Effect of pre-cardiac and adult stages of Dirofilaria immitis in pulmonary disease of cats: CBC, bronchial lavage cytology, serology, radiographs, CT images, bronchial reactivity, and histopathology.

A controlled, blind study was conducted to define the initial inflammatory response and lung damage associated with the death of precardiac stages of Dirofilaria immitis in cats as compared to adult heartworm infections and normal cats. Three groups of six cats each were used: UU: uninfected untreated controls; PreS I: infected with 100 D. immitis L3 by subcutaneous injection and treated topically with selamectin 32 and 2 days pre-infection and once monthly for 8 months); IU: infected with 100 D. immitis L3 and left untreated. Peripheral blood, serum, bronchial lavage, and thoracic radiographic images were collected from all cats on Days 0, 70, 110, 168, and 240. CT images were acquired on Days 0, 110, and 240. Cats were euthanized, and necropsies were conducted on Day 240 to determine the presence of heartworms. Bronchial rings were collected for in vitro reactivity. Lung, heart, brain, kidney, and liver tissues were collected for histopathology. Results were compared for changes within each group. Pearson and Spearman correlations were performed for association between histologic, radiographic, serologic, hematologic and bronchoalveolar lavage (BAL) results. Infected cats treated with selamectin did not develop radiographically evident changes throughout the study, were heartworm antibody negative, and were free of adult heartworms and worm fragments at necropsy. Histologic lung scores and CT analysis were not significantly different between PreS I cats and UU controls. Subtle alveolar myofibrosis was noted in isolated areas of several PreS I cats and an eosinophilic BAL cytology was noted on Days 75 and 120. Bronchial ring reactivity was blunted in IU cats but was normal in PreS I and UU cats. The IU cats became antibody positive, and five cats developed adult heartworms. All cats with heartworms were antigen positive at one time point; but one cat was antibody positive, antigen negative, with viable adult females at necropsy. The CT revealed early involvement of all pulmonary arteries and a random pattern of parenchymal disease with severe lesions immediately adjacent to normal areas. Analysis of CT 3D reconstruction and Hounsfield units demonstrated lung disease consistent with restrictive pulmonary fibrosis with an interstitial infiltrate, absence of air trapping, and decrease in total lung volume in Group IU as compared to Groups UU and PreS I. The clinical implications of this study are that cats pretreated with selamectin 1 month before D. immitis L3 infection did not become serologically positive and did not develop pulmonary arterial hypertrophy and myofibrosis.

Effects of intravenous and subcutaneous heartworm homogenate from doxycycline-treated and untreated donor dogs on bronchial reactivity and lung in cats.

A controlled, blind research study was conducted to define the innate response of lungs in specific pathogen free (SPF) cats to intravenous (n=10) or subcutaneous (n=4) administration of homogenate of adult Dirofilaria immitis from donor dogs compared with lung response in control cats (n=6). There was no difference in cats that received heartworm homogenate IV for 18 days from donor dogs treated with doxycycline for 1 month compared with cats given heartworm homogenate from untreated donor dogs. Cats did not develop clinical signs, and no radiographic changes were noted. Cats given SC heartworm homogenate at lower concentration than IV groups did not develop histologic changes. Cats that received IV heartworm homogenate for 18 days developed mild interstitial and peribronchial myofibrocyte proliferation and smooth muscle proliferation of the pulmonary arteries. Bronchial ring contractility in vitro was blunted in the IV homogenate cats to the agonists acetylcholine and 5-hydroxytryptamine. Cats in the SC group had increased sensitivity to histamine at high concentrations but normal contractility and relaxation responses to other agonists. No increase in mast cells was noted in lung tissues of cats given homogenate. In the absence of bronchial wall remodeling, cats given IV homogenate had blunted responses to bronchial constriction, but normal relaxation to nitroprusside and substance P and increased sensitivity to histamine. In the absence adult heartworms, the homogenate of adult heartworms in the circulation of SPF cats induced a direct effect on lung parenchyma and altered bronchial ring reactivity.