D. B. Northridge

Effects of UK 69 578: a novel atriopeptidase inhibitor.

UK 69 578 is a competitive inhibitor of endopeptidase 24.11 (the enzyme that degrades atrial natriuretic factor) in vitro. In vivo, UK 69 578 has renal and cardiovascular effects similar to low-dose atrial natriuretic factor infusion, and may be a useful agent in hypertension and heart failure.

Non-invasive determination of cardiac output by Doppler echocardiography and electrical bioimpedance.

Cardiac output measured by thermodilution in 25 patients within 24 hours of acute myocardial infarction was compared with cardiac output measured by Doppler echocardiography (24 patients) and electrical bioimpedance (25 patients). The mean (range) cardiac outputs measured by Doppler (4.03 (2.2-6.0) 1/min) and electrical bioimpedance (3.79 (1.1-6.2) 1/min) were similar to the mean thermodilution value (3.95 (2.1-6.2) 1/min). Both non-invasive techniques agreed closely with thermodilution in most patients. None the less, three results with each method disagreed with thermodilution by more than 1 1/min. Both non-invasive techniques were reproducible and accurate in most patients with acute myocardial infarction. Doppler echocardiography was time consuming and technically demanding. Electrical bioimpedance was simple to use and had the additional advantage of allowing continuous monitoring of the cardiac output.

Early treatment with captopril after acute myocardial infarction.

OBJECTIVES--To determine the effects of early treatment with captopril on haemodynamic function, neuroendocrine biochemistry, left ventricular structure, clinical outcome, and exercise capacity over one year from acute myocardial infarction. DESIGN--Randomised, double blind, placebo controlled comparison of captopril and placebo. SETTING--Coronary care units and cardiology departments of two university teaching hospitals in Glasgow. PATIENTS--99 haemodynamically stable patients with acute myocardial infarction, selected on clinical grounds as being at risk of late ventricular dilatation. INTERVENTION--Captopril or identical placebo started between six and 24 hours after start of symptoms and continued for 12 months. Target maintenance dose was 25 mg three times a day. MAIN OUTCOME MEASURES--(a) Acute haemodynamic effects of treatment; (b) neuroendocrine biochemistry from admission to two months; and (c) change in echocardiographic measures of left ventricular size, clinical outcome, and exercise capacity after 12 months of treatment with a separate analysis of the effects of one month of treatment withdrawal on left ventricular volumes. RESULTS--Captopril caused acute reductions in mean (SEM) pulmonary artery pressure (2.48 (0.69) mm Hg) and systemic vascular resistance (260 (103)) dyn.s.cm-5). Over the first 10 hours captopril reduced mean arterial pressure by 12.1 (2.4) mm Hg compared with 3.8 (1.9) mm Hg in the placebo group. No patient had to be withdrawn from the captopril group because of hypotension. From day 1 onwards systolic and diastolic arterial pressures in the captopril treated group were slightly but not significantly lower than on placebo. There was no difference in the incidence of ventricular or supraventricular arrhythmia with treatment. Captopril prevented the day 3 peak in angiotensin II that occurred in the placebo group (peak concentration (interquartile range): 10.1 (4.8-19.4) pg/ml v 16.8 (4.3-46.3) pg/ml)) but had no effect on atrial natriuretic factor, arginine vasopressin, or catecholamines. Plasma atrial natriuretic factor remained above normal in both groups at two months after infarction. After one year left ventricular volume indices had increased less on captopril than on placebo: left ventricular end systolic volume index 5.4 ml/m2 v 14.7 ml/m2 (95% confidence interval (95% CI) of difference -14.6 to -3.9; p = 0.0011); left ventricular end diastolic volume index 8.4 ml/m2 v 19.0 ml/m2 (95% CI of difference, -17.0 to -4.2; p = 0.0016). Withdrawal of captopril for one month did not affect ventricular volumes. There was no difference in exercise capacity. CONCLUSIONS--Captopril started between six and 24 hours after acute myocardial infarction is not associated with significant hypotension. It suppresses activation of the renin angiotensin system but has no effect on plasma concentrations of other neurohormones. Atrial natriuretic factor remains raised at two months after myocardial infarction. Captopril significantly decreases left ventricular dilatation. This effect is not lost after one month of treatment withdrawal and is thus due to an alteration of left ventricular structure and not to a short lived haemodynamic action of captopril. Long-term treatment with captopril does not result in improved aerobic exercise capacity after acute myocardial infarction.

Harnessing the therapeutic potential of atrial natriuretic peptide.

SummaryThe biological actions of Atrial Natriuretic Peptide (ANP) make it potentially useful in the treatment of hypertension and heart failure. We review here the physiology of ANP, the effects of infusion in heart failure and hypertension and preliminary data suggesting that inhibition of endopeptidase 24.11, the enzyme degrading ANP, is an effective mechanism of raising circulating levels of endogenous ANP.Due to the rate of progress in this field we have restricted ourselves to recent work much of which is still available only in abstract form. For more complete accounts the reader is referred to recent reviews [9, 11, 14].