Biomedical subjects

Karsten Heusser

Publications and source records attributed to Karsten Heusser.

10 recordsLinked to original sources

PubMed2006

Influences of norepinephrine transporter function on the distribution of sympathetic activity in humans.

Previous studies suggest that neuronal norepinephrine transporter function may regulate the distribution of sympathetic activity among blood vessels, heart, and kidney; we tested the functional relevance in humans. Sixteen healthy men (26+/-1 years) ingested 8 mg of the selective norepinephrine reuptake transporter inhibitor reboxetine or a matching placebo on 2 separate days in a double-blind, randomized, crossover fashion. We monitored heart rate, thoracic bioimpedance, blood pressure, glomerular filtration rate, and renal blood flow. Ninety minutes after ingestion of the test medication, subjects were tilted to a 45 degrees head-up position, where they remained for an additional 30 minutes. Reboxetine increased supine systolic blood pressure through an increase in cardiac output whereas systemic vascular resistance decreased. Furthermore, reboxetine increased heart rate, particularly with a head-up tilt. Supine plasma renin activity was 0.71+/-0.15 ng angiotensin (Ang)/L per mL/h with placebo and 0.36+/-0.07 ngAng/L per mL/h with reboxetine (P<0.01). Supine plasma Ang II concentrations were also decreased with reboxetine. Both plasma renin activity and Ang II concentrations remained suppressed during head-up tilt. On placebo, renal vascular resistance increased with head-up tilt. The response was abolished with norepinephrine reuptake inhibition. We conclude that norepinephrine reuptake function profoundly influences the distribution of sympathetic activity between the heart, vasculature, and kidney in humans. All of these changes are physiologically relevant because they lead to corresponding changes in organ function.

Adrenergic Uptake Inhibitors↗

PubMed2006

Influence of sibutramine treatment on sympathetic vasomotor tone in obese subjects.

BACKGROUND: Sibutramine, a serotonin and norepinephrine transporter blocker, is used as adjunctive obesity treatment. Studies in healthy subjects suggested that sibutramine might have opposing effects on peripheral and central sympathetic activity; an increase in blood pressure has been claimed. Direct measurements of muscle sympathetic nerve activity (MSNA) in sibutramine-treated patients have not been conducted. METHODS AND RESULTS: Twenty nondiabetic obese men and women completed the study (mean body mass index, 35 +/- 3 kg/m2; mean age, 42 +/- 8 years). They were treated for 5 days with 15 mg sibutramine per day or matching placebo in a randomized, double-blind, crossover fashion. At the end of each intervention, heart rate, blood pressure, and MSNA were recorded. Patients underwent cold pressor testing and phenylephrine and nitroprusside infusions. RESULTS: The mean blood pressure (systolic/diastolic) was 118 +/- 13 mm Hg/70 +/- 9 mm Hg with placebo and 120 +/- 13 mm Hg/69 +/- 8 mm Hg with sibutramine (P = .29). The mean resting MSNA was 28 +/- 14 bursts/min with placebo and 12 +/- 10 bursts/min with sibutramine (P < .0001). Sibutramine attenuated the rise in blood pressure (25 +/- 9 mm Hg/9 +/- 9 mm Hg versus 31 +/- 12 mm Hg/14 +/- 9 mm Hg, P < .01) and MSNA (0.3 +/- 0.5 arbitrary units/min versus 1.0 +/- 1.1 arbitrary units/min, P = .01) in response to cold pressor testing. Baroreflex heart rate control was similar with sibutramine and with placebo. The sympathetic baroreflex was shifted such that at a given blood pressure, MSNA was substantially decreased (top, 44 +/- 1.23 bursts/min versus 58 +/- 2.99 bursts/min [P < .001]; center point, 65 +/- 0.32 mm Hg versus 67 +/- 0.81 mm Hg [P < .05]). CONCLUSIONS: Sibutramine treatment profoundly and selectively reduces sympathetic nerve traffic at rest and attenuates the responsiveness to sympathetic stimuli. Our data support the idea that sibutramine's peripheral sympathomimetic effect is counteracted by a central sympatholytic mechanism.

