Effects of myocardial edema on the development of myocardial interstitial fibrosis.
OBJECTIVE
The mechanism by which chronic myocardial edema causes cardiac dysfunction is poorly understood. We hypothesized that myocardial edema triggers cardiac fibrosis development resulting in cardiac dysfunction. Since collagen is the most abundant constituent of the interstitial matrix, we examined the effects of edema development on cardiac collagen metabolism.


METHODS
We utilized a chronic pulmonary artery banded rat model that produces right ventricular hypertrophy with myocardial edema and left ventricular edema without hypertrophy or hyperplasia. Wet to dry ratios (index of edema), collagen type I and III concentrations, prolyl 4-hydroxylase (P4-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 elevated from 1 to 28 days after pulmonary artery banding compared to sham rats. Right and left ventricular collagen types I and III and P4-H mRNA levels increased significantly at 3 days followed by significant increases in right and left ventricular collagen concentration 7 days after pulmonary artery 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 increase in collagen deposition and that edema may have triggered increased collagen synthesis by fibroblasts. leading to fibrosis development.
Davis
K L
KL
Center for Microvascular and Lymphatic Studies, Department of Anesthesiology, The University of Texas-Houston Medical School, USA.
Laine
G A
GA
Geissler
H J
HJ
Mehlhorn
U
U
Brennan
M
M
Allen
S J
SJ
D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism; D004195:Disease Models, Animal; D004489:Edema, Cardiac / Q000150:complications* / Q000378:metabolism; D004719:Endomyocardial Fibrosis / Q000201:enzymology / Q000209:etiology* / Q000378:metabolism; D006352:Heart Ventricles / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D009929:Organ Size; D011393:Procollagen-Proline Dioxygenase / Q000235:genetics; D011651:Pulmonary Artery / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase; D017364:Collagenases