In vitro hypoxia differentially affects constriction and relaxation responses of isolated pulmonary arteries from broiler and leghorn chickens.

Under normoxic conditions in vitro, isolated pulmonary arteries from broilers exhibit reduced endothelium-dependent relaxation responses when compared with Leghorns. In vivo, hypoxia increases the susceptibility of broiler chickens to pulmonary hypertension syndrome (PHS), whereas Leghorns are considered resistant to PHS. Because L-arginine supplementation decreases the incidence of PHS in vivo and improves the relaxation responses of broiler isolated pulmonary arteries in vitro, we hypothesized that in vitro hypoxia would further reduce the relaxation responses of broilers to endothelium-derived nitric oxide (EDNO)-dependent vasodilators and that L-arginine supplementation would alleviate this impairment. As a test of this hypothesis, pulmonary arteries from broiler and Leghorn chickens were isolated and exposed to normoxia or hypoxia in the presence or absence of L-arginine while their constriction and relaxation responses to vasoactive compounds were recorded. In broilers, hypoxia did not affect the constriction responses of isolated pulmonary arteries but decreased EDNO-dependent acetylcholine-induced relaxation responses. In contrast, in Leghorns hypoxia increased endothelin-1-induced vasoconstriction responses and reduced the EDNO-dependent relaxation responses only to the lowest concentration of acetylcholine used. L-Arginine supplementation augmented the relaxation responses to acetylcholine in broilers and Leghorns under normoxia but failed to augment them under hypoxia. Relaxation responses to the NO donor, sodium nitroprusside, were not affected by hypoxia in Leghorns but were increased by hypoxia in broilers. These results suggest that the increased incidence of PHS in broiler chickens reared under hypoxia may be associated with a hypoxia-induced reduction in the synthesis or activity of EDNO in the pulmonary circulation.

Pulmonary artery vasoactivity in broiler and Leghorn chickens: an age profile.

Vascular function plays a preponderant role in the pulmonary changes that occur with maturation, during birth, and in the development of pulmonary hypertension. This study was designed to characterize the changes in vasoactivity occurring in broiler and Leghorn chickens from late embryonic life to 5 wk of age. Pulmonary arteries were isolated from 19- and 20-d-old embryos, hatchlings, and 1-, 2-, 3-, 4- and 5-wk-old chickens of both lines and subjected to KCl (45.4 mM)- and endothelin-1 (10(-7.5) M)-induced vasoconstrictions followed by acetylcholine (ACh; 10(-5), 10(-6) and 10(-7) M)- and papaverine (10(-4) M)-induced vasodilations. Vasoconstrictions were greatest at hatch and rapidly declined thereafter, whereas vasodilations were greatest in 20-d-old embryos except with 10(-7) M ACh. Broilers grew faster than Leghorns and had lower vasodilation responses to all concentrations of ACh at 2 and 5 wk of age. Broilers also had greater right-to-total ventricular weight ratios at 5 wk of age, whereas ratios were greater in Leghorn embryos at 20 d of incubation and at hatch. Thus, for a brief period before hatch there is a significant increase in pulmonary endothelium-dependent vasodilation capacity in the chicken embryo, which may aid in the transition from chorioallantoic to pulmonary respiration. The absence of differences in vasodilator capacity between broilers and Leghorns before hatch suggests that the differences in pulmonary artery relaxation capacity and pulmonary hypertension observed after hatch in broilers are not necessarily acquired during incubation but may be related to rapid growth of the broiler chicken.

Echocardiographic study of pulmonary hypertension syndrome in broiler chickens.

Echocardiography was used to study cardiovascular structure and function during the development of pulmonary hypertension syndrome (PHS) in broiler chickens. Body weight-normalized right and left ventricular diameters at both end-diastole (RVDD, LVDD) and end-systole (RVDS, LVDS) were determined weekly in broilers reared under either normobaric (altitude, 96.7 m) or hypobaric conditions (simulated altitude, 2900 m) until 5 wk of age. Hypobaric-exposed broilers had larger RVDD at 3 and 4 wk of age and larger RVDS at 3, 4, and 5 wk of age. Hypobaric-exposed broilers also had larger LVDD at 2, 3, 4, and 5 wk of age and larger LVDS at 4 wk of age. Right (RVFS) and left ventricular fractional shortening (LVFS) were smaller in hypobaric- vs. normobaric-exposed broilers at 3, 4, and 5 wk of age and at 4 wk of age, respectively. Among hypobaric-exposed birds, PHS-positive (+) broilers had larger RVDD and RVDS than PHS-negative (-) broilers on week 3 and on weeks 1 and 3 after hypobaric exposure, respectively. PHS-positive (+) broilers also had smaller RVFS on week 1 after hypobaric exposure. Electrocardiographic and post-mortem data indicated that PHS+ broilers also developed right ventricular hypertrophy when compared with PHS-negative (-) broilers. These results are consistent with the hypothesis that PHS develops as a result of pulmonary hypertension and cardiac overload and suggest that PHS+ broilers have a greater and more persistent reaction to hypoxia than PHS- broilers.

