Progress 11/01/93 to 09/30/04
Outputs
When broilers are exposed to high ambient temperatures, their cardiac output can increase by 20 to 50%. Previously, we developed an intravenous micro-particle injection technique to select broilers having a cardio-pulmonary capacity capable of accommodating increases in cardiac output associated with fast growth and cool temperatures. The survivors of micro-particle injections represent the population cohort having the most robust cardio-pulmonary capacity. During cyclic heat challenges these survivors exhibited improved livability, body weight gain, and feed efficiency when compared with their unselected flock mates. Meat quality characteristics and blood gas values did not differ between the groups. Sodium bicarbonate (NaHCO3) has been used successfully in mammals and birds to alleviate pulmonary hypertension. Experiments were designed to provide measurements of arterial and venous blood gas values from unanesthetized male broilers subjected to a cool temperature
challenge and fed either a control diet or the same diet alkalinized by dilution with a level of 1% NaHCO3. We also compared metabolic variations associated with differences in feed intake and environmental temperature. The results demonstrate that changes in diet composition (control vs. 1% NaHCO3 diets) had a minimal impact on arterial and venous blood gas variables when compared with the more dramatic differences associated with feed intake (ad libitum vs. >12 h withdrawal) and environmental temperature (24 vs. 16 C). Evaluations of the hematological inflammatory responses of broilers to intravenous micro-particle injections demonstrated that the acute focal inflammatory responses to micro-particles trapped in the pulmonary vasculature modulated the proportions of leukocytes in the blood within 48 hours post-injection. Comparisons also were conducted of the effect of intravenous endotoxin on blood cell profiles of broilers housed in cages or floor litter environments. Broilers
reared on floor litter experienced a greater environmental challenge (natural exposure to endotoxin), which desensitized their immune system but did not improve their tolerance to a subsequent endotoxin challenge.
Impacts
Broilers are capable of growing so rapidly that their lungs cannot readily accept and oxygenate the large volume of blood that must be pumped by the heart to support tissue metabolism. Micro-particle injections provide broiler geneticists with an efficient technique for rapidly eliminating individual birds that have an inadequate pulmonary vascular capacity. The survivors exhibit parallel resistance (increased growth performance, reduced mortality) during exposure to either cold temperatures or heat stress. These improvements are achieved without altering meat quality characteristics or the capacity of the lungs to regulate the acid-base balance of the blood. Broilers that survive the micro-particle injections may do so, in part, through aggressive inflammatory responses that rapidly eliminate obstructive particulates and reopen the microvascular channels. Co-selection for an aggressive intra-pulmonary immune response appears to be beneficial in terms of preserving the
marginal capacity of the lungs to accommodate the cardiac output. Understanding the metabolic consequences of dietary acid-base balance, environmental temperature, feeding patterns, and chronic exposure to endotoxin on the performance of broilers' lungs will allow geneticists to select for improved productivity in commercial broiler flocks.
Publications
- Wideman, R. F., and Chapman, M. E. 2004. N-Nitro-L-Arginine Methyl Ester (L-NAME) amplifies the pulmonary hypertensive response to endotoxin in broilers. Poultry Sci. 82:485-494, 2004.
- Wideman, R. F., Chapman, M. E., Wang, W., and Erf, G. F. 2004. Immune modulation of the pulmonary hypertensive response to bacterial lipopolysaccharide (LPS, endotoxin) in broilers. Poultry Sci. 83:624-637.
