Effect of delayed intervention with ACE-inhibitor therapy on myocyte hypertrophy and growth of the cardiac interstitium in the rat model of myocardial infarction.
The effectiveness of angiotensin-converting enzyme (ACE)-inhibitor therapy in attenuating ventricular remodeling when initiated immediately following myocardial damage is clearly established. Less information, however, is available on the impact of late therapy on the remodeling process, especially its influence on the cellular components of these structural changes. The purpose of this study was to examine the effects of converting enzyme inhibitor therapy commenced 28 days following infarction in the rat on changes in cardiac myocyte dimension and the interstitium. At 28 days following infarction, myocyte cell length (153.9+/-7.3 v 131.1+/-5.9 micron, P=0.0002) and cell volume in the free wall of the left ventricle (38. 5+/-5.0 x 10(3) v31.4+/-3.1 x 10(3), P=0.009) had increased compared with sham-operated rats. Similar changes were noted in the septum and right ventricle. Captopril therapy administered between 28 and 56 days attenuated a further increase in cell length noted in an untreated group in the left ventricle (153.5+/-15.3 v 167.3+/-13.7 micron, P=0.02), right ventricle (153.8+/-20.5 v 173.8+/-2.3 micron, P=0.01) and septum (158.0+/-20.2 v 179.1+/-16.6 micron, P=0.004). There was an increase in hydroxyproline content in the right ventricle and a similar trend in the left ventricle in the untreated myocardial infarction groups. These changes were not altered by captopril therapy. In summary, even late therapy with captopril attenuates progressive myocyte remodeling, which may contribute to the ability of ACE-inhibitor therapy to slow progressive chamber enlargement following infarction.
McDonald
K M
KM
Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Chu
C
C
Francis
G S
GS
Carlyle
W
W
Judd
D L
DL
Hauer
K
K
Hartman
M
M
Cohn
J N
JN
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D002216:Captopril / Q000627:therapeutic use; D006332:Cardiomegaly / Q000473:pathology*; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000473:pathology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D003094:Collagen; D002216:Captopril; D012083:Renin