Circulation, Vol 82, 609-619, Copyright © 1990 by American Heart Association
GC Li, JA Vasquez, KP Gallagher and BR Lucchesi
Myocardial preconditioning with brief coronary artery occlusions before a
sustained ischemic period is reported to reduce infarct size. To determine
the number of occlusive episodes required to produce the preconditioning
effect, we performed single or multiple occlusions of the left circumflex
coronary artery (LCx) followed by a sustained occlusion (60 minutes) of the
LCx. Anesthetized dogs underwent one (P1), six (P6), or 12 (P12) 5-minute
occlusions of the LCx. Each occlusion period was followed by a 10-minute
reperfusion period. A 60- minute occlusion of the LCx followed the
preconditioning sequences. A control group received a 60-minute occlusion
of the LCx without preconditioning. All groups were subjected to 6 hours of
reperfusion after which the heart was removed for calculating infarct size
(IS), area at risk (AR), and left ventricular mass (LV). The IS/AR ratio
for the control group was 29.8 +/- 4.4% (n = 17), which was substantially
greater (p less than 0.001) than that of the preconditioned groups: P1, 3.9
+/- 1.3% (n = 14); P6, 0.4 +/- 0.3% (n = 5); and P12, 2.9 +/- 2.8% (n = 5).
There were no significant differences in the IS/AR ratio among the three
preconditioned groups. The AR/LV ratio was comparable among all groups and
did not differ statistically: control, 40.4 +/- 1.3%; P1, 36.2 +/- 1.7%;
P6, 36.1 +/- 1.7%; and P12, 37.3 +/- 2.1%. Collateral blood flow to the
inner two thirds of the risk region determined with radiolabeled
microspheres during ischemia did not differ significantly between the
control group (0.03 +/- 0.01 ml/min/g, n = 8) and single occlusion group
(0.06 +/- 0.02 ml/min/g, n = 8), indicating that the marked disparity in
infarct size could not be attributed to differences in collateral blood
flow. The data indicate that preconditioning with one brief ischemic
interval is as effective as preconditioning with multiple ischemic periods.
ARTICLES
Myocardial protection with preconditioning
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0626.
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