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Biomedical subjects

H Ikram

Publications and source records attributed to H Ikram.

At least 127 records · Page 7Linked to original sources

Combined spironolactone and converting-enzyme inhibitor therapy for refractory heart failure.

Three cases are described of severe congestive heart failure which failed to respond to digitalis, high doses of loop diuretics, and converting-enzyme inhibitors. The addition of spironolactone produced a substantial diuresis associated with clinical and radiological improvement in each case. Although a reversible deterioration in renal function was observed, this drug combination represents a therapeutic option in end-stage heart failure.

Adult↗

Ambulatory pulmonary arterial pressures in humans: relationship to arterial pressure and hormones.

Six healthy volunteers were studied by use of a continuous ambulatory recording technique to document the normal range and variability of pulmonary artery pressure (PAP) and to examine its relationship to systemic arterial pressure (SAP) both at rest and during standardized interventions. Vasoactive hormone levels were measured at frequent intervals. Over 8-10 h of study the mean PAP was 15.7/6.3 mmHg. Parallel changes in PAP and SAP were observed at rest and during exercise and eating. On the contrary, PAP rose and SAP fell with hypoxia, whereas smoking was associated with a rise in SAP but no change in PAP. Sympathetic nervous system activity, as gauged by plasma norepinephrine levels, may have contributed to pressure and heart rate changes during exercise and smoking, but activity of the renin-angiotensin system was not altered by any of the maneuvers. These results provide base-line information on the level of PAP and its variability in healthy volunteers under standardized conditions. Pressures within the systemic and pulmonary circuits change in parallel under some circumstances but move in opposite directions under other conditions.

Adult↗

Atrial natriuretic peptide in humans. Production and clearance by various tissues.

Although it is assumed that the human heart secretes atrial peptides, direct proof is not available. We therefore measured immunoreactive atrial natriuretic peptide levels in coronary sinus blood and simultaneously in femoral arterial and venous blood from patients before and during stepwise incremental atrial pacing of up to 200 beats per minute. Since the fate of circulating atrial peptides is unknown, we also measured immunoreactive atrial natriuretic peptide concentrations in arterial and venous blood across the liver, kidney, lower limb, and lung in patients undergoing cardiological investigation. Peptide levels in coronary sinus blood were higher than in samples from the femoral artery or vein. As the heart rate was accelerated by atrial pacing, peptide concentrations increased in coronary sinus blood and to a lesser extent in peripheral samples. Whereas the levels in venous blood draining the liver, kidney, and lower limb were approximately 50% of those in arterial blood, concentrations were similar in samples drawn simultaneously from the pulmonary artery and the aorta. These results show that the human heart produces immunoreactive atrial natriuretic peptide and that secretion increases with atrial tachycardia. The liver, kidney, and lower limb remove the peptide from arterial blood, but there is little change in its concentration during circulation of blood through the lungs.

Adult↗

Diuretics, potassium and arrhythmias in hypertensive coronary disease.

It has been proposed that modest changes in plasma potassium can alter the tendency towards cardiac arrhythmias. If this were so, patients with coronary artery disease might be especially susceptible. Thus, myocardial electrical excitability was measured in patients with mild essential hypertension and known coronary artery disease after 8 weeks of treatment with a potassium-conserving diuretic (amiloride) and a similar period on a potassium-losing diuretic (chlorthalidone) in a randomised study. Plasma potassium concentrations were on average 1 mmol/L lower during the chlorthalidone phase compared to amiloride therapy. Blood pressure and volume states as assessed by bodyweight, plasma renin and noradrenaline (norepinephrine) concentrations were similar on the 2 regimens. Compared to amiloride treatment, the chlorthalidone phase was associated with an increased frequency of ventricular ectopic beats (24-hour Holter monitoring) and a higher Lown grading, increased upslope and duration of the monophasic action potential, prolonged ventricular effective refractory period, and increased electrical instability during programmed ventricular stimulation. The above results indicate that because potassium-losing diuretic therapy can increase myocardial electrical excitability in patients with ischaemic heart disease, even minor falls in plasma potassium concentrations are probably best avoided in such patients.

Chlorthalidone↗

Diurnal patterns of blood pressure, heart rate and vasoactive hormones in normal man.

