COMPARISON BETWEEN THE EFFECTS OF A NOVEL CA++ SENSITIZER AND A PHOSPHODIESTERASE INHIBITOR ON STUNNED MYOCARDIUM

Inotropic agents are used widely for pharmacological bridging of the f ailing heart either until recovery after surgical intervention or unti l transplantation. EMD 57033 is a novel specific Ca++ sensitizing agen t with purportedly minor phosphodiesterase (PDE) III-inhibiting proper ties. It acts as an inotropic agent without raising intracellular Ca+ levels. In turn, the PDE III-inhibitor enoximone has been used for se veral years to treat low cardiac output syndrome. However, little is k nown about its effects on postischemic reperfused (stunned) myocardium . We investigated the effects of EMD 57033 (EMD; 30 mu M) and enoximon e (E20 mu g/ml) on stunned myocardium. The experiments were performed on 16 isolated rabbit hearts perfused with an erythrocyte suspension ( hematocrit = 30%; [Ca++] = 2.5 mM). Hearts were reperfused after a 20 min no-flow ischemia, Measurements were performed at control, 30 min a fter the onset of reperfusion, and after administration of one of the drugs. Both agents significantly improved the depressed systolic funct ion [left ventricular pressure (LVP)(max) from 61 +/- 12 to 93 +/- 18 mmHg, and its derived pressure (dP/dt)(max) from 860 +/- 220 to 1340 /- 300 mmHg/s and LVP(max) from 78 +/- 9 to 83 +/- 15 mmHg, and its de rivative dP/dt(max) from 1040 +/- 230 to 1385 +/- 300 mmHg/s, respecti vely] and early relaxation (dP/dt(min) from 810 +/- 250 to 1260 +/- 34 5 mmHg/s and from 1000 +/- 200 to 1135 +/- 295 mmHg/s, respectively) t hat occurred during postischemic reperfusion. Both coronary blood flow (86 +/- 48 vs. 206 +/- 186 ml/min/100 g and 84 +/- 27 vs. 139 +/- 27 ml/min/100 g, respectively) and oxygen consumption (4.0 +/- 1.2 vs. 7. 4 +/- 2.3 ml/min/100 g and 5.5 +/- 2.2 vs. 7.8 +/- 2.4 ml/min/100 g, r espectively), which was not altered during reperfusion, increased afte r drug administration. Both agents seemed to increase stroke work more than they increased myocardial oxygen consumption as expressed in ter ms of the external efficiency index [EMD: 0.06 to 0.36 arbitrary units (a,u.) enoximone: 0.21 to 0.35 (a.u,). No arrhythmogenic effects were observed with either agent, although enoximone increased heart rate s ignificantly (144 +/- 30 vs. 191 +/- 33/min). Because EMD 57033 exerte d no such tachycardia, this novel Ca++ sensitizing agent might be supe rior in treating the postischemic failing heart.