Pathophysiological mechanisms in cardiac insufficiency induced by chronic pressure overload--an attempt to analyze specific factors in animal experiment.

Experimental results obtained from studies on Goldblatt rats and spontaneously hypertensive rats as well as theoretical considerations render possible an approximate analysis and evaluation of the relative significance of specific factors at different levels of the heart for the manifestation of cardiac failure under chronic pressure overload. In our experimental models congestive failure was never observed independently of structural dilatation. Thus, as a rule dilatation had already set in before symptoms of heart failure became manifest. However, at moderate dilatation of the ventricle, e.g., at double the end-diastolic volume, the geometrical state per se cannot be the cause of hydropic decompensation whereas extreme dilatation would, in principle, cause cardiac pumping failure even in the absence of any impairment of myocardial "contractility". Generally, a more or less marked impairment of myocardial contractile capability was found, which exceeded the effects due to the altered isoenzyme pattern of myosin. As a rule, a reduction in myocardial "contractility" could be ascertained before a marked degree of dilatation was reached. Diffuse fibrosis impairs the contractile capability of the myocardium and certainly contributes to the manifestation of heart insufficiency; although, as a rule, it should not be the main cause. The adaptive transformation of myocardium towards a slower muscle (isoenzyme pattern of myosin; sarcoplasmatic reticulum) as such does not lead to resting insufficiency, not even under persisting pressure load. Further investigations on processes of excitation-mechanical coupling in the advanced stage of cardiac overload are indicated. The absence of sympathetic support to the heart, e.g., following blockade of beta-adrenergic receptors can, in the advanced stage, elicit a transition from the stage of pre-insufficiency to manifest failure. However, this was only observed when dilatation had already occurred. A network of factors are responsible for cardiac insufficiency due to pressure overloading, whereby the respective significance of each component varies, depending on the experimental model used.