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Here we describe the acute myocardial effects of an elapid (red spitting cobra, Naja pallida) and a viper (western diamondback rattlesnake, Crotalus atrox) venom using an ex vivo heart model. Our results reveal two different pathophysiological trajectories that influence heart function and morphology. While cobra venom causes a drop in contractile force, rattlesnake venom causes enhanced contractility and frequency that coincides with differences in myocellular morphology. This highlights the medical complexity of snake venom-induced cardiotoxicity.

This thesis reviews current literature and describes experimental studies on the regulation and modification of coronary flow and contractility in isolated rat hearts. In chapter I and introduction is given to the problems of fatty acid toxicity and myocardial function. Coronary flow rate and pump function of the myocardium are mainly determined by the contractile status of vascular smooth muscle cells and cardiac striated muscle cells, respectively. Therefore in chapters II and III morphological and (ultra)structural aspects of both types of cells have been described. In chapters IV and V functional and metabolic aspects of coronary circulation and contractility are illustrated. In both vascular smooth and cardiac striated muscle cells: (i) the intracellular calcium concentration is the main determinant of the contractile status of actomyosin, (ii) contraction takes place after the action potentialinduced calcium-influx through the plasmamembrane and calcium release from intracellular stores (sarcoplasmic reticulum, mitochondria), (iii) relaxation is achieved after reduction of the cytoplasmic calcium level by calcium-pump systems in the plasmamembrane, sarcoplasmic reticulum and mitochondria, (iv) calcium-ions trigger the coupling between the contraction-relaxation cycle with energy metabolism since glycogenolysis and lipolysis are both stimulated by calcium.

This thesis reviews current literature and describes experimental studies on the regulation and modification of coronary flow and contractility in isolated rat hearts. In chapter I and introduction is given to the problems of fatty acid toxicity and myocardial function. Coronary flow rate and pump function of the myocardium are mainly determined by the contractile status of vascular smooth muscle cells and cardiac striated muscle cells, respectively. Therefore in chapters II and III morphological and (ultra)structural aspects of both types of cells have been described. In chapters IV and V functional and metabolic aspects of coronary circulation and contractility are illustrated. In both vascular smooth and cardiac striated muscle cells: (i) the intracellular calcium concentration is the main determinant of the contractile status of actomyosin, (ii) contraction takes place after the action potentialinduced calcium-influx through the plasmamembrane and calcium release from intracellular stores (sarcoplasmic reticulum, mitochondria), (iii) relaxation is achieved after reduction of the cytoplasmic calcium level by calcium-pump systems in the plasmamembrane, sarcoplasmic reticulum and mitochondria, (iv) calcium-ions trigger the coupling between the contraction-relaxation cycle with energy metabolism since glycogenolysis and lipolysis are both stimulated by calcium.