Abstract 9579: Inhibition of Adverse Myocardial Remodeling and Improvement of Cardiac Function with Postconditioning: Comparison with Preconditioning
We have reported that postconditioning (Postcon) reduces infarct size and preserves cardiac function during extended reperfusion. This study tested the hypothesis that modulation of adverse cardiac remodeling with Postcon is associated with enhancement of angiogenesis and prevention of fibrosis by recruiting host myofibroblasts. Fifty-eight rats were subjected to 45 min ischemia followed by 7 and 42 d reperfusion, respectively. Four cycles of 10/10 s Postcon or two cycles of 5/5 min preconditioning (Precon) were applied at the onset of reperfusion or before ischemia, respectively. At 7 d reperfusion, expression of collagen I and III (Western blot) was significantly down-regulated (85±8* and 89±6* vs. 128±10 Abr. u), and MMP2/TIMP4 ratio (Zymography) was reduced (0.9±0.2* and 1.0±0.6* vs. 4.1±0.8) in the Postcon and Precon groups relative to the Control. The population of myofibroblasts (immunohistological staining) within the infarct area increased significantly relative to the Control (78±9* and 69±10* vs. 45±3//HPF) in these two groups, consistent with significantly enhanced immunoreactivity of VEGF. Along with these changes, angiogenesis was significantly enhanced relative to the Control, evidenced by increased number of α-smooth muscle actin-positive vessels (38±4*, 31±8* vs. 12±3/HPF) and vWF-positive vessels (45±4*, 41±7* vs. 22±5/HPF), respectively. At 42 d reperfusion, histological examination with Masson Trichome staining revealed that the extension of fibrotic zone was markedly reduced with increased mass of viable myocardium in the Postcon and Precon groups. Furthermore, echocardiography showed improvements in end-systolic volume (0.5±0.1*, 0.4±0.2* vs. 0.8±0.3 ml), fractional shortening (29±5*, 27±7* vs. 22±4%) and ejection fraction (56±9*, 50±6* vs. 39±7%) in the Postcon and Precon groups compared with the Control. The wall thickness of the infarct middle anterior septum in the Postcon and Precon was significantly greater than that in the Control (1.7±0.01*, 1.6±0.02* vs. 1.1±0.01 mm). We conclude that Postcon and Precon inhibit adverse myocardial remodeling and preserve cardiac function, potentially mediated by proliferated myofibroblasts and enhanced angiogenesis. * P<0.05 Postcon and Precon vs. Control.
- © 2011 by American Heart Association, Inc.