Although low plasma taurine concentrations have been associated with congestive cardiomyopathy in cats, the cause of taurine depletion in cats consuming adequate quantities of taurine is unknown. Taurine depletion and cardiovascular disease (cardiomyopathy and thromboembolism) developed unexpectedly in 3 of 6 healthy adult cats during a potassium-depletion study. Plasma taurine concentration decreased significantly (P < 0.05) and rapidly over an 8-week period (from 98 to 36 nmol/ml) in 6 cats that consumed a potassium-deficient diet (0.20% potassium, dry matter basis) that was acidified with 0.8% ammonium chloride, despite containing dietary taurine concentrations (0.12% dry matter basis) in excess of amounts currently recommended. Taurine concentrations were significantly lower in cats fed the acidified diet than in 6 cats fed a potassium-deficient diet that was not acidified (36 nmol/ml vs 75 nmol/ml) after 8 weeks. In addition, plasma taurine concentrations did not decrease over a 6-month period in 8 cats that were fed a potassium-replete diet with acidifier. Plasma taurine concentrations were lowest in 3 cats that died of cardiovascular disease in the group receiving potassium-deficient, acidified diets. These data indicated an association between taurine and potassium balance in cats and suggested that development of taurine depletion and cardiovascular disease may be linked to concurrent potassium depletion.

Ticlopidine hydrochloride was evaluated for its effectiveness in inhibiting platelet aggregation and serotonin release in 5 laboratory Beagles before and after heartworm implantation with 7 adult Dirofilaria immitis, and after embolization with 7 dead heartworms to mimic what happens after heartworm adulticide treatment. Five other laboratory Beagles, similarly implanted and embolized with heartworms, were used as nonmedicated controls. During the heartworm-negative stage, the dosage of ticlopidine that inhibited adenosine diphosphate (ADP)-induced platelet aggregation in 5 dogs by at least 50% after 5 days of treatment was 62 mg/kg of body weight once a day. In the same dogs implanted with 7 adult heartworms 21 days previously, mean (+/- SD) ticlopidine dosage required to obtain similar results was 71 (+/- 13) mg/kg given once daily. During the 21 days after dead heartworms were implanted in heartworm-infected dogs, mean ticlopidine dosage was 108 (+/- 35) mg/kg (range, 62 to 150 mg/kg). Ticlopidine treatment was associated with increased platelet numbers in all 5 dogs during the heartworm-negative stage and in 4 of 5 dogs during the heartworm implantation and heartworm embolization stages. Mean platelet volume tended to decrease as platelet numbers increased. At necropsy, gross and histologic pulmonary lesions were less severe in ticlopidine-treated dogs than in nonmedicated control dogs.

The severity of pulmonary thromboembolism and pulmonary hypertension induced by heartworms dying after administration of 2 adulticides was evaluated. Because melarsomine dihydrochloride (RM340) has been shown to be more effective in killing Dirofilaria immitis (heartworms) than the traditional approved adulticide, thiacetarsamide, an attempt was made to determine whether this new adulticide induced more severe lung disease. Before adulticide treatment, 32 dogs with naturally acquired heartworm infections received physical examinations, semiquantitative antigen concentration tests, CBC, platelet counts, serum biochemistry analyses, arterial blood gas determinations, thoracic radiography, pulmonary arteriography, and pulmonary hemodynamic tests. Eight dogs with a low burden and 9 dogs with a high burden of heartworms were treated with thiacetarsamide, and 7 dogs with a low burden and 8 dogs with a high burden were treated with RM340. Except for the heartworm-burden test, tests were repeated at regular intervals during the first 7 weeks after treatment. None of the dogs coughed or had dyspnea after treatment. Six of 9 dogs with high worm burdens and 4 of 8 dogs with low worm burdens had surviving heartworms after thiacetarsamide treatment, in contrast to only 3 of 15 RM340-treated dogs. Differences between the 2 adulticide treatments were minimal as determined by thoracic radiography, pulmonary hemodynamic tests, clinical laboratory analyses, pulmonary arteriography, or necropsy. The RM340 treatment was a more effective adulticide, but it did not increase the severity of hypertension and thromboembolism.

