Biomedical subjects

R F Wideman

Publications and source records attributed to R F Wideman.

At least 37 records · Page 2Linked to original sources

PubMed2002

Hemodynamic responses of broiler pulmonary vasculature to intravenously infused serotonin.

Serotonin is a potent pulmonary vasoconstrictor actively accumulated by mammalian platelets and avian thrombocytes and released into the plasma during platelet or thrombocyte aggregation. Serotonin has been implicated in the mechanisms responsible for pulmonary hypertension in several human and animal studies. However, the role of serotonin in pulmonary hypertension syndrome (PHS, ascites) in broilers previously had not been evaluated. In the present study we evaluated the pulmonary hemodynamic responses of broilers to intravenous infusions of serotonin dissolved in 2.5% (wt/vol) mannitol solution (carrier vehicle). Carrier vehicle infusion alone had no influence on any of the hemodynamic variables. Serotonin infusion triggered rapid increases in pulmonary arterial pressure to approximately 50% above pre-infusion baseline values, accompanied by decreases in mean systemic arterial pressure and cardiac output. The peak pulmonary arterial pressure response occurred within approximately 70 s after the start of serotonin infusion and remained elevated above baseline values over the course of a 10-min infusion period. Pulmonary arterial pressure and cardiac output returned to pre-infusion baseline values upon cessation of serotonin infusion, whereas mean systemic arterial pressure returned toward pre-infusion base-line values. Pulmonary hypertensive responses were associated with increased pulmonary vascular resistance (pulmonary vasoconstriction). The peak pulmonary arterial pressure attainable was inadequate to propel the normal cardiac output through the elevated pulmonary vascular resistance. Consequently, the impeded venous return to the left ventricle caused dependent reductions in stroke volume, cardiac output, and mean systemic arterial pressure. Reductions in cardiac output were associated with reductions in stroke volume but not heart rate. Any factor that reduces the pulmonary vascular capacity or increases the pulmonary vascular resistance theoretically can increase the incidence of PHS. The present study provides direct evidence that serotonin can trigger pulmonary vasoconstriction and pulmonary hypertension in broilers.

Animals↗

PubMed2002

Antioxidant enzyme activities and mitochondrial fatty acids in pulmonary hypertension syndrome (PHS) in broilers.

Major objectives of this study were to assess antioxidant protection and fatty acid profile in lung mitochondria and whole liver in broilers with pulmonary hypertension syndrome [(PHS; with and without high dietary vitamin E (VE)] (Experiment 1) and in broilers that did not develop PHS but were genetically selected (S) or not selected (NS) for resistance to PHS (Experiment 2). In Experiment 1, lung mitochondrial glutathione peroxidase (GSH-Px) activity was elevated in broilers with PHS compared to controls, broilers fed high VE, and broilers fed high VE with PHS (VE-PHS), but there were no differences in GSH reductase (GSH-Rd) among groups. In liver tissue, GSH-Px was also elevated by PHS but was lower in VE and VE-PHS groups than in controls. There were no differences in liver GSH-Rd, superoxide dismutase (SOD), or gamma-glutamylcysteine synthetase (gamma-GCS) activities with the exception that gamma-GCS was higher in the VE-PHS group than in the other groups. In Experiment 2, S lung mitochondria exhibited lower GSH-Px and higher GSH-Rd compared to NS broilers. In the liver, there were no differences in GSH-Px, GSH-Rd, or gamma-GCS, but SOD was lower in S compared to the NS broilers. High VE increased the percentage of saturated fatty acids and decreased the percentage of unsaturated fatty acids in lung mitochondria in Experiment 1; there were no differences in fatty acid content between S and NS mitochondria in Experiment 2. Thus, it appears that GSH recycling enzyme activities are affected by PHS and high VE presumably in response to differences in oxidative stress and that genetic resistance to PHS is associated with an inherently better capability to metabolize oxidants in lung mitochondria. The increase in saturation of lung mitochondrial fatty acids with high dietary VE would presumably make them more resistant to oxidative stress and, thus, reduce the level of PHS-induced oxidative stress.

Animals↗

PubMed2002

Intravenous micro-particle injection and pulmonary hypertension in broiler chickens: cardio-pulmonary hemodynamic responses.

