Evaluation of acute phase proteins, adiponectin and endothelin-1 to determine vascular damage in dogs with heartworm disease (Dirofilaria immitis), before and after adulticide treatment.

Previous studies have shown the existence of an acute phase response in dogs with heartworm (Dirofilaria immitis), probably caused by the vascular inflammation that occurs during the pathogenesis of this disease. In addition, it has been seen that this acute phase response persists after finishing treatment, especially in dogs with pulmonary hypertension (PH). Furthermore, echocardiographic studies have shown that PH and endarteritis appear to persist for at least 10 months after completion of adulticide treatment, suggesting that the vascular changes in these dogs may not be reversible. Therefore, the objective of this study was to evaluate the serum concentrations of different positive acute phase proteins (APP) [C reactive-protein (CRP), haptoglobin and ferritin] and negative APP (albumin and paraoxonase-1 (PON-1)), and the usefulness of the endothelin-1 (ET-1) and adiponectin, in dogs infected by D. immitis to evaluate their usefulness as diagnostic biomarkers of vascular damage and PH and their progression throughout therapy up to 7 months after the end of adulticide treatment. Twenty-five heartworm-infected dogs received adulticide treatment, and serum measurements were performed on the day of diagnosis (day 0), day of discharge (day 90), and 6 months after discharge (day 270). In addition, presence or absence of PH was also echocardiographically determined using the Right Pulmonary Artery Distensibility Index. PH was present in 44% of the dogs on day 0 and day 90, and in 48% of dogs on day 270. Alterations were observed in the concentrations of all APP throughout the study, persisting the alterations in PON-1 and ferritin on day 270. Depending on the presence or absence of PH, CRP showed significant differences throughout the study, as did ET-1. On the other hand, adiponectin did not show variations throughout the study, so it did not seem a useful marker in this disease. These results could reflect the possible persistence of vascular inflammation up to 7 months after finishing treatment, whether or not there was PH, and consolidate the study of APP as useful markers in heartworm disease. Moreover, persistent PH could be the consequent clinical manifestation in dogs with more severe vascular alterations so the study of APP, especially CRP, and ET-1 could be especially advantageous in these patients in the early evaluation of the disease, as well as for the determination of disease severity, monitoring therapeutic responses, and predicting outcomes.

Persistence of pulmonary endarteritis in canine heartworm infection 10 months after the eradication of adult parasites of Dirofilaria immitis.

Pulmonary endarteritis caused by Dirofilaria immitis and pulmonary hypertension (PH) are closely linked and the determination of PH could be validated to assess the severity and chronicity of the vascular damage, i.e. by the use of the Right Pulmonary Artery Distensibility (RPAD) Index. The aim was to evaluate the RPAD Index in dogs 10 months after the last dose of adulticide. The study included 23 client-owned dogs with heartworm brought for adulticide treatment. Echocardiographic exam was carried out to estimate worm burden, RPAD Index as well as other routine echocardiographic values on day 0 (diagnosis), day 120 (discharge), and 10 months after the last dose of adulticide. No significant differences were observed in the RPAD Index over time, neither when microfilaremic status and parasite burden were evaluated. An RPAD Index <29% was found in 52.2% of the dogs on day 0, day 120, and 10 months after the last dose of adulticide. Regarding other echocardiographic parameters, only significant differences were observed on tricuspid annular plane systolic excursion (TAPSE) values between day 0:day 120 (p = 0.008), and day 0:end of the study (p = 0.037). There was not significant improvement in pulmonary damage 10 months after the elimination of the parasites (p = 0.296), suggesting that, once the endarteritis has developed, the vascular changes are chronic and may not be reversible. The modifications of the TAPSE value suggest an improvement in the systolic function of the right ventricle after the disappearance of the worms, independently of the presence of PH. The endarteritis causes a decrease in the elasticity in the pulmonary vasculature and an increase in the resistance that, chronically, and depending on the severity, will cause the development of PH and later right heart failure. This complication of the disease is one of the most damaging and frequent, so it is necessary to adequately monitor PH in dogs undergoing adulticide treatment. Furthermore, knowing the pulmonary status could provide valuable information to help provide an objective prognosis and help assess the need to add additional treatments, once the worms have been eliminated.

