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EXPERIMENTAL STUDY

Vascular remodeling during healing after myocardial infarction in the dog model

Effects of reperfusion, amlodipine and enalapril

Bodh I. Jugdutt, MD, FACC^*,*, Vijayan Menon, BSc^*, Dinender Kumar, PhD^* and Halliday Idikio, MD

^* Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
Department of Pathology, University of Alberta, Edmonton, Alberta, Canada

Manuscript received December 19, 2000; revised manuscript received February 11, 2002, accepted February 14, 2002.

^* Reprint requests and correspondence: Dr. Bodh I. Jugdutt, 2C2.43 Walter Mackenzie Health Sciences Centre, Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada T6G 2R7.
bjugdutt{at}ualberta.ca

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 and Acronyms   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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