THE CELLULAR PATHOPHYSIOLOGY OF PROGRESSION TO HEART-FAILURE

Congestive heart failure is the final common pathway of diverse etiolo gies that result in impaired systolic and diastolic function, deleteri ous activation of neurohumoral pathways, and high morbidity and mortal ity. Many studies published in 1995 significantly added to our underst anding of the pathophysiologies of heart failure at the cellular level . Because a common accompaniment to all forms of low output heart fail ure are hypertrophy and contractile dysfunction of the cardiomyocyte, applications of the techniques of molecular and cell biology to animal models that demonstrate this phenomenon are providing new insights in to the mechanisms responsible for this important clinical problem. In the past year, critical information was derived from animal models tha t mimic human cardiac hypertrophy and failure. Likewise, genetically e ngineered mice in which a gene product of interest is overexpressed or eliminated provided critical information, in particular regarding the roles of phospholamban and beta-adrenergic receptor kinase 1 in media ting the contractile responses of the heart to beta-adrenergic stimula tion. Furthermore, study of human myocardial tissue from patients with end-stage cardiomyopathy continues to provide insight into the divers e etiologies of heart failure. The recent applications of the techniqu es of molecular and cell biology to this clinical problem are likely t o accelerate our understanding of the complex mechanisms responsible f or this syndrome.