Cardiac preconditioning does not require myocardial stunning.

Efforts to minimize the deleterious effects of intraoperative myocardial ischemia-reperfusion (I/R) injury have been primarily directed at optimizing cardioplegic solutions and altering reperfusion conditions. Classically, myocardial I/R has been associated with cardiac mechanical dysfunction ("stunning"). Recently, we reported an alpha 1-adrenergic receptor-mediated mechanism of paradoxical myocardial protection against I/R insult induced by a prior episode of transient ischemia, a phenomenon known as "ischemic preconditioning." Myocardial stunning resulting from transient ischemia has previously been associated with ischemic preconditioning, prompting intuitively negative bias against the clinical application of this phenomenon. The purpose of this study was to determine whether transient ischemia of insufficient duration to cause prolonged mechanical dysfunction (stunning) can induce favorable cardiac preconditioning. Isolated-perfused rat hearts were allowed to equilibrate for 8 minutes and were then subjected to either 2 minutes of global, normothermic transient ischemia or 2 minutes of 50 mumol/L phenylephrine infusion. A stabilization period of perfusion lasting 10 minutes after the termination of transient ischemia or phenylephrine infusion was followed by a standard I/R challenge (20 minutes of global, normothermic ischemia; 40 minutes of reperfusion). Ventricular function (measured as developed pressure in millimeters of mercury) recovered rapidly after transient ischemia such that no impairment was present before the subsequent standard I/R challenge. Phenylephrine treatment was associated with no residual inotropy before I/R challenge. Control hearts were subjected only to the standard I/R challenge after an initial 20-minute equilibration period. After reperfusion control hearts exhibited 54.4% recovery of initial left ventricular developed pressure. Transient ischemia- and phenylephrine-preconditioned hearts recovered 84.4% (p < 0.01) and 82.4% (p < 0.01), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Pretreatment with a nontoxic derivative of endotoxin induces functional protection against cardiac ischemia/reperfusion injury.

We hypothesized that low-dose pretreatment of an intact animal with a nontoxic derivative of endotoxin, monophosphoryl lipid A (MPL), would induce protection against cardiac ischemia/reperfusion (I/R) injury. The purposes of this study were to investigate whether MPL pretreatment would induce functional protection against cardiac I/R injury, to delineate the temporal induction of protection, and to examine antioxidant enzyme induction as a mechanism of protection. Rats were administered a 5 mg/kg dose of MPL at 2 hours and 24 hours before a 25-minute, global, 37 degrees C ischemic insult followed by reperfusion (modified Langendorff). At 40 minutes of reperfusion, ventricular function was assessed (ventricular balloon; developed pressure, rate of contraction, rate of relaxation). Hearts from rats pretreated with MPL 24 hours before isolation exhibited preservation of ventricular function (p less than 0.05). After I/R, hearts from rats pretreated with MPL 24 hours before isolation had increased (p less than 0.05) catalase activity compared to saline pretreated controls and rats pretreated with MPL 2 hours before isolation. We conclude that (1) pretreatment with MPL induces functional protection against cardiac I/R injury, (2) protection (not evident at 2 hours) is maximal at 24 hours, suggesting enzyme induction, and (3) increased catalase activity correlates with the functional protection.