Sodium hydrosulfide prevents hypoxia-induced pulmonary arterial hypertension in broilers.

1. The aim of the study was to determine if H(2)S is involved in the development of hypoxia-induced pulmonary hypertension in broilers, a condition frequently observed in a variety of cardiac and pulmonary diseases. 2. Two-week-old broilers were reared under normoxic conditions or exposed to normobaric hypoxia (6 h/day) with tissue levels of H(2)S adjusted by administering sodium hydrosulfide (NaHS, 10 µmol/kg body weight/day). Mean pulmonary arterial pressure, right ventricular mass, plasma and tissue H(2)S levels, the expression of cystathionine-ß-synthase (CSE) and vascular remodeling were determined at 35 d of age. 3. Exposure to hypoxia-induced pulmonary arterial hypertension was characterized by elevated pulmonary pressure, right ventricular hypertrophy and vascular remodeling. This was accompanied by decreased expression of CSE and decreased concentrations of plasma and tissue H(2)S. 4. Hypoxia-induced pulmonary hypertension was significantly reduced by administration of NaHS but this protective effect was largely abolished by D, L-propargylglycerine, an inhibitor of CSE. 5. The results indicate that H(2)S is involved in the development of hypoxia-induced pulmonary hypertension. Supplementing NaHS or H(2)S could be a strategy for reducing hypoxia-induced hypertension in broilers.

Comparison of the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.

OBJECTIVE: To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis. ANIMALS: 24 Beagles. PROCEDURES: 18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographically and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated. RESULTS: After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.

Increased calcium deposits and decreased Ca2+-ATPase in right ventricular myocardium of ascitic broiler chickens.

Right ventricular hypertrophy and failure is an important step in the development of ascites syndrome (AS) in broiler chickens. Cytoplasmic calcium concentration is a major regulator of cardiac contractile function and various physiological processes in cardiac muscle cells. The purpose of this study was to measure the right ventricular pressure and investigate the precise ultrastructural location of Ca(2+) and Ca(2+)-ATPase in the right ventricular myocardium of chickens with AS induced by low ambient temperature. The results showed that the right ventricular diastolic pressure of ascitic broilers was significantly higher than that of control broilers (P < 0.01), and the maximum change ratio of right intraventricular pressure (RV +/- dp/dt(max)) of ascitic broilers was significantly lower than that of the controls (P < 0.01). Extensively increased calcium deposits were observed in the right ventricular myocardium of ascitic broilers, whereas in the age-matched control broilers, calcium deposits were much less. The Ca(2+)-ATPase reactive products were obviously found on the sarcoplasmic reticulum and mitochondrial membrane of the control right ventricular myocardium, but rarely observed in the ascitic broilers. The data suggest that in ascitic broilers there is the right ventricular diastolic dysfunction, in which the overload of intracellular calcium and the decreased Ca(2+)-ATPase activity might be the important factors.

Plasma taurine levels in broilers with pulmonary hypertension syndrome induced by unilateral pulmonary artery occlusion.

Low plasma levels of taurine are associated with losses of cardiac sarcomeric proteins, leading to heart failure in mammals. Recently, it was proposed that cardiac taurine depletion serves to defend the heart against injury caused by regional ischemia in mammals. The role of taurine has not been well documented in broilers, particularly in relation to pulmonary hypertension syndrome (PHS; ascites). Three independent experiments evaluated plasma taurine in male broilers by utilizing the following treatments: unoperated controls (CONTROL; n = 10 in each experiment); sham operated (SHAM; n = 11, 12, and 10); or, unilaterally pulmonary artery clamped (PAC; n = 18, 29, and 24) that did (PAC-ascites) or did not (PAC-normal) develop ascites within 12 d postsurgery. Plasma samples were collected 9 and 11 d postsurgery in Experiments 1 and 2, respectively, and 2 d before and 4, 8, and 12 d after surgery in Experiment 3. Plasma taurine was analyzed by HPLC. Twelve days postsurgery, the birds were euthanatized, and ventricles were weighed for calculating the right:total ventricular weight ratio (RV:TV). The RV:TV of PAC birds (>0.35) consistently was higher (P < 0.01) than that of CONTROL and SHAM birds (<0.27 and 0.25, respectively). In Experiments 1 and 2, plasma taurine was higher (P < 0.05) in PAC-ascites (380 and 370 nmol/mL) than in SHAM broilers (183 and 186 nmol/mL), whereas CONTROL (262 and 278 nmol/mL) and PAC-normal (362 and 300 nmol/mL) broilers tended to have intermediate plasma taurine levels. In Experiment 3, PAC birds had higher (P < 0.05) plasma taurine at 8 and 12 d postsurgery when compared with presurgery levels, whereas plasma taurine was unchanged over time in CONTROL and SHAM birds. These results suggest cardiac taurine may be released into the plasma as a protective mechanism in response to the induction of pulmonary hypertension, hypoxemia, and right-side heart failure, similar to the mechanism reported for protecting cardiac muscle from ischemia in mammals.

Isolated right-ventricular hypertrophy associated with severe pulmonary vascular apolipoprotein A1-derived amyloidosis in a dog.

A 12-year-old dachshund was referred for respiratory distress, coughing, and weight loss. Cyanosis, dyspnea, tachypnea, and harsh lung sounds were noted on physical examination. Polycythemia with an increased number of nucleated red blood cells; right atrial enlargement; severe interstitial-to-alveolar pattern in all lung fields; and peripheral, echogenic, pulmonary masses were observed. Cytological examination of pulmonary aspirates indicated possible pulmonary carcinoma. The dog was euthanized at the owner's request. Isolated right-ventricular hypertrophy and pulmonary arteriopathy with amyloid deposits of apolipoprotein A1 were identified upon necropsy and histopathology. Pulmonary vascular amyloidosis should be considered in the differential diagnoses of respiratory distress in aged dogs.

Effect of dietary flax oil and hypobaric hypoxia on right ventricular hypertrophy and ascites in broiler chickens.

1. The effect of dietary flax oil on growth rate, blood haemoglobin content, mortality and incidence of pulmonary hypertension and ascites in broilers at ambient pressure and at reduced atmospheric pressure was examined. 2. Birds were housed either in hypobaric chambers simulating 1000, 1500 or 2200 m altitude or in pens at ambient atmospheric pressure and fed on diets containing 100 g/kg added fat as either an animal/vegetable (A/V) blend or flax oil. 3. Birds raised under hypobaric conditions had a decreased growth rate and increased mortality, blood haemoglobin content, and incidence of pulmonary hypertension and ascites compared to the groups at normal atmospheric pressure. 4. Broilers fed on the diet containing flax oil showed no difference in growth rate or blood haemoglobin content compared to birds fed on the A/V fat diet raised at the same altitude. 5. Inclusion of flax oil in the diet decreased mortality and the incidence of ascites at 2200 m and pulmonary hypertension at 1500 m. 6. Flax oil may be an effective method of reducing ascites and pulmonary hypertension in broilers without affecting performance.