Pii: S1010-7940(00)00413-9

Objective: In stunned myocardium oxygen consumption is relatively high compared with the reduced ventricular function. On the other hand, inotropic stimulation is frequently required to improve postischemic ventricular dysfunction. However, inotropic agents which act via intracellular increased calcium result in a higher oxygen demand. Therefore Ca-sensitization might be a favorable alternative. Methods: The effects of a novel Ca-sensitizer (EMD 60263, 10 mM, group 1) were compared with a phosphodiesterase (PDE) III-inhibitor (enoximon, 20 mM, group 2) on 14 isolated, blood-perfused rabbit hearts during reperfusion after a global ischemia of 20 min. Ventricular function, the pressure±volume area (PVA, a measure of total mechanical work), and total myocardial oxygen consumption (MVO2) were assessed. Contractile ef®ciency (EFcont), derived from the reciprocal of the slope of the MVO2±PVA relation, and external ef®ciency (EFex, stroke work/MVO2), were calculated. Results: At matched heart rate (group 1: 141 ^ 10 min 21 group 2: 151 ^ 28 min) and end-diastolic volume (1.3 ^ 0.2 ml) systolic variables were signi®cantly decreased in stunned myocardium: LVPmax to 57 ^ 13% of control value in group 1 and to 76 ^ 7% in group 2, aortic ̄ow to 20 ^ 4 vs. 25 ^ 8%. PVA was decreased to 57 ^ 13 and 67 ^ 11%, MVO2 was non-signi®cantly decreased to 73 ^ 22 and 88 ^ 14%. After administration of either inotropic agent LVPmax was signi®cantly improved to 96 ^ 12 vs. 90 ^ 8% compared with preischemic levels, aortic ̄ow to 103 ^ 24 vs. 88 ^ 9%, and PVA 99 ^ 11 vs. 89 ^ 16%, respectively. EMD 60263 increased MVO2 to control levels (107 ^ 9%), and enoximon raised MVO2 even more signi®cantly above control (139 ^ 13%). Both myocardial ef®ciency indices were signi®cantly diminished during reperfusion: EFex to 14 ^ 9 vs. 23 ^ 7% and EFcont to 71 ^ 7 vs. 65 ^ 9% compared with preischemic levels. EFex (109 ^ 21%) was signi®cantly, but EFcont only slightly (84 ^ 11%) increased after administration of EMD 60263, whereas EFex (57 ^ 13%) and EFcont (71 ^ 12%) remained depressed after enoximon. Conclusions: In stunned myocardium, the decreased ef®ciency indices show that energy utilization is disturbed. Both agents recruited an inotropic reserve, whereas Casensitization seemed to be more favorable in terms of myocardial ef®ciency indices. These results indicate that alteration of myocardial calcium sensitivity contributes a major part to postischemic dysfunction. Therefore, Ca-sensitization may potentially be a superior method for inotropic support in the postischemic heart. q 2000 Elsevier Science B.V. All rights reserved.