PATHOPHYSIOLOGY OF CARDIAC DYSFUNCTION IN CONGESTIVE-HEART-FAILURE

Although various factors, such as myocardial infarction, pressure over load and volume overload, result in the development of congestive hear t failure (CHF), the pathogenesis of contractile dysfunction in this s ituation is poorly understood. Loss of cardiac muscle due to myocardia l 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 horm onal 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 di sease, it is possible that development of CHF due to myocardial infarc tion may vary according to the nature of these pathogenetic entities. While a great deal of research work remains in this area of investigat ion, it is becoming evident that cardiac dysfunction is intimately ass ociated 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 CA(2+), it appears that CA(2+) handli ng 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 f or different protein components or the interactions of proteins with p hospholipids. Accordingly, it is proposed that new interventions, whic h could prevent the remodelling of subcellular organelles, be develope d for improving the therapy of CHF.