Adult↗

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

Baroreflex failure.

The baroreflex receives less attention nowadays because most students of hypertension are convinced that faulty volume regulation by the kidneys is responsible for long-term blood pressure increases. However, unusual patients with bilateral destruction of the normal blood pressure-sensing mechanisms can develop profound chronic hypertension. We present 2 patients with baroreflex failure. Both had volatile hypertension with systolic readings up to 300 mm Hg documented over years. Both had muscle sympathetic nerve activity that was increased even while resting. Treating these patients was a stochastic challenge. The therapy is frequently based on medicines that are no longer commonly prescribed.

Aged↗

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↗

PubMed2004

Effect of erythropoietin on cardiovascular prognosis parameters in hemodialysis patients.

BACKGROUND: Renal anemia is an important determinant for left ventricular hypertrophy in dialysis patients and an independent prognosis parameter for the cardiovascular survival in dialysis patients. In addition, an autonomic dysfunction is associated with the uremic state and influences the cardiovascular risk in patients with end-stage renal disease (ESRD). METHODS: We investigated in this prospective longitudinal study the effect of hemoglobin normalization by a chronic treatment with recombinant human erythropoietin (rhEPO) on cardiovascular prognosis parameters in 23 patients on chronic hemodialysis with renal anemia (hemoglobin concentration < or =10.5 g/dL) and echocardiographically proven left ventricular hypertrophy. We studied muscle sympathetic nerve activity measured by microneurography; cardiopulmonary baroreflex activity by lower-body negative pressure (LBNP-) testing; left ventricular structure and mass index (LVMI) by echocardiography; blood pressure by 24-hour readings; peripheral blood flow and vascular resistance by plethysmography before (U1) and after 7 months of chronic rhEPO treatment (U2). RESULTS: In the anemic state, mean (+/- SD) muscle sympathetic nerve activity in ESRD was elevated (U1 rest, 34 +/- 13 bursts per minute) and cardiopulmonary baroreflex response during LBNP markedly lacking (U1 -15 mm Hg, 34 +/- 13 bursts per minute) reflecting a severely impaired autonomic function. Normalization of the hemoglobin concentration by chronic rhEPO treatment (U1, 10.5 +/- 0.9 g/dL versus U2, 13.4 +/- 3.1 g/dL, P <0.001) did not influence sympathetic nerve activity (U2, 34 +/- 15 bursts per minute, NS) and cardiopulmonary baroreflex sensitivity did not change (U2 -15 mm Hg, 37 +/- 16 bursts per minute, NS). LVMI decreased significantly after chronic treatment with rhEPO (U1, 134 +/- 26 g/m2 versus U2, 97 +/- 25 g/m2, P < 0.001) and left ventricular geometry developed from an asymmetric to a symmetric configuration (U1, relative wall thickness 0.58 versus U2, 0.43, P < 0.001). Under treatment with rhEPO, 24-hour systolic and diastolic blood pressure did not increase (systolic U1, 132 +/- 4 mm Hg versus U2, 128 +/- 3 mm Hg, NS, and diastolic U1, 76 +/- 2 mm Hg versus U2, 73 +/- 2 mm Hg, NS). Peripheral blood flow (U1, 6.1 +/- 3.3 mL/100 mL/min versus U2, 6.2 +/- 0.6 mL/100 mL/min, NS) as well as forearm vascular resistance (U1, 15.7 +/- 3.3 mm Hg/mL/100 mL versus U2, 14.9 +/- 3.1 mm Hg/mL/100 mL, NS) did not change by chronic rhEPO treatment. CONCLUSION: Normalization of hemoglobin by chronic rhEPO treatment in dialysis patients has beneficial cardiovascular effects with regression of left ventricular hypertrophy and improvement of left ventricular geometry. However, a reduction of sympathetic overactivity or a resetting of baroreceptor sensitivity by a rhEPO treatment in dialysis patients in the medium-term could not be demonstrated. The reason for this may be the complex and multifactorial pathomechanism of autonomic dysfunction and cardiovascular disease in ESRD.

