Pretreatment of Human Myocardium with Adenosine During Open Heart Surgery

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Abstract
Depressed myocardial performance after cardiac surgery can be contributed to ischemic reperfusion injury (IRI) incurred during and following the cardiopulmonary bypass (CPB). Myocardial preconditioning (PC) achieved by brief ischemia and subsequent reperfusion appears to be a clinically useful method of improved cardiac protection during surgery involving CPB by retarding IRI. Based on animal studies, activation of cardiac adenosine (ADO) receptors prior to the prolonged ischemic period appears to mimic this PC phenomenon. We investigated whether the human myocardial PC can be mimicked with ADO in the setting of the coronary artery bypass graft (CABG). The specific proposed objective of this study was to determine whether ADO infusion just prior to starting the CPB can improve post-CPB myocardial hemodynamics. Patients undergoing elective CABG with poor ventricular function (ejection fraction approximately 30%), and with at least three-vessel disease were selected for this study (n = 7 ADO, and n = 7 control). Our results show that ADO infusion (250-350 micrograms/kg X 10 min) just prior to CPB resulted in an immediately improved postbypass cardiac index (CI) in the OR (CI increase of 41.5% +/- 11.1% for ADO vs 9.7% +/- 6.0% for control, p < 0.05). Forty hours postoperatively in the intensive care unit, ADO patients had improved CI (3.3 +/- 0.2 L/min per m2 for ADO, vs 2.6 +/- 4 L/min per m2 for control, p < 0.05). ADO patients maintained lowered resting heart rate (90 +/- 6 for ADO, vs 108 +/- 4 for control, p < 0.05) 40 hours after surgery. ADO patients also released significantly less CPK during the first 24 hours of the postoperative period. Based on these measurements, ADO pretreated patients had improved ventricular performance postoperatively. It also appears that ADO pretreatment results in lowered postoperative myocardial energy demand and less myocellular injury during CPB. To our knowledge, this is the first study to demonstrate that human myocardium can be hemodynamically improved with ADO pretreatment, and may be protected against IRI incurred during and following the CPB. We believe that a cardiac surgeon may now have the unique opportunity to confer myocardial protection during and after a cardiac surgical procedure.