Effects of angiotensin type-I receptor blockade on pericardial fibrosis.
BACKGROUND
Reoperative cardiac surgical procedures are associated with a significantly greater complication rate than that of the initial procedure. Enhanced collagen synthesis can occur due to increased production of angiotensin II (Ang-II) and subsequent activation of Ang AT(1) receptor. Accordingly, the goal of the current study is to test the hypothesis that increased Ang AT(1) receptor activity following pericardiotomy contributes to pericardial thickening and fibrosis.


METHODS
Adult pigs were randomly assigned to three protocols: (1) pericardiotomy with 28-day recovery period (n = 5); (2) pericardiotomy with Ang AT(1) receptor blockade instituted throughout the 28-day recovery period using 60 mg/day valsartan (n = 5); and (3) sham controls (n = 6). Pericardium samples were collected and analyzed by biochemical and histomorphometrical methods. Pericardial fibrosis occurred postpericardiotomy as indicated by increased hydroxyproline content from normal value of 50 +/- 3 microg/mg to 75 +/- 4 microg/mg (P < 0. 05).


RESULTS
Pericardial thickness was increased postpericardiotomy to 2.7 +/- 0.4 mm compared to normal values of 0.4 +/- 0.05 mm (P < 0.05). Ang AT(1) receptor blockade reduced pericardial thickness by 50% and the relative degree of fibrosis was comparable to that of the normal group.


CONCLUSIONS
The results from this pericardial fibrosis animal model suggest that Ang AT(1) receptor activation contributes to the development of pericardial thickening and collagen accumulation in the postoperative period. Thus, Ang AT(1) receptor inhibition may provide a novel therapeutic strategy to prevent pericardial fibrosis that follows cardiac surgical procedures.
Loging
J A
JA
Cardiothoracic Surgery, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
New
R B
RB
Baicu
S C
SC
King
M K
MK
Hendrick
J W
JW
Crawford
F A
FA
de Gasparo
M
M
Spinale
F G
FG
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D003094:Collagen / Q000378:metabolism; D005355:Fibrosis; D006909:Hydroxyproline / Q000032:analysis; D008297:Male; D010496:Pericardium / Q000473:pathology*; D011183:Postoperative Complications / Q000517:prevention & control*; D011945:Receptors, Angiotensin / Q000502:physiology; D012086:Reoperation; D013552:Swine; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000068756:Valsartan; D003094:Collagen; D014633:Valine; D006909:Hydroxyproline