Pulmonary Hypertension In Dogs Research Articles

Retrospective Investigation on the Prevalence of Pulmonary Hypertension in Dogs with Bronchial and Upper Respiratory Diseases

Abstract Bronchial and upper respiratory diseases have been associated with hypoxia and subsequent development of pulmonary arterial hypertension (PAH). However, there are no known studies assessing the prevalence of PAH in dogs with these conditions. The aim of this study was to assess the frequency of PAH in dogs with bronchial and upper respiratory diseases. Medical records of dogs with confirmed diagnosis (by endoscopic examination) of bronchial and/or upper respiratory diseases referred for cardiovascular investigation (January 2009 - May 2013) were retrospectively reviewed. Diagnosis of PAH was made by echocardiography (tricuspid regurgitation > 2.8 m/s and/or pulmonic regurgitation > 2.2 m/s); possible PAH was diagnosed when two or more specific echocardiographic findings were present. 52 dogs (30 with upper respiratory diseases, 17 with bronchial disease and 5 with both) were included. Diagnosis of PAH was performed in 3 dogs (5.7%). Two dogs were considered as probably affected by PAH; a total of 5 dogs (9.4%) resulted in being affected or probably affected by PAH. Our study shows that the prevalence of PAH in dogs with bronchial and/or upper respiratory diseases is low; PAH seems to occur mostly in older dogs and/or with very advanced disease: echocardiography may therefore be a useful tool in this category of patients.

Pulmonary Veno-Occlusive Disease: A Newly Recognized Cause of Severe Pulmonary Hypertension in Dogs.

Pulmonary hypertension is a well-known though poorly characterized disease in veterinary medicine. In humans, pulmonary veno-occlusive disease (PVOD) is a rare cause of severe pulmonary hypertension with a mean survival time of 2 years without lung transplantation. Eleven adult dogs (5 males, 6 females; median age 10.5 years, representing various breeds) were examined following the development of severe respiratory signs. Lungs of affected animals were evaluated morphologically and with immunohistochemistry for alpha smooth muscle actin, desmin, CD31, CD3, CD20, and CD204. All dogs had pulmonary lesions consistent with PVOD, consisting of occlusive remodeling of small- to medium-sized pulmonary veins, foci of pulmonary capillary hemangiomatosis (PCH), and accumulation of hemosiderophages; 6 of 11 dogs had substantial pulmonary arterial medial and intimal thickening. Ultrastructural examination and immunohistochemistry showed that smooth muscle cells contributed to the venous occlusion. Increased expression of CD31 was evident in regions of PCH indicating increased numbers of endothelial cells in these foci. Spindle cells strongly expressing alpha smooth muscle actin and desmin co-localized with foci of PCH; similar cells were present but less intensely labeled elsewhere in non-PCH alveoli. B cells and macrophages, detected by immunohistochemistry, were not co-localized with the venous lesions of canine PVOD; small numbers of CD3-positive T cells were occasionally in and around the wall of remodeled veins. These findings indicate a condition in dogs with clinically severe respiratory disease and pathologic features resembling human PVOD, including foci of pulmonary venous remodeling and PCH.

Diagnostic Value of Selected Echocardiographic Variables to Identify Pulmonary Hypertension in Dogs with Myxomatous Mitral Valve Disease

