Brief apnea induces myocardial ischemic tolerance by an opioid-insensitive mechanism

Background ittent brief “preconditioning” (PC) ischemia has been shown to render the heart resistant to a subsequent sustained ischemic insult, in part through an opioid-dependent mechanism. Using the rabbit model, we tested the hypothesis that intermittent in vivo apnea elicits a cardioprotective response similar to that achieved with conventional PC ischemia. In addition, we sought to determine if infarct size reduction seen in this model was stimulated via opioid receptor activation. s etized, intubated rabbits (n=35) were randomized to receive three 4.5-min bouts of apnea interspersed with 5 min normal ventilation or time-matched standard ventilation (controls). Upon completion of the in vivo PC/control period, the hearts were excised and assessed for ischemic tolerance on a modified Langendorff apparatus (40 min global ischemia+2h reperfusion). To assess the contribution of opioid receptor stimulation, two additional control and PC groups received the nonspecific opioid antagonist naloxone (10 mg/kg) prior to the in vivo intervention phase. Infarct size (delineated by tetrazoliam staining and expressed as a percentage of the left ventricle [LV]) was compared among the four groups by ANOVA. s t size was significantly reduced in hearts that received antecedent apneic PC when compared with controls (63±5% vs. 34±8%) of the LV, respectively; P<.05). Pretreatment with naloxone had no significant effect on infarct size in nonpreconditioned hearts (80±6%) and did not inhibit the protective effects of apnea-induced PC (52±10% in naloxone+PC group). sions ittent apnea evokes significant myocardial ischemic tolerance through an opioid-insensitive mechanism.