Evaluation of a prostacyclin analog, iloprost, and a thromboxane A2 receptor antagonist, daltroban, in experimental intimal hyperplasia.
This study evaluated the efficacy of a prostacyclin analog, iloprost, and a thromboxane A2 receptor antagonist, daltroban, as inhibitors of experimental intimal hyperplasia. The vascular injury model used is based on an endothelial injury induced by a brief infusion of air into an isolated segment of the common carotid artery in the rat. Iloprost and daltroban were administered by continuous IV infusion for two weeks. The infusion rates were 0.1 micrograms/kg/min for iloprost and 0.1 mg/kg/hr for daltroban; these dosing rates are associated with significant alterations in eicosanoid-related pharmacologic effects. The animals were sacrificed at two weeks and the carotid arteries fixed in situ for light microscopy. The myointimal thickening was measured as the intima to media area (I/M) ratio. The control animals developed marked intimal thickening, with an I/M ratio of 0.76 +/- 0.12 (mean +/- SEM; N = 7). There was no inhibition of intimal hyperplasia (P greater than 0.05) after either iloprost (I/M ratio: 1.04 +/- 0.13; N = 8) or daltroban (I/M ratio: 0.70 +/- 0.04; N = 6). It is concluded that neither of these two modulators of eicosanoid activity, iloprost and daltroban, inhibit intimal hyperplasia following experimental endothelial injury.
Levitt
M A
MA
Department of Surgery, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA.
Dryjski
M
M
Tluczek
J
J
Bjornsson
T D
TD
D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D020212:Carotid Artery Injuries; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D006965:Hyperplasia; D016285:Iloprost / Q000008:administration & dosage / Q000494:pharmacology*; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D008297:Male; D010648:Phenylacetates / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000502:physiology; D017482:Receptors, Thromboxane; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*
D010648:Phenylacetates; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013928:Thromboxane A2; D016285:Iloprost; C051762:daltroban