TIME-COURSE OF LATE PRECONDITIONING AGAINST MYOCARDIAL STUNNING IN CONSCIOUS PIGS

We have recently found in conscious pigs that a sequence of brief coro nary occlusions induces severe myocardial stunning, but when the same sequence is repeated 24 hours later, the severity of stunning is marke dly reduced (approximate to 50%) (''late preconditioning against stunn ing''). As an initial step toward elucidating the mechanism and potent ial clinical significance of this powerful cardioprotective response, the present study was conducted to define the time course of late prec onditioning against myocardial stunning. Conscious pigs underwent a se quence of ten 2-minute coronary occlusion/2-minute reperfusion cycles and then a second identical sequence at 6 hours (group I, n = 7), 12 h ours (group II, n = 6), 24 hours (group III, n = 10), 3 days (group IV , n = 10), or 6 days (group V, n = 11) after the first. Systolic wall thickening (WTh) in the ischemic/reperfused region remained significan tly depressed for at least 3 hours after the 10th reperfusion of the f irst sequence, indicating myocardial stunning. When the second sequenc e of coronary occlusions was performed 6 hours after the first (group I), the recovery of WTh was similar to the first. In contrast, when th e second sequence was repeated 12 hours after the first (group II), th e recovery of WTh was improved, though not consistently, and the total deficit of WTh decreased by 41% (P < .05) compared with the first seq uence. When the second sequence was repeated 24 hours (group III) and 3 days (group TV) after the first, the recovery of WTh was substantial ly enhanced, with 52% and 49% reductions in the total deficit of WTh, respectively (P < .01 versus the first sequence). When the second sequ ence was repeated 6 days later (group V), the recovery of WTh was indi stinguishable from the first sequence. Thus, late preconditioning agai nst myocardial stunning requires > 6 hours to develop, lasts for at le ast 60 hours after its appearance (with the most effective protection present at 24 hours and 3 days), and disappears within 6 days after th e preconditioning ischemia, a time course that is consistent with the synthesis and degradation of cardioprotective proteins. In view of its sustained duration, this endogenous cardioprotective mechanism is of potential clinical importance.