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Biomedical subjects

A Melcher

Publications and source records attributed to A Melcher.

At least 37 records · Page 2Linked to original sources
PubMed1996

Forearm vasodilator mechanisms during mental stress: possible roles for epinephrine and ANP.

The contribution of epinephrine (Epi) to forearm vasodilator responses to mental stress was evaluated in 12 healthy men by comparing hemodynamic and plasma catecholamine responses to mental stress and to intravenous and intra-arterial infusions of epinephrine. Mental stress decreased forearm vascular resistance (FVR) by 45%, increased arterial Epi from 0.23 to 0.44 nmol/l in arterial plasma, and increased forearm norepinephrine overflow. Intra-arterial Epi infusion decreased FVR concentration dependently by up to 43%. Intravenous Epi infusion decreased diastolic arterial pressure and increased heart rate and systolic blood pressure dose dependently. FVR decreased by up to 39% at 4.60 nmol/l Epi in arterial plasma. The average Epi contribution to forearm vasodilation during mental stress was calculated to be between 9 and 30%, depending on if responses to stress were compared with intravenous or intra-arterial Epi infusion. Arterial atrial natriuretic peptide immunoreactivity increased by 23% during stress, supporting a vasodilator influence, whereas vasopressin immunoreactivity was unaffected. Thus secretion of Epi explains only part of the stress-induced forearm vasodilation. Intravenous infusion of Epi appears to activate sympathetic counterregulation.

Adult↗
PubMed1996

Gastro-oesophageal reflux before and after vertical banded gastroplasty in the treatment of obesity.

OBJECTIVE: To study the long term effect of vertical banded gastroplasty on lower oesophageal sphincter pressure. DESIGN: Prospective study. SETTING: University hospital, Sweden. SUBJECTS: 21 morbidly obese patients (mean body mass index 42.5). INTERVENTIONS: Vertical banded gastroplasty, together with measurements of endoscopic grade, oesophageal manometry, and 24 hour pH before, and a mean of 38 months after, operation. MAIN OUTCOME MEASURES: Weight, grade of oesophagitis according to the Savary-Miller classification, number of episodes of reflux, percentage of time that the pH was < 4, and lower oesophageal sphincter pressure. RESULTS: Before operation 5/14 patients (36%) had evidence of oesophagitis, and 12/21 (57%) had evidence of reflux disease. Two patients had abnormally low lower oesophageal sphincter pressure ( < 10 mm Hg). A mean (SEM) of 32 months after operation (range 6-49) the mean body mass index was 32.7 (1.2), and after a mean of 38 months paired data showed that there had been no significant changes in manometric (n = 11) or 24 hour pH (n = 10) measurements, or in endoscopic grading (n = 7). CONCLUSION: Vertical banded gastroplasty used in the treatment of morbid obesity does not affect the antireflux function of the lower oesophageal sphincter.

Esophagitis, Peptic↗
PubMed1995

Effects of beta receptor antagonists in patients with clinical evidence of heart failure after myocardial infarction: double blind comparison of metoprolol and xamoterol.

OBJECTIVE: To evaluate whether xamoterol, a partial agonist, would improve exercise time more than metoprolol in patients with mild to moderate heart failure after a myocardial infarction. DESIGN: Single-centre double blind randomised parallel group comparison of metoprolol 50-100 mg and xamoterol 100-200 mg twice daily. PATIENTS: 210 patients aged 40-80 years (173 men) with clinical evidence of heart failure early after a myocardial infarction. 106 were given metoprolol and 104 xamoterol. MAIN OUTCOME MEASURES: Exercise test results and performance at three months; the exercise test, quality of life, and clinical assessments at baseline (5-7 days after the infarction) and after 3, 6, and 12 months. RESULTS: Exercise time increased at three months by 22% in the metoprolol group and 29% in the xamoterol group, but with no significant difference between the groups. Patients taking xamoterol showed overall non-significantly higher mean values of exercise time achieved with higher heart rates at rest and exercise. Improvements in quality of life, clinical signs of heart failure, and New York Heart Association functional class were seen in both treatment groups over one year, with minor benefits of xamoterol on breathlessness, peripheral oedema, and functional class. Eighteen patients taking metoprolol and 22 taking xamoterol withdrew from the study during one year, with a low mortality, reinfarction rate, and progress of heart failure in both treatment groups. Mean dose from baseline to 3 months was 135 mg metoprolol and 347 mg xamoterol. CONCLUSION: beta 1 Receptor antagonists with or without partial agonist activity are safe to use in mild to moderate heart failure after a myocardial infarction. Exercise tolerance, quality of life, and clinical signs and functional class of heart failure improve, and few patients show deterioration in their condition. Exercise tolerance is no better with xamoterol than metoprolol.

