Multilevel determinants of ischemic cardiac injury: cellular stress responses, mitochondrial insufficiency, and endothelial dysfunction

Background. Impaired blood supply to the heart leads to profound metabolic, cellular, and microvascular changes that determine the extent of acute injury and the subsequent development of heart failure. Understanding the coordinated action of energy, ionic, mitochondrial, and inflammatory mechanisms is essential for developing modern approaches to the treatment and prevention of complications after acute cardiac ischemia. Purpose – to systematize and summarize current data on the key cellular, molecular, mitochondrial, microcirculatory, and endothelial mechanisms of ischemic and ischemia- reperfusion myocardial injury. Materials and Methods. A literature search was conducted in international scientific databases containing clinical and experimental data on the pathophysiology of cardiac injury. The first stage used thematic keywords. The second stage selected publications based on abstract analysis. The third stage conducted a full-text study and content analysis of sources that covered the cellular, metabolic, and microvascular mechanisms of acute ischemia. Results. Ischemia causes a rapid restructuring of energy metabolism with the accumulation of incomplete oxidation products, the development of acid-base shifts and a violation of the ionic balance. There is a progressive accumulation of calcium, a decrease in the activity of membrane pumps and a loss of structural integrity of the cell. Mitochondria in conditions of oxygen deficiency and restoration of blood flow become a source of excessive oxygen radicals, which trigger the opening of the permeability pore, energy collapse and cell death. Microcirculation disorders and endothelial dysfunction limit the effectiveness of blood flow restoration. The combination of these mechanisms determines the extent of damage, the rate of recovery and the scale of cardiac remodeling. Conclusions. Ischemic and reperfusion injury is the result of an interaction of metabolic, ionic, mitochondrial, and microvascular changes. Identification of their key nodes creates the basis for the development of new methods of targeted therapy.