CARDIAC HYPERTROPHY IN THE ABSENCE OF PRESSURE OVERLOAD: AN EXPERIMENTAL AND CLINICAL REPORT

A stimulated altitude of 7000 m was applied in rats chronically exposed to hypoxia in a hypobaric chamber. In these experimental conditions the contralateral ventricle not exposed to pressure overload (that is, the left) showed a significant degree of hypertrophy. The hypoxic stimulus did not affect systemic artery pressure or the heart rate. Chronic adrenergic stimulation performed in the rat treated with low doses of isoprenaline (a direct stimulating adrenergic drug) or with tyramine (primarily a releaser of endogenous catecholamines) induced hypertrophy of the right ventricle, left ventricle, and interventricular septum without modifying the haemodynamic parameters mentioned above. The development of ventricular hypertrophy in the absence of pressure overload is stressed. A role for neurohumoral factors (that is, adrenergic stimulation and catecholamines) in the development of ventricular hypertrophy is suggested.     

Adrenergic activity as a modulating factor in the genesis of myocardial hypertrophy in the rat

Sprague Dawley male rats (200-220 g) were subjected to a long-term treatment with low doses of catecholamines in an attempt to assess the effect of the adrenergic stimulation on ventricular weights, hemodynamics, and hydroxyproline content in the myocardium. Data are presented indicating that both exogenous catecholamines (i.e., isoproterenol) and endogenous catecholamines (released from tyramine) are able to bring about a degree of myocardial hypertrophy associated with a significant increase in the ventricular concentrations of hydroxyproline, without affecting hemodynamic parameters (blood pressures and heart rate). Thus the modulation of sympathetic tone in the genesis of cardiac hypertrophy is demonstrated, and a direct effect of the catecholamines on cardiac cells is postulated which is independent of hemodynamic changes.     

Response of the left ventricular connective tissue to hypoxia

The collagen content (measured as myocardial concentration of hydroxyproline) and dry weight (expressed as ventricle weight to body weight ratio) were determined in the left ventricle of male Sprague-Dawley rats (200--220 g b.wt.) exposed to a simulated altitude of 7,000 m for 18 h a day for 10 days in a hypobaric chamber. Hypoxia resulted in a significant increase (P less than 0.001) in the mass of the left ventricle with a concomitant significantly increased collagen concentration (P less than 0.001). The data indicate that hypoxia effects the synthesis of a significant amount of connective tissue in the left ventricle, which is the ventricle not exposed to pressure load. These results may be related to clinical, hemodynamic, and pathologic observations showing the left ventricular dysfunction in patients with chronic respiratory insufficiency. Since the amount of collagen in the left ventricle might interfere with contractile function, it is suggested that the hypoxia in these patients could affect the left ventricular myocardium via a direct action on the connective metabolism.