Participation of the Na⁺-H⁺ Exchange Pathway in Cardiac Pathology

Abstract

Since the pioneering work of Jennings and colleagues (1), the involvement of calcium in myocardial damage and necrosis during pathological conditions is firmly established. However, the role of other ions besides calcium in cardiac pathology is not as well recognized today. Increasing evidence supports a role for sodium in cardiac pathologies as diverse as ischemia/reperfusion (2–6), hypoxia/reoxygenation (7,8), glycosidic toxification (9), the calcium paradox (10,11) and various cardiomyopathies (12–14). In the majority of these disease states, the aberrant sodium homeostasis in the myocardium is not a direct cause of cellular necrosis. Calcium remains as a central necrotic factor in cardiac disease. However, this does not lessen the significance of the change in sodium regulation because this alteration in sodium homeostasis appears to be crucial in triggering the intracellular calcium overload which ultimately leads to cell death. Indeed, it has been suggested that normalization of myocardial sodium levels in the heart during specific noxious challenges can protect the heart by preventing alterations in calcium homeostasis (2–6). Thus, sodium too, appears to have a crucial role in myocardial pathophysiology.