Application of phonocardiography for detecting hypoxia-induced cardiovascular adaptation in the chicken.

Phonocardiography was evaluated as a noninvasive technique for diagnosis of cardiovascular adaptation and disease in broiler chickens. Heart sounds (HSs) were compared in a fast-growing (FG) commercial broiler line that is highly susceptible to chronic right heart failure resulting from pulmonary hypertension syndrome (PHS) and in a non-selected slow-growing (SG) broiler line that is resistant to PHS. HSs were analyzed in broilers reared in hypobaric hypoxia (HYP) and normobaric (CON) conditions. PHS was induced by a combination of embryonic hypoxia and HYP exposure. HSs were recorded with a microphone placed at the thoracic inlet of each chicken. Electrocardiograms were used to mark the sampling interval for the first, second, and total HS. Digitized HS signals were analyzed for peak frequency, mean peak frequency, and band width. Birds were examined for PHS lesions when 6 wk of age, at the end of each experiment. HSs were compared by line and treatment (Experiment 1) or by treatment and week (Experiment 2). In addition, HS frequencies were analyzed within the HYP treatment group for differences between birds with severe or no gross PHS lesions. HS frequencies generally decreased with age and were also lower in the FG than the SG line. Hypobaric exposure decreased all HS frequencies in the SG line and components of the first HSs in the FG line. The SG line did not develop gross lesions of PHS. In the FG line, significant differences in HS frequencies were observed between HYP and CON groups but not between PHS- and PHS+ broilers. Frequency changes described in humans with PHS were not observed. Further development to maximize the resolution of the HS waveforms and improved matching of the sampling interval to the electrical or hemodynamic output of the chicken heart may allow its use as a diagnostic tool for differentiating broilers with normal cardiac function or physiologic adaptation from those with cardiovascular disease.

Pulmonary artery endothelium-dependent vasodilation is impaired in a chicken model of pulmonary hypertension.

Among chicken strains, broilers are prone to pulmonary hypertension, whereas Leghorns are not. Relaxations to endothelium-dependent (ACh, A23187) and endothelium-independent [sodium nitroprusside (SNP), papaverine (PPV)] vasodilators were compared in preconstricted pulmonary artery (PA) rings from these chicken strains. ACh (10(-7), 10(-6), and 10(-5) M)- and A23187 (10(-6) and 10(-5.5) M)-induced relaxations were smaller (P < 0.05) in broilers than Leghorns. N(G)-nitro-L-arginine methyl ester (10(-3.5) M) caused similar reductions in ACh-induced relaxations in both strains. L-Arginine (10(-4) M) enhanced ACh-induced relaxations more in broilers than Leghorns. Relaxations to 10(-10)-10(-6) M SNP did not differ between strains, but were greater (P < 0.05) in broilers than Leghorns at higher concentrations (10(-5) and 10(-4) M). PPV (10(-4) M)- and SNP (10(-4) M)-induced maximal relaxations were greater in broilers than in Leghorns (176.2 +/- 14.7 vs. 120.9 +/- 14.7% and 201.3 +/- 7.8 vs. 171.2 +/- 10.7%, respectively, P < 0.05). Broiler PA rings appear to have increased intrinsic tone and reduced endothelium-derived nitric oxide activity, both of which may contribute to the susceptibility of broiler chickens to pulmonary hypertension.

Echocardiographic evaluation of cardiac structure and function in broiler and Leghorn chickens.

This study was conducted to validate echocardiography in chickens, and to compare cardiac structure and function between broiler and Leghorn chickens. Diameters of the right and left ventricles, and thicknesses of the left ventricular free wall and the interventricular septum were measured echocardiographically in 5- and 7-wk-old chickens from both lines. Images were obtained from minimally restrained, standing birds using a 7.5 MHz probe placed in a parasternal position. End-systolic and end-diastolic echocardiographic measurements were compared with post-mortem measurements of the same variables. Comparisons resulted in correlation coefficients greater than 0.70 between in vivo (echocardiographic) and post-mortem measurements of the same variables, with post-mortem measurements more closely resembling end-diastolic echocardiographic measurements. After being normalized to body weight, post-mortem myocardial thicknesses, aortic and left ventricular diameters, heart weight at 5 wk of age, and left ventricular weight at 7 wk of age were smaller in broiler than in Leghorn chickens. Echocardiographic parameters, including ventricular wall thicknesses, ventricular diameters, and left ventricular fractional shortening, were also smaller in the broiler chicken. Right ventricular fractional shortening did not differ between the chicken lines. These results indicate that echocardiography is a useful noninvasive technique for in vivo evaluation of cardiac structure and function in the chicken, and that broiler chickens have a relatively smaller structural and functional heart than Leghorn chickens.