CARDIOVASCULAR EFFECTS OF MNDPDP AND MNCL2 IN DOGS WITH ACUTE ISCHEMIC HEART-FAILURE

Purpose: To examine the cardiovascular effects of MnDPDP in a model of acute heart failure in the dog, and to compare these effects with tho se of MnCl2. Material and Methods: The study involved slow i.v. infusi on of either 10, 60 and 300 mu mol/kg of MnDPDP, or 1, 6 and 30 mu mol /kg MnCl2, in increasing doses to groups of 5 dogs. Acute ischaemic he art failure was first induced by injection of polystyrene microspheres (50+/-10 mu m) into the left coronary artery until a stable left vent ricular end-diastolic pressure of approximately 20 mm Hg was achieved. The following test parameters were measured: left ventricular end-dia stolic pressure; the first derivatives of maximum rate of left ventric ular contraction and relaxation; mean aortic pressure; pulmonary arter y pressure; right atrial pressure; cardiac ouput; heart rate; QT-time; PQ-time; QRS-width; and plasma catecholamines. Results: Slow infusion of MnDPDP at doses up to and including 12 times the clinical dose was well tolerated in dogs without further depression of cardiovascular f unction during acute ischaemic heart failure. At 300 mu mol/kg, i.e. 6 0 times the human dose, only minor haemodynamic and electrophysiologic al effects were seen, and these were similar to those seen after admin istration of 30 mu mol/kg, MnCl2. Conclusion: The present study sugges ts that slow infusion of MnDPDP should not cause further deteroriation of cardiac function in patients with heart failure.