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Biomedical subjects

Andreas L Birkenfeld

Publications and source records attributed to Andreas L Birkenfeld.

8 recordsLinked to original sources
PubMed2006

Beta-adrenergic and atrial natriuretic peptide interactions on human cardiovascular and metabolic regulation.

CONTEXT: Atrial natriuretic peptide (ANP) has well-known cardiovascular effects and modifies lipid and carbohydrate metabolism in humans. OBJECTIVE: The objective of the study was to determine the metabolic and cardiovascular interaction of beta-adrenergic receptors and ANP. DESIGN: This was a crossover study, conducted 2004-2005. SETTING: The study was conducted at an academic clinical research center. PATIENTS: PATIENTS included 10 healthy young male subjects (body mass index 24 +/- 1 kg/m2). INTERVENTION: We infused iv incremental ANP doses (6.25, 12.5, and 25 ng/kg.min) with and without propranolol (0.20 mg/kg in divided doses followed by 0.033 mg/kg.h infusion). Metabolism was monitored through venous blood sampling, im, and sc microdialysis and indirect calorimetry. Cardiovascular changes were monitored by continuous electrocardiogram and beat-by-beat blood pressure recordings. MAIN OUTCOME MEASURES: Venous nonesterified fatty acid, glycerol, glucose, and insulin; and microdialysate glucose, glycerol, lactate, and pyruvate were measured. RESULTS: ANP increased heart rate dose dependently. beta-Adrenergic receptor blockade abolished the response. ANP elicited a dose-dependent increase in serum nonesterified fatty acid and glycerol concentrations. The response was not suppressed with propranolol. Venous glucose and insulin concentrations increased with ANP, both without or with propranolol. ANP induced lipid mobilization in sc adipose tissue. In skeletal muscle, microdialysate lactate increased, whereas the lactate to pyruvate ratio decreased, both with and without propranolol. Higher ANP doses increased lipid oxidation, whereas energy expenditure remained unchanged. Propranolol tended to attenuate the increase in lipid oxidation. CONCLUSIONS: Selected cardiovascular ANP effects are at least partly mediated by beta-adrenergic receptor stimulation. ANP-induced changes in lipid mobilization and glycolysis are mediated by another mechanism, presumably stimulation of natriuretic peptide receptors, whereas substrate oxidation might be modulated through adrenergic mechanisms.

Adipose Tissue↗
PubMed2006

Norepinephrine transporter inhibition prevents tilt-induced pre-syncope.

OBJECTIVES: We tested the hypothesis that pharmacological norepinephrine reuptake transporter (NET) inhibition delays the onset of head-up tilt-induced presyncope in healthy subjects. BACKGROUND: Treatment of neurally mediated syncope is unsatisfactory. In a previous study in a small number of healthy subjects, pharmacologic NET inhibition delayed the onset of head-up tilt-induced pre-syncope. METHODS: We combined data sets from 3 substudies comprising 51 healthy subjects without a history of syncope. In a double-blind, randomized, cross-over fashion, subjects underwent 2 head-up tilt tests, once with placebo and once with a NET inhibitor (sibutramine or reboxetine). Tilt testing was prematurely ended when pre-syncopal symptoms such as dizziness, nausea, or visual disturbances occurred together with a decrease in blood pressure and/or heart rate. RESULTS: The mean tolerated tilt test duration was 29 +/- 2 min with placebo and 35 +/- 1 min with NET inhibition (p = 0.001). The odds ratio for premature abortion of head-up tilt testing was 0.22 (95% confidence interval 0.09 to 0.55, p < 0.001) in favor of NET inhibition. Norepinephrine reuptake transporter inhibition elicited a pressor response and increased upright heart rate. CONCLUSIONS: In healthy subjects, NET inhibition prevents tilt-induced neurally mediated (pre)syncope. Therefore, NET inhibition may be a worthwhile target of drug intervention for larger trials in highly symptomatic patients with neurally mediated syncope.

Blood Pressure↗
PubMed2005

Plasma exchange for primary autoimmune autonomic failure.

We report on a patient with long-standing severe autonomic failure that affected his sympathetic and parasympathetic nervous systems. Antibodies against the ganglionic acetylcholine receptors were detected in the serum. Removal of the antibodies by means of plasma exchange resulted in a dramatic clinical improvement.

Adult↗
PubMed2005

Lipid mobilization with physiological atrial natriuretic peptide concentrations in humans.

