EFFECTS OF POSITIVE INOTROPIC STIMULATION ON POSTISCHEMIC MYOCARDIUM WITH GRADED DYSFUNCTION

Objective: To investigate the effects of moderate prolonged and of max imum short-term positive inotropic stimulation of postischemic myocard ium as a function of the severity of stunning. Methods: Stunned isolat ed rat hearts (n = 116) after 30 min and 45 min of ischemia were stimu lated with dopamine to raise systolic function (double product) back t o control levels. in the isovolumetrically beating hearts, left ventri cular developed pressure, double product, dp/dt(max), coronary flow, a nd myocardial oxygen consumption were determined during steady-state c onditions. After maximum stimulation the contractile reserve was exami ned. Measurements of adenine nucleotides (n = 47) and electron microsc opy (n = 9) were made. Results: 30 min ischemia resulted in moderate p ostischemic dysfunction (LVP 81 +/- 3%; P < 0.05). After 45 min ischem ia, function was more severely reduced (LVP 66 +/- 15%, P < 0.01). Cor onary flow tended to be lower after ischemia. Myocardial oxygen consum ption was not reduced in parallel with the dysfunction. Adenine nucleo tides were gradually reduced after ischemia (ATP: 2.5 +/- 0.2 and 1.2 +/- 0.1 vs. 4.2 +/- 0.2 mu mol/gww; P < 0.01). Contractile reserve als o decreased in relation to the previous ischemic injury (after 45 min ischemia max, LVP 105 +/- 10% vs, max. LVP 152 +/- 8% in controls, P < 0.01). Prolonged stimulation did not result in further reduction in a denine nucleotides and function. Conclusions: Contractile reserve is d ecreased in postischemic myocardium in parallel with the previous isch emic burden. Depending on the degree of contractile dysfunction a dist urbed function-flow-oxygen consumption relation is present. Prolonged stimulation of stunned myocardium with dopamine back to the control ie c-el of function has no harmful short-term effects, indicating suffici ent mitochondrial energy generation.