© 1997 American Heart Association, Inc.
Articles |
The Early and Late Phases of Ischemic Preconditioning
A Comparative Analysis of Their Effects on Infarct Size, Myocardial Stunning, and Arrhythmias in Conscious Pigs Undergoing a 40-Minute Coronary Occlusion
From the Experimental Research Laboratory (Y.Q., X.-L.T., S.-W.P., J.-Z.S., R.B.), Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, Tex, and the Experimental Research Laboratory (Y.Q., X.-L.T., A.K., R.B.), Division of Cardiology, University of Louisville (Ky).
Correspondence to Roberto Bolli, MD, Division of Cardiology, University of Louisville, Ambulatory Care Building, Louisville, KY 40292. E-mail r0boll01{at}ulkyvm.louisville.edu
Abstract The effectiveness of the late phase of
ischemic preconditioning (PC) in protecting against myocardial
infarction and the concomitant contractile dysfunction after sustained
ischemia remains unclear. The early and late phases of PC have
not been compared using the same protocol in the same experimental
model; furthermore, the late phase of PC has not been assessed in the
conscious state in a large animal preparation. The goal of this study
was to directly compare the effects of early and late PC on myocardial
infarct size and postischemic dysfunction in chronically
instrumented, conscious pigs. Four groups of pigs were subjected to a
40-minute coronary occlusion followed by 3 days of reperfusion.
Group 1 (n=7) served as control. Group 2 (n=6) was subjected to ten
2-minute occlusion/2-minute reperfusion cycles 25 minutes before the
40-minute occlusion (early PC). Groups 3 (n=7) and 4 (n=4) were
subjected to 10 and 25 cycles, respectively, of 2-minute
occlusion/2-minute reperfusion 24 hours before the 40-minute occlusion
(late PC). Infarct size averaged 45.1±5.9% of the region at risk in
control pigs, was reduced by 79% (to 9.4±3.2%) in group 2, but did
not differ in groups 3 (33.3±4.8%) and 4 (38.8±8.2%) versus group
1. Power analysis demonstrated that there was an 80%
probability of detecting a 40% decrease in infarct size in groups 3
and 4 versus group 1. The recovery of systolic wall thickening
(measured with ultrasonic crystals) after the 40-minute occlusion was
poor in groups 1, 3, and 4 but markedly enhanced in group 2 throughout
the 3 days of reperfusion; this beneficial effect could have been due
to limitation of infarct size, alleviation of stunning, or both. Thus,
a series of ten 2-minute coronary occlusions had a profound
(
80%) early infarct–limiting effect, which was associated with a
marked functional benefit. This protection, however, disappeared 24
hours later and could not be reinstituted by increasing the number of
PC coronary occlusions to 25. The incidence and duration of
ventricular tachycardia after reperfusion was
not changed by either early or late PC; no conclusions could be drawn
regarding ventricular fibrillation or
ischemia-induced ventricular
tachycardia, since these arrhythmias did not occur
in control animals. Taken together, the present results demonstrate
striking differences between the early and late effects of PC: In
conscious swine subjected to a sustained coronary occlusion, a
PC protocol that induces powerful protection during the early phase of
PC fails to induce any protection during the late phase, indicating
either that a late protective effect of PC does not exist or that, if
it exists, it must be weaker than the early protective effect.
Key Words: preconditioning • swine • ischemia • reperfusion
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