Experiments were conducted to determine whether intravenous injections of micro-particles, having a size suitable to be trapped by the pulmonary precapillary arterioles, could be used to increase the pulmonary vascular resistance and thereby trigger an acute increase in the pulmonary arterial pressure (pulmonary hypertension). Anesthetized male broilers injected intravenously with inorganic (silica gel, polystyrene) or organic (cellulose, Sephadex) micro-particles developed an immediate pulmonary hypertension in proportion to the cumulative quantities of micro-particles injected. Micro-particle occlusion of a portion of the pulmonary arterioles forced the cardiac output to flow at a higher rate through the remaining vascular channels, thereby exposing a diffusion limitation characterized by undersaturation of the systemic arterial blood with oxygen (hypoxemia). The concurrent onset of systemic hypotension (reduced systemic arterial blood pressure) was not due to a reduction in cardiac output but rather was attributed to hypoxemic vasodilation of the systemic vasculature (reduced total peripheral resistance). Preliminary histological evaluations revealed micro-particles lodged in inter- and intraparabronchial arterioles, surrounded by aggregates of thrombocytes and mononuclear leukocytes within 30 min post-injection. These observations infer that intravenously injected micro-particles are carried to the lungs by the returning venous blood, where trapping of the micro-particles by the pulmonary vasculature triggers acute responses (increased pulmonary vascular resistance, pulmonary hypertension, systemic hypoxemia, systemic hypotension) that mirror those previously observed following acute occlusion of one pulmonary artery. Additional studies will be required to determine the extent to which the focal immune response to trapped micro-particles promotes local vasoconstriction that amplifies the pulmonary hypertension attributable to direct physical obstruction of precapillary arterioles.

Animals↗

PubMed2002

Intravenous micro-particle injections and pulmonary hypertension in broiler chickens: acute post-injection mortality and ascites susceptibility.

Intravenously injected micro-particles become trapped within the pulmonary vasculature where they increase the resistance to blood flow and trigger pulmonary hypertension. We tested the hypothesis that i.v. micro-particle injections can be used to trigger acute (24 to 48 h) post-injection mortality in broilers having the most limited pulmonary vascular capacity, or ascites in broilers whose marginal cardiopulmonary capacity renders them susceptible to pulmonary hypertension syndrome (PHS). Progressive inflammation-associated responses were initiated within the lung parenchyma by 10 to 80 microm diameter dextran polymer (Sephadex) and 30 microm diameter cellulose micro-particles, leading to the scavenging of Sephadex micro-particles from the pulmonary vasculature by <5 d post-injection, whereas the cellulose micro-particles persisted for >7 d post-injection. The persistency and size of the cellulose apparently facilitated chronic occlusion of blood flow through precapillary arterioles, thereby triggering appreciable post-injection mortality and PHS at relatively low injection volumes (0.3 to 0.6 mL at 0.02 g/mL). In contrast, the small size of the polystyrene microspheres (15 microm), and the lack of persistency of the Sephadex micro-particles, apparently precluded the reliable occurrence of post-injection mortality or PHS until higher volumes (>0.8 mL at 0.02 g/mL) were injected. Values for the total susceptibility index (TSI: 24 to 48 h post-injection mortality + PHS mortality) following cellulose injections were higher for broilers reared at cool temperatures than at thermoneutral temperatures. The incidences of PHS induced by exposing broilers from different genetic lines to constant cool temperatures qualitatively paralleled the respective post-injection mortalities elicited by injecting the cellulose micro-particle suspension into the same lines. These observations indicate the micro-particle injection methodology potentially can replace unilateral pulmonary artery occlusion as the technique of choice for genetically selecting broilers that have a sufficiently robust pulmonary vascular capacity to resist the onset of pulmonary hypertension and PHS. The functional importance of the relative antigenicity of different micro-particle types, and the extent to which key immune-mediated responses, either beneficial or detrimental, might be co-selected by the micro-particle injection technology, remain to be clarified.

Animals↗

PubMed2002

Pulmonary hypertensive response to endotoxin in cellulose-primed and unprimed broiler chickens.

Previous studies indicate that individual broilers vary widely in their pulmonary vascular responsiveness to i.v. injections of endotoxin. This individual variability may reflect differences acquired during previous respiratory challenges or genetic variability that may be associated with susceptibility to pulmonary hypertension syndrome (ascites). In the present study, we compared the endotoxin responses of 4- to 5- wk-old control broilers (unprimed) and broilers in which the pulmonary vasculature had been immunologically challenged 48 h previously by an i.v. injection of cellulose micro-particles (primed). The injected cellulose micro-particles are carried in the venous blood to the lungs, where they become trapped in the pulmonary vasculature and initiate acute focal inflammatory responses within the surrounding lung parenchyma. Physiological variables (respiratory rate, heart rate, pulmonary and systemic arterial pressures) were evaluated prior to and following the i.v. administration of 1 mg of Salmonella typhimurium endotoxin. Prior to endotoxin injection, the respiratory rate was higher in primed than in unprimed broilers; however, the heart rate, pulmonary arterial pressure, and systemic arterial pressure did not differ between groups. Broilers in both groups exhibited similar ranges of individual variability in their endotoxin responses. The overall time of onset, magnitude, and duration of the pulmonary hypertensive responses were similar for both groups. Accordingly, the initiation of a preexisting inflammatory response within the lung parenchyma did not alter the timing, amplitude, or variability of the subsequent pulmonary hypertensive response to endotoxin in broilers.

