Recruitment of arteriovenous pulmonary shunts may attenuate the development of pulmonary hypertension in dogs experimentally infected with Angiostrongylus vasorum

ObjectivesThe purposes of this study were to evaluate if (1) Angiostrongylus vasorum-infected dogs recruit pulmonary arteriovenous (AV) shunts attenuating the development of pulmonary hypertension (PH), detectable using saline contrast echocardiography, (2) anthelmintic therapy causes an acute increase in pulmonary arterial pressure (PAP), (3) Tissue Doppler Imaging (TDI) allows detection of mild changes in right ventricular function secondary to pulmonary (vascular) disease.Animals6 healthy Beagle dogs, each infected with 200 A. vasorum larvae.MethodsConventional, TDI and contrast echocardiography, invasive PAP measurements before (T0), 7–12 weeks post infection (wpi, T1), and 1–5 days post therapy (dpt, T2).ResultsAll dogs had patent infections 7–8 wpi and respiratory signs 6–9 wpi. PAP was mildly but significantly increased at T2. Saline contrast echo was positive in 3/6 dogs at T1 and 4/6 dogs at T2. Pulmonary transit time did not change. Of all numeric echocardiographic parameters, only a non-significant decrease in the E′ wave and inversion of E′/A′ ratio in 3 dogs at T2 could be observed. Two of these had mild PH and negative saline contrast echocardiography.ConclusionA. vasorum infection causes only a mild increase in PAP following inoculation and anthelmintic therapy. The absence of important PH may in part be explained by the recruitment of AV shunts in the presence of vascular obstructive disease. TDI echocardiographic parameters may be more sensitive to detect mild changes in RV function than conventional parameters.     

THORACIC COMPUTED TOMOGRAPHY FINDINGS IN DOGS EXPERIMENTALLY INFECTED WITH ANGIOSTRONGYLUS VASORUM

To characterize the computed tomography (CT) features of thoracic lesions caused by infection with Angiostrongylus vasorum, pre‐ and postcontrast CT was performed in six experimentally infected Beagles 13 weeks postinoculation and in four of these 9 weeks postchemotherapy. Findings were compared with survey radiographs and necropsy findings. A multicentric bronchoalveolar pattern more pronounced at the lung periphery was present radiographically. On CT, the predominant abnormality underlying this alveolar pattern was multiple large nodules merging to areas of consolidation, and containing air bronchograms of varying extent. These nodular changes corresponded to histopathologic granulomata, consisting mainly of macrophages, multinucleated giant cells, and lymphocytes that had accumulated around larvae and eggs. Morphologically, no bronchial changes were observed on CT or histologically. Quantitatively, however, on CT there was evidence of bronchial thickening at 13 weeks postinoculation and mild very peripheral bronchiectasia 9 weeks postchemotherapy. Regional lymph nodes were enlarged after infection, and smaller after treatment. On postcontrast CT, several suspicious intraluminal filling defects suggestive of thrombosis were found; however, the tortuosity of some pulmonary arteries seen radiographically was not present in CT images. After treatment, the consolidations and large nodules had almost completely disappeared. A remaining radiographic interstitial pattern was characterized on CT as ground‐glass opacifications, subpleural interstitial thickening, subpleural lines, and interface signs. These interstitial changes reflected fibrosis as documented histopathologically. CT allowed very detailed and accurate characterization of pulmonary parenchymal lesions, bronchi, and lymphnodes and closely reflected histopathological changes.     

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)     

Retrospective evaluation of sildenafil citrate as a therapy for pulmonary hypertension in dogs

