healthy, age-matched controls were studied. Seven HTX patients (age: 60 +/- 6 yr; 6 +/- 2 yr of HTX) participated in an outpatient training program, six HTX patients (age: 63 +/- 8 yr; 7 +/- 1 yr of HTX) maintained a sedentary lifestyle without regular physical exercise since transplantation. A healthy control group comprised six subjects (age: 62 +/- 6 yr). Vascular function was assessed by flow-mediated dilation of the brachial artery (FMD). Systemic haemodynamic responses to intravenous infusion of the endothelium independent vasodilator sodium nitroprusside (SNP) and to NG-monomethyl-L-arginine (L-NMMA), an inhibitor of constitutive nitric oxide synthase, were also measured. RESULTS: Resting heart rate was significantly lower (p < 0.05) in healthy controls (66 +/- 13) than in the HTX training group (83 +/- 11) and in non-training HTX patients (91 +/- 9), baseline blood pressure also tended to be lower in healthy subjects and in the training HTX patients. FMD was significantly higher (p < 0.05) in the control group (8.4 +/- 2.2%) and in the training group (7.1 +/- 2.4%), compared with non-training HTX patients (1.4 +/- 0.8%). The response of systolic blood pressure (p = 0.08) and heart rate (p < 0.05) to L-NMMA was reduced in sedentary HTX patients compared with healthy controls and heart rate response to SNP was also impaired in sedentary HTX patients. DISCUSSION: Regular aerobic physical training restores vascular function in HTX patients, who are at considerable risk for developing vascular complications. This effect is demonstrable in conduit and systemic resistance arteries.

Blood Pressure↗

PubMed2002

Adrenoceptor hyporeactivity is responsible for Escherichia coli endotoxin-induced acute vascular dysfunction in humans.

Impaired response to catecholamines contributes to the altered hemodynamics in sepsis, which has been attributed to excessive NO formation. We have studied the systemic hemodynamic and local forearm responses and inducible NO synthase (iNOS) expression during experimental endotoxemia in humans. Escherichia coli endotoxin (lipopolysaccharide [LPS]) was administered at doses of 1 or 2 ng/kg to healthy volunteers. In 10 subjects, the systemic pressor effect of phenylephrine was assessed before and after the administration of LPS. In 9 further subjects, forearm blood flow responses to intra-arterial noradrenaline, acetylcholine, glyceryl trinitrate, and N(G)-monomethyl-L-arginine (L-NMMA) were studied at baseline and after LPS administration. Peripheral blood was collected and analyzed for iNOS mRNA and protein. Four hours after LPS, the response of systolic blood pressure (P<0.0005) and heart rate (P<0.05) to phenylephrine was significantly reduced. In the forearm, noradrenaline-induced vasoconstriction was also reduced by approximately 50% (P<0.01), but L-NMMA responsiveness was unchanged. iNOS mRNA or protein was not increased. Marked vascular adrenoceptor hyporeactivity is detectable in the absence of increased NO activity or iNOS expression in endotoxemia, arguing against major involvement of vascular iNOS activity in the acute systemic vasodilation to LPS.

Adrenergic alpha-Agonists↗

PubMed2002

FFA-induced endothelial dysfunction can be corrected by vitamin C.

Insulin resistance is associated with an inappropriate elevation of plasma FFA and endothelial dysfunction. FFA could stimulate formation of reactive oxygen species, which could be responsible for vascular impairment. In this randomized, double-blind, cross-over study in 10 healthy volunteers (24 +/- 3 yr old), forearm blood flow (FBF) responses to intraarterial acetylcholine (ACh) and glyceryl trinitrate were assessed with coadministration of vitamin C (24 mg/ml) or placebo, respectively, in the presence of increased plasma FFA induced by Intralipid/heparin infusion. The rise in plasma FFA from 320 +/- 64 to 1852 +/- 232 micromol/liter was associated with a reduced response of FBF to ACh by 55% (P < 0.01). During coadministration of vitamin C, the impaired responsiveness of FBF to ACh was completely reversed and not different from that observed under baseline conditions. Vitamin C did not affect plasma FFA concentrations. Glyceryl trinitrate responsiveness was unchanged during FFA elevation, with or without vitamin C. These data suggest that FFA-induced vascular oxidative stress could contribute to endothelial dysfunction in insulin-resistant patients. High concentrations of antioxidants are able to reverse the local effects of FFA on endothelium-dependent vasodilation.

Acetylcholine↗