Adrenergic beta-Antagonists↗
PubMed1995

Long-term prognostic importance of exercise echocardiography after an episode of unstable angina.

The aim of this study was to determine whether exercise echocardiography gives long-term prognostic information in patients with unstable angina. Treadmill exercise echocardiography was performed before discharge in 33 consecutive patients (23 men, 10 women) with unstable angina. A wall motion score index (WMSI) was calculated from visual interpretation of 9 left-ventricular segments, registered with two-dimensional echocardiography. Within an 8-year follow-up period, there were 10 medical events (2 cardiac deaths and 8 myocardial infarctions). New or worsening wall motion abnormalities and a low WMSI immediately after the exercise test were associated with subsequent myocardial infarction or cardiac death during follow-up (p < 0.05). Only 1 of the patients with a WMSI above the median suffered a myocardial infarction, which was not fatal. In contrast, 9 (56%) of the 16 patients with a WMSI below the median suffered myocardial infarction or cardiac death during follow-up. These findings in patients with unstable angina suggest that exercise echocardiography is a sensitive method for detecting those with increased risk of myocardial infarction or cardiac death. These high-risk patients might benefit from a more aggressive therapeutic approach.

Adolescent↗
PubMed1994

Acute and chronic calcium antagonist treatment elevates sympathetic activity in primary hypertension.

Eleven men with mild to moderate primary hypertension were studied at rest and during mental stress before and during intravenous infusion of the calcium antagonist felodipine. Eight of them were restudied during long-term treatment (extended-release felodipine, 10 mg daily). For comparison, 10 normotensive control subjects were studied with the short-term protocol. Heart rate, cardiac output, central cardiovascular pressures, and forearm blood flow were registered. Arterial and venous sampling was performed. Norepinephrine spillovers to arterial plasma and from the forearm were assessed with the use of radiotracer methodology. In the hypertensive patients, felodipine lowered mean arterial blood pressure acutely by 8% (P < .01). Systemic vascular resistance decreased by 22% (P < .001), cardiac output increased by 20% (P < .01), and norepinephrine spillover to arterial plasma increased by 61% (P < .001). Forearm vascular resistance fell by 30% (P < .001), but norepinephrine overflow from the forearm increased by 115% (P < .001). These forearm responses were not seen in normotensive subjects despite similar systemic responses to felodipine infusion. After 8 weeks of treatment, mean arterial pressure decreased to 15% below baseline (P < .001), cardiac output returned toward pretreatment levels, and systemic vascular resistance remained low. Forearm blood flow returned toward basal levels, but forearm vascular resistance remained lowered. Total body and forearm norepinephrine spillover values were as elevated as in the acute situation. The hemodynamic "defense reaction" and the sympathoadrenal response to mental stress were essentially unaffected by felodipine. Stress-induced small elevations of neuropeptide Y-like immunoreactivity persisted during felodipine. Thus, the vasodilatation induced by felodipine elicits sympathetic counterregulation, which persists in the long term with respect to peripheral and total sympathetic activities, despite resetting of the baroreflex control of heart rate.

Calcium Channel Blockers↗
PubMed1993

Cardiovascular and sympatho-adrenal responses to mental stress in primary hypertension.

1. Eleven untreated men with mild to moderate primary hypertension and 10 normotensive control subjects were studied at rest and during a mental stress test (Stroop colour word conflict test), which has previously been used in studies of hypertensive patients with regard to non-invasive cardiovascular variables and venous plasma catecholamine concentrations. 2. Heart rate, central cardiovascular pressures, cardiac output (thermodilution) and forearm blood flow (strain gauge plethysmography) were determined. Systemic and forearm vascular resistances were calculated. Arterial and venous plasma adrenaline and noradrenaline concentrations were measured by h.p.l.c., and arterial noradrenaline spillover and noradrenaline overflow from the forearm were assessed by isotope methodology ([3H]noradrenaline). Neuropeptide Y-like immunoreactivity was measured by radioimmunoassay. 3. In hypertensive patients heart rate, arterial blood pressure, cardiac output and forearm blood flow increased by 28%, 13%, 37% and 115%, respectively, and forearm and systemic vascular resistances decreased by 48% and 21%, respectively (P < 0.001 for all responses), during stress. These responses were not different from those of the control group. 4. Arterial noradrenaline spillover rose by 63% and noradrenaline overflow from the forearm rose by 150% in the hypertensive patients in response to mental stress (P < 0.001); no significant group differences could be demonstrated. However, the forearm noradrenaline overflow response to stress tended to be greater in the hypertensive group (P = 0.11). Arterial adrenaline concentrations doubled in both groups (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1991

Extracellular phospholipase A2 secretion is a common effector pathway of interleukin-1 and tumour necrosis factor action.

