title: Neurohormonal activation in patients with acute myocardial infarction or chronic congestive heart failure. With special reference to treatment with angiotensin converting enzyme inhibitors.
abstract: Neurohormonal activation may provide a pathophysiological link between acute myocardial infarction and chronic congestive heart failure, and modulation of neurohormonal activity may be an important therapeutic target in these conditions. Plasma neurohormones were studied in 55 patients with acute myocardial infarction. Angiotensin II, noradrenaline and ANP were elevated in the early phase but tended to normalize during the first week in patients without signs of heart failure. In patients with heart failure angiotensin II and noradrenaline remained elevated for 1 month and ANP for 4-6 months. During head-up tilt, angiotensin II and noradrenaline increased most in patients with heart failure. In patients with a first myocardial infarction there was a positive correlation between sustained neurohormonal activity and infarct size. Almost complete suppression of plasma ACE activity was achieved within 30 min in 48 patients treated with intravenous enalaprilat, initiated within 24 h from the onset of infarction. The drug was tolerated in dosages of 1.0-1.2 mg given over 1-2h. Patients with systolic blood pressure between 100 and 110 mmHg incurred a greater risk of hypotension than those with higher blood pressure at baseline. Tolerance was not worse among patients treated with intravenous diuretics, metoprolol or nitroglycerin. A total of 98 patients were randomized to treatment with enalapril or placebo, initiated within 24 h from onset of infarction and continued for 4-6 months. During treatment there were no significant differences in plasma levels of angiotensin II, aldosterone, ANP or catecholamines between groups. Echocardiographic recordings were performed in 28 patients. Among patients on placebo there was a positive correlation between plasma levels of noradrenaline at days 5-7 and the increase in left ventricular volumes during the study period, and an inverse correlation between plasma aldosterone at days 5-7 and the increase in left ventricular ejection fraction during the study. No such correlation was found among patients on enalapril. ANP levels at 1 month correlated inversely with the left ventricular ejection fraction at the same time. Plasma neurohormones were measured in 223 patients with mild or moderately severe chronic heart failure, randomized to treatment with ramipril or placebo for 3 months. There was wide variation in hormone levels. Noradrenaline and aldosterone correlated inversely with exercise duration at baseline. Noradrenaline correlated positively with the degree of symptoms. Aldosterone and ANP were reduced with ramipril compared with placebo. Noradrenaline was reduced among patients with baseline levels in the highest tertile. Plasma hormones were also measured at peak exercise in 54 patients. Hormonal levels at rest correlated strongly with those at peak exercise.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Medicine, Ostra Hospital Faculty of Medicine, Göteborg University, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Sigurdsson
mesh_terms: D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000627:therapeutic use; D015773:Enalaprilat / Q000627:therapeutic use; D015444:Exercise; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D009490:Neurosecretory Systems / Q000503:physiopathology; D009638:Norepinephrine / Q000097:blood; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D017257:Ramipril / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D009320:Atrial Natriuretic Factor; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat; D017257:Ramipril; D009638:Norepinephrine