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.

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.

Three studies were conducted to determine the efficacy of milbemycin oxime in the prevention of Dirofilaria immitis infection in dogs. Dogs were given single or multiple experimental inoculations with infective third-stage D immitis larvae and were treated with milbemycin oxime at a target dosage of 0.5 mg/kg of body weight either once or at monthly intervals at various times after inoculation. The compound was effective in preventing infection when 1 dose was administered 30 or 45 days after inoculation. Significant, but incomplete, protection was achieved when single treatments were administered 60 or 90 days after inoculation. Multiple monthly treatments beginning 60 days after inoculation appeared to provide additive effects that resulted in restoration of complete efficacy.

One hundred four heartworm-free Beagles < 1 year old were studied to determine the efficacy of ivermectin chewable tablets and of 2 other ivermectin tablet formulations against heartworm larvae. At 30 days after SC inoculation of dogs with infective Dirofilaria immitis larvae, all ivermectin formulations were given orally at dosage of 6 microgram/kg of body weight. The ivermectin chewable tablets also were given orally at dosage of 2 and 6 microgram/kg at 30 and 45 days, respectively, after injection of larvae. Replicates of 6 or 8 dogs in each study were formed on the basis of gender and body weight and, within replicates, were randomly allocated to treatment groups. At 30 days after injection of larvae, the additional dogs (in replicates of 8) were assigned to the control group and to the group given ivermectin chewable tablets at dosage of 6 microgram/kg. All dogs were housed individually. Necropsy was performed approximately 5 or 6 months after larvae were administered. In both trials, all control dogs had heartworms at necropsy (University of Illinois-geometric mean, 35.0; Florida-geometric mean, 26.1). In both trials, the ivermectin chewable tablet (6 microgram/kg) and both tablet formulations (6 microgram/kg) given at 30 days after larval injection, and the chewable formulation (6 microgram/kg) given at 45 days after larval injection were 100% effective (P < 0.01) in preventing development of induced infection with D immitis. Of 8 dogs at the University of Illinois that were given ivermectin chewable tablets (2 microgram/kg) at 30 days after larval injection, 6 had heartworms (geometric mean, 2.25; efficacy, 93.6%; P < 0.01) and 5 of 7 dogs treated similarly in Florida had heartworms (geometric mean, 4.4; efficacy, 83.3%; P < 0.05). Drug-related adverse reactions were not observed in either trial.