Suppression of intimal hyperplasia in a rabbit model of arterial balloon injury by enalaprilat but not dimethyl sulfoxide.
Intimal hyperplasia appears to result from the deposition of collagen and matrix by medial myofibroblasts, which are stimulated in response to vascular injury. We hypothesized that pharmacologic inhibitors of fibroblast proliferation would suppress the development of intimal hyperplasia. We evaluated the effect of two agents known to inhibit fibroblast proliferation in vitro: enalaprilat, an angiotensin-converting enzyme (ACE) inhibitor, and dimethyl sulfoxide (DMSO), an organic solvent. Thirty-five New Zealand white rabbits underwent standardized balloon catheter injury of the left common carotid artery. Experimental groups received daily intramuscular injections of the following: group I (n = 15), saline solution; group II (n = 10), 0.07 mg/kg enalaprilat; and group III (n = 10), 2 ml/kg of a 25% by weight DMSO solution. Injections were started 1 day prior to injury and continued 5 days a week for 8 weeks. Carotid arteries were perfusion-fixed at 12 weeks and cross-sectioned for measurement by planimetry. Intimal hyperplasia was measured as the ratio of the absolute area of intimal hyperplasia to the normalized area enclosed by the internal elastic lamina (IH/IEL) and was expressed as a percent. Mean values for IH/IEL were as follows: group I (control), 20.6 +/- 2.3%; group II (enalaprilat), 9.5 +/- 0.7%; and group III (DMSO), 17.6 +/- 2.6%. Enalaprilat-treated animals demonstrated a statistically significant suppression of intimal hyperplasia compared with controls (p < 0.01, ANOVA, Student's t test), whereas the DMSO-treated group did not. We conclude that enalaprilat is effective in suppressing the development of intimal hyperplasia in this model of arterial injury.(ABSTRACT TRUNCATED AT 250 WORDS)
Law
M M
MM
Section of Vascular Surgery, UCLA School of Medicine 90024.
Colburn
M D
MD
Hajjar
G E
GE
Gelabert
H A
HA
Quiñones-Baldrich
W J
WJ
Moore
W S
WS
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D020212:Carotid Artery Injuries; D017536:Carotid Artery, Common / Q000187:drug effects / Q000473:pathology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015773:Enalaprilat / Q000494:pharmacology / Q000627:therapeutic use*; D006965:Hyperplasia / Q000517:prevention & control; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*
D015773:Enalaprilat; D004121:Dimethyl Sulfoxide