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The function and role of the heart and the contribution of cardiac beta-adrenoceptors in the pathogenesis of circulatory failure in obstructive jaundice were studied in the 3-day bile duct-ligated (BDL) rat using three different techniques to measure cardiac function and beta-adrenoceptor activity, number, and affinity. The techniques were the pithed rat preparation, the isolated working heart preparation, and a competitive radioligand binding assay for beta-adrenoceptors. The results of these experiments were compared with those obtained in 3-day bile duct-manipulated (sham operated; SO) rats. Impaired indexes of basal cardiac contractility were observed in the BDL pithed rats and isolated working hearts. In these two preparations, responsiveness to norepinephrine and the beta-adrenoceptor agonists, isoproterenol and dobutamine, was unaffected by bile duct ligation. The affinity and number of cardiac beta-adrenoceptors in membranes from the hearts of SO and BDL rats were not significantly different from each other. These experiments have established for the first time that the 3-day BDL rat has a cardiac myopathy associated with intact responsiveness to beta-adrenoceptor agonists, a normal unchanged affinity and number of cardiac beta-adrenoceptors.

Using a finite-difference equation to model cardiac mechanics, we simulated the stable action of the left ventricle. This model describes the left ventricular end-diastolic volume as a function of the previous end-diastolic volume and several physiological parameters describing the mechanical properties and hemodynamic loading conditions of the heart. Our theoretical simulations demonstrated that transitions (bifurcations) can occur between different modes of dynamic organization of the isolated working heart as parameters are changed. Different regions in the parameter space are characterized by different stable limit cycle periodicities. Experimental studies carried out in an isolated working rat heart model verified the model predictions. The experimental studies showed that stable periodicities were invoked by changing the parameter values in the direction suggested by the theoretical analysis. We propose in the present work that mechanical periodicities of the heart action are an inherent part of its nonlinear nature. The model predictions and experimental results are compatible with previous experimental data but may contradict several hypotheses suggested to explain the phenomenon of cardiac periodicities.