Decreased lumen size after balloon injury despite inhibition of neointimal thickening and antivasospastic treatment.
OBJECTIVE
Both calcium antagonists and angiotensin converting enzyme (ACE) inhibitors are known to diminish the development of intimal thickening after a balloon catheter lesion. It was previously shown that narrowing of carotid artery lumen induced by balloon injury was not influenced by treatment, even though the two ACE inhibitors used inhibited neointimal thickening. The aim of the present study was to include a calcium antagonist as well, in order to investigate whether vasospasm contributes to the persistence of lumen narrowing in ACE inhibitor treated rats after a balloon lesion.


METHODS
Six groups of 10 rats were subject to balloon lesion of the left carotid artery. They received spirapril (10 mg.kg-1 x d-1) or isradipine (30 or 100 mg.kg-1 x d-1) or both, given throughout the study in the food. Controls received no drug. Neointimal thickening was measured histologically two weeks after injury. The cross sectional carotid lumen area was measured in vivo by nuclear magnetic resonance imaging, both before and two weeks after balloon injury, and also postmortem by histological techniques.


RESULTS
Two weeks after injury, the lumen area of the left carotid artery was significantly reduced following balloon injury, as measured by both techniques. Treatment did not modify the stenosis process as assessed by either method for measuring lumen size. Neointimal thickening, however, was inhibited by between 4% (low dose isradipine) and 59% (combined spirapril + high dose isradipine) in the various treatment groups.


CONCLUSIONS
Since calcium antagonist treatment was not able to influence the reduction of lumen size, it is unlikely that the narrowing is due to reversible spasm of the carotid artery in the first two weeks after inducing a balloon lesion. Alternatively, chronic vasospasm of neointimal smooth muscle might not be very sensitive to calcium antagonists.
Cook
N S
NS
Preclinical Research, Sandoz Pharma Ltd., Basel, Switzerland.
Zerwes
H G
HG
Pally
C
C
Rudin
M
M
Hof
R P
RP
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D020212:Carotid Artery Injuries; D017536:Carotid Artery, Common / Q000473:pathology; D016893:Carotid Stenosis / Q000473:pathology / Q000517:prevention & control*; D002404:Catheterization / Q000009:adverse effects*; D004656:Enalapril / Q000031:analogs & derivatives / Q000627:therapeutic use; D017275:Isradipine / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004656:Enalapril; C052555:spirapril; D017275:Isradipine