A semiquantitative heartworm test of antigen concentration was evaluated as a predictor of thromboembolism after adulticide treatment. Seventeen dogs with naturally acquired infections of Dirofilaria immitis (heartworms) were studied before and after thiacetarsamide treatment, using physical examinations, arterial blood gas analyses, thoracic radiography, and pulmonary hemodynamic and arteriographic tests. Eight dogs were considered to have a low burden of heartworms and 9 had a high burden. Dogs with a high worm burden had more severe pulmonary thromboembolism with pulmonary hypertension, dilated pulmonary arteries, flow obstruction of the caudal pulmonary arteries, and parenchymal lesions in the caudal lung lobes. Dogs with a low worm burden had minimal changes. Within each group of dogs, the severity of thromboembolism was less in some dogs in which all heartworms were not killed. Six of the 9 dogs with a high burden of heartworms had surviving heartworms, and 1 of these dogs had 38 live heartworms. Only 4 of the 8 low worm burden had complete heartworm mortality, but only 1 dog had more than 3 surviving heartworms. We concluded that dogs with a high worm burden were more likely to have pulmonary thromboembolism after thiacetarsamide treatment and that dogs with a low worm burden were more likely to have minimal changes. A semiquantitative heartworm test of antigen concentration is recommended as part of the pretreatment evaluation of dogs infected with heartworms.

To determine the drug dose required to inhibit platelet reactivity by at least 50%, 2 drug regimens were evaluated in heartworm-negative, heartworm-infected, and heartworm-infected dogs embolized with dead heartworms. Aspirin, or a combination of aspirin and dipyridamole, were administered to 2 groups of Beagles (n = 5 each) for 5 to 9 days; a third group of 5 Beagles served as nontreated controls. For heartworm-negative dogs, mean (+/- SD) aspirin dosage that inhibited collagen-induced platelet reactivity by at least 50% was 6 (+/- 2) mg/kg of body weight given once daily. The aspirin/dipyridamole combination dosage was 1 mg of each drug/kg given every 12 hours. All dogs (n = 15) were implanted with 7 adult heartworms each and remedicated (or not treated) beginning at 21 days after heartworm implantation. In heartworm-infected dogs, mean aspirin dosage required to inhibit collagen-induced platelet reactivity > 50% was 10 (+/- 6) mg/kg. Mean dosage of aspirin/dipyridamole combination was 1.6 +/- (0.5) mg of each drug/kg given every 12 hours. When platelet reactivity in response to collagen was determined to be inhibited by at least 50% in all medicated dogs, each dog (n = 15) was embolized with 7 dead adult heartworms to mimic heartworm adulticidal treatment. Platelet reactivity was monitored for 21 days after treatment, and drug dose was adjusted to maintain platelet inhibition by at least 50%. In embolized dogs, mean aspirin dosage was 17 (+/- 14) mg/kg given once daily. Mean dosage of the aspirin/dipyridamole combination was 2.8 (+/- 1.3) mg of each drug/kg given every 12 hours. All dogs (n = 15) were euthanatized 21 days after heartworm embolization. Each lung lobe was evaluated for severity of lesions and presence of organized or fibrinous thrombi. Lesion severity in the aspirin- and aspirin/dipyridamole-treated dogs was not significantly different from that in control dogs.

Platelet aggregation and release, platelet number, mean platelet volume, antithrombin-III activity, and fibrinogen concentration were evaluated in heartworm-negative and heartworm-infected dogs at baseline and on days 3, 10, and 21 after treatment with thiacetarsamide. Platelet reactivity was enhanced in a group of dogs naturally infected with Dirofilaria immitis, compared with 2 groups of heartworm-negative dogs, but platelet reactivity was not further enhanced after treatment with thiacetarsamide. A significant decrease in antithrombin-III activity was detected 21 days after treatment. The platelets from a group of laboratory Beagles implanted with 50 adult D immitis displayed enhanced reactivity 6 months after implantation, but by 18 months, platelet reactivity had returned to near, or less than, baseline. Platelet reactivity was enhanced after thiacetarsamide treatment in this group. Thiacetarsamide-associated changes were not observed in platelet number or size; antithrombin-III activity decreased, but the change was not significant. Fibrinogen concentration was increased significantly (P < 0.05) on day 10. Enhanced adenosine diphosphate (ADP)-induced platelet aggregation was observed on days 3, 10, and 21 after treatment in heartworm-negative dogs. This change was not observed in 6 control Beagles not treated with thiacetarsamide. Although antithrombin-III activity was decreased on day 3 and fibrinogen concentration was increased on day 10, paralleling changes observed in the heartworm-infected dogs, the changes were not statistically significant. In this study, thiacetarsamide was procoagulatory in heartworm-negative dogs and may be an important contributing factor to the thromboembolism observed with adulticidal therapy.