Molecular and Cellular Mechanisms of Cardioplegic Protection in Surgical Myocardial Revascularization

Abstract

Highlights: What are the main findings? Cardioplegia induces active molecular and cellular myocardial protection by regulating calcium handling, mitochondrial function, oxidative stress, and inflammatory pathways during cardiac arrest. Controlled cardioplegic arrest prolongs myocardial ischemic tolerance by suppressing electromechanical activity and reducing metabolic demand. What are the implications of the main findings? Mechanistic insights into cardioplegic protection support refinement of cardioplegia composition, temperature, and delivery strategies in CABG surgery. Optimization of cardioplegic protocols may improve postoperative myocardial recovery and reduce ischemia–reperfusion-related complications. Coronary artery bypass grafting (CABG) remains the gold standard for patients with advanced multivessel coronary artery disease. Optimal myocardial protection versus ischemia during reversible and controlled cardiac arrest is a cornerstone of successful outcomes. Myocardial ischemia represents a state of reduced coronary perfusion with oxygenated blood, insufficient to meet the metabolic demands of the myocardium. Conventional cardioplegic solutions offer controlled and reversible cardiac arrest while actively modulating the molecular and cellular mechanisms that mediate ischemia–reperfusion injury. Cardioplegia dramatically elongates the reversible period of ischemic injury and restricts cardiomyocyte death by shutting down electromechanical activity, lowering metabolic demand, stabilizing ionic homeostasis, protecting mitochondrial integrity, and slowing oxidative stress and inflammatory signaling. During ischemia, cardiomyocytes shift from aerobic to anaerobic metabolism, resulting in adenosine triphosphate (ATP) depletion, loss of ionic homeostasis and calcium overload that activate proteases, phospholipases and membrane damage. Reperfusion restores oxygen supply and prevents irreversible necrosis but paradoxically initiates additional injury in marginally viable myocardium. The reoxygenation phase induces excessive production of reactive oxygen species (ROS), endothelial dysfunction and a strong inflammatory response mediated by neutrophils, platelets and cytokines. Mitochondrial dysfunction and opening of the mitochondrial permeability transition pore (mPTP) further amplify oxidative stress and inflammation, and trigger apoptosis and necroptosis. Understanding these intertwined cellular and molecular mechanisms remains essential for identifying novel therapeutic targets aimed at reducing reperfusion injury and improving myocardial recovery after ischemic events, particularly in coronary surgery.