PH_II_L: Pharmaceutical Sciences II. Lectures
Tamás Árpádffy-Lovas1, Leila Topal1, Alexandra Polyák1, Noémi Zombori‑Tóth1, Tibor Magyar1, Bence Pászti1, István Baczkó1, Norbert Jost1,2,3, András Varró1,2, Norbert Nagy1,2, László Virág1,3
1 Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Szeged, Hungary
2 MTA-SZTE Research Group of Cardiovascular Pharmacology, Hungarian Academy of Sciences, Szeged, Hungary
3 Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, Hungary
In the population of professional athletes, sudden cardiac death is more prevalent than in the general public. The changes in cardiac morphology (increased ventricular volume and mass, lower resting heart rate) are considered to be accompanied by changes in autonomic innervation, with a shift towards increased parasympathetic tone. The morphological and in vivo physiological changes of the exercised heart have been previously studied rabbits and dogs. However, cellular-level mechanisms, including changes in autonomic regulation, have been primarily studied in rodents, and have described ambiguous results.
We aimed to examine the electrophysiological changes occurring after the activation of the cardiac β-adrenergic receptors (βARs) in a chronically exercised dog model.
Beagle dogs of both sexes were randomized into untrained and trained groups. The dogs in the trained group underwent a 16-week-long endurance training on a large animal treadmill system. Ventricular muslce preparations (VMs) and Purkinje fibers (PFs) were obtained from the hearts, and were studied using the conventional microelectrode technique. Left ventricular cardiomyocytes were isolated from the hearts of female dogs from both groups. The rapid (IKr) and slow (IKs) delayed rectifier potassium currents, and the L-type calcium current (ICaL) were measured using the whole cell configuration of the patch clamp technique.
Under control conditions, no differences were observed in VM preparations (n = 10/7 trained dogs, and n = 9/6 untrained dogs). Adrenaline (1 μM) elicited moderate, but statistically significant abbreviation of the action potential duration in both groups. The baseline frequency of the PFs of untrained dogs was higher (40.2 ± 6.7 vs 30 ± 3.6 BPM). Adrenaline (1 μM) increased the frequency in both groups (62.1 ± 6.7 and 58.6 ± 5.4 BPM) respectively, with no statistical difference. Adrenaline increased the densities of the IKs, IKr and ICaL currents to a similar extent in both groups.
Our findings suggest that the sensitivity of βARs remains unchanged regardless of training in dogs. Therefore, despite the numerous reports available on rodent models, from a translational standpoint, utilization of large animal models is likely to be more appropriate when studying the effects of exercise on the heart.
University of Szeged Faculty of Medicine, Doctoral School of Multidisciplinary Medicine