Inflammatory processes are characterized by increased levels of extracellular phospholipase A2 (PLA2) and cytokines such as interleukin 1 (IL-1) and tumour necrosis factor (TNF). IL-1, TNF and PLA2 share a number of proinflammatory, arthritogenic effects. The sequential induction, first of the cytokines followed by PLA2, suggests that these cytokines may regulate synthesis and secretion of PLA2. To test this postulate, foetal rat calvarial bone-forming cells (FRCC) were treated with recombinant human IL-1 and TNF and extracellular PLA2 release was quantitated. Both IL-1 and TNF induced the de novo synthesis of PLA2 in a concentration-dependent manner. Continuous exposure of FRCC in primary culture to IL-1 (50 units/ml) over 15 days resulted in as much as 100-fold increase in PLA2 secretion. IL-1 (50 units/ml) added to post-confluent cultures for a 48-h pulse increased PLA2 activity 9.4-fold. The combination of IL-1 (50 units/ml) and TNF (500 units/ml) was synergistic with an observed increase in extracellular PLA2 secretion of 146-fold following a 48-h pulse. Interleukin-6, alone or in combination with IL-1 or TNF, did not further enhance PLA2 synthesis of secretion. Cytokine-induced synthesis of PLA2 was inhibited 80% by 10 microM cycloheximide but not by dexamethasone over the range of 10(-6) to 10(-8) M. FRCC-derived PLA2 was neutral-active with a pH optimum of 6-7.5 and was calcium-dependent with optimal activity in the presence of 2-7 mM calcium. It had absolute 2-acyl specificity using micellar phosphatidylcholine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Comparison between isoprenaline infusions and bolus injections to assess beta-adrenoceptor function in man, with special reference to cardiac contractility and the influence of autonomic reflexes.

The present study was performed to characterize cardiovascular responses to isoprenaline and the influence of autonomic reflexes on these responses. Nine healthy volunteers received infusions and bolus injections of isoprenaline before and after 'autonomic blockade' produced by intravenous atropine 0.04 mg kg-1 and clonidine 300 micrograms. Heart rate, blood pressures, systolic time intervals and various echocardiographic measures of cardiac contractility were registered. No significant differences in responsiveness to isoprenaline were seen when infusions were repeated on the same day without 'autonomic blockade'. After 'blockade', delta responses at 1 nmol l-1 isoprenaline (infusions) were increased for diastolic blood pressure and decreased for systolic blood pressure and stroke volume. Bolus injections of 2 micrograms isoprenaline caused enhanced delta responses after 'autonomic blockade' of diastolic blood pressure, left ventricular diameter in systole, ventricular circumferential fibre shortening, mean posterior wall velocity (Vmean PW), stroke volume, systemic vascular resistance, electromechanical systole (QS2) and pre-ejection period. Systolic blood pressure decreased, in contrast to a small increase without 'blockade'. These findings are explained by differences in haemodynamic effects of isoprenaline and by the dependence of responses on reflexes when isoprenaline is administered in different ways. When heart rate was increased by bolus doses of atropine, in the presence of beta-blockade (propranolol), pre-ejection period and left ventricular diameter in systole were unaffected, and Vmean PW and ventricular circumferential fibre shortening showed only small increases (compared with alterations induced by isoprenaline). However, left ventricular ejection time, QS2 and ejection time (by echocardiography), were markedly dependent on heart rate alterations. Thus, pre-ejection period, left ventricular diameter in systole Vmean PW and ventricular circumferential fibre shortening are parameters which can be useful in order to evaluate cardiac beta-adrenoceptor sensitivity in vivo in man.

Adult↗
PubMed1989

Beta-adrenergic receptor responsiveness to isoprenaline in humans: concentration-effect, as compared with dose-effect evaluation and influence of autonomic reflexes.