In order to determine arterial pressure and vasoactive hormone relationships in normotensive man, we measured intra-arterial pressure continuously along with hourly venous hormone levels (renin, angiotensin II, aldosterone and catecholamines) for 24 hours in 5 healthy volunteers under standardized conditions. Mean 24-hour levels of intra-arterial pressure 106/63 +/- 5.4/4.9 mmHg were much lower than in patients with mild essential hypertension studied earlier. A common diurnal pattern was seen for plasma renin, angiotensin II, and catecholamines, with higher levels in the day time and lower levels at night. Aldosterone levels however, paralleled those of cortisol at night. Plasma norepinephrine levels showed close, positive correlations with arterial pressure in all volunteers. We conclude that the level of blood pressure as measured continuously over 24 hours is lower than might be expected from regular clinic recordings; that aldosterone regulation is contributed to by ACTH in the nocturnal hours; and that fluctuations in arterial pressure and sympathetic activity over 24 hours are closely coupled.

Adult↗

Studies on the secretion, metabolism and action of atrial natriuretic peptide in man.

Radio-immunoassay of atrial natriuretic peptide (ANP) and infusions of alpha-human ANP (alpha-hANP) have been used to study the secretion, metabolism, regulation and actions of ANP in man. Plasma immunoreactive ANP (irANP) was twice as high in arterial blood as in simultaneously sampled venous plasma from the femoral, hepatic and renal vein, but no arteriovenous difference was found across the lung. Analysis of plasma extracts by high performance liquid chromatography confirmed that alpha-hANP-like material was a major component in coronary sinus and peripheral arterial and venous plasma. In normal subjects, venous plasma irANP was increased by both acute and chronic sodium loads, and by exercise. The cardiac secretion of irANP, and peripheral venous levels, were markedly increased by atrial pacing in four patients investigated for arrhythmia. Plasma irANP concentrations were elevated in many patients with circulatory disorders, including chronic renal failure, congestive heart failure and during spontaneous tachyarrhythmias. Constant 60-min intravenous infusions of alpha-hANP increased urinary sodium excretion in normal subjects, under conditions of both high- and low-sodium intake, and selectively reduced plasma aldosterone concentrations. These effects were observed at the venous levels of plasma irANP found in some patients with circulatory disease. Taken together, the present studies suggest that ANP has important endocrine functions in human health and disease.

Aldosterone↗

Effect of enalapril on ventricular arrhythmias in congestive heart failure.

Twenty-four-hour Holter electrocardiographic recordings were used to measure the effects of a converting-enzyme inhibitor, enalapril, given for 12 weeks, on the frequency of cardiac arrhythmias in 10 patients with congestive heart failure (New York Heart Association functional class II to III) receiving maintenance therapy with digoxin and furosemide. Nine patients were given placebo, and both study groups were conducted in a double-blind, parallel manner. The placebo group had no change in the frequency of arrhythmias, whereas enalapril-treated patients showed a significant decrease in the frequency of premature ventricular complexes, ventricular couplets and ventricular tachycardia. A minor, nonsignificant reduction in atrial premature complexes was seen in patients who received enalapril. Compared with placebo patients, those who received enalapril had an increase in plasma potassium levels of 0.33 mmol/liter, a decrease in plasma digoxin, and decreases in pulmonary artery wedge, mean pulmonary artery and right atrial pressures. However, none of these indexes were correlated with the concomitant decline in cardiac arrhythmias. It is concluded that enalapril reduces the frequency of ventricular arrhythmias in congestive heart failure, although the underlying mechanisms are not known.

Adult↗

Hyponatraemic-hypertensive syndrome due to unilateral renal ischaemia in women who smoke heavily.

The hyponatraemic-hypertensive syndrome due to renal ischaemia is presumed to be uncommon. We describe four patients who presented with this syndrome over a period of 21 months. All were women who smoked heavily and had unilateral atherosclerotic renal ischaemia. Hypokalaemia was present in each patient, and in one case resulted in recurrent ventricular tachycardia. All had noted thirst, polyuria, and weight loss. Initiation of treatment with a converting-enzyme inhibitor reduced arterial pressure precipitously in two patients. Removal of the ischaemic kidney, or chronic therapy with a converting-enzyme inhibitor reversed the biochemical abnormalities and the presenting symptoms, and lowered arterial pressure. Detailed studies in two patients before and after treatment confirmed the central role of the renin-angiotensin system in the development of the hyponatraemic-hypertensive syndrome.

Aged↗

Renal, haemodynamic, and hormonal effects of human alpha atrial natriuretic peptide in healthy volunteers.

The effects of atrial natriuretic peptide (ANP) were investigated in six healthy male volunteers taking a constant diet (120 mmol sodium and 60 mmol potassium daily). They were given an intravenous bolus of 100 micrograms human alpha-ANP on one day or placebo on another day 1-3 weeks apart in a double-blind randomised study. After ANP, urinary sodium excretion increased four-fold, and urine volume, calcium, magnesium, and phosphorus excretion doubled within 30 min of the injection. ANP induced an immediate fall in arterial pressure, followed by a longer vasodepressor phase which exceeded the duration of the effect on electrolyte excretion. There were no significant changes in plasma renin activity, aldosterone, antidiuretic hormone, or noradrenaline when compared with placebo.

