DIFFERENTIAL HEMODYNAMIC-EFFECTS OF THE NITRIC-OXIDE DONOR PIRSIDOMINE IN COMPARISON TO SIN-1, NITROPRUSSIDE AND NITROGLYCERIN

The systemic and coronary hemodynamic effects of the nitrovasodilator, pirsidomine, were compared with SIN-1, nitroprusside, and nitroglycer in. Four groups consisting of 32 experiments were performed in 17 cons cious dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular dP/dt(max), diastolic coronary blood flow velocity, cardiac output, and subendocardial segment lengt h. On separate experimental days, systemic and coronary hemodynamics w ere recorded during control conditions and after intravenous administr ation of pirsidomine (1.0, 2.0, and 4.0 mg . kg(-1)), SIN-1, (50, 100, and 200 mu g . kg(-1)), nitroprusside (0.5, 1.0, and 2.0 mu g . kg(-1 ) . min(-1)), or nitroglycerin (1.0, 2.0, and 4.0 mu g . kg(-1) . min( -1)). Pirsidomine decreased mean arterial, left ventricular systolic a nd end-diastolic pressures, stroke volume and systemic vascular resist ance. Diastolic coronary blood flow velocity and heart rate were incre ased and coronary vascular resistance decreased by pirsidomine. SIN-1, nitroprusside and nitroglycerin caused similar decreases in preload ( evaluated by left ventricular end-diastolic pressure) and afterload (i ndirectly assessed by mean arterial pressure and systemic vascular res istance) as compared to pirsidomine. However. equihypotensive doses of SIN-1, nitroprusside, and nitroglycerin improved ventricular performa nce as assessed by increases in left ventricular dP/dt(max), cardiac o utput and segment shortening, in contrast to those findings during com parable doses of pirsidomine (4 mg . kg(-1)). Despite similar loading conditions, high doses of pirsidomine did not enhance left ventricular function, suggesting that pirsidomine may have direct negative inotro pic effects.