Effects of Exercise and Coronary Artery Occlusion on the Magnitude and Nature of Cardiac Hypertrophy

Abstract

1229 The factors that distinguish physiological from pathological cardiac hypertrophy are only partially understood, and may require a non-rodent animal model to fully clarify. The miniature swine model of treadmill running produces physiological cardiac hypertrophy with little or no alteration in biochemical parameters. Gradual occlusion of the left circumflex (LCX) artery limits oxygen and nutrient delivery to the left ventricular free wall (LV) and stimulates angiogenesis. PURPOSE: To compare the singular and combined effects of exercise training (E) and gradual coronary artery occlusion (O) on the magnitude and nature of cardiac hypertrophy in the swine heart. It was hypothesized that E and O would induce the physiological and pathological phenotype, respectively, and that E would attenuate O-induced changes in cardiac gene expression. METHODS: Adult Yucatan miniature swine were randomly assigned to one of the following groups (n = 6–9/group): sedentary control (S), exercised-trained (E), sedentary swine subjected to LCX occlusion (SO), and exercised trained swine with LCX occlusion (EO). The LCX was encircled with an ameroid occluder that provided gradual obstruction of the artery. The exercise entailed a progressive treadmill running program conducted 5 d/wk for 16 weeks. Gene expression was studied in the LV and septum (SEP) by RNA blotting. The data are presented as mean ± SE relative to the value for the S group, arbitrarily set at 1.0. Outliers were excluded and hypotheses were tested with two-factor ANOVA (p<0.05). RESULTS: The heart weight/body weight ratios (g/kg) were S: 4.67 ± 0.17; E: 5.38 ± 0.13; SO: 5.28 ± 0.18; EO: 6.13 ± 0.13. E and O each stimulated cardiac hypertrophy independently and the combined effects were additive (p<0.001). The relative levels of ANF mRNA were S: 1.00 ± 0.08; E: 1.00 ± 0.08; SO: 1.15 ± 0.11; EO: 1.47 ± 0.17. There was a significant effect of O but not E on ANF expression in the LV. There were no group differences in ANF expression in the SEP. Exercise decreased the expression of β-myosin heavy chain in the LV, S: 1.00 ± 0.25; E: 0.75 ± 0.13; SO: 1.00 ± 0.17; EO: 0.44 ± 0.08, but not the SEP. Neither E nor O had any significant effects on the levels of α-myosin heavy chain. Chronic exercise retarded the expression of collagen III mRNA in SEP, S: 1.00 ± 0.16; E: 0.57 ± 0.10; SO: 0.88 ± 0.15; EO: 0.60 ± 0.13; expression of collagen III was unchanged in the LV. CONCLUSIONS: The data demonstrate that exercise training and gradual LCX occlusion each stimulate cardiac hypertrophy independently, and suggest that different mechanisms underlie these adaptive responses. Supported by the AHA Midwest Affiliate, The University of Michigan UROP, and by NIH HL-52490.