Pulmonary arterial hypertension (PH) is a pathologic condition in dogs characterized by abnormally high pressures in the pulmonary circulation and has been associated with a poor outcome. Sildenafil is a type V phosphodiesterase inhibitor that produces nitric oxide mediated vasodilatation. Sildenafil treatment decreases pulmonary arterial pressure and pulmonary vascular resistance in people with PH. The purpose of this study was to describe the clinical characteristics and outcome of dogs with PH treated with sildenafil. The cardiology database was searched for dogs with PH treated with sildenafil. PH was defined as systolic pulmonary arterial pressure (PAPs) > or = 25 mmHg at rest. Medical records were reviewed for the following information: signalment, duration and type of clinical signs before treatment, underlying disease, estimated or measured PAPs, dosage and dosing interval of sildenafil, and the effect of treatment on clinical signs and pulmonary arterial pressure and survival time. Thirteen affected dogs were identified. Clinical signs included collapse, syncope, respiratory distress, and cough. Duration of clinical signs before presentation ranged from 3 days to 5 months. An underlying cause was identified in 8 dogs. The median sildenafil dosage was 1.9 mg/kg. Ten dogs received concurrent medications. Median PAPs was 90 mmHg; 8 dogs were reevaluated after therapy, and the median decrease in PAPs was 16.5 mmHg. The median survival time of all dogs was 91 days. Sildenafil appeared to be well tolerated in dogs with PH and was associated with decreased PAPs and amelioration of clinical signs in most. Sildenafil represents a reasonable treatment option for dogs with pulmonary hypertension.     

Serum Cardiac Troponin I Concentration in Dogs with Precapillary and Postcapillary Pulmonary Hypertension

Background: Pulmonary hypertension (PH) is a disease condition leading to right-sided cardiac hypertrophy and, eventually, right-sided heart failure. Cardiac troponin I (cTnI) is a circulating biomarker of cardiac damage.
Hypothesis: Myocardial damage can occur in dogs with precapillary and postcapillary PH.
Animals: One hundred and thirty-three dogs were examined: 26 healthy controls, 42 dogs with mitral valve disease (MVD) without PH, 48 dogs with pulmonary hypertension associated with mitral valve disease (PH-MVD), and 17 dogs with precapillary PH.
Methods: Prospective, observational study. Serum cTnI concentration was measured with a commercially available immunoassay and results were compared between groups.
Results: Median cTnI was 0.10 ng/mL (range 0.10–0.17 ng/mL) in healthy dogs. Compared with the healthy population, median serum cTnI concentration was increased in dogs with precapillary PH (0.25 ng/mL; range 0.10–1.9 ng/mL; P < .001) and in dogs with PH-MVD (0.21 ng/mL; range 0.10–2.10 ng/mL; P < .001). Median serum cTnI concentration of dogs with MVD (0.12 ng/mL; range 0.10–1.00 ng/mL) was not significantly different compared with control group and dogs with PH-MVD. In dogs with MVD and PH-MVD, only the subgroup with decompensated PH-MVD had significantly higher cTnI concentration compared with dogs with compensated MVD and PH-MVD. Serum cTnI concentration showed significant modest positive correlations with the calculated pulmonary artery systolic pressure in dogs with PH and some echocardiographic indices in dogs with MVD and PH-MVD.
Conclusions and Clinical Importance: Serum cTnI is high in dogs with either precapillary and postcapillary PH. Myocardial damage in dogs with postcapillary PH is likely the consequence of increased severity of MVD.     

Cardiovascular effects of romifidine in dogs

OBJECTIVE: To characterize the cardiovascular effects of romifidine at doses ranging from 5 to 100 microg/kg of body weight, IV. ANIMALS: 25 clinically normal male Beagles. PROCEDURE: Romifidine was administered IV at a dose of 5, 10, 25, 50, or 100 microg/kg (n = 5/group). Heart rate, arterial pressure, central venous pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, body temperature, cardiac output, and PCV were measured immediately prior to and at selected times after romifidine administration. Cardiac index, stroke index, rate-pressure product, systemic and pulmonary vascular resistance indices, and left and right ventricular stroke work indices were calculated. Degree of sedation was assessed by an observer who was blinded to the dose administered. RESULTS: Romifidine induced a decrease in heart rate, pulmonary arterial pressure, rate-pressure product, cardiac index, and right ventricular stroke work index and an increase in central venous pressure, pulmonary capillary wedge pressure, and systemic vascular resistance index. In dogs given romifidine at a dose of 25, 50, or 100 microg/kg, an initial increase followed by a prolonged decrease in arterial pressure was observed. Arterial pressure immediately decreased in dogs given romifidine at a dose of 5 or 10 microg/kg. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that IV administration of romifidine induces dose-dependent cardiovascular changes in dogs. However, the 2 lowest doses (5 and 10 microg/kg) induced less cardiovascular depression, and doses > or = 25 microg/kg induced similar cardiovascular changes, suggesting that there may be a ceiling on the cardiovascular effects of romifidine.     

