Enoximone (MDL 17043, 150 mg t.d.s.) and captopril (25 mg t.d.s.) were compared as additional treatment to diuretics in 13 patients with severe chronic heart failure in a cross-over, double-blind, ...and randomised trial. Each treatment was continued for one month. Heart failure was due to cardiomyopathy in six patients and ischaemic heart disease in seven. Exercise capacity and central haemodynamics at rest and on exercise were measured on entry to the study and after each treatment period. Cardiac index at peak exercise time and peak oxygen consumption were increased by both drugs, but there were no differences in these increases between the two drugs after one month's treatment. Minor differences were found in the biochemical and hormonal response to the two drugs. Those patients who improved on captopril also improved on enoximone.
The translational stop signal and polypeptide release factor (RF) complexed with Escherichia coli ribosomes have been shown to be in close physical contact by site-directed photochemical ...cross-linking experiments. The RF has a protease-sensitive site in a highly conserved exposed loop that is proposed to interact with the peptidyltransferase center of the ribosome. Loss of peptidyl-tRNA hydrolysis activity and enhanced codon-ribosome binding by the cleaved RF is consistent with a model whereby the RF spans the decoding and peptidyltransferase centers of the ribosome with domains of the RF linked by conformational coupling. The cross-link between the stop signal and RF at the ribosomal decoding site is influenced by the base following the termination codon. This base determines the efficiency with which the stop signal is decoded by the RF in both mammalian and bacterial systems in vivo. The wide range of efficiencies correlates with the frequency with which the signals occur at natural termination sites, with rarely used weak signals often found at recoding sites and strong signals found in highly expressed genes. Stop signals are found at some recoding sites in viruses where -1 frame-shifting occurs, but the generally accepted mechanism of simultaneous slippage from the A and P sites does not explain their presence here. The HIV-1 gag-pol-1 frame shifting site has been used to show that stop signals significantly influence frame-shifting efficiency on prokaryotic ribosomes by a RF-mediated mechanism. These data can be explained by an E/P site simultaneous slippage mechanism whereby the stop codon actually enters the ribosomal A site and can influence the event.
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.
The mechanisms underlying the increased ventilatory response to exercise seen in patients with chronic heart failure are not clearly understood. Arterial potassium has been suggested as an important ...ventilatory stimulant. The authors have investigated the arterial potassium response in patients with heart failure. Although arterial potassium rises during exercise, no evidence was found to suggest a greater potassium response in patients with heart failure compared to normal subjects. There was no direct correlation between the rise in ventilation and the rise in arterial potassium. It remains possible that there is an increased sensitivity to arterial potassium in patients with heart failure, but it would need to be three times greater than in normal subjects.
This study was designed to determine regional differences in patient characteristics and medication use among patients entered into an international heart failure trial.
Data for this analysis were ...derived from the Assessment of Treatment with Lisinopril and Survival Study (ATLAS), a prospective randomized comparison of high- and low-dose therapy with lisinopril in patients with New York Heart Association class II, III, or IV chronic heart failure, which enrolled 3164 patients in 291 centers in 19 countries on 3 continents. Information was collected at baseline concerning patient demographics, etiology of heart failure, accompanying conditions, prior revascularization procedures, and medication use. The primary findings were a lower incidence of ischemic cardiomyopathy in southern and western Europe, more frequent diabetes in North America, and a greater use of coronary revascularization in the United States and Canada. There was substantial variation in medication use, particularly with regard to digoxin, anticoagulants, and amiodarone.
Although there is considerable overlap in guidelines concerning the treatment of heart failure issued by authorities in Europe and North America, there are significant regional variations in medication use. Some, but not all, of these differences can be explained by differences in patient characteristics.
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