1. Different techniques of assessing beta-adrenoceptor sensitivity in vivo, by use of i.v. infusions or bolus injections of isoprenaline (ISO), were compared in healthy volunteers. The importance of autonomic reflexes for responses to ISO was evaluated by studying the influence of 'autonomic blockade' by atropine and clonidine, which antagonize muscarinic effects and reduce sympathetic activity, respectively. Estimates of in vivo responsiveness to ISO were compared with parameters reflecting beta 2-adrenoceptor function in vitro in lymphocytes. 2. Heart rate responses to infused ISO were not significantly altered by 'autonomic blockade' when evaluated from concentration-effect curves. When related to the infused dose of ISO, however, sensitivity was artefactually increased (P less than 0.05), as the plasma concentrations of ISO were 40% higher after atropine and clonidine. Heart rate responses to bolus injections of ISO were attenuated (P less than 0.05) by 'autonomic blockade', suggesting that facilitatory reflexes contribute to these non-steady state responses. Intersubject variations in heart rate responsiveness to ISO were greater than the intrasubject variability caused by counterregulatory reflexes. 3. 'Autonomic blockade' lowered venous plasma noradrenaline at rest. The noradrenaline response to ISO infusion was attenuated and the diastolic blood pressure response enhanced, indicating that a counterregulatory vasoconstrictor reflex normally is activated by ISO-induced vasodilatation. The plasma cyclic AMP response to ISO, on the other hand, was unaffected by atropine and clonidine and reflects beta 2-adrenoceptor responsiveness in vivo. 4. In vitro data for beta-adrenoceptor binding sites (Bmax;[125I]-IHYP binding) and cyclic AMP responses to ISO in lymphocytes correlated with DBP and noradrenaline responses to infused ISO. No correlations were found between in vitro data and heart rate, plasma cyclic AMP or plasma glycerol responses to infused ISO in vivo. 5. During prolonged ISO infusions (in six other healthy subjects) physiological responses reached greater than 90% of their steady state level after 8 min, but no definite steady state level could be defined for the plasma concentration of ISO during 40 min of infusion. 6. The ISO infusion test showed a good reproducibility, especially when repeated on the same day. Evaluation of plasma concentration-effect relationships increase the precision of the ISO infusion test as confounding inter- and intra-individual variations in ISO concentrations (as caused by e.g. autonomic blockade) will be taken into account.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Chest pain and oesophageal pressure relationships in man following an intravenous bolus of adenosine.

After titration of maximum tolerable i.v. bolus dose of adenosine, this dose was given to seven volunteers (20-42 years), instrumented with a three-lumen oesophageal pressure catheter with recording sites at the levels of the stomach, the lower oesophageal sphincter (LOS) and the oesophagus. In addition to continuous pressure recordings, chest pain was estimated continuously by a 10-graded category-ratio scale. Baseline resting pressures were 8.4 (1.9) mmHg in the stomach, 1.6 (1.7) mmHg in the oesophagus and 20 (2.6) mmHg in the LOS resulting in a net LOS pressure of 11 (+/- 1.3) mmHg. Following injection of adenosine which provoked transient chest pain with a rated maximum of 5.4 (1.0), resting oesophageal pressure did not change while net LOS pressure decreased to -1.3 (1.9) mmHg (P less than 0.0001). Adenosine injection did not affect swallowing-induced peristaltic contractions of the oesophagus and LOS although the peristaltic wave was delayed (P less than 0.05). Thus, chest pain evoked by adenosine cannot be caused by spastic oesophageal contractions. Adenosine may have a relaxing effect on the LOS but does not block its normal reactions to swallowing.

Adenosine↗
PubMed1983

Manometric studies of lower esophageal sphincter in extreme obesity.

Esophageal manometry was performed in a group of extremely obese subjects in order to investigate the lower esophageal sphincter (LES) pressure and its relationship to extreme obesity, weight reduction and altered anatomy of the stomach. Forty subjects were examined before gastric surgery for treatment of their obesity, and 14 of these were reexamined after weight reduction. Normal LES pressure (20 mmHg) was found before operation, and also normal length and position of the LES. No significant changes were found in the group which was examined twice. In persons younger than 50, LES manometric findings do not seem to be influenced by extreme obesity, weight reduction or gastric surgery for obesity.

Body Weight↗
PubMed1981

Inhibition of carotid pressor response by left aortic depressor nerve in dogs.

In 12 conscious dogs, the mean increase of 26 mmHg in arterial pressure during carotid occlusion was augmented by 52 mmHg after section of the left cervical vagus nerve and 6 mmHg after right vagal section. In 18 anesthetized dogs, in which the cervical vagal nerves were reversibly cold blocked, corresponding values were 33, 28, and 6 mmHg, respectively. In nine of these dogs, this left-sided dominance was present after bilateral section of the vagal cardiopulmonary afferents; it was absent after bilateral section of the aortic nerves in the other nine dogs. In five dogs on cardiopulmonary bypass with heart and lungs excluded, pressure within the isolated aorta and major intrathoracic arteries was raised from 120 to 220 mmHg. The resultant hypotension reflexly induced by activation of aortic baroreceptors was reduced by left but not by right vagal cold block. It was concluded that, in the dog, the left aortic nerve provided the major inhibition of the increase in arterial pressure after carotid occlusion.