Animals↗

PubMed2001

Maturation-dependent neointima formation in fowl aorta.

Fowl show spontaneous elevation of blood pressure (BP) and neointimal plaque formation in the abdominal aorta at young ages. Maturation/age-dependent modulation of vascular lesions and a causal relationship between elevated BP and neointima formation, however, have not been clarified. We therefore intended to characterize, first, maturation/age-dependent neointimal plaque formation and vascular lesions and, second, their relationship to BP elevation. The BP measured in conscious domestic fowl, Gallus gallus, White Leghorn breed, DeKalb strain, via an indwelling catheter inserted into the ischiadic artery, increased with maturation in males; and at plateau level, BP (mmHg) was significantly (P<0.01) higher in males (194.0+/-4.6, n=11) than in females (169.3+/-3.1, n=10). Neointimal plaques consisting of neointimal cells and abundant extracellular matrix appeared initially in the distal segment of the abdominal aorta (lesion-prone area) of chicks as early as 6 weeks old. The area (size) of neointimal plaques right above the ischiadic bifurcation increased with maturation, whereas the plaque area became smaller with some degenerative changes in adult birds. In some birds, diffuse subendothelial hyperplasia and more extensive plaque formation at the branching points of the aorta were observed. The plaque area appears to be larger in birds, particularly in males that have higher BP (r=0.68). The width of aortic smooth muscle (SM) layers, measured in regions with no plaque, increased with age, whereas the number of cells per unit of area decreased, suggesting that hypertrophy of vascular SM occurs in response to exposure of the vascular wall to high BP. The number of cells was significantly (P<0.01) higher in the plaque than in underlying aortic SM layers or in layers with no plaque formation. Both neointimal plaques and underlying SM layers are immunohistochemically positive for alpha SM actin, suggesting that neointimal cells are modulated SM cells, whereas the staining with SM myosin heavy chain antibody is low in neointimal plaques. Furthermore, plasma arginine levels dropped in accordance with the time of neointimal plaque formation, whereas plasma cholesterol levels showed an age-dependent increase. The results suggest that spontaneous development of neointimal plaques may be a consequence of exposure to high BP and associated local hemodynamic changes.

Actins↗

PubMed2001

Growth and immunity of broiler chicks as affected by dietary arginine.

A dietary deficiency of Arg may suppress chick immune system functions; however, research evaluating immune function responsiveness of commercial broilers fed dietary Arg levels near NRC (1994) recommendations is sparse. Therefore, three experiments were conducted to evaluate growth and immunity of broilers fed varying Arg levels near NRC (1994) specifications. Because Arg and Lys are similar in structure and are known to compete in intestinal absorption, dietary Lys treatments [near NRC (1994) recommendations] were evaluated to determine if Arg and Lys interact to affect broiler immunity. There were four dietary treatments in Experiment 1 representing a 2 x 2 factorial design of additional Arg (120% of NRC) or additional Lys (120% of NRC) added to a control diet containing 100% of NRC Arg and Lys (six replications per treatment). Experiment 2 contained the following four treatments: the control diet; the control diet plus L-Arg (0.20% Arg of diet); the control diet plus L-Lys HCl (0.20% Lys of diet); and the control diet plus L-Arg-L-Glu (0.10% Arg of diet). Graduations of Arg were fed from 90 to 120% of NRC in 10% increments in Experiment 3. Also, half of the birds were exposed to vaccinations of Newcastle disease virus and infectious bronchitis virus in Experiment 3 to derive a 2 x 4 factorial design. Experiments 1 and 2 were conducted from Days 1 to 18 and Experiment 3 was conducted from Days 1 to 15 in Petersime battery brooders. No interactions occurred between dietary Lys and Arg in Experiment 1. Increasing dietary Arg, but not Lys, from 100 to 120% of the NRC recommendation increased (P < or = 0.05) Day 18 BW gain. Treatment differences in the cutaneous basophil hypersensitivity assay in Experiment 1 did not occur. In Experiment 2, treatment differences in growth responses, lymphoid organ development, and primary antibody titers to SRBC did not occur. Unvaccinated birds in Experiment 3 fed an Arg-deficient diet had lower (P < or = 0.05) feed conversion in comparison with vaccinated birds fed an Arg-deficient diet. Vaccinated birds had lower (P < or = 0.05) Day 15 BW than unvaccinated birds, but higher (P < or = 0.05) titers to Newcastle disease virus. Increasing dietary Arg in Experiment 3 increased plasma Arg (P < or = 0.05), but did not affect plasma Lys. Although increased dietary Arg improved BW gain in Experiment 1, minimal effects were noted in growth and immune system parameters throughtout this study. A dietary Arg level near the NRC (1994) recommendation should support proper immune system functions in healthy chicks.

