Cardiovascular effects of MnDPDP and mncl2 in Dogs with Acute Ischaemic Heart Failured

Purpose: To examine the cardiovascular effects of MnDPDP in a model of acute heart failure in the dog, and to compare these effects with those of MnCl2.Material and Methods: The study involved slow i.v. infusion of either 10,60 and 300 μmol/kg of MnDPDP, or 1, 6 and 30 μmol/kg MnCl2, in increasing doses to groups of 5 dogs. Acute ischaemic heart failure was first induced by injection of polystyrene microspheres (50 ± 10 μm) into the left coronary artery until a stable left ventricular end-diastolic pressure of approximately 20 mm Hg was achieved. The following test parameters were measured: left ventricular end-diastolic pressure; the first derivatives of maximum rate of left ventricular contraction and relaxation; mean aortic pressure; pulmonary artery 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 function during acute ischaemic heart failure. At 300 μmol/kg, i.e. 60 times the human dose, only minor haemodynamic and electrophysiological effects were seen, and these were similar to those seen after administration of 30 μmol/kg MnCl2.Conclusion: The present study suggests that slow infusion of MnDPDP should not cause further deteroriation of cardiac function in patients with heart failure.