Improvement in pulmonary arterial lesions after heartworm removal using flexible alligator forceps

Improvement of pulmonary arterial lesions after heartworm removal using flexible alligator forceps was investigated by measuring pulmonary arterial pressure (PAP), and by angiographic and histopathological examinations in 11 dogs. PAP obtained immediately after worm removal corresponded well with angiographic abnormalities. In 2 dogs, high PAP immediately after worm removal fell gradually by 12 weeks, and obstructions on angiogram were resolved at 4 to 12 weeks. In 4 dogs, slightly high PAP fell to the normal range at 4 weeks, and angiographic abnormalities were considerably reduced at 4 to 12 weeks. In 5 dogs, PAP returned to normal range immediately after worm removal, and angiographic changes almost disappeared at 4 to 8 weeks. On biopsy immediately after worm removal, samples of the main pulmonary arteries showed severe intimal proliferations with villous or papillary protrusion into the lumen. Autopsy at 12 to 20 weeks indicated that the intimal protrusions were remarkably reduced as compared with the biopsy samples in all cases. However, villous intimal protrusions were seen in the caudal lobar arteries in cases with remaining alive worms. New vessels seemed to develop into thromboemboli with time. From these findings, it is clear that the pulmonary arterial lesions improved after heartworm removal, and the clinical signs disappeared following the improvement in hemodynamics. Aspirin therapy (5 mg/kg/day) for 4 weeks after worm removal in 5 dogs did not improve the intimal lesions as compared to 3 control dogs.     

COMPUTED TOMOGRAPHIC CHANGES ASSOCIATED WITH THE PREPATENT AND EARLY PATENT PHASE OF DIROFILARIASIS IN AN EXPERIMENTALLY INFECTED DOG

Evolution of pulmonary arterial and parenchymal changes as assessed with computed tomography (CT) is described in a dog experimentally infected with Dirofilaria immitis. The dog was imaged 125, 168, 216, and 402 days after infection. Initial changes during the prepatent phase of infection included enlargement of the peripheral caudal lobar pulmonary arteries and intermittent periarterial interstitial infiltrates. The changes were progressive, involving additional arteries over time, but remained mild. With the presence of adult filariae a filling defect was observed in the caudal lobar pulmonary artery using CT angiography. Recognizing thoracic CT findings associated with the prepatent phase of canine heartworm infection may be important in endemic areas.     

RADIOGRAPHIC AND ANGIOGRAPHIC EVALUATIONS OF FERRETS EXPERIMENTALLY INFECTED WITH DIROFILARIA IMMITIS

Five ferrets of each sex were each inoculated with 15 third-stage infective larvae of Dirofilaria immitis to study radiographic and angiographic changes in the cardiopulmonary system following heartworm infection; 5 additional ferrets of each sex served as noninfected controls. Prior to inoculation and every 8 weeks thereafter until 40 weeks, the infected and noninfected ferrets were radiographed; angiographic examinations were done prior to necropsy. At necropsy, the worms in the heart, lungs, and associated vessels were counted, and lung histosections were prepared and examined for changes. Radiographic changes were seen in the right side of the heart and associated vessels of infected ferrets as compared with the noninfected ferrets, but changes were less prominent than those seen in heartworm-infected dogs and cats. The changes were primarily an increase in the size of the right side of the heart, especially the right atrium. Radiographically, no changes could be visualized in the pulmonary vascular system. Worms in the enlarged cranial vena cava, azygous vein, and left caudal lobar pulmonary artery of infected animals were delineated by angiography. Histologically, no changes were seen in the pulmonary vascular tissues.     

Relationship between pulmonary arterial pressure and pulmonary thromboembolism associated with dead worms in canine heartworm disease.

