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)
Mitchell
M B
MB
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262.
Winter
C B
CB
Locke-Winter
C R
CR
Banerjee
A
A
Harken
A H
AH
D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D010656:Phenylephrine / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left
D010656:Phenylephrine