Disorders of Ca2+ handling and cell-to-cell coupling are implicated in the development of acute heart failure in intact animal hearts: An ultrastructural study

Abstract

bACKgRoUND: It has been previously reported that various acute interventions causing myocardial abnormalities in Ca 2+ handling and defects in intercellular coupling facilitate the occurrence of malignant arrhythmias. objECTIVES: To comprehensively determine the impact of such Ca 2+ -related disorders induced in intact animal hearts on the ultrastructure of the cardiomyocytes before occurrence and during sustaining of severe arrhythmias. METhoDS: Three types of acute experiments known to be accompanied by disturbances in Ca 2+ handling were performed. Langendorff-perfused rat and guinea pig hearts were subjected to K + -deficient perfusion to induce ventricular fibrillation; Langendorff-perfused guinea pig heart underwent burst atrial pacing to induce atrial fibrillation; and open chest pig heart was used for intramyocardial noradrenaline infusion to induce ventricular tachycardia. Tissue samples for electron microscopy examination were obtained during basal conditions, previous occurrence and during sustaining of malignant arrhythmias. RESUlTS:The comparative findings suggest that myocardial heterogeneity of high [Ca 2+ ]i-induced subcellular injury of the cardiomyocytes and their junctions is a common feature that precede occurrence ventricular tachycardia, ventricular fibrillation or atrial fibrillation regardless of the species and atria/ventricular-related differences in Ca 2+ handling and intercellular coupling. The primary changes consisted of nonuniform sarcomere shortening, which most likely reflects cytosolic Ca 2+ oscillations; disturbances in Ca 2+ wave propagation; and Ca 2+ overload. These disturbances were linked with defects in cardiac cell-to-cell coupling that increased the propensity of the heart to malignant arrhythmias. Moreover, Ca 2+ overload led to disruption of myofilaments, jeopardizing contractile function. CoNClUSIoNS:The results provide a novel paradigm linking Ca 2+ -related arrhythmogenesis and contractility disorders that may contribute to acute heart failure.