To examine effects of thromboemboli due to dead worms on pulmonary arterial pressure (PAP), 20 to 50 dead heartworms were inserted into the pulmonary arteries of 4 heartworm uninfected dogs (uninfected group) and 11 dogs infected with heartworms (infected group). In the uninfected group, the mean PAP rose 1 week after worm insertion (10.9 to 166. mmHg), but it recovered by the 4th week. Clinical signs, hemodynamics and blood gas findings also deteriorated at the 1st week, but recovered at the 4th week. Angiographic and pathological findings indicated that blood flow recovered through the spaces between thromboemboli and vessel walls at the 4th week. The infected dogs were divided into three groups. In the infected-I group (5 dogs), the intimal lesions of the pulmonary arteries were slight, and clinical and laboratory findings showed changes similar to those of the uninfected group. In the infected-II group (4 dogs), the pulmonary arterial lesions were severe and the mean PAP was higher (25.7 mmHg) than in the uninfected group before worm insertion. An increase in PAP (34.1 mmHg) and worsening of clinical and laboratory findings were noticed till the 4th week. Thromboemboli adhered extensively to the vessel walls. Two dogs in the infected-III group died of severe dyspnea on the 9th and 10th day, and the mean PAP rose remarkably at the 1st week (from 19.4 to 28.2 mmHg). Severe pulmonary parenchymal lesions with edema or perforation were observed. From the above results, it was clarified that effects of dead worms on PAP and clinical signs depended on the severity of pulmonary arterial lesions before worm insertion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Morphologic Changes in the Lungs of Cats Experimentally Infected With Dirofilaria immitis

The morphologic response of the pulmonary arteries and lungs in cats was studied after a five month heartworm infection produced by transplantation of four adult heartworms/cat. One group of seven heartworm infected cats was not treated, another group of seven cats was treated with 97.5 mg of aspirin given twice a week, and the third group of six cats was given aspirin at a sufficient dosage to block in vitro platelet aggregation throughout the study. A fourth group of eight noninfected cats served as controls. Five months after heartworm infection, the cats were euthanized and the lungs perfusion fixed for light microscopy and scanning electron microscopy of the pulmonary arterial surfaces. All cats in the three heartworm-infected groups had live heartworms and the typical pulmonary arterial changes of heartworm disease at necropsy. The arterial surfaces, as viewed with scanning electron microscopy, had villus proliferations that were more numerous and exuberant than similar infections in dogs. Mean percentage of arterial surface involvement with villus proliferation of the nontreated heartworm infected cats was 67.3%; the aspirin treated cats, 73.8%; and the adjusted aspirin treated cats, 75.9%. The villi were myointimal proliferations in the small and medium-sized arteries. The more elastic arteries had a predominance of fibromuscular proliferation. All heartworm infected cats had arterial muscular hypertrophy of the small arteries, in contrast to only three of eight of the nonheartworm infected cats. The caudal lobar arteries were frequently obstructed with either villus proliferation, thrombi, and/or dead heartworms. The muscular arteries had branches with marked dilation, a condition associated with pulmonary hypertension in man. However, only three cats, one in each group, had pulmonary hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary thromboembolism during therapy of dirofilariasis with thiacetarsamide: modification with aspirin or prednisolone

The effects that 4 weeks of treatment of dirofilaria-infected dogs with either aspirin or prednisolone had on the pulmonary thromboembolism which occurs after they are given thiacetarsamide were determined, using light and electron microscopies. Pulmonary lesions in control dogs at 4 weeks after thiacetarsamide was given were compared with lesions in dogs which were treated with either aspirin (22 mg/kg daily) or prednisolone (1 mg/kg daily) during the 4-week period after adulticide was given. Pulmonary vascular and perivascular lesions were most severe in the prednisolone-treated dogs and least severe in the aspirin-treated dogs. The aspirin-treated dogs had greater resolution of pulmonary arterial proliferative disease, and prednisolone-treated dogs had the lesser resolution.     

COMPUTED TOMOGRAPHY ANGIOGRAPHY FOR EVALUATION OF PULMONARY EMBOLISM IN AN EXPERIMENTAL MODEL AND HEARTWORM INFESTED DOGS

This study was performed to characterize pulmonary embolism with computed tomography pulmonary angiography in experimental pulmonary embolism and heartworm infected dogs. In the experimental group, there were pulmonary changes after pulmonary embolism induction as follows: hypoattenuating round filling defects in pulmonary arteries, arterial dilations with straight and abrupt cut‐off appearances in the pulmonary embolism regions, pulmonary infarctions, a cavity formation and spontaneous pneumothorax, and emboli migration. In the heartworm‐infected group, three out of eight dogs developed pulmonary embolism, especially in the right caudal arteries. Arterial dilations with typical tortuosity were also identified, mainly in the right caudal arteries in five dogs. Computed tomography pulmonary angiography can be an important imaging modality in the diagnosis of pulmonary embolism and the evaluation of pulmonary arterial and parenchymal changes in dogs.     

