Effects of myocardial edema on the development of myocardial interstitial fibrosis

Objective: The mechanism by which chronic myocardial edema causes cardiac d ysfunction is poorly understood. We hypothesized that myocardial edema trig gers cardiac fibrosis development resulting in cardiac dysfunction. Since c ollagen is the most abundant constituent of the interstitial matrix, we exa mined the effects of edema development on cardiac collagen metabolism. Methods:We utilized a chronic pulmonary artery banded rat model that produc es right ventricular hypertrophy with myocardial edema and left ventricular edema without hypertrophy or hyperplasia. Wet to dry ratios (index of edem a), collagen type I and III concentrations, prolyl 4-hydroxylase (P+H) and collagen type I and III mRNA levels, collagenase activity and transforming growth factor-beta were measured in both ventricles. Results: Right and left ventricular wet to dry ratios were significantly el evated from 1 to 28 days after pulmonary artery banding compared to sham ra ts. Right and left ventricular collagen types I and III and P+H mRNA levels increased significantly at 3 days followed by significant increases in rig ht and left ventricular collagen concentration 7 days after pulmonary arter y banding. Right ventricular collagenase activity increased at 3 days while left ventricular collagenase activity decreased 7 days after PA banding. Conclusions: We conclude that myocardial edema preceded the observed increa se in collagen deposition and that edema may have triggered increased colla gen synthesis by fibroblasts, leading to fibrosis development.