BackgroundPulmonary hypertension (PH) is commonly associated with myxomatous mitral valve disease (MMVD). Because dogs with PH present without measureable tricuspid regurgitation (TR), it would be useful to investigate echocardiographic variables that can identify PH.AimTo investigate associations between estimated systolic TR pressure gradient (TRPG) and dog characteristics and selected echocardiographic variables.Animals156 privately owned dogs.Materials and MethodsProspective observational study comparing the estimations of TRPG with dog characteristics and selected echocardiographic variables in dogs with MMVD and measureable TR.ResultsTricuspid regurgitation pressure gradient was significantly (P < .05) associated with body weight corrected right (RVIDDn) and left (LVIDDn) ventricular end‐diastolic and systolic (LVIDSn) internal diameters, pulmonary arterial (PA) acceleration to deceleration time ratio (AT/DT), heart rate, left atrial to aortic root ratio (LA/Ao), and the presence of congestive heart failure. Four variables remained significant in the multiple regression analysis with TRPG as a dependent variable: modeled as linear variables LA/Ao (P < .0001) and RVIDDn (P = .041), modeled as second order polynomial variables: AT/DT (P = .0039) and LVIDDn (P < .0001) The adjusted R 2 ‐value for the final model was 0.45 and receiver operating characteristic curve analysis suggested the model's performance to predict PH, defined as 36, 45, and 55 mmHg as fair (area under the curve [AUC] = 0.80), good (AUC = 0.86), and excellent (AUC = 0.92), respectively.Conclusion and Clinical ImportanceIn dogs with MMVD, the presence of PH might be suspected with the combination of decreased PA AT/DT, increased RVIDDn and LA/Ao, and a small or great LVIDDn.

Prevalence and prognostic importance of pulmonary hypertension in dogs with myxomatous mitral valve disease.

BackgroundPulmonary hypertension (PH) is common in dogs with myxomatous mitral valve disease (MMVD) but its effect on clinical outcome has not been investigated.Hypothesis/objectivesThe presence of PH worsens the outcome in dogs with MMVD. To compare survival times of dogs with MMVD and PH to those without PH.AnimalsTwo hundred and twelve client‐owned dogs.MethodsCase review study. Medical records of dogs diagnosed with ACVIM stage B2 and C MMVD between January 2010 and December 2011 were retrospectively reviewed. Long‐term outcome was determined by telephone interview or from the medical record. End of the observation period was March 2013. PH was identified if tricuspid regurgitation peak velocity was >3 m/s.ResultsTwo hundred and twelve were identified. Eighty‐three dogs (39%) had PH. PH was more commonly identified in stage C compared to B2 (P < .0001). One hundred and five (49.5%) dogs died during the observation period. Median survival time for the entire study population was 567 days (95% CI 512–743). Stage C (P = .003), the presence of PH (P = .009), left atrial to aortic root ratio (LA/Ao) >1.7 (P = .0002), normalized left‐ventricular end‐diastolic diameter (LVEDn) >1.73 (P = .048), and tricuspid regurgitation pressure gradient (TRPG) >55 mmHg (P = .009) were associated with worse outcomes in the univariate analyses. The presence of TRPG >55 mmHg (HR 1.8 95% CI 1–2.9; P = .05) and LA/Ao > 1.7 (HR 2 95% CI 1.2–3.4; P = .01) remained significant predictors of worse outcome in the multivariate analysis.Conclusions and Clinical ImportanceIn dogs with MMVD, moderate to severe PH worsens outcome.

Retrospective evaluation of moderate-to-severe pulmonary hypertension in dogs naturally infected with Angiostrongylus vasorum.

The outcome in dogs with pulmonary hypertension associated with natural Angiostrongylus vasorum infection is unclear. This study aimed to report long-term outcome of dogs with A. vasorum and pulmonary hypertension, and to evaluate factors associated with pulmonary hypertension development. It was hypothesised that dogs with pulmonary hypertension had a shorter survival time than dogs without pulmonary hypertension. Retrospective review of clinical records of dogs diagnosed with A. vasorum. Dogs were classified as having or not having pulmonary hypertension based on clinical signs and imaging findings. Signalment, signs and outcome were recorded. DNA obtained from banked samples was genotyped for the PDE5a:E90K polymorphism, a possible factor in development of pulmonary hypertension. The proportion of dogs with moderate-to-severe pulmonary hypertension and A. vasorum infection in the study population was 14 · 6%. No difference in the population characteristics or PDE5a genotype was detected between dogs with and without pulmonary hypertension. Dogs with pulmonary hypertension had a significantly shorter survival time (P = 0 · 006) and a greater risk of death within 6 months of diagnosis (odds ratio 12 · 5, 95% confidence interval 2 · 1 to 74 · 9; P = 0 · 0053). A. vasorum-associated pulmonary hypertension is an important problem in naturally infected dogs and has a negative effect upon survival.