Evaluation of lung pathology in Dirofilaria immitis-experimentally infected dogs treated with doxycycline or a combination of doxycycline and ivermectin before administration of melarsomine dihydrochloride

Adulticide therapy in heartworm (Dirofilaria immitis)-infected dogs can lead to thromboembolism, which can seriously compromise post-treatment health status. Lung pathology following adulticide therapy was evaluated in three groups of experimentally infected dogs. Group 1 was treated with doxycycline at 20 mg/kg per os once daily for 30 days post infection followed by an intramuscular injection of melarsomine dihydrochloride (2.5 mg/kg) at Week 12, followed 1 month later by two injections 24 h apart. Group 2 was treated as described for Group 1, with the addition of ivermectin at 6 mcg/kg given monthly per os for 24 weeks post-infection. Group 3 received melarsomine alone, as described above. All dogs were necropsied at Week 24 and lung pathology was evaluated. Lesion criteria included perivascular inflammation and endothelial proliferation. Lesions were scored by two independent pathologists who were blinded as to treatment. Results indicate that doxycycline treatment alone or combined with ivermectin had lower lesion scores than lungs from dogs who had received melarsomine alone. Dogs that received the combined doxycycline/ivermectin protocol and treated with adulticide showed less severe arterial lesions and the virtual absence of thrombi.     

Histopathological and enzyme histochemical observations on mast cells in pulmonary arterial lesion of dogs with Dirofilaria immitis infestation

Histopathological and enzyme histochemical observations were performed on mast cells in pulmonary arterial lesion of Dirofilaria immitis in dogs. The results showed that chymase- and tryptase-positive mast cells were diffusely present in the lesions, especially in the adventitia and proliferated intima. At 2 weeks after surgical worm transplantation, mast cells already appeared in the intima and media, and chymase-positive cells were dominant in the adventitia. Results of this study suggested a possibility that mast cells would be involved in the pathogenesis of pulmonary arterial lesion of dogs with Dirofilaria immitis infestation.     

CARDIAC AND PULMONARY ARTERY MENSURATION IN FELINE HEARTWORM DISEASE

A retrospective study was undertaken to quantify thoracic radiographic changes in cats with heartworm diseases, ( Dirofilaria immitis ). Using a blinded study format, the cardiac silhouette, thoracic cavity and pulmonary arteries were measured from thoracic radiographs of 21 cats with feline heartworm disease and 30 cats without known cardiac or pulmonary vessel pathology. Measured data were normalized to the thoracic cavity or bony structures within the radiographic field of view. The measurements were compared between the two groups of cats using an unpaired, two-tailed Student's t -test, with a p value of < 0.05 being considered significant. Cats with feline heartworm disease had enlargement of the craniocaudal aspect of the cardiac silhouette and normalized cardiac:thoracic ratio (p < 0.05) on the lateral view. Also, there was significant enlargement of the central and peripheral caudal lobar pulmonary arteries and their normalized ratios (p < 0.05) in the heartworm infected cats as visualized on the ventrodorsal projection. Tortuosity of the pulmonary arteries was seen in three of the 21 infected cats. Eleven of the 21 cats with feline heartworm disease had pulmonary parenchymal changes. Based on the present study, central and peripheral pulmonary artery enlargement as viewed on the ventrodorsal radiograph was the single best radiographic indicator of feline heartworm disease.     

THORACIC RADIOGRAPHIC ABNORMALITIES IN 200 DOGS WITH SPONTANEOUS HEARTWORM INFESTATION

Thoracic radiographs of 200 dogs with spontaneously occurring heartworm disease were reviewed. Radiographs of 28 dogs (14%) were normal. In the remaining 172 dogs various combinations of cardiopulmonary abnormalties were found. The most frequently observed combination, noted in 61 of 200 dogs, was right ventricular, main pulmonary, and right cranial lobar pulmonary artery enlargemetn. Dogs with severe increse of one parameter generally had severe increase of the other two parameters also. One hundred five of the 200 dogs had a right cranial lobar pulmonary artery of normal size. Thus, right cranial lobar pulmonary artery size, when normal, is not a sensitive indicator of the absence of heartworm disease. There was a statistically significant positive relation between the size of the caudal vena cava and that of the right ventricle.     