Animals↗

PubMed2001

Taurine, cardiopulmonary hemodynamics, and pulmonary hypertension syndrome in broilers.

Previous studies have suggested cardiac taurine is released into the plasma in response to hypoxemia (low blood oxygen levels) during the pathogenesis of pulmonary hypertension syndrome (PHS, ascites). In the present study, broilers reared under cool temperature conditions (16 C) were provided tap water (control group), tap water supplemented with taurine, or tap water supplemented with the taurine transport antagonist beta-alanine. When compared with control values, taurine supplementation consistently elevated free taurine concentrations in the plasma but not in cardiac tissues, whereas beta-alanine supplementation consistently reduced free taurine concentrations in cardiac tissues but not in the plasma. Neither the incidence of PHS nor specific predictors of PHS susceptibility (electrocardiogram Lead II S-wave amplitude, % saturation of hemoglobin with oxygen, heart rate, right to total ventricular weight ratio) were affected by taurine or beta-alanine supplementation. Cardiopulmonary hemodynamic evaluations were conducted to compare control and beta-alanine supplemented broilers breathing room air or air containing 12% oxygen (low oxygen challenge). While breathing room air, the betaalanine-supplemented broilers had higher baseline values for cardiac output (186.2 vs. 146.9 mL/min/kg BW) and pulmonary arterial pressure (27.4 vs. 22.4 mm Hg), similar values for mean systemic arterial pressure (100 vs. 104 mm Hg) and pulmonary vascular resistance (0.062 vs. 0.064 resistance units), and lower values for total peripheral resistance (0.228 vs. 0.296 resistance units) when compared with control broilers breathing room air. During low oxygen challenges, the beta-alanine-supplemented broilers exhibited larger reductions in cardiac output, mean systemic arterial pressure, and pulmonary arterial pressure and greater increases in pulmonary vascular resistance than control broilers. These observations indicate that beta-alanine-supplemented broilers breathing room air had a higher systemic demand for oxygen as evidenced by their lower total peripheral resistance (systemic vasodilation) and had a capacity sufficient to pump a higher cardiac output and, thereby, maintain a similar mean systemic arterial pressure when compared with control broilers. However, cardiac function rapidly deteriorated in beta-alanine-supplemented broilers during low oxygen challenges, leading to substantially greater reductions in cardiac output, stroke volume, and mean systemic arterial pressure when compared with control broilers. Concurrent changes in pulmonary arterial pressure within the beta-alanine group reflect interactions between cardiac output and pulmonary vascular resistance. Overall, depleting cardiac taurine did not appear to initiate PHS, but systemic hypoxemia developing during the mid- to late-pathogenesis of PHS may expose and incipient cardiac weakness attributable to depleted taurine reserves.

Animals↗

PubMed2001

Minimal number of chicken daily growth velocities for artificial neural network detection of pulmonary hypertension syndrome (PHS).

Previously, evaluation of the first 2 wk of daily growth velocity with an artificial neural network (ANN) provided an effective noninvasive approach for predicting the susceptibility of broilers to pulmonary hypertension syndrome (PHS). This study was conducted to define the minimum number of days of growth data and the type of ANN required for the best prediction of PHS susceptibility. Four experiments were conducted in which broilers were weighed daily at 0800 h. In Experiment 1, Hubbard male broilers were reared to 50 d of age, with 13 developing PHS and 33 remaining normal (N), for a PHS:N ratio of 13:33. In Experiment 2, ANAK broilers were exposed to cool temperatures (16 to 17 C) from 17 to 42 d of age, resulting in a PHS:N ratio of 16:46 for males. In Experiments 3 and 4, Hubbard male and female chicks from a base population and a PHS-resistant line were exposed to cool temperatures from 17 to 42 d (Experiment 3) or 49 d of age (Experiment 4). The PHS:N ratios were 40:68 for males and 6:96 for females in Experiment 3 and 26:91 for males and 10:58 for females in Experiment 4. Four ANN, back propagation (BP3), Ward back propagation (WardBP), probabilistic (PNN), and general regression (GRNN), were evaluated for their ability to predict PHS in the shortest number of days based on daily growth velocities (BWd+1-BWd). A 100% prediction of PHS and N birds was considered the criterion of success. Starting with 14 d of data, each ANN was trained on daily growth velocity, and the number of predictive days was reduced with each run of the ANN. The best ANN was a GRNN, which correctly diagnosed PHS and N male broilers on 4 and 6 d of growth velocity data for Experiments 1 and 2, respectively. The results were poorer with the BP3, WardBP, and PNN. The diagnostic ability of the neural network was not consistent over all four experiments. In Experiment 2, a minimum of 6 d was required for 100% PHS detection for males. In Experiment 3, the best diagnostic value for males was 93% PHS detection and 100% N detection at 15 d. For females, the 100% PHS detection occurred at a minimum of 8 d. In Experiment 4, males had 100% PHS and N detection at a minimum of 11 d. Females had a 100% PHS and N detection at a minimum of 10 d. An attempt to build a single neural network that would detect PHS susceptibility in Hubbard (Experiment 1) and ANAK (Experiment 2) broilers was unsuccessful. The application (validation) of neural networks between experiments also was not successful (data not presented). However, these studies demonstrate that within a breed or line reared under similar selection pressures for ascites, a GRNN based on the first 14 d of growth velocity can detect, with at least 93% accuracy, broilers susceptible to PHS.

