Opposite effects of amlodipine and enalapril on infarct collagen and remodelling during healing after reperfused myocardial infarction.
OBJECTIVE
To compare the effects of the calcium channel blocker amlodipine versus the angiotensin-converting enzyme inhibitor enalapril with or without reperfusion on infarct collagen and remodelling during healing after anterior myocardial infarction (MI).


METHODS
In vivo left ventricular (LV) remodelling and function (by quantitative echocardiography) and hemodynamics were measured over six weeks in dogs that were randomized 24 h after reperfusion (2 h after anterior MI) or no reperfusion to oral amlodipine (5 mg bid, n=6), enalapril (5 mg bid, n=6), placebo (bid, n=6) or sham surgery (n=6) for six weeks. Ex vivo infarct size, infarct collagen (hydroxyproline), collagen volume fraction and LV topography were measured at six weeks.


RESULTS
Compared with placebo controls without reperfusion over six weeks in vivo, enalapril or amlodipine with or without reperfusion produced LV unloading and preserved volumes, shape and function, but enalapril limited LV hypertrophy more than amlodipine. However, compared with no reperfusion, amlodipine preserved infarct wall thickness and shape while enalapril decreased infarct wall thickness and increased the shape index. Ex vivo at six weeks, scar size as a percentage of risk was similar in the MI groups. Importantly, enalapril decreased infarct collagen already lowered by reperfusion, while amlodipine preserved infarct collagen after reperfusion and increased collagen volume fraction in spared myocardium.


CONCLUSIONS
Preservation of infarct collagen limits infarct remodelling during healing after reperfused MI and preserves LV shape. Amlodipine and enalapril exert opposite effects on infarct collagen and remodelling after reperfused MI.
Jugdutt
B I
BI
Walter Mackenzie Health Sciences Centre, University of Alberta, Edmonton, Canada. bjugdutt@cha.ualberta.ca
Musat-Marcu
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D017311:Amlodipine / Q000494:pharmacology*; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003094:Collagen / Q000187:drug effects* / Q000378:metabolism; D004285:Dogs; D004656:Enalapril / Q000494:pharmacology*; D005260:Female; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery*; D015425:Myocardial Reperfusion; D011897:Random Allocation; D020257:Ventricular Remodeling / Q000187:drug effects*; D014945:Wound Healing / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D017311:Amlodipine; D004656:Enalapril; D003094:Collagen