Coagulation abnormalities associated with acute Angiostrongylus vasorum infection in dogs

Ten dogs were experimentally infected with 150 3rd-stage larvae of the lungworm Angiostrongylus vasorum (Baillet, 1866). Blood samples obtained once a week for 5 weeks after infection was induced were examined for coagulation alterations. Thrombocytopenia developed in infected dogs before and after parasitic patency, which occurred 6 weeks after infection was induced. Prolongation of activated partial thromboplastin time and thrombocytopenia initially were associated with periods of larval migration and, later, at patency, with pulmonary egg embolism and hatching of 1st-stage larvae in the lung. Decreased factor-V activity, significantly shortened values for the prothrombin time, and increased factor-VIII activity were evident during postpatent periods of parasitic infection. Significant changes were not found in factors-XII and -IX activities throughout the course of infection. Coagulation abnormalities were attributed to excessive intravascular coagulation. Immature adults and first stages of the parasite seemed to have initiated the coagulopathy in the prepatent phase of infection, with subsequent coagulation abnormalities occurring at the time of patency.     

Radiographic findings in dogs with pulmonary blastomycosis: 125 cases (1989-2006)

OBJECTIVE: To identify radiographic patterns in dogs with pulmonary blastomycosis and radiographic factors associated with outcome. DESIGN: Retrospective case series. ANIMALS: 125 dogs with pulmonary blastomycosis. PROCEDURES: Medical records were reviewed, and for each lung lobe, the primary radiographic pattern and percentage of lobar involvement at the time of initial examination were recorded. RESULTS: 79 dogs survived, 38 died, and 8 were euthanized without treatment. The initial radiographic pattern was variable and not significantly associated with outcome. Mean half-time for radiographic resolution of pulmonary infiltrates was 41.4 days for all patterns except masses, for which mean half-time to resolution was 90.8 days. Transient radiographic worsening was seen in 20 of 87 (23%) dogs but was not associated with a poor prognosis. Pulmonary bullae were seen in 20 (16%) dogs, most often in association with an alveolar pattern. Accuracy of using percentage of right caudal lung lobe involvement ( 20%) to predict outcome was 74.4%; accuracy of using number of affected lobes (< 4 vs >or= 4) to predict outcome was 65.8%. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that a nonuniform distribution of pulmonary infiltrates was equally as likely as a diffuse nodular interstitial pattern in dogs with pulmonary blastomycosis. On the basis of half-time for resolution of pulmonary infiltrates, follow-up radiography should be performed no more often than every 4 to 6 weeks in clinically stable patients. Transient radiographic worsening that occurred during the initial weeks of treatment was not associated with a poorer prognosis.     

D-dimer deposits in lungs and kidneys suggest its use as a marker in the clinical workup of dogs with heartworm (Dirofilaria immitis) disease

It has been reported that dogs with heartworm disease (Dirofilaria immitis) show increased plasma levels of D-dimer, a fibrin degradation product present in the blood after a blood clot is degraded by fibrinolysis. In the present study the authors show that, in dogs with both experimental and natural infections with D. immitis, D-dimer deposits in lungs and kidneys are associated with pulmonary thromboembolism and microfilariemic status, as well as there was a clear association between increased plasma values of D-dimer and positive staining in immunohistochemistry. Results suggest that the monitoring of D-dimer levels in infected dogs could be useful in evaluating the presence of pulmonary thromboembolism in the lungs and that microfilariae may induce microthrombosis in kidneys, thus contributing to renal pathology.     