Age Factors↗

PubMed2001

Plasma levels of arginine, ornithine, and urea and growth performance of broilers fed supplemental L-arginine during cool temperature exposure.

Two experiments (Experiment 1 and 2) were conducted to evaluate growth performance, ascites mortality, and concentrations of plasma Arg, urea, and ornithine in male broilers raised in floor pens (2 x 4 factorial experiment, six pens for treatment) and exposed to cool temperatures averaging 16 C after 21 d of age. Broilers were fed low- or high-CP diets in both Experiments. In Experiment 1, Arg treatments consisted of control (no supplemental Arg); 0.15 or 0.3% supplemental Arg in the diet (low- and medium-Arg feed, respectively); and 0.3% supplemental Arg in the drinking water (Arg-water). Arginine levels were increased in Experiment 2 and consisted of the following: control (no supplemental Arg); 0.3 or 0.85% supplemental Arg in the diet (medium- and high-Arg feed, respectively); and 0.6% supplemental Arg in the drinking water (Arg-water). The water treatment followed a 3-d cyclic regimen, with supplemental Arg being provided for 24 h, followed by tap water for 48 h. When the broilers reached 37 d of age and all groups had consumed tap water for the previous 48 h, blood samples were collected from one bird per pen (Time 0, 0700 h); then supplemental Arg was provided in the Arg-water group, and additional blood samples were collected from the control and Arg-water groups at 3, 6, 12, and 36 h after Time 0. Plasma amino acids were analyzed using HPLC. Birds fed the high-CP diet were heavier at 49 d than birds fed the low-CP diet in Experiment 1, but not in Experiment 2. No differences were found in feed conversion or ascites mortality due to CP or Arg treatments in either experiment. In both experiments, plasma Arg was similar for all groups at Time 0, but increased in the Arg-water group at 3, 6, and 12 h after Arg was provided in the water. Within 12 h after returning to tap water, plasma Arg levels of the Arg-water group did not differ from the control group. Plasma urea and ornithine were parallel to plasma Arg concentrations, and the high-CP diets resulted in higher plasma levels of urea and ornithine compared with low-CP diets. These results indicate that kidney arginase was readily activated by Arg provided in the water, resulting in an immediate increase in plasma urea and ornithine. Plasma Arg was increased significantly, but no effects were observed in ascites mortality.

Animals↗

PubMed2001

Pulmonary wedge pressures confirm pulmonary hypertension in broilers is initiated by an excessive pulmonary arterial (precapillary) resistance.

High retrograde pressure through the pulmonary venous system caused by failure of the left ventricle or left atrio-ventricular valve may result in the elevated pulmonary arterial pressure and right ventricular hypertrophy associated with pulmonary hypertension syndrome (PHS; ascites) in broiler chickens. In the present study, unanaesthetized male broilers from an ascites-resistant line, the base population from which the resistant line was derived, and a separate unselected line were used to determine whether changes in wedge pressure (thought to be similar to left atrial pressure) are predictive of differences in the pulmonary arterial pressure of clinically healthy and pre-ascitic broilers. Venous, right atrial, right ventricular, pulmonary arterial, and wedge pressures were obtained by inserting a catheter into a wing vein and progressively advancing the catheter into a pulmonary branch artery until the catheter tip became wedged in and occluded the flow through a terminal artery. Mean right ventricular and pulmonary arterial pressures were lower in the resistant line than in the base population, but wedge pressures did not differ between the resistant, base, and unselected lines. Right:total ventricular weight ratios (RV:TV) and the percentage saturation of hemoglobin with oxygen in arterial blood ranged in value from 0.18 to 0.44 and 65 to 96%, respectively. Wedge pressure, however, remained similar when pre-ascitic broilers with high RV:TV values and low oximetry values were compared with clinically healthy broilers. In all birds, whether healthy or showing pre-ascitic characteristics, the wedge pressure was slightly higher than the right atrial pressure but substantially lower than pulmonary arterial pressure. These observations provide definitive proof that pulmonary hypertension is initiated as a consequence of excessive pulmonary arterial or arteriole resistance. Pulmonary venous pressure is estimated by measuring the pulmonary arterial wedge pressure, and high wedge pressures would be evident if pulmonary hypertension was caused by the elevated downstream resistances associated with left-sided heart failure.