CONTEXT: Atrial natriuretic peptide (ANP) in pharmacological concentrations stimulates lipid mobilization in humans. OBJECTIVE: The objective was to determine the hemodynamic and metabolic response to physiologically relevant ANP concentrations. DESIGN: The design was a human physiological study, conducted in 2004. SETTING: The study was conducted at an academic research institute. PARTICIPANTS: Fourteen healthy normal-weight men (30 +/- 1.2 yr) participated in the study. INTERVENTION: Intravenous infusion of human ANP (h-ANP) was administered at rates of 6.25, 12.5, and 25 ng/kg.min. MAIN OUTCOME MEASURES: We studied local changes in blood flow and glucose and lipid metabolism of abdominal sc adipose tissue and femoral skeletal muscle by microdialysis. Overall changes in energy expenditure and substrate oxidation rates were monitored by indirect calorimetry. RESULTS: The increase in serum nonesterified fatty acids and glycerol concentrations were correlated with ANP plasma concentrations (r(2) = 0.86 and r(2) = 0.76, respectively). In adipose tissue, glycerol increased from 53 +/- 6 micromol/liter to 87+/-13 micromol/liter (P < 0.001). In femoral skeletal muscle, glycerol concentrations did not change, whereas lactate-to-pyruvate ratio decreased from 91 +/- 23 to 32 +/- 4 (P < 0.001). Indirect calorimetry indicated an increase in lipid oxidation (P < 0.05) concomitantly with a decrease in carbohydrate oxidation (P < 0.01), without changes in overall energy expenditure. CONCLUSIONS: ANP briskly stimulates lipid mobilization and oxidation at plasma concentrations that are encountered in conditions such as heart failure. Natriuretic-peptide induced lipid mobilization might contribute to cardiac cachexia. Drugs that interfere with the natriuretic peptide system should be evaluated for potential metabolic side effects.

Adipose Tissue↗
PubMed2005

Paradoxical effect of sibutramine on autonomic cardiovascular regulation in obese hypertensive patients--sibutramine and blood pressure.

BACKGROUND: Sibutramine, a serotonin and norepinephrine transporter blocker, is a common adjunctive obesity treatment. Acute studies in healthy subjects suggested that an inhibitory central nervous mechanism might attenuate the peripheral stimulatory effect on the sympathetic nervous system. This notion has not been tested in overweight and obese patients. METHODS: We conducted a randomized, controlled clinical study in hypertensive patients with BMI > or = 27 to < 40 kg/m(2). After 4 week placebo run-in period patients were randomized to four different antihypertensive treatments or placebo. After 4 weeks of antihypertensive therapy, patients were additionally treated with sibutramine 15 mg o. d. for 3 months. Patients underwent cardiovascular autonomic reflex testing and a graded head-up tilt test at the end of each phase. RESULTS: Mean body weight decreased from 98.5+/-4 to 94.7+/-4 kg (p<0.05) between end of placebo run-in and end of sibutramine treatment. Supine blood pressure was 154+/-3/80+/-2, 145+/-3/76+/-2 and 150+/-3/79+/-2mmHg at the end of placebo run-in, after antihypertensive titration (ns) and end of sibutramine treatment (ns), respectively. Blood pressure was affected similarly during head up tilt testing. The systolic blood pressure response to cold pressor testing was diminished with sibutramine (p<0.01). Sibutramine decreased low frequency systolic blood pressure oscillations in the supine position (p<0.01). CONCLUSIONS: Resting blood pressure tends to increase with sibutramine, whereas blood pressure during sympathetic stimulation and low frequency blood pressure oscillations are decreased. These paradoxical changes are consistent with previous studies in healthy subjects and suggest a combination of peripheral and central nervous system mechanisms.

Adolescent↗
PubMed2002

Paradoxical effect of sibutramine on autonomic cardiovascular regulation.

BACKGROUND: Sibutramine, a serotonin and norepinephrine transporter blocker, is widely used as an adjunctive obesity treatment. Norepinephrine reuptake inhibition with sibutramine conceivably could exacerbate arterial hypertension and promote cardiovascular disease. METHODS AND RESULTS: In 11 healthy subjects (7 men, age 27+/-2 years, body mass index 23.1+/-0.7 kg/m2), we compared the effect of sibutramine or matching placebo (ingested 26, 14, and 2 hours before testing) on cardiovascular responses to autonomic reflex tests and to a graded head-up tilt test. In addition, we tested sibutramine in combination with metoprolol. Testing was conducted in a double-blind and crossover fashion. Supine systolic blood pressure was 113+/-3 mm Hg with placebo, 121+/-3 mm Hg with sibutramine (P<0.001 versus placebo), and 111+/-2 mm Hg with the combination of sibutramine and metoprolol. Similarly, sibutramine increased upright blood pressure. Sibutramine substantially increased upright heart rate. This effect was abolished with metoprolol. The blood pressure response to cold pressor and handgrip testing was attenuated with sibutramine compared with placebo. Furthermore, sibutramine decreased low-frequency oscillations of blood pressure and plasma norepinephrine concentrations in the supine position. CONCLUSIONS: The cardiovascular effect of the antiobesity drug sibutramine results from a complex interaction of peripheral and central nervous system effects. The inhibitory clonidine-like action of sibutramine on the central nervous system attenuates the peripheral stimulatory effect. Our findings strongly suggest that current concepts regarding the action of sibutramine on the sympathetic nervous system should be reconsidered.

Adrenergic beta-Antagonists↗