Cardiac function and β-adrenergic receptor responsiveness in the isolated human diabetic myocardium

Abstract

The prevalence of type 2 diabetic mellitus is closely associated with cardiovascular complications. Diabetic patients with preserved ejection fraction (EF) are at high risk of developing heart failure. Until now, little is known about the etiology of the impaired cardiac performance in diabetic patients with preserved EF. Hence this study aimed to address this by investigating the cardiac function of these diabetic patients. We hypothesised that isolated cardiac muscles from diabetic patients will have reduced cardiac performance both at basal conditions, and after β-adrenoceptor (β-AR) stimulation mimicking a physiological stress response.

Using isolated cardiac muscles obtained from right atrial appendages of patients undergoing coronary artery bypass grafting, functional characteristics of non-diabetic (n = 8) and diabetic myocardium (n = 6) were compared. (Samples from patients who had acute coronary artery disease and reduced EF (< 40%) were excluded.) Contractile and relaxation parameters of both cohorts were first determined under basal conditions, then in response to a β-AR agonist (dobutamine, 1x10-7 to 1x10-5 M). In addition, Langendorff-perfused isolated hearts from non-diabetic and diabetic ZDF rats were also implemented to compare cardiac function.

Compared to non-diabetics patients, the developed force (Fdev) of diabetic human cardiac muscles was not different. However, a slower rate of maximum contraction (+dF/dtmax) and relaxation (-dF/dtmax), as well as prolonged relaxation times during the force-length relationship were observed in diabetic muscles (p < 0.05). A significantly longer relaxation time was also observed during force-frequency relationship in the diabetic muscles (p < 0.05). Moreover, diabetic cardiac muscles were less responsive to β-AR stress response, as shown by the reduced increase in Fdev, +dF/dtmax and -dF/dtmax, as well as smaller reduction in relaxation times. These observations were consistent with the results obtained from the isolated rat hearts.

Ultimately, this study showed that diabetic patients with adequate systolic function, as indicated by preserved ejection fraction, suffer from diastolic dysfunctional characteristics and exhibit a reduction in the β-AR.