Animals↗

PubMed2001

Lung mitochondrial dysfunction in pulmonary hypertension syndrome. I. Site-specific defects in the electron transport chain.

The main objectives of this study were to determine a) site-specific defects in the electron transport chain of lung mitochondria of broilers with pulmonary hypertension syndrome (PHS), b) if these defects are attenuated by high dietary vitamin E, and c) if these defects have a genetic basis. In Experiment 1, lung mitochondria were isolated from broilers with and without PHS fed diets containing 15 IU and 100 IU dl-alpha-tocopherol acetate/kg (VE); the four treatments were control, VE, PHS, and VE-PHS, respectively. Hydrogen peroxide (H2O2) generation in isolated lung mitochondria was monitored by dichlorofluorosein (DCF) fluorescence in response to chemicals that inhibit electron flow at specific sites on the electron transport chain using a 96-well microplate with Cytoflour (excitation/emission 480/530 nm). Basal H2O2 production was higher in PHS than in control mitochondria. Differences in H2O2 production between control and PHS were magnified by inhibition of Complexes I and III (Coenzyme Q) of the respiratory chain in mitochondria. Functional defects in PHS mitochondria were attenuated by high dietary VE. In Experiment 2, basal H2O2 production and that following inhibition of Complexes I and III were lower in lung mitochondria isolated from broilers selected for genetic resistance to PHS than in nonselected birds in the base population. The results of this study indicate that site-specific defects in Complexes I and III may underlie lung mitochondrial dysfunction in broilers with PHS, that these defects are attenuated by high dietary vitamin E, and that these defects may be related to genetic predisposition to PHS.

Animals↗

PubMed2001

Intravenous endotoxin triggers pulmonary vasoconstriction and pulmonary hypertension in broiler chickens.

Bacterial endotoxins stimulate endothelin-mediated, thromboxane-dependent increases in pulmonary vascular resistance in mammals, and thromboxane has been shown to cause an immediate but transient pulmonary vasoconstriction in broiler chickens. In the present study, i.v. injections of 1 mg endotoxin into anesthetized male broilers caused a pulmonary vasoconstrictive response that was delayed in onset by 15 min and that elevated the pulmonary arterial pressure by 10 mm Hg within 25 min postinjection. Thereafter, pulmonary hemodynamic variables gradually (> or = 15 min) returned toward pre-injection levels, and supplemental injections of 4 mg endotoxin during this recovery period failed to reinitiate pulmonary hypertension. In contrast, injecting the thromboxane A2 mimetic U44069 during the endotoxin recovery period triggered pulmonary vasoconstriction and pulmonary hypertension similar in magnitude to the responses triggered by U44069 before endotoxin had been administered. The time course and magnitude of the pulmonary hemodynamic responses to endotoxin were highly variable among individual broilers, whereas the individual responses to U44069 were more consistent. Unanesthetized broilers resembled anesthetized broilers in the time course, magnitude, and variability of their pulmonary hemodynamic responses to endotoxin. Overall, these observations are consistent with the hypothesis that endotoxin initiates a biochemical cascade, culminating in the delayed onset of pulmonary vasoconstriction and pulmonary hypertension within 20 min postinjection. Subsequently, the pulmonary vasculature remains responsive to large bolus injections of exogenous thromboxane mimetic; however depletion of endogenous vasoconstrictive components of the endotoxin-mediated cascade, a compensatory increase in endogenous vasodilators, or the induction of a transient cellular tolerance to endotoxin prevented fourfold higher doses of endotoxin from reversing the return toward a normal pulmonary vascular tone. Individual differences among broilers in their susceptibility to pulmonary hypertension syndrome (ascites) may be related to innate or acquired variability in their pulmonary vascular responsiveness to vasoactive mediators.

Animals↗

PubMed2001

Lung mitochondrial dysfunction in pulmonary hypertension syndrome. II. Oxidative stress and inability to improve function with repeated additions of adenosine diphosphate.

