DIURETIC THERAPY IN EXPERPIMENTAL RIGHT HEART FAILURE OF THE RHESUS MONKEY

¹ Pharmacology Department, Division of Medical and Scientific Affairs, Parke, Davis and Company, Ann Arbor, Michigan

Despite several studies of experimental congestive heart failure (CHF) in laboratory animals, none have dealt directly with effects of diuretic agents on electrolyte and water metabolism. The purpose of this study was to induce CHF in rhesus monkeys which would possess typical electrolyte alterations seen in human CHF, with subsequent evaluation of diuretic compounds in this model. CHF was surgically induced in rhesus monkeys by partial constriction of the main pulmonary artery followed with tricuspid avulsion. Pitting edema of dependent portions of the body and ascites developed in monkeys within two weeks after successful surgery. This was associated with oliguria, Na and Cl retention and body Weight gain. Readily exchangeable Na showed a marked increase, as did body fluid compartments. Diuretic therapy elicited extensive natriuresis and chloruresis; body weight loss paralleled the degree of saluresis. The following drug regimens were used: diapamide, 5 and 10 mg/kg/day; chlorothiazide, 20 mg/kg/day: furosemide, 1, 2, 4 and 5 mg/kg/day. These values represented human therapeutic doses. Diapamide and furosemide were dependable diuretic agents in this model; dosage could be adjusted to produce gradual weight loss and then maintenance of control weight. Chlorothiazide was not a dependable agent at the dose used.