Effect of the Addition of Adenosine on Myocardial Protection During Cardiopulmonary Bypass: A Double-Blind Randomized Clinical Trial

Myocardial ischemia-reperfusion injury remains a key contributor to postoperative myocardial dysfunction and adverse outcomes in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Despite refinements in cardioplegic solutions and perfusion strategies, biochemical evidence of myocardial injury and transient or persistent ventricular dysfunction remain common, particularly among older patients and those with preexisting ventricular impairment. These observations underscore the ongoing need for adjunctive strategies that enhance myocardial protection during both the ischemic arrest and early reperfusion phases.

Adenosine is an endogenous purine nucleoside with pleiotropic cardioprotective properties, including negative chronotropic and dromotropic effects, coronary vasodilation, attenuation of calcium influx, and modulation of inflammatory and endothelial pathways. Experimental data and small clinical studies suggest that adenosine administration at the onset of ischemia or during early reperfusion may reduce ischemia-reperfusion injury by facilitating rapid electrical arrest, limiting intracellular calcium overload, improving microvascular perfusion, and attenuating inflammatory activation. However, the optimal timing, dosing strategy, and clinical relevance of adenosine administration as an adjunct to modern cardioplegia in routine adult cardiac surgery remain incompletely defined.

This prospective, randomized, double-blind, placebo-controlled, parallel-group trial is designed to evaluate whether a single bolus of adenosine administered immediately after aortic cross-clamping and immediately before infusion of standard del Nido cardioplegia improves myocardial protection in adult patients undergoing elective coronary artery bypass grafting and/or valve surgery with CPB. Following cross-clamp application, patients allocated to the intervention group will receive adenosine at a concentration of 1.2 mmol/L (total dose 24 mg) delivered into the aortic root, while control patients will receive an equivalent volume of sterile water. Thereafter, cardioplegia delivery and all subsequent intraoperative management will proceed according to institutional standards, ensuring that the only protocolized difference between groups is the administration of adenosine or placebo.

Randomization will be performed using permuted blocks to ensure balanced group allocation. Blinding will be maintained for patients, surgeons, anesthesiologists, perfusionists, investigators, outcome assessors, and data analysts throughout the study period. Anesthesia management, CPB strategy, myocardial protection techniques, and postoperative care will follow standardized institutional protocols to minimize confounding.

The extent of myocardial injury will be assessed primarily through serial measurements of high-sensitivity cardiac troponin T obtained preoperatively and at predefined intervals following aortic cross-clamp removal. Hemodynamic support requirements will be quantified using the vasoactive-inotropic score (VIS), providing an integrated assessment of postoperative circulatory support needs. In addition to biochemical and hemodynamic endpoints, myocardial protection will be directly evaluated using transesophageal echocardiography (TEE). Comprehensive TEE examinations will be performed immediately before initiation of CPB and again after successful weaning from CPB, allowing for paired assessment of global and regional ventricular function, wall motion abnormalities, and overall myocardial performance in the immediate reperfusion period.