Adequate surgical reperfu- sion is important in determining outcome, even though it may initially induce reperfusion injury. Various studies delineat- ing the major mediators of reperfusion injury have focused attention on the mitochondrial permeability transition pore, the opening of which during reperfusion uncouples oxidative phosphorylation, ultimately leading to cell death.205 Although several pharmacological interventions targeting components of reperfusion injury have been tried, none has been found to be efficacious for this purpose.182,184 189,205 207 The severity of reperfusion injury is influenced by numer- ous factors, including 1) the status of the patient s coronary circulation, 2) the presence of active ongoing ischemia or infarction, 3) preexisting medical therapy (Sections 4.3 and 4.5), 4) concurrent use of mechanical assistance to improve coronary perfusion (ie, intra-aortic balloon counterpulsation), and 5) the surgical approach used (on pump or off pump). CPB with ischemic arrest is known to induce the release of cytokines and chemokines involved in cellular homeostasis, thrombosis, and coagulation; oxidative stress; adhesion of blood cell elements to the endothelium; and neuroendocrine stress responses; all of these may contribute to myocardial injury.208,209 Controlled reperfusion strategies during CPB, involving prolonged reperfusion with warm-blood cardiople- gia in conjunction with metabolic enhancers, are rarely used in lieu of more routine methods of preservation (eg, asystolic arrest, anterograde or retrograde blood cardioplegia during aortic cross-clamping). Several studies suggest that the mag- nitude of SIRS is greater with on-pump CABG than with Initial studies of preconditioning used mechanical occlusion of arterial inflow followed by reperfusion via aortic cross- clamping immediately on institution of bypass or with coronary artery occlusion proximal to the planned distal anastomosis during off-pump CABG.190,191,214 217 Because of concerns of the potential adverse cerebral effects of aortic manipulation, enthu- siasm for further study of this technique in on-pump CABG patients is limited (Section 5.2.1). 