Myocardial protection using diadenosine tetraphosphate with pharmacological preconditioning

Background. We have reported a similar cardioprotective effect and mechanism of diadenosine tetraphosphate (AP4A) and ischemic preconditioning in rat hearts. In this study, the applicability of AP4A administration to cardiac surgery was tested by using a canine cardiopulmonary bypass model. Methods. Hearts underwent 60 minutes of cardioplegic arrest (34°C) by a single dose of cardioplegia. Cardioplegia contained either AP4A (40 μmol/L; n = 6) or saline (n = 6). Beagles were weaned from cardiopulmonary bypass 30 minutes after reperfusion, and left ventricular function was evaluated after another 30 minutes by using the cardiac loop analysis system. Results. Administration of AP4A significantly improved the postischemic recovery of cardiac function and reduced the leakage of serum creatine kinase compared with saline. Systemic vascular resistance, mean aortic blood pressure, and the electrocardiographic indices were not significantly altered by AP4A administration. Conclusions. Administration of AP4A was cardioprotective without apparent adverse effects. Because the cardioprotective mechanism may be similar to that of ischemic preconditioning, the addition of AP4A into cardioplegia may be a novel safe method for clinical application of preconditioning cardioprotection.