Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, C008

Oral Communications

Exercise training increases myocardial capillary density rather than coronary artery size or function in the healthy and diabetic heart

I. Heinonen1,2, O. Sorop2, R. van Duin2, M. Alkio1, K. Anttila1, D. Merkus2, D. Duncker2

1. University of Turku, Turku, Finland. 2. Erasmus University Medical Center, Rotterdam, Netherlands.

Introduction: Exercise training (EX) is postulated to improve myocardial vascular structure and function, but this idea has not been consistently verified. On the other hand, diabetic metabolic derangement (DMD) is often associated with impaired vascular function. Here we tested the hypothesis that EX enhances myocardial capillary densities, and improves coronary small artery function and produces an increase in epicardial artery diameter thereby opposing DMD-induced coronary structural and functional abnormalities. Methods: DMD was produced in adult male Göttingen miniswine by streptozotocin injections and high fat diet, while control animals (CON) remained on normal pig chow. At 3-month (mo) follow-up, swine were randomized into 2-month exercise training (EX) on a treadmill, 3-times per week or remained untrained (UT), ultimately resulting in 5mo of study and four study groups (N=8 in CON-UT and CON-EX and N=9 in DMD-UT and DMD-EX groups). Results: Robust DMD developed, evidenced by hyperglycemia, hypercholesterolemia and hypertriglyceridemia. Under local nitroglycerin infusion, angiographically assessed mean diameter of left anterior descending, circumflex, or right coronary arteries were not affected by DMD or by EX in either group. Moreover, EX did not improve endothelium-dependent relaxation to bradykinin in in coronary small arteries, whereas it increased bradykinin-induced relaxation in skeletal muscle small arteries. Also, EX did not restore the DMD-induced impairment in endothelium-independent relaxation to nitroprusside of coronary small arteries. Finally, myocardial capillary density was not affected by DMD, but it was increased significantly by EX (capillaries/mm2, mean±SEM: 1358±85 CON-UT, 1510±123 DMD-UT, 2084±258 CON-EX and 1929±209 DMD-EX, p=0.0036). Protein levels of VEGF were not different between the groups, but EX groups showed higher HIF levels (p=0.03), which correlated with myocardial capillary density (r=0.44, p=0.01). Conclusion: Both in health and DMD, short term (2 months) exercise training appears to induce more prominent changes at the capillary level at this stage, as compared to epicardial or small artery function, suggesting that capillary changes precede changes in large and small arteries.

Where applicable, experiments conform with Society ethical requirements