Aspirin and prednisolone modification of postadulticide pulmonary arterial disease in heartworm-infected dogs: arteriographic study.
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Biomedical subjects
Publications and source records attributed to J W McCall.
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Occult heartworm infection, ie, infection with adult Dirofilaria immitis in the absence of circulating microfilariae, was detected in dogs with prepatent infection, unisexual heartworm infection, drug-induced sterility of adult heartworms, and an immune-mediated infection. In the immune-mediate occult infection, female heartworms contained microfilariae that were antigenically similar to circulating microfilariae but were in a privileged site inasmuch as the intrauterine microfilariae were not coated with circulating antimicrofilarial immunoglobulin G. Transplantation of these female worm into heart-worm-negative dogs resulted in microfilaremia.
Ferrets inoculated subcutaneously with 150--200 infective larvae of Brugia malayi (subperiodic strain) usually developed patent infection during the 3rd month post inoculation. Microfilaremia was transient, and most animals became amicrofilaremic after the 6th month of infection. Ferrets developed a persistent eosinophilia at the time of patency. At necropsy, 5--8 months post infection, adult worms were recovered principally from lymphatic vessels and recovery ranged from 0.5--13% of the inoculated larvae. The inflammatory response of ferrets to microfilariae was characterized by nodules 1--5 mm in diameter in the liver, lungs, spleen, and submucosa of the gastrointestinal tract. The center of these lesions contained a degenerated microfilaria or the cast of a microfilaria embedded in Splendore-Hoeppli substance. The Splendore-Hoeppli substance was surrounded by eosinophils and/or foreign body giant cells. Identical lesions were observed in ferrets experimentally infected with Brugia pahangi. Sera from ferrets infected with B. malayi demonstrated a 3- to 5-fold increase in IgG by the 4th month of infection and these sera produced 2--3 precipitin bands in double gel diffusion assays with an extract of B. malayi microfilarial antigen. Skin tests with B. malayi microfilarial antigen showed that the majority of the infected ferrets had immediate hypersensitivity responses, but none had Arthus or delayed hypersensitivity responses.
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Thoracic radiography of 7 Beagles was performed before heartworm infection, during a 1-year heartworm infection, and for 1 year following appropriate treatment. Cardiac and vascular lesions on thoracic radiographs were compared with angiographic changes. Within 3 months of obstructed blood flow in the caudal lobar arteries, associated increased focal parenchymal densities were detected. These lesions were regarded as characteristic of heartworm disease. Although the most severe arteriographic changes were in the caudal lobar arteries, lobar arterial changes on a lateral view were best detected in the right cranial lobar artery. These arteries increased in size during infection and decreased in size after treatment. It was concluded that the dorsoventral view is best for evaluation of the caudal lobar arteries. The most marked parenchymal lesions were detected during the first 6 months following adulticide treatment. These lesions and the other radiographic alterations then decreased in severity. Persistence of the parenchymal lesions were related to persistence of heartworm infection.
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A formulation of mebendazole was used to determine the optimal dosage level against induced and/or naturally occurring infections of Toxocara cati, Ancylostoma tubaeforme, and Taenia taeniaeformis in cats. Amounts of 11 mg/kg of body weight/day or 22 mg/kg/day were given for 2, 3, or 4 days. Feces were collected for 7 days and were examined for expelled parasites. Cats were necropsied to recover retained parasites. A regimen of 22 mg/kg/day for 3 days was determined to be optimal with efficacies of 100%, 99%, and 50% against T cati, A tubaeforme, and Taenia taeniaeformis, respectively.
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The effect of existing Brugia pahangi infections on the establishment of a subsequent population was studied using jirds which had pre-challenge infections of 4 and 8 months duration. Necropsies were performed 28 days post-challenge inoculation in order to separate challenge and initial worm populations. The results indicate that existing infections of 4 or 8 months duration increase the susceptibility to subsequent homologous infections. The location of challenge population worms in tissue sites examined did not differ significantly between previously infected and uninfected groups. Previous infections did not affect the early growth of challenge population worms as indicated by their length.
