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)     

Relationship between pulmonary arterial pressure and lesions in the pulmonary arteries and parenchyma, and cardiac valves in canine dirofilariasis.

The relationship between pulmonary hypertension and lesions was examined in 41 dogs infested naturally with heartworms, which consisted of 28 cases with pulmonary heartworm disease and 13 cases with caval syndrome. Pulmonary arterial pressure (PAP) was measured before and 1 or 7 days after heartworm removal with a flexible alligator forceps. In these dogs, lesions were examined after the last measurement of PAP. The mean PAP was 28.2 +/- 16.0 mmHg (10.9 to 81.4 mmHg in range) at post-removal phase. Pulmonary arterial intimal lesions, pulmonary thromboemboli, pneumonic lesions, tricuspid valvular lesions and mitral valvular lesions were macroscopically recognized in 95, 59, 39, 54 and 56% of cases, respectively. These lesions were classified by severity and the relationship with PAP was examined by the multiple correlation analysis. The multiple coefficient correlation was found the highest between PAP and thromboemboli, followed by mitral valvular lesion, tricuspid valvular lesion, and pneumonic lesion. There was no significant correlation between PAP and intimal lesions. The coefficient of determination showed the highest value in thromboemboli when one variable was used, and increased only very slightly when a variable of thromboemboli was added to those of other lesions. The cases with high PAP had fresh thromboemboli in large pulmonary arteries. From these evidences, it was concluded that thromboemboli following natural death of heartworm was the most important factor causing an increase in PAP and developing clinical signs in canine heartworm disease.     

Cardiopulmonary function in dogs with serious chronic heartworm disease.

Cardiopulmonary function was examined in 18 dogs with serious chronic heartworm disease showing ascites, subcutaneous edema, prostration, weakness, jaundice and so on. After surgical heartworm removal from the pulmonary arteries, 10 dogs recovered (surviving group), and 8 dogs died or were euthanatized because of poor prognosis (nonsurviving group). The number of live heartworms residing in the pulmonary arteries of the surviving group tended to be larger than that in the nonsurviving group. At necropsy, severe pulmonary arterial lesions such as thromboembolism including dead heartworms, proliferative and villous lesions and intimal hyperplasia were noticed in all dogs examined, and tended to be severer in the nonsurviving group. Heartworm-coiling around the tricuspid valve chord was found in 1 dog of the surviving group and 4 dogs of the nonsurviving group. Before heartworm removal, there was no significant difference in the mean pulmonary arterial pressure (MPAP) between the surviving and nonsurviving group. Right atrial pressure (v-wave) was higher, and the cardiac index (CI) was lower in the nonsurviving group. Arterial oxygen tension was lower in the surviving group than in the heartworm-free group, and it was lower in the nonsurviving group than in the surviving group. Carbon dioxide tension was lower in the surviving group than in the heartworm-free group. Bicarbonate concentration (HCO3-) was lower both in the surviving and nonsurviving groups than in the heartworm-free group. One week after heartworm removal, MPAP decreased (P less than 0.05), and CI and HCO3- tended to increase in the surviving group.     

Treatment of canine dirofilariasis: pulmonary thromboembolism caused by thiacetarsamide--microscopic changes

Light and scanning electron microscopies were used to study the pulmonary embolism occurring in Dirofilaria immitis-infected dogs after treatment with thiacetarsamide. Lesions in control dogs (nontreated) which had been infected for 4 weeks with 9 Dirofilaria immitis adults were compared with lesions occurring in infected dogs at 2 weeks and at 4 weeks after they were treated with the adulticide. Extensive thromboembolism occurred in the caudal lobar pulmonary arteries of dogs at posttreatment weeks 2 and 4. Complicated villous proliferations were present at posttreatment week 2. The characteristic myointimal proliferation of dirofilariasis showed resolution in the large pulmonary arteries of the dogs at week 4. However, the caudal lobar pulmonary arterial and lung lesions were more severe in the later group. The pathophysiology of adulticide-induced thromboembolism and associated lung parenchymal changes were discussed.     

