Myocardial efficiency in stunned myocardium. Comparison of Ca(2+)-sensitization and PDE III-inhibition on energy consumption.
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(2+)-sensitization might be a favorable alternative.


METHODS
The effects of a novel Ca(2+)-sensitizer (EMD 60263, 10 microM, group 1) were compared with a phosphodiesterase (PDE) III-inhibitor (enoximon, 20 microM, 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 (MVO(2)) were assessed. Contractile efficiency (EF(cont)), derived from the reciprocal of the slope of the MVO(2)-PVA relation, and external efficiency (EF(ex), stroke work/MVO(2)), were calculated.


RESULTS
At matched heart rate (group 1: 141+/-10 min(-1) group 2: 151+/-28 min(-1)) and end-diastolic volume (1.3+/-0.2 ml) systolic variables were significantly decreased in stunned myocardium: LVP(max) to 57+/-13% of control value in group 1 and to 76+/-7% in group 2, aortic flow to 20+/-4 vs. 25+/-8%. PVA was decreased to 57+/-13 and 67+/-11%, MVO(2) was non-significantly decreased to 73+/-22 and 88+/-14%. After administration of either inotropic agent LVP(max) was significantly improved to 96+/-12 vs. 90+/-8% compared with preischemic levels, aortic flow to 103+/-24 vs. 88+/-9%, and PVA 99+/-11 vs. 89+/-16%, respectively. EMD 60263 increased MVO(2) to control levels (107+/-9%), and enoximon raised MVO(2) even more significantly above control (139+/-13%). Both myocardial efficiency indices were significantly diminished during reperfusion: EF(ex) to 14+/-9 vs. 23+/-7% and EF(cont) to 71+/-7 vs. 65+/-9% compared with preischemic levels. EF(ex) (109+/-21%) was significantly, but EF(cont) only slightly (84+/-11%) increased after administration of EMD 60263, whereas EF(ex) (57+/-13%) and EF(cont) (71+/-12%) remained depressed after enoximon.


CONCLUSIONS
In stunned myocardium, the decreased efficiency indices show that energy utilization is disturbed. Both agents recruited an inotropic reserve, whereas Ca(2+)-sensitization seemed to be more favorable in terms of myocardial efficiency indices. These results indicate that alteration of myocardial calcium sensitivity contributes a major part to postischemic dysfunction. Therefore, Ca(2+)-sensitization may potentially be a superior method for inotropic support in the postischemic heart.
Sunderdiek
U
U
Department of Thoracic and Cardiovascular Surgery, Heinrich-Heine University, Moorenstrasse 5, 40225, Düsseldorf, Germany. usunderdiek@aol.com
Korbmacher
B
B
Gams
E
E
Schipke
J D
JD
D000818:Animals; D017335:Enoximone / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics; D066298:In Vitro Techniques; D008297:Male; D017682:Myocardial Stunning / Q000378:metabolism / Q000503:physiopathology*; D010101:Oxygen Consumption / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013829:Thiadiazines / Q000494:pharmacology*; D018754:Ventricular Dysfunction / Q000503:physiopathology*
D010726:Phosphodiesterase Inhibitors; D013829:Thiadiazines; C088204:EMD 60263; D017335:Enoximone