Pathophysiology of cardiac dysfunction in congestive heart failure.

Although various factors, such as myocardial infarction, pressure overload and volume overload, result in the development of congestive heart failure (CHF), the pathogenesis of contractile dysfunction in this situation is poorly understood. Loss of cardiac muscle due to myocardial infarction appears to activate several humoral and hormonal pathways, including the renin-angiotensin and sympathetic systems which serve as adaptive mechanisms to maintain cardiovascular performance at early stages of failure. However, under chronic conditions, an altered hormonal profile produces deleterious effects and permits transition from the compensated heart to the failing heart. Since several risk factors--such as hypertension, hypercholesteremia, stress, diabetes, smoking, ageing, obesity and lack of exercise--precipitate ischemic heart disease, it is possible that development of CHF due to myocardial infarction may vary according to the nature of these pathogenetic entities. While a great deal of research work remains in this area of investigation, it is becoming evident that cardiac dysfunction is intimately associated with calcium handling abnormalities of cardiac cells. In view of the role of sarcolemma, sarcoplasmic reticulum and mitochondria in regulating the intracellular concentration of Ca2+ and the importance of myofibrillar interaction with Ca2+, it appears that Ca2+ handling and Ca2+ interaction abnormalities in the failing heart are due to remodelling of different subcellular organelles. Such a remodelling of the subcellular organelles may be due to changes in gene expression for different protein components or the interactions of proteins with phospholipids. Accordingly, it is proposed that new interventions, which could prevent the remodelling of subcellular organelles, be developed for improving the therapy of CHF.