Contribution of live heartworms harboring in pulmonary arteries to pulmonary hypertension in dogs with dirofilariasis

To investigate whether adult heartworms harboring in the pulmonary arteries contribute to pulmonary hypertension, we determined the cardio-pulmonary values immediately before and after removal of heartworms from the pulmonary arteries and before and after insertion of live worms in their place. In 10 heartworm-infected dogs, 8 to 46 worms were removed. The mean pulmonary arterial pressure fell significantly from 24.5 +/- 7.9 mmHg to 16.3 +/- 4.9 mmHg (p less than 0.01) immediately after removal. The right cardiac output decreased in 7 of the 10 cases. The total pulmonary resistance and right ventricular stroke work index also decreased. At 24 hours after removal, live heartworms were put back into the pulmonary arteries of their host dog. The mean pulmonary arterial pressure elevated significantly (p less than 0.01) immediately after insertion. The right cardiac output further decreased in 7 of the 10 dogs, and the total pulmonary resistance and right ventricular stroke work index increased. Separate from this, 12 to 42 heartworms were transplanted into the pulmonary arteries of 5 heartworm-free dogs. Immediately after transplantation, the pulmonary arterial pressure did not show any significant change. However, the stroke volume decreased, and the total pulmonary resistance increased. These facts suggest a contribution of live heartworms to the pulmonary hypertension, although there is a complicated interaction among the presence of heartworms, the pulmonary lesions and the pulmonary hypertension.     

Heartworm migration toward right atrium following artificial pulmonary arterial embolism or injection of heartworm body fluid

Heartworms harboring in the pulmonary arteries migrated toward the right atrium following insertion of dead heartworms or heartworm-like silicone tubes, or intravenous injection of body fluid extract of a female heartworm. The migration occurred within 3 hr (early group) or 1 to 7 days (late group) after insertion of dead worms, 1 to 11 days after insertion of silicone tubes, and immediately after infusion of heartworm-body fluid. The cardiac output decreased to an unmeasurably low level, and the pulmonary arterial pressure was also reduced in the early group. Although the output decreased, the pulmonary arterial pressure and the total pulmonary resistance increased gradually in the late group. In dogs with heartworm migration, in which silicone tubes had been inserted, the changes in cardiopulmonary values were the same as those in dogs of the late group. In dogs to which the body fluid had been administered intravenously, the changes in cardiopulmonary values were well accord with those in the early group. The systemic blood pressure also fell immediately after the administration with the shock-like state. These results suggest that the death of a part of the heartworms may be closely associated with the migration of heartworms toward the right atrium through the pulmonary arterial embolism and/or shock-like reaction by heartworm body fluid.     

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.     

Investigation of Caval Syndrome in Dogs Experimentally Infected With Dirofilaria immitis

Nine of 16 dogs inoculated with 200 infective heartworm larvae developed caval syndrome (CS) of heartworm disease (HWD). There was no difference between dogs that did and did not develop CS with regard to total heartworm burden, burden relative to body weight, or female heartworm burden, indicating that factors other than worm mass are involved in the pathogenesis of CS. Male dogs were twice as frequently affected as females, although this finding was not statistically significant. Dogs afflicted with CS exhibited radiographic, pathologic, and hemodynamic evidence of chronic HWD. In a model of single heartworm exposure, these findings strongly support the theory that CS develops due to retrograde migration of adult worms from the pulmonary arteries and right ventricle to the right atrium and venae cavae. Pulmonary artery pressures were dramatically and significantly greater in dogs with CS (60 +/- 18 torr) as compared to non-CS (30 +/- 4 torr) dogs with equal worm burdens.     

Catheter-guided percutaneous heartworm removal using a nitinol basket in dogs with caval syndrome

Carval syndrome is a severe heartworm infection where the worms have migrated to the right atrium and vena cava; this condition is associated with a myriad of clinical signs. Several non-surgical and interventional methods are currently used for mechanical worm removal. However, the success rate and complications related to these methods are heavily dependent on methodology and retrieval devices used. In this study, we developed a catheter-guided heartworm removal method using a retrieval basket that can easily access pulmonary arteries and increase the number of worms removed per procedure. With this technique, we successfully treated four dogs with caval syndrome.     

