Acute cardiac effects of exercise in the healthy and diseased

Abstract

A growing trend in modern society is a polarization of the population into two distinct health groups. On the one hand, we see a steady increase in people who are health conscious and interested in exercise, while on the other hand, there is a parallel increase in inactivity and lifestyle-related diseases such as type 2 diabetes. In recent years it has been observed that prolonged and exhausting training sessions, such as those seen in marathon and ultramarathon participants, can cause acutely reduced heart function. Interestingly, reports shows that the right heart chamber appears to be more affected by these extreme activities, which is paradoxical given that cardiac research interest is often focused on the left ventricle. This thesis aimed to investigate the cellular and molecular underpinnings behind these previous observations. In the first study, we investigated the response in cardiomyocytes isolated from healthy untrained rats following a simulated marathon, and observed a greater reduction in right ventricle cardiomyocyte function compared to those from the left ventricle. The degree of impaired cardiomyocyte function we found in vitro following the prolonged, exhaustive exercise was comparable with previous research on humans in vivo. Furthermore, we saw that the calcium transient amplitude was considerably reduced during systole, concomitant with reduced emptying of calcium during diastole. In the second study, we carried out an acute bout of interval training in a cohort of diabetic model mice. We used a single session of a training protocol that has been found to reverse diabetic symptoms in this model when the sessions were performed 5 times a week for 16 weeks. Here, we did not find functional changes after a single session of exercise. However, we found significantly elevated expression of genes involved in calcium regulation. This showed that the effect of training was initiated immediately after the first training session. Furthermore, we compared the acute exercise response in human subjects with type 2 diabetes and healthy controls, using a variety of cardiovascular-specific methods. Here we found a very similar response in heart function after acute exercise, as assessed by echocardiography, despite large differences in fitness level. Both groups had reduced diastolic function in the left ventricle, though the diabetic group had somewhat greater reduced function in the right ventricle. The results of this thesis enhance our knowledge of the mechanisms in the heart affected by acute exercise, both in healthy and diseased states. This work demonstrates that aerobic exercise acutely reduces cardiac function and reveals mechanisms that over time may aid recovery and improve function from baseline.