Predictive model for the detection of pulmonary hypertension in dogs with myxomatous mitral valve disease.

Pulmonary hypertension (PH) often occurs due to a left heart disease, such as myxomatous mitral valve disease (MMVD), in dogs and is diagnosed using Doppler echocardiography and estimated pulmonary arterial pressure. Diagnosis of PH in dogs requires expertise in echocardiography: however, the examination for PH is difficult to perform in a clinical setting. Thus, simple and reliable methods are required for the diagnosis of PH in dogs. The purpose of this study was to develop models using multiple logistic regression analysis to detect PH due to left heart disease in dogs with MMVD without echocardiography. The medical records of dogs with MMVD were retrospectively reviewed, and 81 dogs were included in this study and classified into PH and non-PH groups. Bivariate analysis was performed to compare all parameters between the groups, and variables with P values of <0.25 in bivariate analysis were included in multiple logistic regression analysis to develop models for the detection of PH. In multiple logistic regression analysis, the model included a vertebral heart scale short axis of >5.2 v, and a length of sternal contact of >3.3 v was considered suitable for the detection of PH. The predictive accuracy of this model (85.9%) was judged statistically adequate, and therefore, this model may be useful to screen for PH due to left heart disease in dogs with MMVD without echocardiography.

Evaluation of C-reactive protein as a clinical biomarker in naturally heartworm-infected dogs: A field study

Canine heartworm disease caused by Dirofilaria immitis is considered a pulmonary disease, which leads to pulmonary hypertension, and in the late stage, may induce right cardiac insufficiency. Adult worms are localized in the pulmonary arteries, which undergo endothelial damage (proliferative endoarteritis), the severity of which depends on the duration of infection and the worm burden. C-reactive protein (CRP) is a major canine acute-phase protein that rapidly increases in a wide range of inflammatory conditions and rapidly decreases when inflammation resolves. CRP is therefore considered a sensitive but nonspecific marker of inflammation. Pulmonary arterial damage in canine heartworm may induce an increase in CRP concentrations similar to what occurs in humans with endoarteritis. The aim of the present study was to investigate whether CRP may be a diagnostic and/or prognostic marker in canine heartworm, whether it may be used for staging and monitoring canine heartworm, and whether its concentration depends on worm burden or on pulmonary arterial damage. Serum CRP concentrations were determined in 57 dogs with heartworm disease, 47 of which were grouped according to parasite burden (low: n=11; high: n=10) or on severity of pulmonary hypertension (mild: n=16; severe: n=10). An additional 23 heartworm-free cardiopathic dogs were grouped on the absence of pulmonary hypertension (n=8), presence of dilated cardiomyopathy (DCM) (n=6), or presence of cardiomyopathy and pulmonary hypertension (n=3) due to previous heartworm disease that had been treated (n=6). Twenty control dogs also were sampled for CRP concentrations. Results show that CRP was significantly increased (p<0.001) in dogs with heartworm or cardiomyopathy compared with concentrations in controls. In the heartworm group, CRP was significantly increased (p<0.001) in dogs with mild or severe pulmonary hypertension but not in dogs with low or high parasite burden without pulmonary hypertension. Heartworm-free cardiopathic dogs had significantly high (p<0.01) CRP concentrations if affected by DCM or pulmonary hypertension. ROC curves showed that CRP has good discriminating power for pulmonary hypertension (AUC=0.92 for the entire dataset, 1.00 for dogs with heartworm) and that pulmonary hypertension in heartworm must be suspected when CRP values are higher than 6.8mg/dL. Conversely, severe pulmonary hypertension is suspected only if CRP values are very high (>29.8mg/L). In conclusion, CRP can be used as a marker of endothelial arteritis and pulmonary hypertension in dogs with heartworm.

