Physiology and physiopathology in cardiology

Abstract

The project includes two sub-projects aiming to evaluate: 1) the physiological bases of the Frank-Starling mechanism studied in isolated dog hearts; 2) the influence of the infarctectomy on the cardiac performance of rat hearts with largo myocardium infarctions. The first sub-project returns to a line of investigation in which the coordinator has already worked and which will be settled in the isovolumetric blood-perfused dog heart preparation. The preparation is maintained in isovolumetric contractions and the developed pressure (DP) is used as the index of the contractile state. Through the confirmation of four protocols the following will be studied: 1) the influence of the heart rate on the length dependent activation; 2) possible changes in the myofilaments' sensitivity to calcium (Ca++) during the contractile response of the left ventricle (LV) to sudden dilation. The possible interference of the myocardial stretch on the affinity of myofilaments to (Ca++) will be evaluated comparing the ventricular response to sudden dilation before and after the promotion of contractile depression that follows ischemia (stunned myocardium). Stunned is recognized as a maneuver that reduces the myofilaments calcium (Ca++) sensitivity. Defining its influence upon the DP response to ventricular expansion will provide information to judge whether the myofilaments (Ca++) affinity can be accentuated by stretch; 3) the participation of myocardial stretch receptors in the intensification of contraction promoted by myocardial stretching. Myocardial stretch receptors regulate the (Ca++) transit through the sarcollema. The possibility of calcium should be internalized by intervenience of these receptors following ventricular expansion will be evaluated by analyzing the cardiac response to dilation before and after blocking of the stretch receptors with gadolinium chloride; 4) the influence of blocking the sarcoplasmic reticulum with ryanodine in the ventricular response to sudden dilation. The contraction enhancement due to myocardial stretching may be conditioned by a greater liberation of (Ca") by the sarcoplasmic reticulum. This hypothesis will be tested by comparing the DP response to IV dilation before and after administration of ryanodine to the preparation. The second sub-project will analyze the influence, in the cardiac function and in the survival of animals, of the surgical resection of the fibrous scar from large myocardium infarctions provoked in rats. Experimental data and the report of great clinical trials showed that the dilation of the ventricular cavity that occurs after myocardium infarction constitutes an important pathogenic factor in the process of ventricular dysfunction and in the congestive heart failure that occur in the chronic phase of the disease... (AU)