Pulmonary Hypertension Induced in Dogs by Hypoxia at Different High-Altitude Levels

Chronic natural hypoxia at 2300 m altitude induces mild pulmonary hypertension (PH) in healthy dogs. The influence of more severe hypoxia on the same group of dogs was evaluated by re-examining such dogs at 3500 m, after they had regularly exercised at this altitude level for half a year. Despite severe hypoxaemia at 3500 m (P _aO₂ 52±5 mmHg), none of the dogs developed erythrocytosis, and their PCV at 3500 m (48%±4%) did not differ from that at 2300 m (49%±4%). There was a tendency towards an elevated systemic BP, with a significant increase in diastolic BP (105±13 mmHg at 3500 m versus 98±17 at 2300 m). Tricuspid regurgitation (TR) was detected in 7 dogs at 3500 m compared to 8 dogs at 2300 m. The mean TR V _max was significantly higher at 3500 m, and all 7 dogs had systolic PH at 3500 m (33.6–54.8 mmHg), when PH was defined as TR V _max 2.8 m/s, i.e. a peak pressure gradient >30 mmHg. Hence, in dogs, increasing altitude and the concomitant hypoxia result in a progressively more pronounced PH and an elevated systemic BP. Intermittent severe hypoxaemia of around 50 mmHg may not cause erythrocytosis in healthy dogs, even over a prolonged period.     

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.     

低温诱发肉鸡肺动脉高压中肺血管重塑的作用

采用低温处理肉仔鸡的方法,通过测定肺动脉压、肺小动脉中膜厚度占外径百分比及中膜面积与血管总面积比的变化,探讨肉鸡肺动脉高压的发生机制.结果表明:肺血管重塑在低温诱发肉鸡的肺动脉高压发生发展中起重要作用.     

Evaluation of collagenase-induced mitral valve regurgitation in dogs

OBJECTIVE: To investigate the hemodynamic changes induced by injecting collagenase into the mitral valve to induce mitral valve regurgitation (MVR) in dogs. ANIMALS: 9 healthy Beagles. PROCEDURE: Dogs were randomly assigned to 3 groups: control (saline [0.9% NaCl] solution; n = 3), single collagenase injection (C1; 3), and 2 collagenase injections (C2; 3). Open-heart surgery was performed, and saline or collagenase solutions were injected into the mitral valve. Before and weekly for 11 weeks after surgery, radiography, echocardiography, and phonocardiography were performed. Mean pulmonary arterial pressure and mean pulmonary arterial wedge pressure (mPAWP) were measured before and 11 weeks after surgery. Postmortem examinations were performed after dogs were euthanatized. RESULTS: No changes were detected in the control group during the 11-week follow-up period. A systolic murmur and MVR developed 1 week after surgery in groups C1 and C2. The murmur changed from a protosystolic to a pansystolic murmur, and left atrial diameter and the left atrial-to-aortic root diameter ratio increased with time. Mean pulmonary arterial pressure and mPAWP were greater 11 weeks after surgery in groups C1 and C2, compared with presurgery values. During necropsy, tissue loss was detected in the mitral valve at the site of collagenase injection. Degree of regurgitation corresponded to lesion size. CONCLUSIONS AND CLINICAL RELEVANCE: Injection of collagenase into the mitral valve of healthy dogs induced MVR, and dogs with MVR developed progressive hemodynamic changes without acute overload. Collagenase-induced MVR may be an appropriate model for evaluation of prognostic markers of idiopathic MVR in dogs.     