Sitagliptin improved glucose assimilation in detriment of fatty-acid utilization in experimental type-II diabetes: role of GLP-1 isoforms in Glut4 receptor trafficking.

BACKGROUND: The distribution of glucose and fatty-acid transporters in the heart is crucial for energy consecution and myocardial function. In this sense, the glucagon-like peptide-1 (GLP-1) enhancer, sitagliptin, improves glucose homeostasis but it could also trigger direct cardioprotective actions, including regulation of energy substrate utilization. METHODS: Type-II diabetic GK (Goto-Kakizaki), sitagliptin-treated GK (10 mg/kg/day) and wistar rats (n = 10, each) underwent echocardiographic evaluation, and positron emission tomography scanning for [18F]-2-fluoro-2-deoxy-D-glucose (18FDG). Hearts and plasma were isolated for biochemical approaches. Cultured cardiomyocytes were examined for receptor distribution after incretin stimulation in high fatty acid or high glucose media. RESULTS: Untreated GK rats exhibited hyperglycemia, hyperlipidemia, insulin resistance, and plasma GLP-1 reduction. Moreover, GK myocardium decreased 18FDG assimilation and diastolic dysfunction. However, sitagliptin improved hyperglycemia, insulin resistance, and GLP-1 levels, and additionally, enhanced 18FDG uptake and diastolic function. Sitagliptin also stimulated the sarcolemmal translocation of the glucose transporter-4 (Glut4), in detriment of the fatty acyl translocase (FAT)/CD36. In fact, Glut4 mRNA expression and sarcolemmal translocation were also increased after GLP-1 stimulation in high-fatty acid incubated cardiomyocytes. PI3K/Akt and AMPKα were involved in this response. Intriguingly, the GLP-1 degradation metabolite, GLP-1(9-36), showed similar effects. CONCLUSIONS: Besides of its anti-hyperglycemic effect, sitagliptin-enhanced GLP-1 may ameliorate diastolic dysfunction in type-II diabetes by shifting fatty acid to glucose utilization in the cardiomyocyte, and thus, improving cardiac efficiency and reducing lipolysis.

Evaluation of pulmonary hypertension and clinical status in dogs with heartworm by Right Pulmonary Artery Distensibility Index and other echocardiographic parameters.

BACKGROUND: Pulmonary hypertension (PH) is a frequent and severe phenomenon in heartworm disease caused by Dirofilaria immitis, mainly caused by intimal proliferation of the arteries and pulmonary thromboembolisms. Transthoracic echocardiography is the method of choice for diagnosing PH in dogs although the diagnosis is often based on indirect and subjective parameters. The Right Pulmonary Artery Distensibility Index (RPAD Index) is a method that has been recently validated to estimate the presence and severity of PH in heartworm-infected dogs. This study compared some echocardiographic parameters commonly used to estimate PH in 93 dogs infected by D. immitis and evaluated the impact of the parasite burden, microfilaremia, sex or origin of the dog (client-owned/shelter). RESULTS: None of the studied echocardiographic variables seemed useful in the estimation of the evaluated clinical aspects, except for the PA/Ao ratio for parasite burden. The RPAD Index was determined in 88 of the dogs; of these, 70.4% had PH (mild: 37.5%, moderate: 19.3%, severe: 13.6%). This Index showed non-significant differences according to microfilaremia, sex, origin or parasite burden. Symptomatic dogs showed PH more often and displayed more severe PH, in addition the presence of symptoms was greater among dogs with high burden; on the other hand 64.4% of asymptomatic dogs had some degree of PH according to the RPAD Index. Apart from the PA/Ao ratio, the other evaluated echocardiographic variables were not useful in evaluating of the hypertensive status of the heartworm-infected dog compared to the RPAD Index. CONCLUSIONS: The estimation of most common indirect parameters is not useful in predicting PH in heartworm-infected dogs. The results confirm the RPAD Index as an objective and supportive test in the monitoring and evaluation of PH in the heartworm-infected dog, and show a potential diagnostic value for the detection of PH in asymptomatic animals.

