What is the clinical evidence from this study?

Study design: RCT. Population: Chronic coronary occlusion. Intervention: Exercise training (treadmill) vs. Sedentary (SED). Primary outcome: Vasodilation responses to VEGF165 in coronary arterioles (p=<0.05).

February 9, 2004

Exercise Training Enhances Vasodilation Responses to Vascular Endothelial Growth Factor in Porcine Coronary Arterioles Exposed to Chronic Coronary Occlusion

Q: What are the key findings of this study?

14 weeks of exercise training markedly enhanced VEGF165-induced vasodilation of collateral-dependent coronary arterioles compared to sedentary controls (P<0.05).

Key Result

14 weeks of exercise training markedly enhanced VEGF165-induced vasodilation of collateral-dependent coronary arterioles compared to sedentary controls (P<0.05).

Study Design

Type

RCT

Randomization

Randomized

Structured PICO

Does 14-week exercise training improve VEGF165-induced vasodilation in coronary arterioles exposed to chronic coronary occlusion in a porcine model?

Population

Female Yucatan miniswine with surgically induced chronic coronary occlusion, randomized to 14 weeks of exercise or sedentary protocols.

Intervention

14-week exercise training (treadmill; 5 days/week)

Comparator

14-week sedentary protocol

Outcome

Vasodilation responses to VEGF165 in isolated coronary arterioles assessed by videomicroscopysurrogate

Exercise training enhances VEGF-induced vasodilation in collateral-dependent coronary arterioles following chronic occlusion, an effect mediated by nitric oxide.

Main Result

p-value: p=<0.05

Abstract

BACKGROUND: Chronic coronary occlusion (CCO) impairs endothelial function of distal collateral-dependent microvasculature; however, long-term exercise training (EX) seems to improve endothelial dysfunction. We hypothesized that EX enhances vasodilation responses to vascular endothelial growth factor (VEGF165), mediated via nitric oxide (NO), in arterioles exposed to CCO. METHODS AND RESULTS: The proximal left circumflex coronary artery (LCx) of female Yucatan miniswine was surgically instrumented with an ameroid occluder to induce CCO; 8 weeks after surgery, animals were randomized into 14-week sedentary (SED) or EX (treadmill; 5 d/wk) protocols. Coronary arterioles ( approximately 100 microm in diameter) were isolated from collateral-dependent (LCx) and nonoccluded (left anterior descending; LAD) perfused myocardium of SED and EX animals. Vasodilation was assessed by videomicroscopy and MacLab data acquisition. Responses to VEGF165 were unaffected by EX in nonoccluded LAD arterioles; in contrast, EX markedly enhanced VEGF165-induced vasodilation of collateral-dependent LCx arterioles (P<0.05; EX versus SED). Furthermore, VEGF165-induced vasodilation of EX LCx arterioles exceeded that of EX or SED LAD arterioles (P<0.05). Enhanced vasodilation of EX LCx arterioles was abolished by inhibition of NO synthase and tyrosine kinase activity. Combined inhibition of NO synthase and cyclooxygenase decreased VEGF165-induced vasodilation of all vessels. CONCLUSIONS: EX enhances VEGF165-induced vasodilation in arterioles distal to CCO; EX effects seem to be mediated through increases in NO.