Haemodynamic effects of ATP in dogs during hypoxia-induced pulmonary hypertension

Pulmonary hypertension may result from an increase in vascular resistance caused by persistent hypoxia. We have investigated the effects of adenosine triphosphate (ATP), administered into the pulmonary artery, on haemodynamic changes occurring in anaesthetized adult dogs subjected to acute hypoxic pulmonary vasoconstriction. Hypoxia alone (ventilation with 10% O2/90% N2) caused significant increases in mean pulmonary arterial blood pressure (PAP), central venous pressure (CVP), and cardiac index (CI) by 71, 102 and 38%, respectively. ATP (0.03-3.0 micromol/kg/min approximately 0.02-1.65 mg/kg/min), when infused under hypoxic conditions, significantly reduced both mean PAP and systemic arterial blood pressure (ABP) in a dose-dependent manner. The maximum decrease in mean PAP amounted to 20%; mean ABP, on the other hand, was decreased by up to 52% (P<0.01). Heart rate, CI, CVP and pulmonary occlusion pressure were not dose-dependently affected by ATP. Our data indicate that while pulmonary arterial administration of ATP in mature dogs during hypoxic pulmonary hypertension causes dilation in the pulmonary vascular bed, it is even more effective in dilating the systemic vasculature. This result suggests a need for further evaluation and warrants cautious use of ATP in the treatment of hypoxic pulmonary hypertension in adult dogs.     

Thrombin‐activatable fibrinolysis inhibitor activity in healthy and diseased dogs

Background: In people, increased thrombin‐activatable fibrinolysis inhibitor (TAFI) antigen has been associated with increased risk of thrombosis, and decreased TAFI may contribute to bleeding diathesis. TAFI activity in dogs has been described in experimental models, but not in dogs with spontaneous disease. Objective: The aim of this study was to compare TAFI activity in healthy dogs with TAFI activity in dogs with spontaneous disease. Methods: Plasma samples from 20 clinically healthy Beagles and from 35 dogs with various diseases were analyzed using a commercial chromogenic assay that measured TAFI activity relative to activity in standardized pooled human plasma. Results: Median TAFI activity for the 20 Beagles was 46.1% (range 32.2–70.8%) compared with 62.6% (29.1–250%) for the 35 diseased dogs, and 14/35 (40%) had TAFI activities >the upper limit for controls. The highest individual activities (>225%) were in 3 dogs with malignant neoplasms and 1 dog with thrombocytopenia. For data grouped by diagnosis, median TAFI activity was 61.7% for benign neoplasia (n=5), 64.9% for malignant neoplasia (n=8), 75.5% for Angiostrongylus vasorum infection (n=4), 68.8% for bacterial sepsis (n=7), and 58.7% for miscellaneous diseases (n=11). Compared with TAFI activity in control dogs, median TAFI activity was significantly increased only in the group of dogs with bacterial sepsis. Conclusion: Bacterial sepsis was associated with significantly increased TAFI activity, and individual dogs with increased TAFI activities were found in all disease groups. The role of TAFI in the pathogenesis of hemostatic disorders in dogs and its value as a prognostic indicator deserve further investigation.     

Clinical Efficacy of Sildenafil in Treatment of Pulmonary Arterial Hypertension in Dogs

Background: Pulmonary arterial hypertension (PAH) in dogs carries a poor prognosis. Sildenafil increases exercise capacity and improves hemodynamics in people with PAH. Hypothesis/Objectives: Dogs receiving sildenafil will have lower pulmonary arterial pressure, increased exercise capacity, and better quality of life (QOL) than dogs receiving placebo. Animals: Thirteen dogs with echocardiographic evidence of PAH. Methods: Prospective short‐term, randomized, placebo controlled, double‐blind, crossover study. Dogs with PAH were randomly allocated to receive sildenafil or placebo for 4 weeks, followed by the alternative treatment for 4 weeks. Results: Dogs receiving sildenafil had a significantly lower estimated pulmonary arterial pressure (median, 56 mmHg; range, 34–83 mmHg) than at baseline (median, 72 mmHg; range, 61–86 mmHg; P= .018), but not significantly lower than those receiving placebo (median, 62 mmHg; range, 49–197 mmHg). Exercise capacity was significantly greater in dogs receiving sildenafil than those receiving placebo (mean activity count per minute: 101 ± 47 versus 74 ± 32; P= .05). QOL scores were significantly higher in dogs receiving sildenafil than dogs receiving placebo. Conclusions and Clinical Importance: Sildenafil decreases systolic pulmonary arterial pressure from baseline in dogs with PAH and is associated with increased exercise capacity and QOL when compared to treatment with placebo.     