Doppler echocardiographic evidence of pulmonary hypertension in dogs: a retrospective clinical investigation

Pulmonary hypertension (PH) decreases resistance to fatigue and life expectancy. The aim of this study was to correlate some indirect Doppler indices of PH with tricuspid and pulmonary regurgitation criteria and to relate PH on different indices with the severity of clinical signs. Furthermore the pathogenetic mechanisms associated to PH development were discussed. Dogs with Doppler echocardiographic evidence of PH diagnosed by assessment of pulmonary and tricuspid regurgitant jet velocity were selected, their clinical records were reviewed and a clinical score was computed. Seventeen cases of PH were identified. The degree of PH was assessed based on systolic or diastolic pulmonary pressure and the indirect Doppler indices (AT/ET and Tei Index) were calculated; data were statistically evaluated. Indirect Doppler indices were calculated also in a control group of seven healthy dogs. The most common clinical signs were coughing, dyspnea and syncope; the most common condition associated to PH development was the left-sided valvular heart disease. A significant positive correlation was found between Tei Index and both the systolic pressure and the severity of PH while no correlations were found between PH on different indices and clinical score and/or severity of clinical signs. Results of this study suggest that Tei-index could be an useful support not only to reveal PH but also to give information on the severity of PH. The clinical picture in dogs with PH is apparently unpredictable and not strictly correlated with the severity of PH.

Efficacy of sildenafil therapy for pulmonary hypertension in dogs: a systematic review

This systematic review aimed to assess the efficacy of sildenafil in the treatment of pulmonary hypertension (PH) in dogs and, when possible, to propose recommendations for or against its use. Electronic searches were carried out using six international databases. The inclusion criterion was in vivo clinical trials that assessed the efficacy of sildenafil in the treatment of naturally occurring PH. The scoring system was designed to take into account aspects such as the form of distribution and masking of experimental treatments, the number of animals, association with other drugs, diagnostic methods for PH, evaluations of the clinical response to treatment and adverse effects. A total of five papers were found. In general, the clinical condition and quality of life of the animals improved after sildenafil therapy, and the occurrence of adverse effects was uncommon. Echocardiographic findings provided evidence for changes in pulmonary arterial pressure which could be associated with alterations in physical activity and survival time. Still, the methodological quality of the studies was low, only one of them was a randomised, placebo-controlled and double-blind clinical trial. Furthermore, with modest evidence, this study allowed the recommendation that sildenafil is an important therapy which can play a positive therapeutic role in the treatment of canine PH. Additionally, prospective, randomised, blinded and controlled studies with a larger number of animals assessing physical activity and the adverse effects of sildenafil and other drugs in association are recommended to evaluate the efficacy of this drug in dogs.

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.

The Novel Soluble Guanylate Cyclase Activator PPCA Reverses Acute Hypoxia‐induced Pulmonary Hypertension in Dogs

Nitric oxide (NO) plays a critical role in regulating pulmonary vascular tone. Impaired bioavilability of the NO receptor, soluble guanylate cyclase (sGC), and/or response to endogeneous NO has been implicated in the pathogenesis of pulmonary hypertension (PH). We hypothesize that activating sGC in a NO‐independent manner will provide a valuable therapy for patients with PH.We generated a novel NO‐independent type 2 sGC activator, PPCA, and tested it in a canine model of hypoxia‐induced pulmonary hypertension. Under normoxic conditions PPCA dose‐dependently (3–100 μg/kg, IV) decreased mean arterial pressure (MAP) and pulmonary arterial pressure (PAP) in anesthetized and catheterized beagle dogs (n=5). Following 20 minutes of hypoxia (10% O2), either saline or PPCA (15μg/kg, IV) was administered. PPCA significantly decreased PAP (−25.1±4.1%) vs. vehicle (−7.6±1.4%, P&lt; 0.05), MAP (−16.1± 0.1%) vs. vehicle (−2.7±0.1%, P&lt;0.05), PCWP and LVEDP. In addition, PPCA improved SaO2 and relieved labored breathing as compared to vehicle controls. In contrast, renal blood flow, LV dP/dtmax and cardiac output were not altered by PPCA. Early administration of PPCA (30μg/kg, IV) at 5 minutes after hypoxia completely blocked the hypoxic pulmonary vasoconstriction for over 80 minutes.These data suggest that activation of sGC by PPCA improves pulmonary hemodynamics and function in hypoxia‐induced pulmonary hypertension.