The major objective of this study was to examine lung mitochondrial dysfunction and antioxidants in pulmonary hypertension syndrome (PHS) in broilers. Lung mitochondria were obtained from broilers fed diets containing 15 IU (control) and 100 IU dl-alpha-tocopherol acetate, i.e., vitamin E (VE)/kg with and without PHS; the four treatment groups were control, VE, PHS, and VE-PHS, respectively (Experiment 1), or from healthy broilers genetically selected or not selected for resistance to PHS (Experiment 2). Mitochondrial function was assessed with sequential additions of adenosine diphosphate (ADP) to mimic a repeated demand for energy. Compared to controls, PHS mitochondria in Experiment 1 exhibited mitochondrial dysfunction [lower respiratory control (RCR) and ADP:O ratios and an inability to improve function with repeated energy demand] and oxidative stress [lower alpha-tocopherol and reduced glutathione (GSH) and higher oxidized glutathione levels (GSSG)]. High dietary alpha-tocopherol had no effect on lung mitochondrial function in healthy broilers (VE vs. controls) but attenuated dysfunction in VE-PHS mitochondria. In Experiment 2, there were no differences in selected and nonselected mitochondrial function following a single addition of ADP, but nonselected mitochondria exhibited lower RCR and ADP:O values with repeated energy demand. Higher GSSG levels were also observed in nonselected lung. The results indicate that lung mitochondrial dysfunction present in broilers with PHS was associated with oxidative stress and may be attenuated by high dietary vitamin E. Furthermore, genetic resistance to PHS was associated with more efficient oxidative phosphorylation in lung mitochondria and an inherently lower degree of oxidative stress.

Adenosine Diphosphate↗

PubMed2001

Furosemide does not facilitate pulmonary vasodilation in broilers during chronic or acute unilateral pulmonary arterial occlusion.

Furosemide (FURO) is a diuretic and a putative pulmonary vasodilator that, when added to broiler diets, previously has been shown to reduce the cumulative pulmonary hypertension syndrome (PHS) mortality induced by cold temperatures. The objective of the present study was to evaluate the influence of dietary FURO on the pulmonary vasculature in broilers undergoing chronic or acute unilateral pulmonary arterial occlusion. Broilers were fed a standard ration throughout the entire experiment (Control group) or the same ration supplemented with 0.015% (wt/wt) FURO from Day 14 to 42 (FURO group). In the present study chicks were chosen at random at 16 to 18 d of age to undergo sham surgery or a chronic unilateral pulmonary artery clamp (PAC) procedure. Diet and surgical treatments resulted in Control-Sham, FURO-Sham, Control-PAC, and FURO-PAC groups. The Control-PAC and FURO-PAC groups did not differ in body weight or right:total ventricular weight ratios (RV:TV). The postsurgical mortality, ascites mortality, and mortality due to other causes did not differ between the Control-PAC and FURO-PAC groups. Plasma Na+ (P < or = 0.05) was lower in the FURO-Sham group than in the Control-Sham group. Broilers from the same hatch were fed Control or FURO diets and surgically prepared for acute unilateral pulmonary arterial occlusion by using a snare. Tightening of the snare triggered characteristic increases in pulmonary blood flow, pulmonary arterial pressure, and pulmonary vascular resistance. Across all of these variables, the Control and FURO groups did not differ during any sample interval. Dietary FURO did not affect body weight, hematocrit, or RV:TV. Dietary FURO at 0.015% (wt/wt) does not appear to influence the pulmonary vasculature in broilers, but it may prolong the survival of broilers during the pathophysiological progression of PHS.

Animals↗

PubMed2000

Measurements of pulmonary arterial pressure in anesthetized male broilers at two to seven weeks of age.

Pulmonary hypertension (an elevated pulmonary arterial pressure) is the defining symptom of the pathophysiological progression leading to pulmonary hypertension syndrome (ascites) in broilers. Previously, closed-thorax techniques had not been reported for measuring the pulmonary arterial pressure in young (<5 wk of age) broilers. The objective of this research was to evaluate continuous pulmonary arterial pressure in anesthetized male broilers at weekly intervals (2 to 7 wk of age) by inserting a cannula directly into the pulmonary artery. Body weights, heart rates, and the right:total ventricular weight ratio were also recorded. Clinically healthy individuals were selected from two separate hatches without prior assessment of electrocardiograms or the percentage of saturation of hemoglobin with oxygen. The pulmonary arterial pressure increased (P < or = 0.05) from 20 to 25 mm Hg between Weeks 2 and 3, remained at approximately 25 mm Hg during Weeks 4 and 5, and then returned to 19 mm Hg during Weeks 6 to 7. Body weight increased with age, the heart rate and body weight-normalized right and total ventricular weights remained constant through Week 5, and the right:total ventricular weight ratio remained constant through Week 7. This technique is useful for determining age-related changes in pulmonary arterial pressure that may contribute to a mismatch between pulmonary vascular capacity and cardiac output in apparently healthy broilers during the pathogenesis of pulmonary hypertension syndrome.

