Basic mechanisms of myocardial dysfunction: Cellular pathophysiology of heart failure

Many studies published in 1994 significantly added to our understanding of the pathophysiology of heart failure at the cellular and subcellular level. This field continues to advance using different but complementary approaches. One approach is to study human myocardium, thereby providing data that is directly relevant to clinical disease. Another approach is to study mouse myocardium, taking advantage of transgenic technology to alter gene expression and directly study cause-and-effect relationships. Additionally, other animal models of heart failure (eg, pressure overload, volume overload, and paced tachycardia) continue to provide important information. Abnormalities of calcium cycling, myofilament sensitivity to calcium, cross-bridge kinetics, the myocyte cytoskeleton, and energetics have all been observed in animal models or failing human myocardium. The cellular and molecular basis for these abnormalities is now being explored. This understanding is essential for developing novel treatment strategies that may one day include gene therapy.