Pulmonary thromboembolism in dogs: 47 cases (1986-1987)

Medical records of 47 dogs with pulmonary thromboembolism were reviewed. Middle-aged to older dogs predominated and dyspnea and arterial hypoxemia were consistent clinical findings. Thoracic radiographic findings were variable. Cardiac disease, neoplasia, hyperadrenocorticism, disseminated intravascular coagulation, and sepsis were identified most frequently. Multiple disease processes were identified in 64% of the dogs.     

Pulmonary manifestations of heartworm disease

The clinical signs associated with heartworm disease are the result of changes in the pulmonary arterial system. These clinical signs are the result of either pulmonary hypertension or lung parenchymal disease associated with vascular changes. An increase in pulmonary arterial pressure produces an increase in right ventricular afterload, which may lead to exercise intolerance, syncope, and right-sided congestive heart failure. Coughing, dyspnea, and hemoptysis are the results of pulmonary parenchymal disease.     

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.     

Sildenafil citrate therapy in 22 dogs with pulmonary hypertension

BACKGROUND: Pulmonary hypertension (PH) is a disease condition characterized by abnormally increased pulmonary artery pressures and often is associated with a poor prognosis. Sildenafil is a phosphodiesterase inhibitor that causes pulmonary arterial vasodilation and reduction in pulmonary artery pressures. HYPOTHESIS: Treatment with sildenafil will improve echocardiographic determinants of PH in dogs, while also improving quality of life and survival. ANIMALS: Twenty-two dogs with clinical and echocardiographic evidence of pulmonary hypertension. METHODS: A retrospective study evaluating the effects of sildenafil on physical examination, ECG and radiographic findings, blood pressure and echocardiographic findings of PH, clinical score, and outcome was completed. PH was defined as a peak tricuspid regurgitation flow velocity > or = 2.8 m/s or a peak pulmonic insufficiency flow velocity > or = 2.2 m/s. RESULTS: Sixteen of 22 dogs with PH were elderly females of small body size. Their clinical score was significantly improved (P = .0003) with sildenafil treatment, but physical examination findings remained unchanged. Heart rate, respiratory rate, vertebral heart size, ECG heart rate, and systolic blood pressure did not change significantly with sildenafil treatment (P > .05). Peak tricuspid regurgitation flow velocities did not change significantly with the treatment of sildenafil, but selected systolic time intervals were significantly improved. Survival times for all dogs ranged from 8 to > 734 days. CONCLUSIONS AND CLINICAL IMPORTANCE: Sildenafil did not significantly lower the degree of measurable PH in dogs. Clinical improvement and increased quality of life was seen with sildenafil treatment, despite lack of significant change in other variables.     

Angiostroneylosis in Cornwall: Clinical presentations of eight cases

Clinical signs in eight dogs with Angiostrongylus vasorum infection included chronic cough, dyspnoea, lumbar pain, hindleg paresis/paralysis, abdominal pain, weakness and collapse; two of the dogs were asymptomatic. Thrombocytopenia was present in two dogs and a mild anaemia in one. Thoracic radiographs showed mild right heart enlargement in two out of three dogs and a pneumothorax in one. At post mortem examination in three dogs, the lungs were swollen with a mottled appearance and there was dilatation of the right ventricle. Adult A vasorum were found in the right heart, the pulmonary artery and its branches. Adult worms were also found in the systemic vasculature in one dog, associated with thromboembolism. Treatment with ivermectin in two dogs and fenbendazole in three dogs resulted in the resolution of clinical signs and no demonstrable larvae in the faeces one to two weeks later.