Effect of arsenical drugs on in vitro vascular responses of pulmonary artery from heartworm-infected dogs

Abstract

Abstract Objective To test the effect of thiacetarsamide and melarsomine on vascular responses in isolated rings of pulmonary artery from heartworm-infected dogs. Animals 18 heartworm-infected dogs. Procedure Isolated rings of pulmonary artery from heartworm-infected dogs were randomly treated with thiacetarsamide (30 μg/ml) or melarsomine dihydrochloride (30 μg/ml) for 30 minutes; untreated rings from the same dog served as control. Cumulative dose-response relations to norepinephrine, nitroglycerin, and methacholine were determined. Results Norepinephrine-induced constriction was not altered by treatment with either thiacetarsamide or melarsomine. Treatment with thiacetarsamide depressed nitroglycerin-induced relaxation, compared with values for untreated control rings and rings treated with melarsomine. Treatment of rings with thiacetarsamide or melarsomine depressed methacholine-induced relaxation, compared with values for untreated rings. Histologic examination of rings indicated that treatment with thiacetarsamide or melarsomine resulted in loss of endothelial cells. Conclusion Endothelial cell loss as a direct drug effect may be responsible for impaired endothelium-dependent relaxation in pulmonary artery from heart-worm-infected dogs. Thiacetarsamide appears to have additional effects on vascular smooth muscle, which may explain why fewer complications are observed in dogs treated with melarsomine. Clinical Relevance Melarsomine may be a safer drug than thiacetarsamide and could be a better treatment for dogs with heartworm infection. (Am J Vet Res 1997;58:389–393)