Structural and ultrastructural changes in the lungs of cats Felis catus (Linnaeus, 1758) experimentally infected with D. immitis (Leidy, 1856)

Clinical signs are seldom observed in feline heartworm disease, and the pathophysiological changes in the lungs of infected animals remain undefined. The goal of this study was to evaluate the structural and ultrastructural changes in the lungs of cats experimentally infected with Dirofilaria immitis. Six healthy cats were each infected with two adult heartworms by intravenous transplantation (Receptor Group, RG). The control group consisted of two uninfected animals kept under the same conditions as the RG. At 42 days after transplantation, all cats were euthanized and necropsied for worm recovery and collection of lung samples for examination by light microscopy (LM) and transmission electron microscopy. By LM, lung sections from the six infected cats exhibited bronchial and bronchiolar lesions. Alterations in all tissues of the pulmonary arteries were observed in the infected animals. In conclusion, cats infected experimentally with D. immitis developed lesions in their lungs as a consequence of arterial disease and intense interstitial pneumonia.     

Inoculation of dogs with artificial larvae similar to those of Dirofilaria immitis: distribution within the pulmonary arteries

Two hundred artificial larvae, similar in size to those of Dirofilaria immitis, were inoculated into the venous system of 20 clinically healthy dogs and the distribution pattern was evaluated. One hundred forty-four (73%) of the larvae were located in the right lung and fifty-one (26%) in the left lung. Of those larvae in the lung, 50% were in the right caudal branch and 21% in the left caudal branch of the pulmonary artery. These findings help to explain why the right caudal lung lobe usually is more affected in canine dirofilariasis.     

Scanning electron microscopy of vascular corrosion casts and histologic examination of pulmonary microvasculature in dogs with dirofilariosis

OBJECTIVE: To characterize structural changes in pulmonary vessels of dogs with dirofilariosis. ANIMALS: 8 dogs with dirofilariosis and 2 unaffected control dogs. PROCEDURE: Pulmonary artery pressure was measured in affected dogs, and dogs then were euthanatized. Scanning electron microscopy was used to examine vascular corrosion casts of pulmonary vasculature. Tissue sections of pulmonary vasculature were evaluated by use of histologic examination. RESULTS: Pulmonary artery pressure was higher in dogs with severely affected pulmonary vessels. In tissue sections, dilatation, as well as lesions in the tunica intima and proliferative lesions resulting in constriction or obstruction, were frequently observed in branches of the pulmonary artery. Numerous dilated bronchial arteries were observed around affected pulmonary arteries. Hyperplastic venous sphincters were observed in small pulmonary veins and venules. In corrosion casts, affected pulmonary lobar arteries had dilatation, pruning, abnormal tapering, constriction, and obstruction. In small arteries and arterioles, surface structures representing aneurisms and edema were seen. Bronchial arteries were well developed and extremely dilated, and they formed numerous anastomoses with pulmonary arteries at all levels, from the pulmonary trunk to peripheral vessels. Capillaries in the lungs were dilated with little structural change. Small pulmonary veins and venules had irregular annular constrictions that were caused by hyperplastic smooth muscle cells of venous sphincters. CONCLUSIONS AND CLINICAL RELEVANCE: Scanning electron microscopy of microvascular casts delineated links between the bronchial and pulmonary circulations in dogs with dirofilariosis. Results of scanning electron microscopy provided a structural explanation for the development of pulmonary circulatory disturbances and pulmonary hypertension in dogs affected by dirofilariosis.     

Pulmonary Arteriography and Hemodynamics During Feline Heartworm Disease

The ability of aspirin to block arterial disease and thromboembolism of the pulmonary arteries was studied in heartworm-infected cats. Three groups of cats were transplanted with four heartworms per cat and studied. One group of eight cats (aspirin group) received aspirin (97.5 mg, twice a week) for the five-month infection and another group of eight cats served as the nontreated control group (nontreated group). Based upon the results of the first two groups, the third group (adjusted aspirin group) of six cats was studied in which the aspirin dosage was adjusted in order to maintain an inhibition of in vitro platelet aggregation. Cats were studied by nonselective pulmonary arteriograms before heartworm transplantation and by selective arteriograms, aortograms, and pulmonary hemodynamics five months after heartworm transplant. Pulmonary hypertension, (mean pulmonary artery pressures greater than 16 mmHg), was discovered in three cats with one cat in each group. There were no differences in the mean pulmonary artery pressure or vascular resistance between the groups. Many of the arterial diameters for the nontreated and aspirin groups were greater after the five-month infection than before heartworm infection. All of the postinfection caudal arteries were tortuous and had aneurysms. Some of the caudal lung lobes had perfused areas that appeared to have a hypervascular microvasculature. The proportion of obstructed right and left distal caudal pulmonary arteries and the resulting nonperfused area of the caudal lung lobe in the nontreated and aspirin treated groups were each greater than in the adjusted aspirin group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Indirect fluorescent antibody test in occult dirofilariasis.