Pulmonary hypertension in dogs with heartworm before and after the adulticide protocol recommended by the American Heartworm Society.

Pulmonary hypertension (pH) is a frequent and severe phenomenon in heartworm disease (Dirofilaria immitis). There is a lack of studies assessing the evolution of the proliferative endarteritis and pH caused by D. immitis after the death of the parasites, so this study evaluated the influence that the elimination of the worms exerts over the pulmonary pressure and therefore evolution of the endarteritis, through the evaluation of the Right Pulmonary Artery Distensibility (RPAD) Index and other echocardiographic measurements in 2D mode, M-mode and Doppler echocardiography in 34 dogs naturally infected by D. immitis on day 0, and one month after the last adulticide dose (day 120). pH, based on the determination of the RPAD Index, was present in 68% of the dogs (n=23) on day 0 and on day 120. No significant differences were observed between the RPAD Index between the two measurements, and only significant differences were found in pulmonary deceleration time, ejection time, and left ventricular internal diameter in telediastole when measurements from day 0 and day 120 were compared. There was not any worsening in the development of pH after the elimination of the parasites, independently of the parasite burden. During the adulticide treatment, the death of the worms causes thromboembolism and tends to worsen the vascular damage and presence of pH . It seems that following the adulticide protocol recommended by the American Heartworm Society with the previous elimination of Wolbachia and reduction of microfilariae followed by the stepped death of the worms did not cause a significant aggravation of the pulmonary damage of the treated dogs. Neither is present any significant improvement in the RPAD Index on day 120; probably, more time is needed before appreciating some positive changes after the elimination of the worms and Wolbachia from the vasculature and further studies are necessary.

Evaluation of an oesophageal Doppler device for monitoring cardiac output in anaesthetised healthy normotensive dogs.

OBJECTIVES: To compare cardiac output measured by oesophageal Doppler and by thermodilution monitoring and to correlate the Doppler cardiac output-generated minute distance with thermodilution cardiac output in healthy anaesthetised beagle dogs. MATERIALS AND METHODS: Prospective experimental study. Six healthy adult beagle dogs were pre-medicated with intramuscular acepromazine (0 · 05 mg/kg) and methadone (0 · 3 mg/kg). Anaesthesia was induced with intravenous propofol (dose-effect) and maintained with isoflurane in oxygen. Simultaneously, a constant rate infusion of dopamine (3 µg/kg/minute) was administered to the dogs to prevent hypotension. The minute distance, Doppler and thermodilution cardiac outputs were assessed at three different end-tidal concentrations of isoflurane (1 · 0, 1 · 3 and 2 · 0%). RESULTS: Correlation between Doppler and thermodilution cardiac output (r(2) = 0 · 582) and between minute distance and thermodilution cardiac output (r(2) = 0 · 658) were moderately good, but the limits of agreement between Doppler and thermodilution cardiac outputs were above the recommended values (±39%, for a recommended value up to 30%). CLINICAL SIGNIFICANCE: Doppler and minute distance cannot be considered as an alternative method to thermodilution to monitor cardiac output in the healthy anaesthetised dog.

Is Wolbachia participating in the bronchial reactivity of cats with heartworm associated respiratory disease?

