The origin of cardiomyopathies, a major cause of cardiac disability and death, has been largely unexplained. Pathologic features, common to all cardiomyopathies independent of origin, include ventricular hypertrophy and diffuse scarring with variable amounts of ventricular dilatation. This problem was studied experimentally in 2 models of congestive cardiomyopathy: the hereditary cardiomyopathic Syrian hamster and the hypertensive-diabetic rat. In both the genetic and the acquired disease models, there is focal myocytolytic necrosis followed by healing with focal scars, ventricular wall hypertrophy, ventricular dilatation with congestive heart failure and, ultimately, death. In view of the heterogeneous pathologic features of both diseases, silicone rubber perfusions have been used to study the microcirculation of the heart in these animals; microvascular spasm has been demonstrated early in the disease associated with small areas of myocytolytic necrosis that undergo subsequent fibrosis. Reactive hypertrophy then ensues as a compensatory response to this myocellular necrosis; it is the combination of cell loss and slowly decreasing contractility resulting from the reactive hypertrophy, which culminates in a cardiomyopathy. Administration of verapamil or prazosin to the cardiomyopathic Syrian hamster prevents microvascular spasm and development of cardiomyopathic changes in the myocardium. In view of these and other findings related to the anatomy and hyperreactivity of microcirculation, it is concluded that hypertrophic congestive cardiomyopathies may be caused by focal cell loss due to microvascular spasm and reperfusion injury, with the subsequent development of focal fibrosis and reactive hypertrophy in response to the myocardial necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)