Is adenosine preconditioning truly cardioprotective in coronary artery bypass surgery?

Background. The large number of experimental studies showing that adenosine "turns on" the protein kinase C (PKC)-mediated pathway that accounts for t he cardioprotection conferred by ischemic preconditioning contrasts with th e scarcity of clinical data documenting the preconditioning-like protective effect of adenosine during cardiac operations on humans. Methods. Forty-Eve patients undergoing coronary artery bypass were randomiz ed to receive, after the onset of cardiopulmonary bypass, a 5-minute infusi on of adenosine (140 mu g . kg(-1) . min(-1)) followed by 10 minutes of was hout before cardioplegic arrest (n = 23) or an equivalent period (15 minute s) of prearrest drug-free bypass (controls, n = 22). Outcome measurements i ncluded troponin I release over the first 48 postoperative hours and activi ty of ecto-5'-nucleotidase, an admitted reporter of PKC activation, as asse ssed on right atrial biopsies taken before bypass and at the end of the pre conditioning protocol (or after 15 minutes of bypass in control patients). Results. Aortic cross-clamping times were not different between the two gro ups. Likewise, prebypass values of ecto-5'-nucleotidase (nanomoles/mg prote in per minute) were similar in control (3.14 +/- 1.02) and adenosine-treate d (2.66 +/- 1.08) patients. They subsequently remained unchanged in control patients (3.87 +/- 1.65) whereas they significantly increased after adenos ine preconditioning (4.47 +/- 1.96, p < 0.001 versus base line values). How ever, peak postoperative values of troponin I (mu g/L) were not significant ly different between control (4.8 +/- 2.8) and adenosine-preconditioned pat ients (5.9 +/- 6.6) nor were the areas under the curve. There were no adver se effects related to adenosine. Conclusions. Adenosine, given at a clinically safe dose, can turn on the PK C-mediated signaling pathway involved in preconditioning but this biochemic al event does not translate into reduced cell necrosis after coronary arter y surgery, suggesting that a preconditioning-like protocol may not be the b est suited for exploiting the otherwise well-documented cardioprotective ef fetcs of adenosine. (C) 2000 by The Society of Thoracic Surgeons.