Adult↗

PubMed2003

AT1 antagonism by eprosartan lowers heart rate variability and baroreflex gain.

INTRODUCTION: Blockade of the renin-angiotensin system (RAS) by ACE inhibitors has been demonstrated to reduce total mortality in cardiovascular diseases. This advantage was attributed in part to changes of autonomic cardiovascular control, exemplified by an increase of heart rate variability (HRV) and baroreflex gain (BRG). We sought to assess the effects of the angiotensin type 1 (AT1) receptor blocker eprosartan on HRV and BRG. MATERIALS AND METHODS: In a double-blind randomized cross-over design 25 young males took eprosartan (600 mg/day) and placebo each for a period of 7 days with a wash-out period of at least 4 weeks in between. At the end of the intake phases simultaneous recordings of arterial blood pressure (AP; Finapres) and electrocardiogram (ECG) were taken. Power spectra of HRV and arterial blood pressure variability (APV) were calculated by fast Fourier transform (FFT) and served to calculate BRG. Ang-II levels were measured by radioimmunoassay. RESULTS: Eprosartan tended to lower mean AP, it slightly increased heart rate (HR) (p<0.05), and markedly increased circulating Ang-II levels (p<0.01). Eprosartan diminished the total power of HRV (p<0.05) and the BRG (p<0.01). The low/high frequency (LF/HF) ratio of HRV and the APV were not altered. CONCLUSIONS: AT1 antagonism by eprosartan lowers heart rate variability and baroreflex gain. We speculate that these findings are due to the marked increase in circulating angiotensin II (Ang II). Further studies are needed to clarify whether angiotensin type 1 (AT1) blockers with potential actions inside the blood-brain barrier (BBB) may have different effects on HRV and BRG.

Acrylates↗

PubMed2003

Elevation of sympathetic activity by eprosartan in young male subjects.

BACKGROUND: Selective blockade of the type 1 angiotensin II receptors (AT1 receptors) reduced blood pressure (BP) elevation caused by sympathetic stimulation in the pithed rat model. This has been attributed to blockade of AT1 receptors located presynaptically on sympathetic nerve endings normally facilitating norepinephrine release. We examined the effects of AT1 receptor blockade on the sympathetic nervous system in humans. METHODS: Twenty-nine young white men with normal to mildly hypertensive BP values participated in a double-blind, placebo-controlled, randomized cross-over protocol receiving 600 mg/d of eprosartan or placebo for 1 week. At the last day of intake we measured hemodynamic parameters, muscle sympathetic nerve activity by microneurography, and plasma levels of norepinephrine, epinephrine, and angiotensin II during rest and cardiovascular stress. RESULTS: Eprosartan lowered resting mean arterial pressure (73.6 +/- 11.0 v 78.0 +/- 10.3 mm Hg, P <.05; Finapres, Ohmeda, Englewood, CO), and elevated heart rate (64.4 +/- 7.6 v 61.1 +/- 6.8 beats/min, P =.01), muscle sympathetic nerve activity (14.1 +/- 10.4 v 9.8 +/- 6.3 bursts/min, P <.05) and plasma angiotensin II (37.0 +/- 33.7 v 6.9 +/- 2.8 ng/L, P <.01), as well as norepinephrine levels (234.2 +/- 87.6 v 187.8 +/- 59.3 ng/L, P <.01). Eprosartan did not blunt sympathetic activation caused by lower body negative pressure or mental stress. CONCLUSIONS: These results contrast with animal data showing antiadrenergic properties of this drug. If any, it appeared, that eprosartan causes augmented central neural vasoconstrictor outflow paralleled by increased plasma levels of norepinephrine, which casts doubt on its ability to dampen norepinephrine release from peripheral sympathetic nerve endings in humans. We hypothesize that eprosartan leads to a resetting of the baroreflex, presumably by the markedly elevated circulating angiotensin II.

