Broad-spectrum cardioprotection with adenosine

Ischemia-reperfusion results in contractile dysfunction, necrosis, and vasc ular injury. This postischemic injury is mediated in part by superoxide rad ical production, neutrophils, dysfunction to ionic pumps, and edema formati on. Adenosine is an autacoid released tonically by myocytes, endothelium, a nd neutrophils; the release of adenosine from the myocyte compartment into the interstitium is increased during ischemia. The major effects of adenosi ne are mediated by specific receptors identified as A(1), A(2a), A(2b), and A(3). Each receptor subtype contributes to physiological responses that in fluence ischemia-reperfusion injury. Adenosine has potent cardioprotective properties exerted during three major windows of opportunity: pretreatment, ischemia, and reperfusion. The cardioprotective effects exerted during pre treatment and ischemia may involve metabolic changes and hyperpolarization via K-ATP-channel activation, mediated through A(1) receptor mechanisms. Th e cardioprotective mechanisms exerted during reperfusion involve inhibition of neutrophils directly (superoxide anion generation, expression of adhesi on molecules), and by inhibiting activation of the endothelium through A(2) receptor-mediated mechanisms, thereby preventing neutrophil-endothelial ce ll interactions, which initiate the inflammatory-like component of reperfus ion injury. Activation of the newly identified A(3) receptor has been shown to be cardioprotective partially by inhibition of neutrophil adherence to endothelium and by neutrophil-independent mechanisms. These mechanisms of c ardioprotection have been suggested to play major roles in the reduction of infarction and apoptosis after myocardial ischemia, cardioplegic arrest, a nd subsequent reperfusion. Adenosine has been used as an adjunct to both cr ystalloid and blood cardioplegia, but its potential as a cardioprotective a gent has not been fully explored. (C) 1999 by The Society of Thoracic Surge ons.