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 ?2.8 m/s or a peak pulmonic insufficiency flow velocity ?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 &gt; .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 &gt;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.

Sildenafil Citrate Therapy In 22 Dogs with Pulmonary Hypertension

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. Treatment with sildenafil will improve echocardiographic determinants of PH in dogs, while also improving quality of life and survival. Twenty-two dogs with clinical and echocardiographic evidence of pulmonary hypertension. 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. 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. 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.

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) 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.

Doppler Echocardiographic Prediction of Pulmonary Hypertension in West Highland White Terriers with Chronic Pulmonary Disease

Background: Pulmonary hypertension (PH) is commonly diagnosed by Doppler echocardiography (DE) of tricuspid regurgitation (TR). However, TR may be absent or difficult to measure.Hypothesis: Doppler‐derived systolic time intervals of pulmonary artery (PA) flow may be used to predict PH in dogs.Animals: Seventy‐three healthy dogs and 45 West Highland white terriers (WHWT) with interstitial pulmonary disease (IPD).Methods: Echocardiographic studies, including determination of right ventricular acceleration time (AT), ejection time (ET), and AT:ET ratio; right ventricular shortening fraction (RV‐SF); and TR velocity, were performed. Pulmonary hypertension was defined by TR &gt; 3.1 m/s.Results: In healthy WHWT, AT (median, range) was 73 ms (53 to 104) and AT:ET was 0.40 (0.28 to 0.55). AT:ET was minimally affected by age (R2= 0.04, 95% confidence interval [CI] 0.01–0.07, P &lt; .001) but not by heart rate, body weight, or RV‐SF. In all WHWT with TR, AT and AT: ET were inversely related to calculated systolic PA pressure (R2= 0.52, 95% CI 0.42–0.62, P &lt; .001 andR2= 0.36, 95% CI 0.29–0.42, P = .001). Clinical cutoffs to predict systolic PH were defined for AT (58 ms; sensitivity [Se] 88% and specificity [Sp] 80%) and AT:ET (0.31; Se 73% and Sp 87%).Conclusion and Clinical Importance: PH is common in WHWT with IPD. Analysis of right ventricular AT and AT: ET may be predictive of PH and should be particularly useful if TR is absent.

Doppler Echocardiographic Prediction of Pulmonary Hypertension in West Highland White Terriers with Chronic Pulmonary Disease

Pulmonary hypertension (PH) is commonly diagnosed by Doppler echocardiography (DE) of tricuspid regurgitation (TR). However, TR may be absent or difficult to measure. Doppler-derived systolic time intervals of pulmonary artery (PA) flow may be used to predict PH in dogs. Seventy-three healthy dogs and 45 West Highland white terriers (WHWT) with interstitial pulmonary disease (IPD). Echocardiographic studies, including determination of right ventricular acceleration time (AT), ejection time (ET), and AT : ET ratio; right ventricular shortening fraction (RV-SF); and TR velocity, were performed. Pulmonary hypertension was defined by TR >3.1 m/s. In healthy WHWT, AT (median, range) was 73 ms (53 to 104) and AT : ET was 0.40 (0.28 to 0.55). AT : ET was minimally affected by age (R2 = 0.04, 95% confidence interval [CI] 0.01-0.07, P < .001) but not by heart rate, body weight, or RV-SF. In all WHWT with TR, AT and AT : ET were inversely related to calculated systolic PA pressure (R2 = 0.52, 95% CI 0.42-0.62, P < .001 and R2 = 0.36, 95% CI 0.29-0.42, P = .001). Clinical cutoffs to predict systolic PH were defined for AT (58 ms; sensitivity [Se] 88% and specificity [Sp] 80%) and AT : ET (0.31; Se 73% and Sp 87%). PH is common in WHWT with IPD. Analysis of right ventricular AT and AT : ET may be predictive of PH and should be particularly useful if TR is absent.

