SUMMARY Acute left anterior descending coronary artery occlusion was produced in 21 conscious, chronically instrumented dogs. Forty minutes after coronary occlusion, nine dogs were given i.v. teprotide, 25 ,ug/kg/min, followed by oral doses of captopril, 10 mg/kg every 8 hours for 24 hours. The remaining 12 dogs served as saline-infused controls. In all dogs, acute coronary occlusion increased plasma renin activity and peripheral vascular resistance and reduced cardiac output, but did not change mean aortic blood pressure significantly. Teprotide significantly (p < 0.05) decreased peripheral vascular resistance (from 3804 ± 1158 to 2876 ± 816 dyn-sec-cm-5) ( ± SD) and mean aortic pressure (from 117 ± 12 to 107 ± 15 mm Hg), and increased cardiac output (from 2.63 ± 0.67 to 3.12 ± 0.74 I/min). Teprotide also produced a relative increase in flow to the renal and splanchnic circulations compared with the saline-treated controls. There were, however, no differences in segmental systolic shortening, blood flow in the normal or ischemic myocardium, or infarct size. These results indicate that the renin-angiotensin system may play an important role in dogs with acute coronary occlusion and that blockade of this system lowers systemic blood pressure and improves cardiac output. However, direct effects of renin-angiotensin system blockade on the myocardium are lacking; there were no changes in myocardial blood flow, myocardial mechanics or infarct size.THE EXTENT to which the renin-angiotensin system participates in the hemodynamic response to acute myocardial ischemia is unknown. Acute systemic hypoxia elevates plasma renin activity and alters hemodynamic responses, and converting-enzyme inhibition attenuates the hemodynamic responses during severe hypoxia. ' Recently, the major focus of interest in the effect of the renin-angiotensin system on hemodynamics has been during acute and chronic congestive heart failure.2'-2 Most reports conclude that after convertingenzyme inhibition, hemodynamic improvement occurs in both acute and chronic congestive heart failure.During acute myocardial infarction, plasma catecholamines are elevated.'3 Sympathetic stimulation of the renin-angiotensin system triggers the release of renin into the peripheral circulation. However, whether renin plays a role during acute coronary ischemia is unknown. Angiotensin increases coronary vascular resistance,'4 but whether converting-enzyme inhibition alters coronary flow during acute ischemia is not known. Ertl et al.'5 showed that infarct size was reduced by converting-enzyme inhibition in barbiturateanesthetized dogs and attributed this effect to an increase in collateral flow and afterload reduction. However, anesthesia may by itself activate the reninangiotensin system,'6' 17 making interpretation of these results difficult. The purpose of the present study was to evaluate the effects of converting-enzyme inhibition on global and regional cardiac performance, myocardial blood flow and peripheral tissue perfusion in a conscious canine model of m...

We infused dobutamine (20 microgram/kg per min) intravenously, once before and once after coronary artery occlusion, in 10 chronically instrumented dogs. Both infusions increased cardiac output and left ventricular dP/dt and dP/dt/P, but divergent effects on heart rate and aortic blood pressure were observed. Dobutamine decreased heart rate and increased mean aortic blood pressure before coronary artery occlusion, whereas after occlusion it increased heart rate while mean aortic blood pressure remained unchanged. A greater decrease in total peripheral vascular resistance occurred during dobutamine infusion after coronary artery occlusion than before. These differences may relate to withdrawal of enhanced sympathetic tone after coronary occlusion. Similar infusions of normal saline (n = 9) produced no systemic hemodynamic changes either before or after coronary artery occlusion. Myocardial blood flow increased to both non-ischemic and ischemic regions of the heart during dobutamine infusion, but the endocardial:epicardial blood flow ratio did not change significantly. In addition, infarct size, measured by nitroblue tetrazolium stain, was smaller in the dobutamine group (10 +/- 1 g) than in the normal saline group (15 +/- 2 g). Neither left ventricular weight nor risk zone differed between the two groups. These results indicate that dobutamine may be a useful inotropic agent during acute myocardial infarction.

The diuretic and clinical efficacy and safety of piretanide, a new high-ceiling loop diuretic, was determined in patients with mild to moderately severe congestive heart failure. Piretanide (n = 20) administered orally in a daily dosage of up to 24 mg was compared with placebo (n = 18) for 28 days, using a double-blind, randomized, parallel design. Patients were hospitalized during the first 5 days of the study when dosage titration was established and 24-hour fractionated urine collections were obtained. Piretanide caused significant diuresis for 3 hours after ingestion with a natriuretic response noted for up to 6 hours. While occasional kaliuretic response was noted, it did not significantly increase 24-hour urinary potassium excretion. Only one patient treated with the highest allowed dose of piretanide developed mild hypokalemia. An improvement in New York Heart Association functional class status was noted after piretanide therapy. In contrast, patients who received placebo exhibited no significant improvement. BUN increased in nine piretanide-treated patients; two were discontinued from the study because of progressive azotemia. However, there was no significant increase in serum creatinine levels. Other blood, physical, ECG, and audiometric examinations also revealed no significant abnormalities. The study suggests that oral piretanide is a relatively safe and effective diuretic for treating congestive heart failure with a potential advantage of having potassium-sparing properties.