Cardiopulmonary function values before and after heartworm removal in dogs with caval syndrome

Cardiopulmonary function values were determined before and after surgical removal of adult heartworms in 25 dogs with spontaneous and 4 dogs with drug-induced caval syndrome (CS). Fifteen dogs with spontaneous CS (recovery group) and 4 dogs with drug-induced CS (drug-induced CS group) recovered after removal, and 10 dogs with spontaneous CS were euthanatized or died (nonsurviving group). Before heartworm removal, injected radiographic contrast medium was regurgitated from the right ventricle to the right atrium. Mean pulmonary arterial pressure and total pulmonary resistance were not statistically different between the recovery and nonsurviving groups of dogs, but the end-diastolic right ventricular pressure (mean +/- SD, 6.9 +/- 9.1 mm of Hg) and the a (8.7 +/- 9.2 mm of Hg)- and v (6.3 +/- 8.5 mm of Hg)-waves of the right atrial pressure curve in the recovery group were less, respectively, than the end-diastolic right ventricular pressure (17.3 +/- 6.0 mm of Hg) and the a (15.8 +/- 6.1 mm of Hg)- and v (21.4 +/- 6.9 mm of Hg)-waves in dogs of the nonsurviving group. After heartworm removal, contrast medium regurgitation disappeared, and cardiac output of the right ventricle increased in dogs of the recovery (from 2.08 +/- 0.72 to 2.38 +/- 0.68 L/min; P less than 0.05) and drug-induced CS (from 1.42 +/- 0.19 to 1.88 +/- 0.26 L/min, P less than 0.05) groups. However, regurgitation remained, and cardiac output did not increase in some dogs of the nonsurviving group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Possible role of histamine in the genesis of pulmonary arterial disease in cats infected with Toxocara cati

Kittens between 12 and 20 weeks of age were orally dosed with 6000 infective ova of Toxocara cati. Animals were sacrificed at intervals between one and eight weeks after infection to study the development of pulmonary arterial lesions. After two weeks, marked leucocyte infiltration and mild thickening of the media of some of the smaller arteries was apparent histologically . Cellular inflammatory activity progressively increased up to four weeks after infection when intimal proliferation was evident in many of the arteries. After six weeks, the arterial walls were grossly thickened with pronounced intimal proliferation which after eight weeks had resulted in complete occlusion of some vessels. The progressive arterial occlusion was associated with a three- to four-fold increase in the parenchymal mast cell population and a corresponding increase in lung histamine content. The possible role of histamine in the genesis of the arteriopathy is discussed.     

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)     

Dirofilaria immitis: worm burden and pulmonary artery proliferation in dogs from Michigan (United States)

Despite the ability to prevent heartworm disease, infection with Dirofilaria immitis continues to be a major problem for domestic dogs. To determine worm burden in heartworm-positive dogs from three county animal shelters in the state of Michigan in the United States and to assess the relationship between gross intimal proliferation and worm burden, necropsy was done on 176 heartworm-positive dogs. Adult heartworms were found in the heart and pulmonary artery of 170 of the 176 (96.6%) dogs examined. Mean worm burden was 14 +/- 13 (range 0-85). Fifty-nine percent of dogs had < or =10 heartworms. In contrast, 52% of dogs in a published report from the southern US (Florida) had worm burdens >10 [C.H. Courtney, Q.Y. Zeng, The structure of heartworm populations in dogs and cats in Florida, in: Proceedings of the American Heartworm Symposium, 1989]. These data suggest that mean worm burden in northern areas may be < or = that in warmer areas. Also, since diagnostic tests are less sensitive with lower worm burdens, diagnosis of heartworm infection in Michigan and other surrounding more northern states may be a greater challenge than in areas with higher worm burdens.     

Percutaneous heartworm removal from dogs with severe heart worm (Dirofilaria immitis) infestation

Canine heart worm disease is often life-threatening due to its various complications, including right side heart failure, caval syndrome and pulmonary eosinophilic granulomatosis. Several preventive medications and melarsomine have been developed and they are very effective to control heartworm infestation. However, in a case of severe infestation, melarsomine therapy often results in an unfavorable outcome because of the severe immune reaction caused by rapid killing of the adult worm. Surgical removal and an interventional method using flexible alligator forceps have been well described in the literature. Despite the usefulness of mechanical removal using flexible alligator forceps, the methodology still needs to be upgraded for increasing the applicability for treating dogs with severe infestation. We describe herein a newly developed percutaneous removal method for heartworms and this was successfully applied to 4 dogs with severe heartworm infestation. The follow-up studies also showed favorable outcomes with no complications.     

