Some studies have reported the adulticidal effect of long-term ivermectin on adult heartworms in dogs; however, there are no detailed reports on the course of the pulmonary artery embolism caused by the dead heartworms during the administration period. In this study, the pulmonary embolism caused over time by the dead worms was observed with computed tomography (CT). The authors subcutaneously inoculated 2 beagles with 100 infective third-stage larvae (L3) of Dirofilaria immitis. The dogs were orally administered a formulation containing 272 mcg of ivermectin and 652 mg of pyrantel pamoate (Panamectin Chewables P272; meiji.co.jp/en/) at monthly intervals, beginning from 10 months after the subcutaneous inoculation. Starting 1 month after the ivermectin administration, peripheral dilatation of the pulmonary artery (suspected to be pulmonary embolism) and pneumonia were observed in the CT images; however, these findings improved over time. Lesions appeared and disappeared in all the lobes during the drug administration period, and clinical signs of pulmonary embolism were not recognized. After 1 month of drug administration, chest radiographic examination revealed radiopaque lesions in only 1 dog. Heartworms were observed on echocardiography in the pulmonary arteries of both dogs from 6 months after subcutaneous inoculation to the end of the study. Microfilariae disappeared from the peripheral blood at 1 month after ivermectin administration in 1 dog and at 7 months in the other. The adult heartworm antigen test yielded positive results starting from 6 months after subcutaneous inoculation in 1 dog and after 7 months in the other dog; these results remained positive until the end of the study. After the initiation of drug administration, the alkaline phosphatase and creatine kinase levels were transiently elevated. At 15 months the dogs were euthanized, and the numbers of adult worms collected at necropsy were 25 in 1 dog and 31 in the other. Histopathologic examination revealed that the peripheral pulmonary artery dilatations detected by CT were the emboli that resulted from the bodies of the dead heartworms. Moreover, vessel recanalization and inflammation along with lymphocyte infiltration around the vessels was observed. These results showed that long-term ivermectin administration has a gradual adulticidal effect on heartworms in dogs but can cause pulmonary embolism. From the results reported here, long-term ivermectin administration can potentially be used for adulticidal treatment in clinical cases where it is difficult to perform surgical extirpation and administer arsenic therapy.

COMMENTARY: These findings support the belief that ivermectin treatment gradually eliminates heartworms in infected dogs. Pulmonary emboli caused by ivermectin administration were not severe, in contrast to many emboli caused by arsenic treatments, and the animals were free of clinical signs throughout the study. In cases where arsenic therapy or surgical removal of worms is not practical, ivermectin may provide a safer treatment alternative. Good candidates for ivermectin treatment do not have severe worm loads and are relatively healthy, as they may need to endure several more years of heartworm infection.

Computed tomography (CT) observation of pulmonary emboli caused by long-term administration of ivermectin in dogs experimentally infected with heartworms. Takahashi A, Yamada K, Kishimoto M, et al. VET PARASITOL 155:242-248, 2008.