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Progress 01/01/03 to 12/31/03
Outputs
When broilers are exposed to high ambient temperatures, their cardiac output can increase by 20 to 50%. Previously, we developed an intravenous micro-particle injection technique to select broilers having a cardio-pulmonary capacity capable of accommodating increases in cardiac output associated with fast growth and cool temperatures. The survivors of micro-particle injections represent the population cohort having the most robust cardio-pulmonary capacity. During cyclic heat challenges these survivors exhibited improved livability, body weight gain, and feed efficiency when compared with their unselected flock mates. Meat quality characteristics and blood gas values did not differ between the groups. Sodium bicarbonate (NaHCO3) has been used successfully in mammals and birds to alleviate pulmonary hypertension. Experiments were designed to provide measurements of arterial and venous blood gas values from unanesthetized male broilers subjected to a cool temperature
challenge and fed either a control diet or the same diet alkalinized by dilution with a level of 1% NaHCO3. We also compared metabolic variations associated with differences in feed intake and environmental temperature. The results demonstrate that changes in diet composition (control vs. 1% NaHCO3 diets) had a minimal impact on arterial and venous blood gas variables when compared with the more dramatic differences associated with feed intake (ad libitum vs. >12 h withdrawal) and environmental temperature (24 vs. 16 C). Evaluations of the hematological inflammatory responses of broilers to intravenous micro-particle injections demonstrated that the acute focal inflammatory responses to micro-particles trapped in the pulmonary vasculature modulated the proportions of leukocytes in the blood within 48 hours post-injection. The intra-pulmonary inflammatory response to trapped micro-particles caused transient changes in blood leukocyte profiles that are indicative of the normal role of
the immune system in clearing particulates from the pulmonary vasculature. Comparisons also were conducted of the effect of intravenous endotoxin on blood cell profiles of broilers housed in cages or floor litter environments. Broilers reared on floor litter experienced a greater environmental challenge (natural exposure to endotoxin), which desensitized their immune system but did not improve their tolerance to a subsequent endotoxin challenge.
Impacts
Broilers are capable of growing so rapidly that their lungs cannot readily accept and oxygenate the large volume of blood that must be pumped by the heart to support tissue metabolism. Micro-particle injections provide broiler geneticists with an efficient technique for rapidly eliminating individual birds that have an inadequate pulmonary vascular capacity. The survivors exhibit parallel resistance (increased growth performance, reduced mortality) during exposure to either cold temperatures or heat stress. These improvements are achieved without altering meat quality characteristics or the capacity of the lungs to regulate the acid-base balance of the blood. Broilers that survive the micro-particle injections may do so, in part, through aggressive inflammatory responses that rapidly eliminate obstructive particulates and reopen the microvascular channels. Co-selection for an aggressive intra-pulmonary immune response appears to be beneficial in terms of preserving
the marginal capacity of the lungs to accommodate the cardiac output. Understanding the metabolic consequences of dietary acid-base balance, environmental temperature, feeding patterns, and chronic exposure to endotoxin on the performance of broilers' lungs will allow geneticists to select for improved productivity in commercial broiler flocks.
Publications
- Wideman, R. F., Chapman, M. E., Owens, C. M., Devabhaktuni, M. K., Cavitt, L. C., Wang, W., and Erf, G. F. 2003. Broiler survivors of intravenous micro-particle injections: Evaluation of growth, livability, meat quality, and arterial blood gas values during a cyclic heat challenge. Poultry Sci. 82:484-495.
- Wideman, R. F., Hooge, D. M., and Cummings, K. R. 2003. Dietary sodium bicarbonate, cool temperatures, and feed withdrawal: Impact on arterial and venous blood-gas values in broilers. Poultry Sci. 82:560-570.
- Wang, W., Wideman, R. F., Bersy, T. K., and Erf, G. F. 2003. Pulmonary and hematological immune responses to intravenous micro-cellulose particles in broilers. Poultry Sci. 82:771-780.
