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EXPERIMENTAL STUDIES

Effects of reperfusion on arrhythmias and death after coronary artery occlusion in the rat: increased electrical stability independent of myocardial salvage

^a Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA

Manuscript received October 19, 1997; revised manuscript received March 11, 1998, accepted March 20, 1998.

Address for correspondence: Dr. Janice M. Pfeffer, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115
jmpfeffer{at}rics.bwh.harvard.edu

Objectives. This study sought to delineate salvage-dependent from salvage-independent coronary reperfusion in acute myocardial infarction and the effects on spontaneously occurring arrhythmias and arrhythmic death in rats.

Background. Reperfusion of the infarct-related artery might increase electrical stability independently of salvage of ischemic myocardium.

Methods. In 98 conscious rats the electrocardiogram was monitored by telemetry for 48 h after MI, and all episodes of ventricular tachycardia (VT) and ventricular fibrillation (VF) were analyzed. Reperfusion at 45 min (RP45) (n = 15), 90 min (RP90) (n = 18) and 180 min (RP180) (n = 30) min was compared with permanent coronary artery occlusion (CAO) (n = 35) with respect to the post-reperfusion periods.

Results. RP45, RP90 and RP180 reduced the incidence of VT by 93%, 98% and 88% and VF by 89%, 97% and 92%, respectively (all p < 0.01 vs. CAO). The all-cause mortality rate was reduced from 47% (CAO) to 8% (RP45, p < 0.05) and 0% (RP90, p < 0.01); after RP180 it was 17% (CAO 42%, p = 0.08). All reperfusion regimens reduced arrhythmic deaths: 47% to 8% (RP45, p < 0.05), 47% to 0% (RP90, p < 0.01) and 42% to 8% (RP180, p < 0.05). Infarct size was identical to that during CAO (49 ± 10% [mean ± SD]) and RP180 (49 ± 10%), whereas preferentially epicardial salvage occurred at RP45 (36 ± 8%, p < 0.001) and RP90 (38 < 10%, p < 0.001).

Conclusions. Early and late reperfusion reduce the incidence and duration of VT and VF in conscious rats with acute MI. Thereby, arrhythmia-related mortality is improved through the prevention of fatal VF episodes. Thus, reperfusion increases the electrical stability of the heart independently of myocyte salvage, as proposed by the open artery hypothesis.

Abbreviations and Acronyms   CAO = coronary artery occlusion   ECG = electrocardiogram, electrocardiographic   IRA = infarct-related artery   MI = myocardial infarction   RP45, RP90, RP180 = reperfusion at 45, 90 and 180 min, respectively   TTC = triphenyltetrazolium chloride   VF = ventricular fibrillation   VT = ventricular tachycardia

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