Marked differences exist in the electrical and mechanical properties of cardiac myocytes across the wall of the ventricle. These differences are thought to exist in part due to the different mechanical conditions presented to subendocardium and epicardium during the normal contraction cycle. Hypertrophy of cardiomyocytes resulting from a myocardial infarction is known to be associated with both mechanical and electrical dysfunction of the whole heart. One possible cause for these properties is the disruption of the normal transmural differences in myocyte characteristics. In this presentation I will describe a series of measurements made on tissue and cells isolated from endocardial and epicardial regions of the left ventricle of a rabbit model of left ventricular dysfunction (LVD). LVD was induced by chronic (8 week) ligation of the large circumflex branch of the left coronary artery. This model of LVD displays many of the characteristics common to the human syndrome of heart failure including marked reduction of ejection fraction, dilated end-diastolic volume and raised end-diastolic pressure (Ng et al. 1998). The isolated ventricle displayed a significantly lower threshold to pacing-induced ventricular fibrillation (Burton & Cobbe, 1998). I will review previous work indicating that the normal transmural differences in action potential duration are markedly changed in the model of LVD. Similarly changes in the intracellular Ca²⁺ signal in the cardiomyocytes isolated from the LVD model were not uniform across the ventricular wall (McIntosh et al. 2000). I will then discuss recent data on the abundance of Ca²⁺ handling proteins in endocardial and epicardial samples and discuss the relationship between these changes and the characteristics of excitation-contraction coupling in cardiomyocytes isolated from endocardial and epicardial cardiomyocytes, studied using fura-2 fluorescence measurements in voltage-clamped cells.

Research work was financially supported by the British Heart Foundation.