Atrial Natriuretic Factor↗

Pharmacokinetics and plasma-concentration-effect relationships of prenalterol in cardiac failure.

Prenalterol was administered as an intravenous infusion at three incremental rates (60, 120 and 240 nmol/min) to five patients with severe cardiac failure. Haemodynamic, hormonal and metabolic variables were measured at the same time as plasma prenalterol concentrations, and the pharmacokinetics of the drug were studied by following plasma concentrations and urinary excretion during and after the infusion. Concentration-dependent increases in cardiac index, stroke index and stroke work index were observed without increases in arterial pressure, heart rate or myocardial oxygen demand. The reninangiotensin-aldosterone system was stimulated, although the extent of stimulation varied among patients. No strong correlations were found between the logarithm of the plasma prenalterol concentration and effect. Plasma clearance of the drug was lower in cardiac patients than in normal volunteers, but a large decrease in renal clearance was partially balanced by an increase in nonrenal clearance. Over the observed range of concentrations, no deviation from linearity was evident, and plasma concentrations of about 150 nmol/l were effective in improving cardiac function without significant side-effects.

Adrenergic beta-Agonists↗

Hormone and haemodynamic effects of angiotensin II infusion during captopril treatment for heart failure.

Withdrawal of captopril therapy for cardiac failure results in increments in plasma cortisol, noradrenaline and heart rate. To determine whether these changes related to the concomitant rise in circulating angiotensin II, we infused angiotensin II at 0.5, 2, 4 and 8 ng/kg/minute, each infusion lasting for 1 hour, in 4 patients during maintenance captopril therapy for heart failure. A control solution of 5% dextrose was infused over a similar time interval on a separate day. The study was performed under metabolic balance conditions, with constant body posture and continuous haemodynamic monitoring. Angiotensin II induced the expected rise in arterial pressure and in plasma aldosterone. In contrast the diurnal decline in plasma ACTH and cortisol was not altered, and no changes in noradrenaline or heart rate were observed. Plasma angiotensin II appears to have little or no effect on ACTH, cortisol, noradrenaline and heart rate under the conditions of this study.

Adrenocorticotropic Hormone↗

Arrhythmogenic potential of diuretic induced hypokalaemia in patients with mild hypertension and ischaemic heart disease.

In view of evidence suggesting an association of mild hypokalaemia with cardiac arrhythmia, the arrhythmogenic potentials of potassium losing and potassium sparing diuretic treatments were compared in a controlled prospective crossover study of 10 patients with mild hypertension and ischaemic heart disease. Mean (SEM) plasma potassium was 4.3(0.06) mmol/l and 3.3(0.07) mmol/l after potassium sparing and potassium losing treatments respectively. Blood pressure and volume depletion as assessed by weight change, plasma renin activity, and noradrenaline concentrations did not differ significantly in the two treatment periods. The potassium losing treatment phase was associated with an increased frequency of ventricular extrasystoles, a higher Lown grading during ambulatory electrocardiographic monitoring, prolonged duration and decreased phase 0 velocity of the monophasic action potential, a prolonged ventricular effective refractory period, and increased myocardial electrical instability as assessed by programmed ventricular stimulation. It is concluded that minor changes in plasma potassium concentration are associated with increased ventricular electrical instability in patients with ischaemic heart disease. Mild hypokalaemia in such patients may predispose to life threatening arrhythmias and should be avoided.

Amiloride↗

Effects of enalapril on clinical status, biochemistry, exercise performance and haemodynamics in heart failure.

The effects of enalapril on clinical well-being, treadmill exercise performance, haemodynamic measurements, hormone levels, and plasma biochemistry in patients with moderate heart failure, were assessed in a 12-week placebo-controlled, double-blind study. Maintenance frusemide and digoxin treatment was continued throughout the study. Compared with placebo, enalapril treatment improved clinical status and increased exercise capacity. The most obvious haemodynamic change was a fall in pulmonary artery wedge pressure and pulmonary artery pressure. Enalapril-induced increases in left-ventricular ejection fraction and cardiac index, and falls in systemic arterial pressure, were small. Of the hormone indices measured, plasma renin activity rose 4-fold, angiotensin II and aldosterone fell slightly, and plasma catecholamines were unaltered by enalapril. Plasma potassium increased on average by 0.3 mmol/L during enalapril therapy. No adverse clinical or biochemical effects were observed. Enalapril has a sustained beneficial action in patients with moderate heart failure.

Adult↗