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

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 micrograms/ml) or melarsomine dihydrochloride (30 micrograms/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 heartworm-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.

Effect of heartworm infection on in vitro contractile responses of canine pulmonary artery and vein.

OBJECTIVE: To test the effect of heartworm infection on agonist-induced constriction of canine pulmonary artery and vein in vitro. PROCEDURE: Cumulative concentration-response relations to norepinephrine, serotonin, histamine, prostaglandin F2 alpha, and the thromboxane A2 analog U-44069 were determined, using isolated rings of pulmonary artery and vein from control and heartworm-infected dogs. To determine the role of endothelial cells in histamine constriction, some rings were denuded of endothelial cells in both artery and vein. ANIMALS: Noninfected control and heartworm-infected dogs. RESULTS: There was no difference in constriction response to norepinephrine, serotonin, prostaglandin F2 alpha, or U44069 of pulmonary artery or vein from control or heartworm-infected dogs. Histamine-induced constriction of pulmonary artery from heartworm-infected dogs was not different from control values, however, when endothelial cells were removed from control, but not heartworm-infected pulmonary artery, histamine-induced constriction was enhanced. Histamine-induced constriction of pulmonary vein from heartworm-infected dogs was significantly depressed, compared with that of control pulmonary vein. However, removal of endothelial cells in pulmonary vein from heartworm-infected, but not control dogs significantly increased constriction. CONCLUSION: Heartworm infection alters histamine-induced constriction responses of pulmonary artery and vein. These changes may reflect high circulating histamine concentrations in heartworm-infected dogs, compared with that in controls. Increased circulating histamine concentrations in vivo could bring about decreased sensitivity of histamine receptors o decreases in the number of receptors expressed. CLINICAL RELEVANCE: Mast cells and histamine may be important factors in altered endothelium-mediated responses associated with heartworm disease.

Thiacetarsamide depresses relaxation of canine pulmonary artery in vitro.

Little information is available on the primary pharmacological effects of thiacetarsamide on mammalian systems, particularly on blood vessels. The effects of thiacetarsamide on arterial responses was studied in isolated rings from canine pulmonary artery. Vessels were exposed to thiacetarsamide and dose-response relationships were applied to methacholine and nitroglycerin. To rule out non-specific effects of antihelmintics, the effects of two other antifilarial drugs, diethylcarbamazine and ivermectin, were also tested. Thiacetarsamide significantly depressed relaxation of canine pulmonary artery to both methacholine and nitroglycerin, and significantly enhanced constriction to norepinephrine. Neither diethylcarbamazine nor ivermectin altered vascular response. These direct effects of thiacetarsamide on arterial responsiveness may be responsible, in part, for acute pulmonary complications observed in dogs infected with Dirofilaria immitis after adulticide treatment.