- Wang, W., Wideman, R. F., Chapman, M. E., Bersy, T. K., and Erf, G. F. 2003. Effect of intravenous endotoxin on blood cell profiles of broilers housed in cages and floor litter environments. Poultry Sci. 82:1886-1897
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Progress 01/01/02 to 12/31/02
Outputs
Broilers are genetically susceptible to pulmonary hypertension syndrome (PHS, ascites) when their pulmonary vascular capacity is inadequate to accommodate the cardiac output necessary to support fast growth. We invented the i.v. micro-particle injection technique as an improved procedure for efficiently selecting PHS-resistant broiler lines. Micro-particles are injected into a systemic vein, and are carried by the returning venous blood to the pulmonary microvasculature where pulmonary blood flow is occluded in proportion to the numbers of particles injected. The micro-particle injections cause broilers with the most limited pulmonary vascular capacity to rapidly succumb to respiratory insufficiency, those with a marginal pulmonary vascular capacity develop PHS, and those having a robust pulmonary vascular capacity thrive as clinically healthy/resistant survivors. Breeder parents selected for one generation using micro-particle injections produced progeny exhibiting a
reduced susceptibility to PHS when compared with the unselected (Base) population. We demonstrated that broiler survivors of i.v. micro-particle injections exhibit an improved resistance to heat stress. Acute heat stress causes the cardiac output to increase by 20 to 50%, and the lungs of broilers having a robust pulmonary vascular capacity readily accommodate large increases in cardiac output. We continue to investigate the basis for the pulmonary hypertensive response to endotoxin in broilers. Some individual broilers exhibit minimal physiological responsiveness to endotoxin, whereas others develop severe pulmonary hypertension in response to endotoxin. The individual variability in the pulmonary hypertensive response to endotoxin now appears to be related to the balance between leukocyte-mediated release of vasoconstrictors vs. vasodilators.
Impacts
Broiler chickens are capable of growing so rapidly that their lungs cannot readily accept and oxygenate the large volume of blood that must be pumped by the heart to support tissue metabolism. Broilers exposed to extreme temperatures are particularly susceptible to cardio-pulmonary limitations because their heart must pump additional blood to support increased metabolic heat production during cold weather, or increased heat dissipation during hot weather. Techniques that permit broiler geneticists to efficiently select for improved cardio-pulmonary performance will substantially improve the growth and livability of commercial broilers. Micro-particle injections provide broiler geneticists with an efficient technique for rapidly eliminating individual birds that have an inadequate pulmonary vascular capacity. The surviving broilers will possess a robust cardio-pulmonary capacity that conveys parallel resistance (increased growth performance, reduced mortality) during
exposure to either cold temperatures or heat stress. Broiler growers will benefit from improved livability accompanied by improved flock growth performance. Endotoxin is a component of the cell wall of gram-negative bacteria, and endotoxin is present in large quantities in the dust inhaled by commercial broilers. Determining the biological basis for the variability in broilers' responsiveness to endotoxin will allow geneticists to select for improved productivity in commercial broiler flocks.
Publications
- CHAPMAN, M. E., AND WIDEMAN, R. F., 2002. Hemodynamic responses of broiler pulmonary vasculature to intravenously infused serotonin. Poultry Sci. 81:231-238.
- WIDEMAN, R. F., AND ERF, G. F., 2002. Intravenous micro-particle injection and pulmonary hypertension in broiler chickens: Cardio-pulmonary hemodynamic responses. Poultry Sci. 81:877-886.
- WIDEMAN, R. F., ERF, G. F., CHAPMAN, M. E., WANG, W., ANTHONY, N. B., AND XIAOFANG, L., 2002. Intravenous micro-particle injection and pulmonary hypertension in broiler chickens: Acute post-injection mortality and ascites susceptibility. Poultry Sci. 81:1203-1217.
- WANG, W., WIDEMAN, R. F., AND ERF, G. F., 2002 Pulmonary hypertensive response to endotoxin in cellulose-primed and unprimed broiler chickens. Poultry Sci. 81:1224-1230.
- WANG, W., ERF, G. F., AND WIDEMAN, R. F., 2002. Effect of cage vs. floor litter environments on the pulmonary hypertensive response to intravenous endotoxin and on blood-gas values in broilers. Poultry Sci. 81:1728-1737.
