| Severe coronary stenosis(CS) produces hibernating myocardium(HM) with progressive LV remodeling including left ventricular wall thinning, LV dilataton and myocyte hypertrophy. Previous work from our laboratory demonstrated that progressive gross LV remodeling associated with hibernating myocardium is accompanied by increasing myocyte hypertrophy and interstitial fibrosis. Previous investigators have reported that the presence of abnormal intramural coronary arteries in hypertrophic cardiomyopathy similar to those describe in this report. Such vessels were also present hi hypertensive heart disease, diabetes mellitus, cardiac allograft vasculopathy and Marfan syndrome.To test the hypothesis that progressive LV remodeling is caused by chronic, repetitive myocardial ischemia and that {3-Blockers (|3æ¡ž) attenuate LV remodeling by preventing ischemia in HM in the cellular mechanisms for chronic hibernating myocardium, we studied 24 pigs in 3 groups: Group 1: 9 pigs with 4-week severe proximal LAD coronary stenosis to reduce coronary flow (CF) by 30-40% with LV dysfunction; Group 2: 9 pigs is the same as in Group 1+ Metoprolol (lOOmg x 2 / day) for 4 weeks; Group 3: 6 pigs as control. Coronary flow(CF), LV wall thickening (WT) in hibernating region, LV mass, morphometry of myocardium-which include myocyte density, myocyte width and interstitial fibrosis are tested. Hearts were fixed with 10% formalin . Ecocardiogram was used to measure wall thickening(WT, %), LV mass, and LV volume. The myocyte density of LV was counted and myocytewidth was measured with 400x magnification on trichrome slides by a computerized light microscopy. LV sections were paraffin-embeded and stained with HE, trichrome and elastica van Gieson. Wall thickness of intramyocardial coronary artery (WT) and WT/lumen (WT/L) ratio were measured with a computerized imaging system. Ki-67 antibody (proliferative marker) and a-actin antibody were used to identify cell proliferation and cell type.Result: CF(36? % reduction), WTm were significantly reduced in Group 1 (9 ?5 ) and Group2 (16 ?4) compared to control group (16 ?4) (p<0.01) . End-diastolic wall thickness decreased by 34 ? (p<0.01) accompanied by a decrease in myocyte number across the wall(378 ?10 numbers) and in myocyte density (37.85 ?1.10 numbers/mm), a significant increase in myocyte width (21.90?4.08 um) andinterstitial tissues in 4 weeks hibernating region, and significant increases in LV diastolic volume and in LV mass at 4 weeks. After Metoprolol therapy (group2) , LV volume decreased, LV ejection fraction improved, and myocyte hypertrophy regressed with a decreased LV mass index with a significant change in interstitial tissue. Significant wall thickening of small intramural vessels with reduced luminal diameters was found in GroupA (WTa/Lda=1.15?.27, Lumen%=15.96?.93%) and in group B (WTa/Lda = 0.44?.05, Lumen% = 29.20?.29%) compared to controls (WTa/Lda =0.33?.04, Lumen%=38.48?.13%, both p<0.05) . Metoprolol significantly reduces WTa with increased Lda in GroupB compared to GroupA (both p<0.01) . The myocyte width and interstitial fibrosis were characterized by all kinds of staining. The thickened arterial wall was characterized by intimal hyperplasia(Figure). The increased cells in the vessel wall were stained positively with ki-67 and a-actin antibody, a-actin+EvG staining showed that the a-actin positive smooth muscle cells were located in middle or intimal of vessel wall.Conclusions: We therefore concluded that presence of a large region of hibernating myocardium was associated with gross LV remodeling accompanied by cavity dilatation, wall thinning, eccentric LV hypertrophyand global LV remodeling. The gross LV remodeling was associated with myocyte hypertrophy(increased myocyte width) ,decreased myocyte density and increased myocardial interstitial fibrosis and narrowing of intramural coronary arteries on histology. The gross and pathohistological LV remodeling with hibernating myocardium. Intramyocardial small vessel remodel...
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