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Biomedical subjects

A Melcher

Publications and source records attributed to A Melcher.

At least 19 recordsLinked to original sources
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↗
PubMed1978

Exercise energy expenditure in extreme obesity: influence of ergometry type and weight loss.

Bicycle and treadmill exercise tests including oxygen uptake (VO2) and heart rate (HR) determination were carried out on a total of thirty patients with obesity, seventeen of whom were reinvestigated after weight loss. During both types of work VO2 for a given load was higher when compared to healthy controls. The increase of VO2 was more marked when cycling was performed in sitting position than in supine. The mechanical efficiency of sitting bicycle exercise averaged 17.8% and was negatively related to the percentage overweight; the slope of the VO2/load regression line was slightly less in comparison to the controls, while no such difference was found during treadmill walking. After weight reduction the VO2/load regression line was skifted downwards, the slopes being unchanged, thus the mechanical efficiency improved. This study not only confirms the observation of a low mechanical efficiency of obese subjects but also demonstrates that the change is quantitatively related to the overweight. The lowered efficiency was caused by body mechanical factors and there was no support for an abnormal muscular efficiency. Exercise tests should be combined with VO2 determination, if used to assess the circulatory capacity of obese subjects.

Adult↗
PubMed1976

Effects of cedilanid-D in combination with metoprolol on exercise tolerance and systolic time intervals in angina pectoris.

The interaction between cedilanid-D and metoprolol, a selective beta receptor blocking agent, on exercise tolerance and systolic intervals was studied in 15 patients with angina pectoris. The patients had been treated with metoprolol for several months in a dose of 50 mg, three times daily (one patient received 25 mg three times daily). Each patient participated in two studies separated by at least 1 week. After arriving at the laboratory each received 50 mg of metoprolol orally; thereafter, either cedilanid-D or placebo was infused intravenously in a double-blind study performed in randomized order. When the effect of the drugs was maximal, the systolic intervals and the heart volume were recorded at rest, and the exercise tolerance was tested with a bicycle ergometer. The mean maximal value of plasma concentrations of metoprolol assessed during the study was about 50 ng/ml but the variation among subjects was great (20 to 187 ng/ml). After administration of cedilanid-D there was a shortening of the pre-ejection period and left ventricular ejection time compared with results after placebo; the reduction was similar to that found after administration of cedilanid-D without beta blocking drugs. The total heart volume decreased by an average of 55 ml, but the individual variation was great. The patients' average work capacity, expressed as total work, was not altered by cedilanid-D when compared with results after placebo. No relation was found between initial heart size and the effect of cedilanid-D on capacity for physical work. It therefore appears that there is no indication for the routine use of digitalis during beta blocking therapy in patients with angina pectoris who do not have cardiac failure.

Adrenergic beta-Antagonists↗
PubMed1976

Sinus arrhythmia in man: influence of tidal volume and oesophageal pressure.

The effect of tidal volume (VT) and of the intrathoracic pressure (Poes) on the respiratory sinus arrhythmia (RSA) was studied in healthy subjects. They breathed into a spirometer with a VT of 1, 1.5, and 2 1, at a standardized, slow respiratory rate, 6-min-1 (A). Poes was varied by (B) adding a negative inspiratory pressure (NIP) of 5 cm of water and by (C) intermittent positive pressure ventilation (IPPV) at identical VT and respiratory frequency. In separate study (D), intermittent negative pressure ventilation (INPV) was induced by applying negative pressure on the thorax. In A, increasing VT provoked an augmented RSA by a more marked tachycardia as well as bradycardia. On increasing the amplitude of Poes in B, RSA was somewhat more marked due to a lower minimum heart rate. Whem comparing respiratory cycles that had similar Poes but a different VT, the larger VT caused a slight increase in the RSA amplitude due to a more marked deceleration of the heart rate. IPPV almost abolished RSA, whereas INPV did not reduce the arrhythmia. It is concluded that pulmonary stretch reflexes to a minor extent contribute to RSA, whereas the hypothesis of a central nervous origin does not gain support. Cardiovascular reflexes remain the main possible cause of RSA.

Adult↗
PubMed1976

Respiratory sinus arrhythmia in man: relation to cardiovascular pressures.