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Progress 01/01/01 to 12/31/01
Outputs
Previous research for this project confirmed the hypothesis that PHS-susceptible broilers have an inherent potential to outgrow their pulmonary vascular capacity. We demonstrated that a dominant gene codes for a highly significant proportion of the PHS-susceptibility. Definitive proof that pulmonary hypertension is initiated as a consequence of an excessive pulmonary arterial resistance was obtained through measurements of pulmonary wedge pressures. Cardio-pulmonary inadequacy was shown to alter the pattern of daily growth velocities in PHS-susceptible broilers, and an artificial neural network based on day 1-14 growth velocities successfully detected PHS-susceptibility with at least 93% accuracy. Supplementation of the drinking water with arginine as a source of the pulmonary vasodilator nitric oxide did not reduce the incidence of PHS because renal arginase was readily activated and converted increased plasma arginine to urea and ornithine. Bacterial endotoxins
stimulate endothelin-mediated, thromboxane-dependent increases in pulmonary vascular resistance in mammals, and we previously demonstrated that thromboxane causes an immediate but transient pulmonary vasoconstriction in broilers. Intravenous injections of 1 mg endotoxin caused a pulmonary vasoconstrictive response in broilers that was delayed in onset by 15 min, and that elevated the pulmonary arterial pressure by 10 mm Hg within 25 min post-injection. The time course and magnitude of the pulmonary hemodynamic responses to endotoxin were highly variable among individual broilers. 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 such as endotoxin. Furosemide (FURO) is a diuretic and a putative pulmonary vasodilator that, when added to broiler diets, previously has been shown to reduce the cumulative PHS mortality
induced by cold temperatures. Studies were conducted to evaluate the influence of dietary FURO on the pulmonary vasculature in broilers undergoing chronic or acute unilateral pulmonary arterial occlusion. Dietary FURO at 0.015% (wt/wt) did not appear to influence the compliance or flow-dependent vasodilation of the pulmonary vasculature, but FURO's diuretic efficacy apparently prolongs survival during the pathogenesis of PHS by reducing the rate of development of central venous hypertension and ascites fluid accumulation. Previous studies indicated cardiac taurine is released into the plasma in response to hypoxemia during the pathogenesis of PHS. Cardio-pulmonary hemodynamic evaluations were conducted using broilers provided tap water alone, or supplemented with taurine or the taurine transport antagonist beta-alanine. The results demonstrate that cardiac function rapidly deteriorated in beta-alanine supplemented broilers during low oxygen challenges. Depleting cardiac taurine did
not appear to initiate PHS, but systemic hypoxemia developing during the mid- to late-pathogenesis of PHS may expose an incipient cardiac weakness attributable to depleted taurine reserves.
Impacts
We have demonstrated that a dominant gene is responsible for the majority of PHS susceptibility in broilers, and that an elevated pulmonary vascular resistance is the cause of pulmonary hypertension in susceptible broilers.We are proceeding to clarify the cause of the elevated pulmonary vascular resistance.
Publications
- Wideman, R. F., 2001. Pathophysiology of Heart/Lung Disorders: Pulmonary Hypertension Syndrome in Broiler Chickens. World's Poultry Science Journal 57:289-307.
- Forman, M. F., and Wideman, R. F., 2001 Furosemide does not facilitate pulmonary vasodilation in broilers during chronic or acute unilateral pulmonary artery occlusion. Poultry Sci. 80:937-943.
- Nishimura, H., Xi, Z., Zhang, L., Kempf, H., Wideman, R. F., and Corvol, P., 2001. Maturation-dependent neointima formation in fowl aorta. Comparative Biochemistry and Physiology A 130:39-54.
- Ruiz-Feria, C. A., and Wideman, R. F., 2001. Taurine, cardio-pulmonary hemodynamics, and pulmonary hypertension syndrome in broilers. Poultry Sci. 80:1607-1618.
- Kidd, M. T., Peebles, E. D., Whitmarsh, S. K., Yeatman, J. B., and Wideman, R. F., 2001. Growth and immunity of broiler chicks as affected by dietary arginine. Poultry Sci. 80:1535-1542.
- Iqbal, M., Cawthon, D., Wideman, R. F., and Bottje, W. G., 2001. Lung mitochondrial dysfunction in pulmonary hypertension syndrome. I. Site specific defects in electron transport chain. Poultry Sci. 80:485-495.
- Iqbal, M., Cawthon, D., Wideman, R. F., and Bottje, W. G., 2001. Lung mitochondrial dysfunction in pulmonary hypertension syndrome II. Oxidative stress and inability to improve function with repeated additions of adenosine diphosphate. Poultry Sci. 80:656-665.
