Does cardiopulmonary bypass alone elicit myoprotective preconditioning?

Abstract

Brief episodes of ischemia can precondition myocardium. Ischemic preconditioning (PC) has been proposed as an adjuvant method of improving myocardial protection during cardiac surgery. It is unknown whether CPB without an episode of ischemia generates the PC response. To prove that PC occurs in sheep, groups 1 (non-CPB control) and 2 (non-CPB ischemic PC, three 5-minute episodes of normothermic regional ischemia) were studied. Groups 3 (CPB alone), 4 (CPB-alpha receptor blockade, phentolamine 5 mg/kg), and 5 (CPB-adenosine receptor blockade, 8-sulfophenyltheophylline 5 mg/kg) were placed on CPB for 30 minutes and subsequently weaned. All groups underwent 60 minutes of normothermic regional ischemia and 150 minutes of reperfusion. The area at risk (AR) was delineated by Monastryl blue pigment, whereas the infarct size (IS) was determine by tetrazolium staining. Body mass, left ventricular mass, and AR were not different between groups. Ischemic PC was demonstrated in this ovine model by a 54% reduction of IS relative to AR (group 1 versus group 2, P < .01). CPB alone produced a similar percentage IS reduction without ischemia (group 3 versus group 1, P < .01) that was prevented by either alpha-adrenergic receptor (group 4 versus group 3, P < .01) or adenosine receptor (group 5 versus group 3, P < .01) blockade. CPB alone appears sufficient to elicit the PC response important for myocardial protection during cardiac surgery. These data suggest that myocardial alpha-adrenergic receptor and adenosine receptor stimulation are involve in initiating CPB-induced PC.