Understanding feline heartworm infection: disease, diagnosis, and treatment

Feline heartworm disease is a very different clinical entity from canine heartworm disease. In cats, the arrival and death of immature heartworms in the pulmonary arteries can cause coughing and dyspnea as early as 3 months postinfection. Adult heartworms suppress the function of pulmonary intravascular macrophages and thus reduce clinical disease in chronic feline heartworm infection. Approximately 80% of asymptomatic cats self-cure. Median survival time for symptomatic cats is 1.5 years, or 4 years if only cats living beyond the day of presentation are considered. Aberrant worm migration is more frequent than it is in dogs, and sudden death can occur with no prior clinical signs. The bacterial endosymbiont Wolbachia likely contributes to the inflammatory pathology of heartworm disease, but its role is not yet fully clear. Unfortunately, the diagnosis, treatment, and management of feline heartworm disease are far from simple. Antemortem diagnosis is hampered by low worm burdens, the frequency of all-male infections, and nonspecific radiographic lesions. It is up to the veterinarian to determine the correct index of suspicion and choose the right combination of diagnostic tests to achieve an answer. Treatment is symptomatic because adulticide therapy is risky and does not increase survival time. Despite the dangers of feline heartworm disease, less than 5% of cats in the United States are on chemoprophylaxis. It is important for veterinarians to take a proactive preventive stance because heartworm infection in cats is a multisystemic disease that has no easy cure.     

Dogs with patent Dirofilaria immitis infection have higher expression of circulating IL-4, IL-10 and iNOS mRNA than those with occult infection

Dirofilaria immitis is the agent of canine heartworm disease, in which adult worms reside in the pulmonary arteries, producing first stage larvae (microfilariae) that are released into the bloodstream. The present work describes the cytokine and iNOS mRNA expression in the peripheral blood of naturally infected dogs classified as either microfilariemic or amicrofilariemic. Results show that microfilariemic dogs had higher expression of IL-4 and iNOS mRNA than amicrofilariemic dogs. Furthermore, IL-10 mRNA expression was strongly expressed in dogs with circulating microfilariae, compared to only negligible expression in amicrofilariemic dogs. Finally, mf+ status was associated with a predominance in IgG1 production against worm antigens. These results would suggest that circulating mf may stimulate, like in other filarial infections, an immune bias towards unresponsiveness in D. immitis-infected dogs, consenting long-term adult worm survival.     

Pulmonary Artery Thrombosis in Experimental Angiostrongylus vasorum Infection Does Not Result in Pulmonary Hypertension and Echocardiographic Right Ventricular Changes

Background: Dogs experimentally inoculated with Angiostrongylus vasorum develop severe pulmonary parenchymal lesions and arterial thrombosis at the time of patency. Hypothesis: A. vasorum‐induced thrombosis results in arterial hypoxemia, pulmonary hypertension (PH), and altered cardiac morphology and function. Animals: Six healthy Beagles experimentally inoculated with A. vasorum. Methods: Thoracic radiographs and arterial blood gas analyses were performed 8 and 13 weeks postinoculation (wpi) and 9 weeks posttherapy (wpt). Echocardiography was done before and 2, 5, 8, 13 wpi and 9 wpt. Invasive pulmonary artery pressure (PAP) measurements were obtained 8 wpi. Two untreated dogs were necropsied 13 wpi and 4 treated dogs 9 wpt. Results: All dogs had patent infections at 7 wpi and clinical respiratory signs at 8 wpi. Moderate hypoxemia (median PaO₂ of 73 and 74 mmHg) present at 8 and 13 wpi had resolved by 9 wpt. Echocardiographically, no evidence of PH and no abnormalities in cardiac size and function were discernible at any time point. PAP invasively measured at 8 wpi was not different from that of control dogs. Severe radiographic pulmonary parenchymal and suspected thrombotic lesions at 13 wpi were corroborated by necropsy. Most histopathologic changes had resolved at 9 wpt, but focal inflammatory, thrombotic, and fibrotic changes still were present in all dogs. Conclusion: In experimentally infected Beagles, pulmonary and vascular changes induced by A. vasorum are reflected by marked radiographic changes and arterial hypoxemia. These did not result in PH and echocardiographic changes in cardiac size and function.     

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.     

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.