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.

Endogenous NO does not regulate baseline pulmonary pressure, but reduces acute pulmonary hypertension in dogs.

It has remained unclear whether endogenous production of nitric oxide (NO) plays an important role in the regulation of physiologically normal pulmonary pressures. Severe alveolar hypoxia is accompanied by decreased pulmonary NO production, which could contribute to the development of hypoxic pulmonary hypertension. On the other hand, pharmacological NO inhibition further augments this hypertensive response. The aims of the present study were to test: (a) whether NO contributes importantly in the maintenance of baseline pulmonary pressure; and (b) to which degree NO is involved in the pulmonary haemodynamic adjustments to alveolar hypoxia. In anaesthetized dogs (n=37), the systemic and pulmonary haemodynamic effects of the NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME, 20 mg kg(-1)) and substrate, L-arginine (200-500 mg kg(-1)), were determined at baseline and during alveolar hypoxia. Constant blood flows were accomplished by biventricular bypass, and systemic normoxaemia was maintained by extracorporeal oxygenation. The primary findings were: (a) L-NAME failed to increase baseline mean pulmonary arterial pressure (10.1 +/- 0.7 vs. 10.5 +/- 0.5 mmHg, P=ns), despite effective NO synthase inhibition as evidenced by robust increases in systemic arterial pressures; (b) L-NAME augmented the pulmonary hypertensive response to alveolar hypoxia (10.2 +/- 0.7 to 19.5 +/- 1.7 with L-NAME vs. 9.9 +/- 1.1 to 15.5 +/- 1.0 mmHg without L-NAME, P<0.05); and (c) L-arginine failed to decrease baseline or elevated pulmonary pressures. Instead, prolonged L-arginine caused increases in pulmonary pressure. These findings suggest that NO plays no significant role in the tonic physiological control of pulmonary pressure, but endogenous NO becomes an important vasodilatory modulator during elevated pulmonary pressure.

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

To characterize structural changes in pulmonary vessels of dogs with dirofilariosis. 8 dogs with dirofilariosis and 2 unaffected control dogs. 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. 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. 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.

Spasmolytic effects of prostaglandin E1 on serotonin-induced bronchoconstriction and pulmonary hypertension in dogs.

In this study, we simultaneously evaluated the spasmolytic effects of prostaglandin E1 (PGE1) on serotonin-induced bronchoconstriction and pulmonary hypertension. Eleven mongrel dogs (8-12 kg) anaesthetized with pentobarbital were assigned to two groups: saline (n = 4) and PGE1 (n = 7). Bronchoconstriction and pulmonary hypertension were elicited with serotonin 10 micrograms kg-1 + 1 mg kg-1 h-1 and assessed as the percentage change in bronchial cross-sectional area (BCA) measured by bronchoscopy and pulmonary vascular resistance (PVR), respectively. Thirty minutes after starting the serotonin infusion, saline or PGE1 0 (saline), 0.01, 0.1, 1.0 or 10 micrograms kg-1 i.v. was given. %BCA and %PVR (basal = 100%) were assessed before and 30 min after serotonin, and 30 and 60 min after saline (saline group) or 5 min after each dose of PGE1 (PGE1 group). In the saline group, pulmonary hypertension and bronchoconstriction were stable. In the PGE1 group, PGE1 at > or = 0.1 microgram kg-1 significantly decreased %BCA and 10 micrograms kg-1 almost fully reversed the constriction (from mean (SEM) 56.2% (4.9%) to 94.4% (3.7%)). %PVR was significantly decreased at 10 micrograms kg-1 (from 230% (24%) to 176% (11%)) only. We suggest that PGE1 may produce bronchodilation rather than pulmonary vasodilation.