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Microvascular spasm as a cause of cardiomyopathies and the calcium-blocking agent verapamil as potential primary
Insights
Cardiomyopathy development, characterized by heart muscle cell loss and scarring, may stem from microvascular spasms and reperfusion injury. Medications like verapamil and prazosin show promise in preventing these cardiac changes.
Area of Science:
- Cardiology
- Pathology
- Physiology
Background:
- Cardiomyopathies are a leading cause of heart failure and death, with origins often unclear.
- Common pathological features include ventricular hypertrophy, scarring, and dilatation, regardless of the initial cause.
Purpose of the Study:
- To investigate the underlying mechanisms of cardiomyopathies using experimental models.
- To explore the role of cardiac microcirculation in disease development.
Main Methods:
- Utilized two models of congestive cardiomyopathy: hereditary cardiomyopathic Syrian hamsters and hypertensive-diabetic rats.
- Employed silicone rubber perfusions to examine cardiac microcirculation.
- Administered verapamil and prazosin to assess their effects on disease progression.
Main Results:
- Identified focal myocytolytic necrosis followed by fibrosis and reactive hypertrophy in both disease models.
- Demonstrated early microvascular spasm associated with myocytolytic necrosis.
- Observed that verapamil and prazosin prevented microvascular spasm and cardiomyopathic changes.
Conclusions:
- Concluded that hypertrophic congestive cardiomyopathies may result from focal cell loss due to microvascular spasm and reperfusion injury.
- Reactive hypertrophy following myocardial necrosis contributes to the progression of cardiomyopathy.
- Microvascular dysfunction is a key factor in the pathogenesis of these cardiac conditions.
Abstract:
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)