title: Computed tomography (CT) observation of pulmonary emboli caused by long-term administration of ivermectin in dogs experimentally infected with heartworms.
abstract: Some studies have reported the adulticidal effect of long-term ivermectin (IVM) administration on adult heartworms in canines; however, there are no detailed reports on the course of the pulmonary artery embolism caused by the bodies of dead heartworms during the administration period. In this study, the pulmonary embolism caused over time by the dead worms was observed using computed tomography (CT). We subcutaneously inoculated 2 beagles with 100 infective third-stage larvae (L3) of Dirofilaria immitis. The dogs were orally administered a formulation containing 272 microg of IVM and 652 mg of pyrantel pamoate (Panamectin Chewables P272; Meiji Seika, Tokyo, Japan) at monthly intervals, beginning from 10 months after the subcutaneous inoculation. Along with IVM administration, periodic CT examination of the chest was performed. At 15 months after the initiation of IVM administration, the dogs were euthanized, the living heartworms were collected, and histopathological examination was performed. Starting from 1 month after the IVM administration, peripheral dilation of the pulmonary artery (suspected to be pulmonary embolism) and pneumonia were observed in the CT images; however, these findings improved over time. The appearance and disappearance of these lesions were observed in all the lobes during the IVM administration period. During this period, the clinical symptoms of pulmonary embolism were not recognized. After 1 month of IVM administration, chest radiographic examination revealed radiopaque lesions in 1 dog. Only some of the lesions detected by CT could be detected by radiography. Using echocardiography, heartworms were observed in the pulmonary arteries of both dogs from 6 months after subcutaneous inoculation to the end of the study period. Microfilaria disappeared from the peripheral blood at 1 month after IVM administration in 1 dog, and at 7 months in the other dog. 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 period. After the initiation of IVM administration, the ALP and CK levels were transiently elevated. The number of surviving adult worms collected at necropsy was 25 in 1 dog and 31 in the other. Histopathological examination revealed that the peripheral pulmonary artery dilation detected by CT was the embolus 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 revealed that long-term IVM administration has a gradual adulticidal effect on heartworms in canines and embolism. From recovery findings showed pulmonary embolism in the CT image and histopathologic examination, long-term IVM administration can potentially be used for adulticidal treatment in clinical cases where it is difficult to perform surgical extirpation and administer arsenic therapy.
authors.affiliation: Department of Clinical Veterinary Science, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan.
authors.forename: Ayuto
authors.initials: A
authors.lastname: Takahashi
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Yamada
authors.forename: Miori
authors.initials: M
authors.lastname: Kishimoto
authors.forename: Junichiro
authors.initials: J
authors.lastname: Shimizu
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Maeda
mesh_terms: D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D004183:Dirofilaria immitis / Q000302:isolation & purification / Q000502:physiology*; D004184:Dirofilariasis / Q000188:drug therapy*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004452:Echocardiography; D005260:Female; D005369:Filaricides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007559:Ivermectin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000469:parasitology / Q000473:pathology; D011655:Pulmonary Embolism / Q000000981:diagnostic imaging* / Q000469:parasitology* / Q000473:pathology; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000909:Antibodies, Helminth; D005369:Filaricides; D007559:Ivermectin