Heartworm associated respiratory disease is a pulmonary syndrome in cats that results from the vascular and parenchymal inflammatory response associated with the arrival and death of Dirofilaria immitis worms into the distal pulmonary arteries. This parasite harbors intracellular Wolbachia, an endosymbiont bacteria. The association between the parasite and the bacteria is obligatory. Some studies suggest the involvement of Wolbachia in the development of the inflammatory reaction and in the polarization of the host immune response against the parasite. Barometric whole-body plethysmography is a non-invasive pulmonary function test that allows a dynamic study of breathing patterns and is useful to study airway disease and the response to different treatments. The aim of this prospective non-blinded study was to compare the influence of Wolbachia upon the respiratory function variables in a population of cats seropositive to D. immitis by use of Barometric whole-body plethysmography. Fourteen seropositive cats to Wolbachia and eight seronegative cats were put into the plethysmograph chamber and different respiratory variables were measured. The results were analyzed and compared between the two groups of animals. Significant differences were found for bronchoconstriction index variables PAU (pause) (P-value<0.05) and Penh (enhanced pause) (P-value<0.05). The results obtained in our study suggest that Wolbachia seems to produce a greater acute inflammatory response at bronchial, vascular and parenchymal level worsening the state of broncho-reactivity associated with the presence of seropositivity to D. immitis in cats.

Arrhythmogenic right ventricular cardiomyopathy in boxer dogs: a retrospective study of survival.

The aim of the present study was to retrospectively evaluate survival in a population of 62 boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC), without left ventricular systolic failure, based on the following factors: age at diagnosis, presence of syncopal episodes, Holter arrhythmia classification and administered treatment. Medical records of boxer dogs with a diagnosis of ARVC between 2000 and 2010 were reviewed. Results showed that median survival time (MST) was longer in younger ARVC dogs than in the older ones P<0.001). MST was statistically different (P=0.012) between dogs with syncope (365 days) and dogs without syncope episodes (693 days), the probability of death within a year being 4.8 times greater in dogs with syncope (95% CI 1.48 to 15.99) than in dogs without syncope. Regarding Holter classification results, MST was 547.5 days in Holter class-2 dogs and 365 days in Holter class-4 dogs (P=0.030). There were no differences regarding treatment options; MST was 365 days (95% CI 193.615 to 536.4) in the sotalol group, 365 days (95% CI 92.86 to 637.14) in the mexiletine plus atenolol group, and 547.50 days (95% CI 170.45 to 924.55) in the procainamide group (P=0.383). According to this study, the best prognosis is for the younger boxer dog without syncope. There were no differences in survival times in relation to the different treatment options used.

Evaluation of pulmonary function variables by using plethysmography in cats with respiratory disease associated to Dirofilaria immitis.

Heartworm Associated Respiratory Disease (HARD) is a pulmonary syndrome that results from the vascular and parenchymal inflammatory response associated with the arrival and death of Dirofilaria immitis in the distal pulmonary arteries. Barometric whole-body plethysmography (BWBP) is a non-invasive pulmonary function test (PFT) that allows a dynamic study of breathing patterns and is useful to study airway disease and the response to different treatments. The aim of this prospective non-blinded study was to compare respiratory function variables between healthy cats and HARD cats (seropositive to D. immitis) by use of BWBP. Twenty-five healthy cats and six HARD cats were put into the plethysmograph chamber and different respiratory variables were measured. The results were analyzed and compared between the two groups of animals. There were significant differences for bronchoconstriction index variables Pause (P-value<0.001) and enhanced pause (P-value<0.001), minute volume (P-value<0.05) and tidal volume (P-value<0.05) between healthy and HARD cats. There were no significant differences in respiratory rate and inspiratory and expiratory times between both groups of animals. The results obtained in our study support that HARD cats show significant differences in pulmonary function variables obtained by BWBP due to an acute inflammatory response at bronchial, vascular and parenchymal level. This PFT could be a useful method to facilitate the diagnosis of pathological states of bronchoconstriction in HARD cats.

Verminous pneumonia due to Filaroides hirthi in a Scottish terrier in Spain.

A previously healthy Scottish terrier developed verminous pneumonia due to Filaroides hirthi. The disease was diagnosed on the basis of cytology of a transtracheal wash, which contained 17 per cent eosinophils and a large number of parasite larvae. Treatment with 50 mg/kg bodyweight fenbendazole daily for three weeks eliminated the parasites and improved the clinical condition of the dog.