Abnormal intracellular calcium handling in acute and chronic heart failure: role in systolic and diastolic dysfunction.

Acute or chronic heart failure may be caused by one or more of a variety of abnormalities including changes in excitation-contraction coupling processes (i.e. decreased availability of activator Ca2+ or a change in myofilament Ca2+ responsiveness), a change in myocardial energetics, or a change in extracellular factors, such as connective tissue content. Most of the animal and human models of acute cardiac failure that we have studied in our laboratory (i.e. negative inotropic responses to drugs, hypoxia, acidosis and ischaemia) appear to involve changes in excitation-contraction coupling as the predominant cause of dysfunction. On the other hand, the models of chronic cardiac dysfunction that we have studied (i.e. chronic right ventricular pressure overload in ferrets, hypertrophic cardiomyopathy in Syrian hamsters, hypertensive cardiomyopathy in rats, hypothyroidism in ferrets, end-stage dilated and hypertrophic cardiomyopathy in man) predominantly appear to reflect a combination of changes involving abnormalities in both excitation-contraction coupling and extracellular factors involving myocyte drop-out and increases in connective tissue content. However. In most of these models of acute and chronic heart failure, abnormal intracellular Ca2+ handling appears to be a major cause of both systolic and diastolic dysfunction.