Recovery of contractile function of postischemic, reperfused myocardium: influence of 2,3-butanedione-2-monoxime.
Inhibition of mechanical activity during ischemia could improve recovery of stunned myocardium. In this study, the effect of 2,3-butanedione-2-monoxime (BDM), an agent that disrupts excitation-contraction coupling, on the time course of recovery of contractile function of postischemic reperfused myocardium was studied in open-chest anesthetized dogs. Ischemia was produced by occluding the left anterior descending coronary artery (LAD) for 15 mins. In separate experimental groups, during the occlusion period, 6 ml of either 100 mM BDM or drug vehicle (0.9% normal saline) was infused into the distal perfusion bed subjected to occlusion. Regional myocardial function (percentages of segment shortening % SS) was assessed by sonomicrometry. LAD occlusion resulted in similar degrees of dyskinesia in both experimental groups. Subsequent recovery of contractile function during reperfusion was evaluated for 3 h. In control experiments, segment shortening remained significantly (p < 0.05) decreased throughout the reperfusion period, returning to only 36.1 +/- 9.2% of the preocclusion value at 3 h postreperfusion. In BDM experiments, regional contractile function returned to 72.4 +/- 11.3% of the preocclusion value at 1 h of reperfusion. Rapid recovery was sustained throughout reperfusion. Regional stroke work area (RSWA) also demonstrated rapid sustained recovery of function after treatment with BDM. RSWA was significantly greater in BDM experiments as compared with control experiments at all times during the reperfusion period. These results demonstrate that selective intracoronary (i.c.) administration of BDM during ischemia markedly enhances postischemic recovery of contractile function. The underlying mechanism for this action may involve modulation of several aspects of impaired cellular function in postischemic tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
O'Brien
P
P
Department of Medicine/Division of Cardiology, Medical College of Wisconsin, Milwaukee 53226.
Bosnjak
Z
Z
Warltier
D C
DC
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002863:Chromogenic Compounds / Q000494:pharmacology*; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology
D002863:Chromogenic Compounds; C004717:diacetylmonoxime; D003931:Diacetyl