Aging↗

PubMed2000

Evaluation of broiler growth velocity and acceleration in relation to pulmonary hypertension syndrome.

An evaluation was made of the relationship between individual daily growth patterns and susceptibility of broiler chickens to pulmonary hypertension syndrome (PHS). In the first experiment, 46 male broilers were weighed for each of 50 d, during which time 13 developed PHS. Three temporal phases (0 to 15, 16 to 35, and 36 to 50 d) of broiler growth velocity and acceleration were examined. Correlation dimensions and Lyapunov exponents suggested evidence of chaos in growth velocity and acceleration, but the absence of detectable differences between broilers in the normal and PHS categories led us to reject the hypotheses that growth is more chaotic in normal broilers than in broilers susceptible to PHS. Growth velocity and acceleration values for mean and SD were statistically evaluated as response variables for each growth phase. Mean values for velocity during the third phase were different between broilers in the normal and PHS categories (velocity: 68.8 vs 48.9 g/d, P = 0.03, respectively) and (acceleration: 0.3 vs -1.4 g/d2, P = 0.07, respectively). The third phase SD (reflecting oscillation for velocity and acceleration) was greater for normal than for PHS birds (velocity: 26.1 vs 21.3 g/d, P = 0.13, respectively; acceleration: 39.7 vs 28.2 g/d2, P = 0.03, respectively). The hypothesis was accepted that normal birds have greater oscillations in growth velocity and acceleration than birds susceptible to PHS. A general regression neural network (GRNN) with genetic adaptive calibration was trained to predict PHS based on individual growth phases and their combinations. Data representing the first, first two, and all three phases of growth were determined to have potential for computerized diagnostic weighing. With the GRNN, birds in all three data sets were successfully classified (100%) with or without PHS. A third hypothesis, therefore, was accepted that artificial neural networks could be used to distinguish the difference between normal broilers and those susceptible to PHS. In the second experiment, only one bird was diagnosed with PHS. Velocity and acceleration neural networks from Phase 1 and Phases 1 and 2 in the first experiment were applied to the growth velocity and acceleration data of Experiment 2. The Phase 1 neural networks were the most promising in that they correctly identified 71.6 and 72.4% of the birds as normal for velocity and acceleration data, respectively. In general, data in the second experiment exceeded the neural network range of training for both velocity and acceleration, which reflected increased oscillation during the second phase of growth.

Animals↗

PubMed2000

Cardio-pulmonary function in broilers reared at warm or cool temperatures: effect of acute inhalation of 100% oxygen.

Fast growth and cool temperatures are the primary triggers for pulmonary hypertension syndrome (PHS, ascites) during commercial broiler growout. We evaluated cardio-pulmonary function in male broilers that initially were reared together at normal brooding temperatures and then were randomly assigned to chambers maintained at 28 C (warm group) or 16 C (cool group). Cardio-pulmonary evaluations were conducted between 35 and 42 d of age. The groups initially did not differ in body weight, right:total ventricular weight ratio, respiratory rate, heart rate, total peripheral resistance, or pulmonary vascular resistance, nor did their arterial blood gas values differ for the partial pressure of carbon dioxide, bicarbonate concentration, or hydrogen ion concentration. When compared with the warm group, the cool group had heavier total ventricular weights and higher values for pulmonary arterial pressure, cardiac output, stroke volume, mean systemic arterial pressure, and hematocrit and a marginally lower (P = 0.06) partial pressure of oxygen. Inhaling 100% O2 for 20 min caused equivalent increases in the arterial partial pressure of oxygen (> or =388 mm Hg) and the percentage saturation of hemoglobin with oxygen (99.9%) in both groups. The respiratory rate was reduced and total peripheral resistance in both groups was increased; the pulmonary arterial pressure, cardiac output, and heart rate in the cool group were also reduced. Cool temperatures contributed to the increase in pulmonary arterial pressure primarily by increasing the metabolic demand for oxygen, as reflected by incipient hypoxemia (reduced blood oxygen and elevated hematocrit), generalized ventricular hypertrophy, and an elevated cardiac output. It was the elevated cardiac output rather than hypoxemic pulmonary vasoconstriction that increased the pulmonary arterial pressure in the cool group when compared with the warm group.

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