Effect of angiotensin-converting enzyme inhibition on infarct collagen deposition and remodelling during healing after transmural canine myocardial infarction.
BACKGROUND
Angiotensin-converting enzyme (ACE) inhibition for six weeks after myocardial infarction (MI) lowers the collagen content of infarct scars in dogs. However, temporal changes in collagen content of the infarct zone (IZ) with ACE inhibition during healing over six weeks after MI and their possible relation to IZ remodelling have not been determined.


METHODS
IZ collagen (hydroxyproline) was measured over six to seven weeks in dogs treated with captopril (50 mg bid), enalapril (2.5 mg bid) or placebo, beginning on the second day following transmural anterior MI (or sham). In vivo changes in IZ and global left ventricular (LV) remodelling, mass and function (echocardiograms) and hemodynamics among six-week survivors were also measured.


RESULTS
Compared with placebo, both inhibitors decreased IZ collagen (P < 0.001) over the seven weeks. Among the six-week survivors, both inhibitors lowered IZ collagen (P < or = 0.001) and increased the collagen type I:III ratio. However, preload was lower, increase in diastolic volume and mass were less and systolic function improved. Although the doses of captopril (but no enalapril) decreased afterload, inhibition of IZ collagen was less, IZ bulging and global LV dilation were less and systolic function was better with captopril than with enalapril. In all three MI groups, deaths over the seven weeks correlated with greater infarct size, LV volume and dysfunction and lower IZ collagen.


CONCLUSIONS
ACE inhibition suppresses the temporal increase in IZ collagen and attenuates IZ expansion, thinning and bulging, and LV enlargement and aneurysm formation during healing after MI.
Jugdutt
B I
BI
Department of Medicine, University of Alberta, Edmonton. jugdutt@tachy.uah.ualberta.ca
Lucas
A
A
Khan
M I
MI
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use*; D003094:Collagen / Q000032:analysis / Q000187:drug effects*; D004285:Dogs; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D006352:Heart Ventricles / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology; D006909:Hydroxyproline / Q000032:analysis; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D014463:Ultrasonography
D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril; D003094:Collagen; D002216:Captopril; D006909:Hydroxyproline