Experimental heartworm infection was established in ten dogs. Five had mild infections (8 to 21 worms) and five had severe infections (41 to 96 worms). After larval inoculation, dogs were radiographed each month for 1 year to evaluate cardiopulmonary changes occurring as the heartworm disease developed. Changes seen radiographically during the first year of heartworm infection were related to the magnitude of the worm burden. In mild infections, changes mainly involved the terminal portion of the right caudal lobar pulmonary artery and were minimal. In severe infections, changes mainly involved the entirety of the right caudal lobar pulmonary artery. In some dogs, an increase in size of the right cranial lobar pulmonary artery was seen. Gross changes in the size of the right ventricle and main pulmonary artery did not frequently occur during the first year.
Microscopic examination, particularly by scanning electron microscopy, of the tunica intima of the pulmonary arteries of dogs experimentally infected with a known number of larvae of Dirofilaria immitis revealed various numbers and shapes of intimal thickenings. The number and morphology of these thickenings were related to the degree of infection. At 11 months after infection, dogs having adult worm populations of 8 to 21 worms had scattered discrete intimal lesions, whereas in dogs with 41 to 68 adult worms, the intima was diffusely affected. Discrete lesions took the form of rugous or verrucous protrusions, and in severely affected animals, the intima was extensively covered with anatomosing ridges. Light microscopy and transmission electron microscopy confirmed earlier reports that the thickenings were mainly confined to the tunica intima, that the surface was covered by endothelium, and that many of the cells in the intimal swellings were derived from smooth muscle.
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Pulmonary arterial perfusion was evaluated by perfusion lung scans in ten dogs experimentally infected with heartworm. After larval inoculation, scans were done once a month for 11 months. In 8 of 10 dogs, pulmonary arterial perfusion deficits were detected. The perfusion deficits involved the left cranial, right cranial, and right caudal lung lobes. Generally, there was a poor correlation between vascular abnormalities detected on the survey thoracic radiographs and the perfusion deficits detected by lung scanning. The perfusion deficits did not produce clinical signs or pulmonary infarction.
cis-and trans-1,2-cyclobutanediamines bearing appropriate N-methyl and N-acyl substituents were prepared as analogues of diethylcarbamazine (DEC). None displayed activity against Litomosoides carinii in the gerbil despite substantial structural and sterochemical similarities to the parent drug. The inactivity of these drugs is rationalized in terms of eclipsed pharmacophore configurations and the increased population of unfavorable rotational conformations made possible by the exocyclic position of both pharmacophores. To provide perspective for these conclusions, the literature on DEC analogues is briefly summarized and structure-activity data are discussed in terms of critical structural factors associated with microfilaricidal activity. Generalizations on structural principles governing activity are advanced which encompass test results for the large majority of DEC analogues.
A method is described whereby substantial quantities of infective larvae of Litomosoides carinii can be obtained with relative ease. In each of 2 separate experiments, over 5,000 infective larvae were recovered by soaking the pelts of 5 or 7 Mongolian jirds (Meriones unguiculatus) that had been exposed for 6 or 7 hr to infected tropical rat mites (Ornithonyssus bacoti). The mites had been infected either 7 to 8 or 9 to 10 days earlier by exposure to jirds with patent infections. Ninety-four percent of the total number of infective larvae recovered and migrated out of the pelts within 2 1/2 hr. Jirds inoculated subcutaneously with infective larvae collected in this manner exhibited high mean percent recoveries at necropsy, i.e. 79 and 60 at 5 and 29 days postinoculation, respectively. In addition, the ranges in worm recoveries were narrow.
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infective larvae of Dipetalonema viteae produced infections in Mongolian jirds (Meriones unguiculatus) after storage of infected ticks (Ornithodoros tartakovskyi) in the presence of dimethyl sulfoxide (DMSO, 5%) for 7 or 595 days in liquid nitrogen (-196 C). Infectivity of these larvae was only partially impaired. Microfilaremias of test jirds were generally lower than those of control jirds given nonfrozen larvae; however, the majority of test jirds developed microfilarial counts suitable for use in infecting ticks. In contradistinction, larvae frozen free of the tick failed to retain infectivity. Apparently the tick, in conjunction with DMSO, protects the larvae during freezing and thawing.
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