Abstract 10315: The Role of Perivascular Fibrosis in Non-infarcted Myocardium in Congestive Heart Failure in Rats.
This study attempts to explore the role of perivascular fibrosis in remote myocardium in development of congestive heart failure (CHF).
Methods: Eighty-seven Sprague Dawley male rats (200g) were used. Ascending aorta was banded (Ab) to induce hypertrophy. Two months after Ab, left anterior descending (LAD) coronary artery was ligated for 30 minutes and reperfused to induce I/R injury. One month after Ab+I/R, aortic banding suture was released (DeAb) for another month to observe hypertrophic regression. Ab 4 months, Ab+DeAb, I/R 24 hours, I/R 2 months and LAD ligation 2 months (MI-2m) were used as parallel objects. Echocardiography and hemodynamic analysis were performed to evaluate changes of cardiac function. Myocardial infarction (MI) size was assessed by TTC staining and direct digital imaging. Collagen fibers in the hearts were stained by Masson's Trichrome.
Results: LV hypertrophy and increasing fibrosis were observed in Ab-4m group, but heart function was not seriously decreased (Fraction of Shortening (FS) = 68 ± 3%;, SEM, n=10, p>0.05 vs sham control FS = 74 ± 3%;, n=13). Aortic deconstriction induced regression of LV hypertrophy and fibrosis (n=9). I/R 24 hours (n=12) and I/R 2 months (n=7) induced moderate MI (14.6 ± 1.5%; of LV) with mild impairment of LV function (FS = 48 ± 3%;). LAD ligation for 2 months induced large MI (19 ± 1%; of LV) and significant heart dysfunction (FS = 34 ± 3%;, n=11, p<0.01 vs control). Fibrosis was obvious in ischemic border and infarct area, not in remote myocardium in I/R-2m and MI-2m rats. Aortic banding for 2 months followed by I/R 2 months (Ab+I/R) resulted moderate MI (15.2 ± 2%;) with low cardiac function (FS = 39 ± 3%;, n=18, p<0.01 vs control). DeAb after Ab+I/R could not restore the depressed heart function (FS = 41 ± 2%;, n=10). Increase of perivascular fibrosis in non-infarcted myocardium in Ab+I/R (fiber area/vessel diameter (F/V) = 7.8 μm2/μm) and Ab+I/R+DeAb (F/V = 4.9 μm2/μm, p<0.01 vs control of 0.98 μm2/μm) groups was associated with decrease of heart function. Fibrillate neointima was observed in coronary vessels in some Ab+I/R+DeAb hearts.
Conclusions: Myocardial I/R injury could significantly accelerate hypertrophy to progress CHF. Fibrosis in remote myocardium plays a very important role in development of CHF in rats.
- © 2010 by American Heart Association, Inc.