Atrial myocyte structure, function and calcium handling in cardiac disease: Effects of maximal oxygen uptake

Abstract

Atrial function, through its refilling of the ventricles, plays an important role in cardiac performance. The atrial contribution is particularly important during periods of high heart rates, such as during exercise or stress. A chronic increase in workload on the heart may lead to pathological dilatation of the atria and impaired atrial contractility. However, the cellular and molecular mechanisms behind these alterations are incompletely understood. The Calcium ion (Ca2+) is considered as one of the most important ions in the process of excitation-contraction coupling. We used two different rat models to study atrial myocytes of hearts with reduced global cardiac function; rats selected for low inborn aerobic capacity with a high-risk cardiovascular profile and rats with post myocardial infarction heart failure. In addition, we studied the effect of exercise training on atrial myocyte function and Ca2+ handling in the rat model of post-infarction heart failure. Contractile dysfunction was associated with impaired Ca2+ handling in both rat models, although it was less pronounced in low aerobic capacity rats. We found that high intensity training partly reversed atrial myocyte function and mishandling of Ca2+ in heart failure rats.

Despite increasing evidence that alterations in atrial myocyte structure and Ca2+ handling constitute key elements in the underlying pathophysiology of atrial fibrillation, studies on myocytes from human atria are limited. We determine, for the first time, the occurrence of surface membrane invaginations (T-tubules) and the localization and pattern of proteins important for Ca2+ regulation in both left and right atria of patients with and without atrial fibrillation. We observed a mixed population of cells in left and right atria of both sinus rhythm and AF patients, where some cells had clear T-tubule like structures, while others were totally devoid of T-tubules.

Taken together, this thesis improves our knowledge about structure, function and Ca2+ handling in cardiac disease. In addition, we identify potential targets for improving atrial function by exercise training.