The effect of the converting enzyme inhibitor captopril as long term treatment was investigated in 14 patients with severe congestive heart failure in a double blind trial. Captopril reduced plasma concentrations of angiotensin II and noradrenaline, with a converse increase in active renin concentration. Effective renal plasma flow increased and renal vascular resistance fell; glomerular filtration rate did not change. Serum urea and creatinine concentrations rose. Both serum and total body potassium contents increased; there were no long term changes in serum concentration or total body content of sodium. Exercise tolerance was appreciably improved, and dyspnoea and fatigue lessened. Left ventricular end systolic and end diastolic dimensions were reduced. There was an appreciable reduction in complex ventricular ectopic rhythms. Adverse effects were few: weight gain and fluid retention were evident in five patients when captopril was introduced and two patients initially experienced mild postural dizziness; rashes in two patients did not recur when the drug was reintroduced at a lower dose; there was a significant reduction in white cell count overall, but the lowest individual white cell count was 4000 X 10(6)/l. Captopril thus seemed to be of considerable value in the long term treatment of severe cardiac failure.

SUMMARY The extent ofneuroendocrine activation, its time course, and relation to left ventricular dysfunction and arrhythmias were investigated in 78 consecutive patients with suspected acute myocardial infarction. High concentrations of arginine vasopressin were found within six hours of symptoms, even in the absence of myocardial infarction (n = 18). Plasma catecholamine concentrations also were highest on admission, whereas renin and angiotensin II concentrations rose progressively over the first three days, not only in those with heart failure but also in patients with no clinical complications. Heart failure, ventricular tachycardia, and deaths were associated with extensive myocardial infarction, low left ventricular ejection fraction, and persistently high concentrations of catecholamines, renin, and angiotensin II up to 10 days after admission, whereas in uncomplicated cases concentrations had already returned to normal.The clinical presentation of acute myocardial infarction varies widely. Some patients have only mild constitutional upset, while others suffer intense vasoconstriction, arrhythmias, heart failure, or shock. In common with other major acute illnesses, myocardial infarction is accompanied by many metabQlic and hormonal changes which may be related to the severity ofillness and clinical outcome.' Although stimulation of neuroendocrine systems may be an appropriate response to acute myocardial injury, those hormones that promote vasoconstriction or tachycardia might also be harmful.Ofthe vasoconstrictor mechanisms, catecholamine release has been the most extensively studied.

The effects of acute hypoglycemia on the heart and cardiovascular system were examined in humans using radioisotopic techniques, complemented by measurement of heart rate and blood pressure. The heart rate increased from 62 +/- 3 to 87 +/- 3 beats/min in response to hypoglycemia; this increase was accompanied by a significant increase in systolic blood pressure, a fall in diastolic blood pressure, with no change in the mean arterial blood pressure. The left ventricular ejection fraction increased from 47 +/- 3 (SE) to 72 +/- 5% in response to hypoglycemia. The increases in heart rate and ejection fraction were abolished during parenteral nonselective beta-adrenergic blockade with propranolol but were unaffected by either alpha-adrenergic blockade with phentolamine or cholinergic blockade with atropine. During beta-adrenergic blockade, there were significant increases in diastolic and mean arterial blood pressure in response to hypoglycemia. During alpha-adrenergic blockade the systolic, diastolic, and mean arterial pressures fell significantly after hypoglycemia. The blood pressure responses to hypoglycemia were unaffected by cholinergic blockade. Thus the increases in ejection fraction and in heart rate in response to hypoglycemia are mediated by beta-adrenoreceptors, whereas the blood pressure responses to hypoglycemia are mediated by alpha- and by beta-adrenoreceptors.

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