Showing papers by "Philip A. Poole-Wilson published in 1987"
TL;DR: Diuretics bring about a considerable clinical improvement in patients with chronic heart failure but they stimulate the renin-angiotensin system, which occurs as a response to diuretic treatment rather than as a result of the disease process itself.
Abstract: The clinical and neuroendocrine response to diuretic treatment was assessed at rest and on exercise in 12 patients with heart failure. Before treatment all patients were limited by breathlessness on exercise; one was oedematous. Plasma renin activity and aldosterone were normal but plasma noradrenaline was raised both at rest and on exercise. After one month's treatment with frusemide (40 mg) and amiloride (5 mg) weight was significantly reduced by a mean of 3.5 kg and exercise capacity had doubled. Plasma noradrenaline fell to normal at rest but remained abnormally raised on exercise. Plasma renin activity and aldosterone increased significantly both at rest and on exercise. Diuretics bring about a considerable clinical improvement in patients with chronic heart failure but they stimulate the renin-angiotensin system. Activation of the renin-angiotensin system in moderate heart failure occurs as a response to diuretic treatment rather than as a result of the disease process itself.
500 citations
TL;DR: Dopexamine, a new vasodilator possessing both postjunctional dopaminergic and β2-adrenoceptor agonist actions, may have a role in the management of severe low output cardiac failure.
Abstract: Dopexamine (FPL 60278) is a new vasodilator possessing both postjunctional dopaminergic and beta 2-adrenoceptor agonist actions. Its acute haemodynamic effects were compared in a cross-over study with those of dobutamine, captopril, and glyceryl trinitrate (GTN) in eight adult patients with chronic heart failure. Dopexamine, 1 microgram/kg/min intravenously (i.v.) for 10 min, increased cardiac index, systolic blood pressure, and heart rate while reducing systemic vascular resistance. Pulmonary artery end-diastolic pressure was unchanged. Plasma norepinephrine (NE) increased during dopexamine infusion. No arrhythmias occurred. Dobutamine, 5 micrograms/kg/min i.v. for 10 min, increased cardiac index and systolic blood pressure similarly but did not increase heart rate or reduce vascular resistance. Captopril, 25 mg orally, did not alter cardiac index at 1 h, but reduced heart rate, blood pressure, pulmonary diastolic pressure, and vascular resistance. GTN, 100 micrograms sublingually, reduced pulmonary diastolic pressure but did not affect other variables at 5 min. Dopexamine, because it combines some of the properties of dopamine and salbutamol, may have a role in the management of severe low output cardiac failure.
31 citations
TL;DR: Central haemodynamics and regional blood flow were studied comprehensively in conscious New Zealand White rabbits before and during the development of chronic low output cardiac failure produced by administration of the anticancer agent adriamycin, and systemic toxic effects of adRIamycin could be limited by treating the animals for eight weeks with adriamicin and then allowing a two week recovery period before haemodynamic study.
Abstract: Central haemodynamics and regional blood flow were studied comprehensively in conscious New Zealand White rabbits before and during the development of chronic low output cardiac failure produced by administration of the anticancer agent adriamycin. After eight weeks of adriamycin treatment, cardiac index fell from 326(40 to 225(56) ml·min−1·kg−1. This was accompanied by an increase in heart rate and total peripheral resistance but no change in mean systemic blood pressure. Myocardial function was shown to be depressed by the measurement of Frank-Starling curves, the slopes of which were appreciably flatter in adriamycin treated rabbits. Regional blood flow (measured by the radioactive microsphere technique) was redistributed. There were decreases in renal, splenic, small gut, and skeletal muscle blood flow, whereas myocardial and cerebral blood flow were unchanged. There was an increase in total body exchangeable sodium, indicating some salt and water retention. Systemic toxic effects of adriamycin could be limited by treating the animals for eight weeks with adriamycin and then allowing a two week recovery period before haemodynamic study. This would appear to be the optimal dosage schedule.
30 citations
TL;DR: During hypoxic substrate free perfusion potassium loss was due to an increased efflux with no evidence of altered influx, and the extrusion of accumulating anions, such as lactate ions, from the myocardium is one mechanism for the early potassium loss during hypoxia.