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Progress 01/01/00 to 12/31/00
Outputs
ONGOING IMPROVEMENT WAS DEMONSTRATED IN THE ASCITES RESISTANCE OF PROGENY FROM 3RD GENERATION BROILER BREEDERS SELECTED USING UNILATERAL PULMONARY ARTERY OCCLUSION TECHNIQUE. DIFFERENCES IN RENAL FUNCTION BETWEEN NORMAL AND PREASCITIC BROILERS DEMONSTRATE THAT SYSTEMIC HYPOTENSION TRIGGERS RENAL MECHANISMS RESPONSIBLE FOR FLUID AND SOLUTE RETENTION DURING THE PATHOGENESIS OF ASCITES. ACUTELY REVERSING THE SYSTEMIC HYPOXEMIA IN PREASCITIC BROILERS, ACCOMPLISHED BY ALLOWING THEM TO BREATHE 100% OXYGEN, DID NOT REDUCE THEIR SUSTAINED PULMONARY HYPERTENSION OR ELEVATED PULMONARY VASCULAR RESISTANCE, BUT DID INCREASE THEIR TOTAL PERIPHERAL RESISTANCE AND MEAN SYSTEMIC ARTERIAL PRESSURE, WHILE REDUCING THEIR CARDIAC OUTPUT. COOL TEMPERATURES WERE SHOWN TO CONTRIBUTE TO PULMONARY HYPERTENSION BY INCREASING THE METABOLIC DEMAND FOR OXYGEN, THEREBY CAUSING AN INCREASE IN CARDIAC OUTPUT THAT CHALLENGED AND OVERLAODED THE PULMONARY VASCULAR CAPACITY. THE PATTERNS OF GROWTH IN
INDIVIDUAL BROILERS WERE EVALUATED USING CHAOS THEORY AND NEURAL NETWORKS TO DETECT POSSIBLE CORRELATIONS WITH THE ONSET OF PULMONARY HYPERTENSION SYNDROME. NORMAL BROILERS HAD GREATER OSCILLATIONS IN GROWTH VELOCITY AND ACCELERATION THAN BIRDS SUSCEPTIBLE TO PHS. A NEURAL NETWORK WAS TRAINED TO DISTINGUISH THE DIFFERENCES IN GROWTH PATTERNS BETWEEN NORMAL AND ASCITES-SUSCEPTIBLE BROILERS. PULMONARY ARTERIAL PRESSURES MEASURED IN MALE BROILERS FROM 2 TO 7 WEEKS OF AGE. A KEY INTERVAL (WEEKS 3 TO 5) WAS REVEALED DURING WHICH A MISMATCH DEVELOPS BETWEEN CARDIAC OUTPUT AND PULMONARY VASCULAR CAPACITY. EXPERIMENTS USING UNILATERAL PULMONARY ARTERY OCCLUSION TO TRIGGER THE ONSET OF PULMONARY HYPERTENSION REVEALED THAT CARDIAC TAURINE IS RELEASED INTO THE PLASMA IN RESPONSE TO THE ONSET OF PULMONARY HYPERTENSION, HYPOXEMIA, AND RIGHT-SIDED CONGESTIVE HEART FAILURE. ENDOTOXIN WAS SHOWN TO TRIGGER PULMONARY HYPERTENSION IN BROILERS.
Impacts
Worldwide, approximately 2% of all broiler chickens die of a metabolic problem known as pulmonary hypertension syndrome (PHS, ascites). The estimated cost of PHS/ascites mortality to the international broiler industry exceeds $1 billion worldwide. This cost can be reduced if broiler lines can be developed that are genetically resistant to PHS/ascites. Dr. Wideman's research has conclusively demonstrated that broilers are susceptible to PHS/ascites when the capacity of the blood vessels in their lungs (pulmonary vascular capacity) is inadequate to accommodate the requisite cardiac output (volume of blood pumped by the heart per minute). Dr. Wideman collaborated with Dr. Howard French (Senior Geneticist, Hubbard ISA, Walpole, NH) to evaluate the genetic component of ascites susceptibility in broilers. Dr. Wideman developed a technique to eliminate susceptible individuals from the genetic stock, and a broiler line that is highly resistant to PHS has been developed.