The relationship of respiratory sinus arrhythmia (RSA) to the accompanying oscillations of cardiovascular pressure has been studied in five healthy subjects. Tidal volume (VT) of 1.0, 1.5, and 2.0 1 at the breathing rate of 6 c-min-1 were used as reference. With identical VT oesophageal pressure was varied by negative inspiratory pressure (NIP) and intermittent positive-pressure ventilation (IPPV). Compared with control, NIP with 1.01 significantly increased RSA, the oscillations of brachial artery pressures (PBA), and the net filling pressures of the ventricles. IPPV did not significantly change the variations of PBA but reduced RSA and the respiratory variations of the right ventricular end-diastolic net pressure. During control breathing and with NIP the acceleration of heart rate during inspiration was associated with rising PBA and rising net filling pressures of both ventricles. The results indicate that RSA may be elicited by cardiovascular reflexes due to changes in venous filling of the heart rather than by the variations in systemic arterial pressure.

Adult↗
PubMed1976

Respiratory sinus arrhythmia in man: relation to right ventricular output.

The respiratory effects on heart rate (HR), right ventricular stroke volume (SV RV) and the pulmonary arterial flow (PAF) have been studied beat-by-beat in seven conscious, healthy subjects. Tidal volumes (VT) of 1.0 and 2.0 liters at a breathing rate of 6 c x min-1 were used as controls. With identical VT and respiratory rate intrathoracic was affected by (A) negative inspiratory pressure (NIP) of 5 cm of water and (B) with intermittent positive pressure ventilation (IPPV). In the control experiments all subjects exhibited an inspiratory increase in HR (respiratory sinus arrhythmia) as well as in SV RV. With VT of 1.0 liter, NIP augmented the inspiratory increase in SV RV and the respiratory oscillations of PAF. IPPV decreased SV RV and HR during inspiration. It is concluded that NIP and IPPV affect the SV RV and the right heart blood flow. The similar effects on HR and SV RV suggest a causal relationship which might be explained by heart rate regulating reflexes from the heart.

Adult↗
PubMed1976

Respiratory sinus arrhythmia in man: effects of carotid sinus baroreceptor stimulation.

1. The role played by the carotid sinus baroreflex in the genesis of the respiratory sinus arrhythmia (RSA) was studied in nine healthy subjects. The carotid sinus baroreceptors were stimulated by the application of subatmospheric to the neck. 2. Reducing the normal respiratory arterial pressure oscillations and changing the phase between the pressure oscillations and the respiration did not affect the RSA. 3. Stimuli applied during expiration only, augmented the arrhythmia, while inspiratory stimulation was without any effect. 4. It is suggested that changes in the arterial baroreflex set point and/or gain during the respiratory cycle contribute to RSA in man.

Adult↗
PubMed1976

Respiratory sinus arrhythmia in man: relation to cardiovascular pressures.

The relationship of repiratory sinus arrhythmia (RSA) to the accompanying oscillations of cardiovascular pressures has been studied in five healthy subjects. Tidal volumes (VT) of 1.0, 1.5, and 2.0 1 at a breathing rate of 6 c-min(-1) were used as reference. With identical VT, oesophageal pressure was varied by negative inspiratory pressure (NIP) and intermittent positive-pressure ventilation (IPPV). Compared with control, NIP with 1.01 significantly increased RSA, the oscillations of brachial artery pressures (PBA), and the net filling pressures of the ventricles. IPPV did not significantly change the variations of PBA but reduced RSA and the repiratory variations of the right ventricular end-diastolic net pressure. During control breathing and with NIP the acceleration of heart rate during inspiration was associated with rising PBA and rising net filling pressures of both ventricles. The results indicate that RSA may be elicited by cardiovascular reflexes due to changes in venous filling of the heart rather than by the variations in systemic arterial pressure.

Adult↗
PubMed1976

Respiratory sinus arrhythmia in man: relation to right ventricular output.