Abstract: To determine the role of lactate in the causation of potassium efflux during hypoxia, the effect of lactate ions on the uptake and efflux of 42potassium was studied in the isolated arterially perfused interventricular septum of the rabbit. Septa were equilibrated with lactate (50 mmol·litre−1) under isosmotic conditions before switching to a perfusate containing the inert and impermeant anion isethionate (50 mmol·litre−1). A reduction in tissue 42potassium content was detected, which could only partly be accounted for by increased efflux. During hypoxic substrate free perfusion potassium loss was due to an increased efflux with no evidence of altered influx. The extrusion of accumulating anions, such as lactate ions, from the myocardium is one mechanism for the early potassium loss during hypoxia.
18 citations
TL;DR: The increase in coronary sinus potassium concentration after angioplasty balloon deflation is attributable to a washout of accumulated extracellular potassium during reperfusion, and may be an important factor accounting for early electrophysiologic changes.
12 citations
TL;DR: In individual patients the peak fall in coronary sinus pH was related to the duration of occlusion of the left anterior descending coronary artery and a rise in coronary Sinus pH (alkalosis) was never seen.
Abstract: Coronary sinus pH was measured continuously in eight patients undergoing angioplasty to the left anterior descending coronary artery. A catheter tip pH sensitive electrode with a response time of less than 300 ms and an output of greater than or equal to 57 mV/pH unit was placed high in the coronary sinus. Recordings were obtained during a total of 24 balloon occlusions of the left anterior descending coronary artery varying in duration from 5 to 45 s. Continuous 12 lead surface electrocardiograms were recorded. During or after balloon inflation of greater than or equal to 12 s (n = 4) there was no change in coronary sinus pH or the electrocardiogram. During balloon inflation of greater than or equal to 15 s (n = 20) coronary sinus pH was unaltered but between 4 and 6 s after balloon deflation coronary sinus pH fell transiently by between 0.010 and 0.120 pH units before returning to the control value within 65 s. Ischaemic changes were seen on the electrocardiogram during 15 balloon occlusions. In individual patients the peak fall in coronary sinus pH was related to the duration of occlusion of the left anterior descending coronary artery. A rise in coronary sinus pH (alkalosis) was never seen. In man acidosis occurs in the myocardium after short periods (greater than or equal to 12 s) of ischaemia. The fall of pH precedes ischaemic changes on the surface electrocardiogram and occurs concurrently with the earliest reported changes in contractile function.
11 citations
TL;DR: No difference was detected between the hemodynamic response to the 2 drugs after 1 month treatment either at rest or during exercise, and systemic vascular resistance at peak exercise was not lowered by either drug.
Abstract: A double-blind, randomized, crossover trial was undertaken to compare the effect of enoximone (150 mg, 3 times daily) and captopril (25 mg, 3 times daily) added to conventional therapy with diuretics in the treatment of 13 patients with severe chronic heart failure. Each treatment was continued for 1 month. Heart failure was due to idiopathic dilated cardiomyopathy in 6 patients and coronary artery disease in 7. Hemodynamic measurements were made at rest and during exercise, on entry to the study and after each treatment period. The cardiac index at rest was 1.9 ± 0.2 liters min−1 m2 (mean ± 1 standard deviation) and did not change with either drug. Systemic vascular resistance at rest decreased with enoximone (p < 0.05) and was unchanged with captopril. Systemic vascular resistance at peak exercise was not lowered by either drug. Both drugs caused an increase of cardiac index at peak exercise (p < 0.04) and a prolongation of exercise time (p < 0.05). No difference was detected between the hemodynamic response to the 2 drugs after 1 month treatment either at rest or during exercise.
9 citations
TL;DR: Diuretic-induced hypokalaemia may account for some of the small differences in mortality from heart disease that have been reported in subgroups of patients from recent trials aimed at the prevention of coronary heart disease or treatment of hypertension.
Abstract: Hypokalaemia in man is associated with an increased incidence of cardiac arrhythmias. Thiazide diuretics cause hypokalaemia in a proportion of otherwise healthy hypertensive patients, and there is a risk that in these patients hypokalaemia induced by diuretics may initiate serious cardiac arrhythmias and even sudden death. The data suggest that such circumstances are rare and a study designed to demonstrate an effect on mortality would need to be larger than any reported or current trial. Diuretic-induced hypokalaemia may account for some of the small differences in mortality from heart disease that have been reported in subgroups of patients from recent trials aimed at the prevention of coronary heart disease or treatment of hypertension. There are several therapeutic regimens by which diuretic-induced hypokalaemia may be detected, treated or prevented. Most physicians already take heed of this problem so that it is no longer a major therapeutic issue.
9 citations