Acrylates↗

PubMed2003

Effects of angiotensin II receptor antagonism on the renal hemodynamic response to cardiovascular stress.

BACKGROUND: To elucidate the effect of the angiotensin type 1 (AT1) receptor antagonist (AT1RA) eprosartan (E) on renal hemodynamics in normotensive and borderline hypertensive subjects, we investigated the hormonal and renal hemodynamic responses during cardiopulmonary stress testing. METHODS: In a prospective, double-blind, randomized, placebo-controlled crossover study, the effects of E on renal plasma flow (RPF), renal blood flow (RBF), glomerular filtration rate (GFR), and the concentration of angiotensin II (Ang II) levels were measured with the subjects at rest and during perturbation of cardiopulmonary baroreceptors using lower body negative pressure (LBNP). Ten normotensive male subjects (NT) versus 14 males with mild hypertension (HT), matched for age and body mass index, who were all free of any medication, were randomly assigned to receive placebo or E 600 mg/day PO for seven days (intake phase 1). After a washout period of four weeks the subjects started the intake of the other substance for seven days in a crossover manner (intake phase 2). The measurements were taken on day 7 of both intake phases. RESULTS: During the LBNP test, RPF and RBF were reduced significantly in all subjects; GFR, however, decreased significantly during cardiopulmonary stress testing in the subjects taking the placebo (P < 0.05) and remained unchanged in those under treatment with AT1RA. Ang II levels increased significantly during cardiopulmonary stress test only in the subjects with hypertension who were on placebo, whereas the Ang II levels did not change in normotensive subjects or those treated with the AT1RA. CONCLUSIONS: The data confirm that with cardiovascular stress simulating orthostasis or volume depletion, subjects with AT1RA can maintain their GFR level, suggesting that AT1RA potentially is renoprotective. Additionally, the neurohumoral system is activated after cardiovascular stress in subjects even at an early stage of hypertension.

Acrylates↗

PubMed2002

Hypertension in patients with neurovascular compression is associated with increased central sympathetic outflow.

Recent data suggest a causal relationship between essential hypertension and neurovascular compression (NVC) at the rostral ventrolateral medulla. An increase of central sympathetic outflow might be an underlying pathomechanism. The sympathetic nerve activity to muscle was recorded in 21 patients with hypertension with NVC (NVC+ group) and in 12 patients with hypertension without NVC (NVC- group). Heart rate variability, respiratory activity, BP, and central venous pressure at rest and during unloading of cardiopulmonary baroreceptors with lower-body negative pressure and during a cold pressor test were also measured. Resting sympathetic nerve activity to muscle was twice as high in the NVC+ group compared with the NVC- group (34 +/- 22 versus 18 +/- 6 bursts/min; P < 0.05). Resting heart rate (P = 0.06) and low- to high-frequency power ratio values (P = NS) (as indicators of cardiac sympathovagal balance) tended to be augmented as well in the NVC+ group. The sympathetic nerve activity to muscle response to the cold pressor test was increased in the NVC+ group versus the NVC- group (+15 +/- 11 versus 6 +/- 12 bursts/min; P = 0.05), but hemodynamic and sympathetic nerve responses to lower-body negative pressure did not differ between the two groups. It is concluded that NVC of the rostral ventrolateral medulla in patients with essential hypertension is accompanied by increased central sympathetic outflow. Therefore, these data support the hypothesis described in the literature: in a subgroup of patients, essential hypertension might be causally related to NVC of the rostral ventrolateral medulla, at least in part, via an increase in central sympathetic outflow.

Adult↗