Depression of Collateral Blood Flow Following Arterial Thrombosis

Abstract

Permanent ligation of the feline aorta at the iliac bifurcation is followed by rapid opening of pre-existing collateral blood vessels. However, if ligation is combined with formation of a clot these protective collateral vessels do not function. This study was undertaken to determine if drugs which alter serotonin (5-HT) function can improve collateral blood flow after arterial thrombosis. Permanent ligations were placed at the iliac bifurcation, circumflex iliac and sixth lumbar arteries in all cats. Control cats (8) were acutely ligated. In all other cats a clot was produced in the aorta by injection of 0.1 ml of thromboplastin. Clotted cats were untreated (8); had blood 5-HT depleted using a single dose of reserpine (0.1 mg/kg i.m.) followed by para-chlorophenylalanine (p-CPA) (100 mg/kg orally) every 3 days (9); or were treated prior to surgery with a 5-HT antagonist cinanserin HCl (4 mg/kg i.v.) (8). Collateral circulation was determined by blood flow measurements and aortograms 3 days after occlusion of the aorta. The hindlimb blood flow of untreated clotted animals was 20% of the acutely ligated control animals 3 days following aortic occlusion. However, hindlimb blood flow was 90% of control in reserpine and p-CPA treated cats and 60% of control in cinanserin HCl treated cats. Blood flow measurements correlated with aortograms. These results suggest: (1) The clinical consequences of arterial thrombosis cannot be entirely attributed to mechanical occlusion of an artery, but may be due to depression of protective collateral blood flow induced by thrombosis, (2) Serotonin is an important factor in this depression of collateral blood flow, and (3) Isolation of the factors responsible for collateral inhibition could permit the development of therapeutic interventions.