Experimental study
Vascular remodeling during healing after myocardial infarction in the dog model: Effects of reperfusion, amlodipine and enalapril

https://doi.org/10.1016/S0735-1097(02)01805-3Get rights and content
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Abstract

Objectives

We sought to determine whether reperfusion and the calcium channel blocker amlodipine or the angiotensin-converting enzyme inhibitor enalapril, during healing over six weeks after myocardial infarction (MI), limit structural vascular remodeling in the noninfarct zone (NIZ).

Background

The effect of reperfusion and amlodipine or enalapril on structural vascular remodeling during healing of MI has not been determined.

Methods

We randomly assigned 54 dogs to reperfused or nonreperfused MI, followed by twice-daily doses of oral placebo, amlodipine (5 mg) or enalapril (5 mg) for six weeks and three days off treatment, or to three matching sham groups. We measured in vivo hemodynamic data and left ventricular (LV) function and remodeling (by echocardiography) over the six weeks, as well as ex vivo structural vascular, ventricular and collagen remodeling in the hearts after six weeks.

Results

Compared with placebo and sham groups, both amlodipine and enalapril with or without reperfusion produced LV unloading and limited structural LV remodeling and dysfunction over six weeks in vivo, and also decreased the NIZ resistance vessel media/lumen area ratio at six weeks ex vivo. In addition, amlodipine, but not enalapril, preserved infarct scar collagen and increased the border zone collagen volume fraction and perivascular fibrosis, as well as NIZ resistance vessel media thickness. Enalapril, but not amlodipine, decreased transforming growth factor-beta in the border zone and NIZ.

Conclusions

The results indicate that therapy with amlodipine and enalapril during healing after reperfused MI limits structural vascular remodeling in the NIZ, probably by different mechanisms.

Abbreviations

ACE
angiotensin-converting enzyme
CVF
collagen volume fraction
IZ
infarct zone
LV
left ventricular
MI
myocardial infarction
NIZ
noninfarct zone
PVF
perivascular fibrosis
TGF
transforming growth factor

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The study was supported in part by a grant from the Medical Research Council of Canada, Ottawa, Ontario.