Vascular remodeling during healing after myocardial infarction in the dog model: effects of reperfusion, amlodipine and enalapril.
OBJECTIVE
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.
Jugdutt
Bodh I
BI
Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. bjugdutt@ualberta.ca
Menon
Vijayan
V
Kumar
Dinender
D
Idikio
Halliday
H
D017311:Amlodipine / Q000494:pharmacology* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D015415:Biomarkers; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D003094:Collagen / Q000187:drug effects* / Q000378:metabolism; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D004285:Dogs; D004452:Echocardiography; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use; D006909:Hydroxyproline / Q000378:metabolism; D066298:In Vitro Techniques; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D015425:Myocardial Reperfusion / Q000379:methods; D016212:Transforming Growth Factor beta / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D002121:Calcium Channel Blockers; D016212:Transforming Growth Factor beta; D017311:Amlodipine; D004656:Enalapril; D003094:Collagen; D006909:Hydroxyproline