In clinical studies,
calcium channel blockers have been found to cause adverse cardiovascular reactions after
myocardial infarction; however, such effects appear limited to short-acting agents. Thus, our aim was to evaluate the response to a long-acting
calcium channel blocker,
amlodipine, in terms of both survival and, cardiac and
vascular remodeling after
infarction. One week after permanent
coronary occlusion, rats were randomized to no treatment or daily
amlodipine (5 mg/kg) continued for up to 9 months.
Amlodipine resulted in improved survival at 200 days (65% versus 26%; p < 0.05), but no difference at 9 months. However, rats with large
infarcts died earlier than untreated animals, while those with smaller
infarcts died later or survived for nine months.
Amlodipine produced no difference in
collagen content in non-infarcted tissue or myocyte cross-sectional area versus untreated hearts; however,
scar length was increased. In addition,
amlodipine was associated with
vascular remodeling; muscle:lumen ratio increased in non-infarcted myocardium as did perivascular
fibrosis. Vessels within the
scar had reduced lumen area because of smooth muscle proliferation. We also examined infarcted hearts subjected to one week of intravenous
amlodipine (1 mg/kg) initiated before occlusion and examined three weeks later. In this study,
amlodipine exacerbated muscle proliferation in
infarct vessels and was associated with less
scar collagen. The
vascular remodeling associated with
amlodipine treatment is considered unfavorable and so the adverse survival for rats with large
infarcts was no surprise. However, the prolonged survival associated with smaller
infarcts raises the possibility that these vascular changes, under certain circumstances, are beneficial.