Animals↗
PubMed1981

Maintained ability of carotid baroreflex to regulate arterial pressure during exercise.

In conscious dogs bilateral carotid occlusion increased arterial pressure by similar amounts at rest (+ 27 mmHg) and during graded exercise (+ 29 mmHg). During exercise stimulus-response curves for arterial pressure and heart rate derived from isolated carotid sinuses were displaced upward proportionately to the work load, but the curve characteristics were unchanged. After acute bilateral vagotomy similar responses to carotid occlusion were obtained at rest (+ 85 mmHg) and at 21% grade (+ 84 mmHg); the range and maximal slope of the arterial pressure stimulus-response curve during exercise was similar to that at rest, but the exercise curve was displaced downward and to the left. It was concluded that the carotid baroreflex was able to modulate arterial pressure as well during running as at rest. Dogs with neither carotid, aortic, or cardiopulmonary receptors able to respond to the exercise stress became and remained hypotensive during mild exercise; during severe exercise hypotension was present initially, but after 90 s arterial pressure recovered toward the preexercise level. The data indicated that arterial and cardiopulmonary baroreceptors have a major role in the support of arterial pressure in the first moments of exercise.

Animals↗
PubMed1981

Metoprolol treatment after acute myocardial infarction. Effects on ventricular arrhythmias and exercise tests during 6 months.

One hundred and six patients on double-blind treatment with placebo or metoprolol, 100 mg b.i.d., during the first 6 months after an acute myocardial infarction were investigated. The patients were stratified and randomized to treatment according to type of ventricular arrhythmias on a six-hour ECG registration, size of infarct estimated by enzyme maximum and age. During the follow-up period, a further three six-hour ECG recordings and three exercise tests were performed. In the metoprolol group the incidence of malignant ventricular ectopic beats decreased significantly (p less than 0.05) after three days' treatment. This decrease lasted for one month but was not observed at the six-month registration. No difference in working capacity was seen between the two groups, nor were there any differences in ischemic ST depressions on ECG during exercise. The proportion of patients terminating exercise because of angina pectoris was similar, but significantly more patients in the metoprolol group (p less than 0.05) discontinued exercise at six months because of fatigue. Large heart volumes were observed somewhat more often in the metoprolol group but there was no extended need of treatment for cardiac failure.

Adult↗
PubMed1981

Effect of carotid endarterectomy on the antihypertensive properties of the carotid sinus reflex.

In eight patients subjected to carotid reconstructive surgery, the reflex effect on systemic pressure of an increase in carotid sinus transmural pressure was studied, before and two months after endarterectomy. The increase in carotid sinus transmural pressure was obtained by applying subatmospheric pressure to the neck. It was found that the closed loop gain of the carotid sinus reflex, calculated as the ratio of change in systemic pressure to change in carotid sinus transmural pressure, was 0.53 before and 0.52 two months after endarterectomy. It is thus concluded that carotid endarterectomy has no persisting effect on the antihypertensive properties of the carotid sinus reflex.

Blood Pressure↗
PubMed1980

Carotid baroreflex heart rate control during the active and the assisted breathing cycle in man.

The interaction between the phase of the breathing cycle and the carotid baroreflex heart rate control was studied in fifteen healthy subjects with special reference to respiratory sinus arrhythmia (RSA). Carotid baroreceptors were stimulated by neck suction. With a standardized breathing pattern, two types of experiment were performed. (a) Neck suction applied in counter phase with the respiratory arterial pressure variations; this reduced the amplitude and shifted the phase of the transmural carotid arterial pressure oscillations but did not influence the RSA. (B) During active as well as ventilator assisted breathing, brief periods of neck suction were applied during either inspiration (insufflation) or expiration. Neck suction during active inspiration did not change the amplitude of the RSA but when applied during expiration, increased it by 6.8 beats X min-1 (P less than 0.001). In the ventilator experiments, neck suction during insufflation and expiration augmented the RSA equally, by 5.3 beats X min-1 (P less than 0.05). The results indicate a decreased sensitivity of the carotid arterial baroreflex during active inspiration, with no equivalent during assisted breathing, and suggest that the change in baroreflex sensibility is a prerequisite for the rise of the RSA.

Adult↗