The respiratory effects on heart rate (HR), right ventricular stroke volume (SVRV), and the pulmonary arterial flow (PAF) have been studied beat-by-beat in 7 conscious, healthy subjects. Tidal volumes (VT) of 1.0 and 2.0 liters at a breathing rate of 6 cXmin-1 were used as controls. With identical VT and respiratory rate intrathoracic pressure was affected by (A) negative inspiratory pressure (NIP) of 5 cm of water and (B) with intermittent positive pressure ventilation (IPPV). In the control experiments all subjects exhibited an inspiratory increase in HR (respiratory sinus arrhythmia) as well as in SVRV. With VT of 1.0 liter, NIP augmented the inspiratory increase in SVRV and the respiratory oscillations of PAF. IPPV decreased SVRV and HR during inspiration. It is concluded that NIP and IPPV affect the SVRV and the right heart blood flow. The similar effects on HR and SVRV suggest a relationship which might be explained by heart-rate-regulating reflexes from the heart.

Adult↗
PubMed1975

Exercise tolerance in patients with angina pectoris after pentaerythritol trinitrate and alprenolol studied by two different methods.

Exercise tolerance has been studied by two different methods, heart-rate-controlled exercise and stepwise increased load, in 12 patients with angina pectoris. The response to a beta-adrenergic blocking agent, alprenolol, and an alkyl nitrate derivative, pentaerythritol trinitrate (PETRIN) was studied by the two methods after double-blind administration of the drugs. Rating scales were used to quantitate the degree of dyspnoea, angina pectoris and tiredness in the legs. After PETRIN both methods showed significant increases in exercise tolerance (19 and 21 per cent). The heart-rate-controlled test showed a significant increase (33%) after alprenolol, but the change was not significant by the other method. In the patients studied, heart-rate-controlled exercise discriminated between active drug and placebo better than the stepwise increased load test, what might have been due to more optimal matching of the loads obtained in the heart-rate-controlled test. Indications are given about how to design an exercise study in patients with angina pectoris.

Aged↗
PubMed1975

Circulatory and respiratory adaptation in man to acute withdrawal and reinfusion of blood.

In eight healthy men 950 g of blood (12.2 17.6% of the blood volume) was withdrawn and reinfused after about half an hour. Respiration and circulation were studied by analyses of expiratory gas, blood gases and data from right heart catheterization. On hemorrhage oxygen uptake and cardiac output decreased by 10 and 28%, repectively; both varied indirectly with the blood loss. The pressures in the right ventricle, pulmonary and systemic arteries fell without relation to the cardiac output. Mean heart rate did not change significantly, but a moderate positive covariation (P less than 0.05) between heart rate and arterial blood pressure was found during bleeding. This result was confirmed by the relative bradycardia noted in the period prior to reinfusion. On refilling of the bood the oxygen uptake and the pulmonary arterial pressures increased above the initial value. The heart rate varied directly with the arterial pressure also during reinfusion. The observations demonstrate a depression of the metabolism and circulation on moderate hemorrhage. Part of these effects is tentatively referred to a lowered set point of the arterial baroreflexes.

Adaptation, Physiological↗
PubMed1975

Sinus arrhythmia in man: influence of tidal volume and oesophageal pressure.

The effect of tidal volume (VT) and of the intrathoracic pressure (Poes) on the respiratory sinus arrhythmia (RSA) was studied in healthy subjects. They breathed into a spirometer with a VT of 1, 1.5, and 2 1, at a standardized, slow respiratory rate, 6-min-1 (A). Poes was varied by (B) adding a negative inspiratory pressure (NIP) of 5 cm of water and by (C) intermittent positive pressure ventilation (IPPV) at identical VT and respiratory frequency. In a separate study (D), intermittent negative pressure ventilation (INPV) was induced by applying negative pressure on the thorax. In A, increasing VT provoked an augmented RSA by a more marked tachycardia as well as bradycardia. On increasing the amplitude of Poes in B, RSA was somewhat more marked due to a lower minimum heart rate. When comparing respiratory cycles that had similar Poes but a different VT, the larger VT caused a slight increase in the RSA amplitude due to a more marked deceleration of the heart rate. IPPV almost abolished RSA, whereas INPV did not reduce the arrhythmia. It is concluded that pulmonary stretch reflexes to a minor extent contribute to RSA, whereas the hypothesis of a central nervous origin does not gain support. Cardiovascular reflexes remain the main possible cause of RSA.

Adult↗