Indirect fluorescent antibody titers to Dirofilaria immitis microfilaria (IFA-mf) and peripheral eosinophilia were recorded from 15 to 52 months in ten experimentally infected dogs with occult dirofilariasis (heartworm infection without microfilaremia). Five dogs which were experimentally sensitized with D immitis microfilaria did not exhibit microfilaremia after inoculation with infective-stage larvae. In three other dogs, microfilaremia suddenly ceased after 4 to 7 months. In these three dogs, antimicrofilarial antibodies were detectable by IFA-mf test as soon as microfilaremia ended. In the remaining two dogs, which exhibited spontaneous occult dirofilariasis, antibodies were detected at the end of the prepatent period of 6 months. The presence of adult worms was confirmed by angiocardiography. Significant IFA=mf titers (greater than or equal to 1:8) persisted after successful treatment with an adulticide. Reinfection of treated dogs reestablished occult dirofilarasis. Eosinophilia was present in all dogs and peaked at about 3, 6, and 9 months after they were inoculated with infective-stage larvae. At necropsy, the ten dogs harbored gravid, reproducing adult worms in the heart and pulmonary arteries.     

Activity of pulmonary intravascular macrophages in cats and dogs with and without adult Dirofilaria immitis

Pulmonary intravascular macrophages (PIMs), large (20-80 microm diameter) monocytes are present in sheep, pigs, and horses, but not in dogs, rats, rabbits, or primates. The present study evaluated the phagocytic activity of various organs in cats and dogs and determined the influence of Dirofilaria immitis infections on PIM activity. Live or dead adult heartworm (HW) was transplanted via jugular venotomy into cats and dogs. Cats (four per group) were allocated to five groups: surgical controls--no HW, dead HW for 1 week, live HW for 1 week, dead HW for 3 weeks, or live HW for 3 weeks. Radioactive technetium (Tc-99m, 1.2mCi in 0.3ml) sulfa-colloid was injected intravenously. All cats with HW were clinically asymptomatic and developed radiographic pulmonary parenchymal changes. No gross changes were visible at necropsy for cats with HW; inflammatory changes were less severe in cats with live HW. In cats with dead HW for 3 weeks, worms were present but folded, flattened, and located in distal pulmonary arteries. Uninfected control dogs and those with dead HW did not demonstrate any PIM activity. In control cats, lungs were the primary phagocytic organ after systemic IV colloid injection (72.5% of the total recovered radioactive dose). The lung and liver together represented over 95% of the recovered Tc-99m colloid in all cats. In each group of cats with HW, phagocytic activity of the lung was significantly less (p < 0.001) than the PIM activity of controls. Cats with dead HW at 1 week (50.1%) had a significant (p < 0.019) decrease in PIM activity compared with cats with dead HW at 3 weeks (59.5%). The PIM activity in cats with live HW was significantly decreased (p < 0.001) from that in groups with dead HW, but there was no significant difference between the two groups infected with live worms. There were no significant differences in recovery between any groups in pairwise analysis of the spleen, heart, skeletal muscle, kidney, bone marrow, or blood. Significant increases (p < 0.001) in liver activity for each group inversely reflected the decreased lung activity; consistent with increased hepatic uptake of Tc colloid "escaping" a relatively suppressed lung macrophage system. Transmission electron microscopy confirmed PIM glycocalyx changes and vacuolization, moderate Type 1 cell damage and Type II cell hypertrophy in cats with dead HW. There was no evidence of PIM death. The significant decrease in PIM activity in groups with dead HW and a greater decrease in groups with live HW are consistent with a down-regulation of PIM function in cats with live HW.