Recent improvements in selection procedures for PHS resistance were awarded a provisional US Patent, and have been submitted for a full international patent. The dramatic improvement in ascites resistance demonstrates that, with appropriately focused and sufficiently rigorous selection pressures, major advances can be accomplished in reducing the frequency of undefined genes responsible for ascites susceptibility in commercial broilers.
Publications
- FORMAN, M. F., AND WIDEMAN, R. F., 1999. Renal responses of normal and preascitic broilers to systemic hypotension induced by unilateral pulmonary artery occlusion. Poultry Science 78:1773-1785.
- WIDEMAN, R. F., FEDDE, M. R., TACKETT, C. D., AND WEIGLE, G. E., 2000. Cardio-pulmonary function in preascitic (hypoxemic) or normal broilers inhaling ambient air or 100
- WIDEMAN, R. F., AND TACKETT, C. D., 2000. Cardio-pulmonary function in broilers reared at warm or cold temperatures: effect of acute inhalation of 100
- ROUSH, W. B., AND WIDEMAN, R. F., 2000. Evaluation of growth velocity and acceleration in relation to pulmonary hypertension syndrome (PHS). Poultry Science 79:180-191.
- FORMAN, M. F., AND WIDEMAN, R. F., 2000. Measurements of pulmonary arterial presure in anesthetized male broilers at two to seven weeks of age. Poultry Sci. 79:1645-1649.
- RUIZ-FERIA, C. A., KIDD, M. T., AND WIDEMAN, R. F., 2001. Plasma levels of arginine, ornithine, and urea, and growth performance of broilers fed supplemental L-arginine during cool temperature exposure. Poultry Sci. (in press).
- CHAPMAN, M. E., AND WIDEMAN, R. F., 2001. Pulmonary wedge pressures confirm pulmonary hypertension in broilers is initiated by excessive pulmonary arterial (precapillary) resistance. Poultry Sci. (in press).
- WIDEMAN, R. F., CHAPMAN, M. E., AND ERF, G. F., 2001. Intravenous endotoxin triggers pulmonary vasoconstriction and pulmonary hypertension in broiler chickens. Poultry Sci. (in press).
- ROUSH, W. B., WIDEMAN, R. F., A. CAHANER, AND CRAVENER, T. L., 2001. Minimum daily growth velocity data collection for pulmonary hypertension syndrome (PHS) as detected by artificial neural networks. Poultry Sci. (in press).
- FORMAN, M. F., 2000. The Renal Contribution to Pulmonary Hypertension Syndrome in Broilers (Ph.D. Dissertation; WIDEMAN, Dissertation Director).
- RUIZ-FERIA, C. A., 2001. The Role of L-Arginine and Taurine in the Pathophysiology of Pulmonary Hypertension Syndrome in Broiler Chickens (Ph.D. Dissertation; WIDEMAN, Dissertation Director).
- WIDEMAN, R. F., et al., 2000. In Ovo use of L-arginine and salts thereof for the prevention and/or treatment of pulmonary hypertension syndrome in avians. US Patent Number 6,127,421 awarded.
- WIDEMAN, R. F., et al., 2001. Intra-Vascular administration of particles to induce pulmonary hypertension syndrome and ascites in animals. Patent Application submitted under Univ. of Arkansas File No. ARK007/00038PCT.
- WIDEMAN, R. F., 2000. Cardio-pulmonary hemodynamics and ascites in broiler chickens. In: Poultry and Avian Biology Reviews. Ed. R. R. Dietert and M. A. Ottinger. Volume 11(1):21-43.
- WIDEMAN, R. F., AND FRENCH, H., 2000. Ascites resistance of progeny from broiler breeders selected for two generations using chronic unilateral pulmonary artery occlusion. Poultry Science 79:396-401.
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Progress 01/01/99 to 12/31/99
Outputs
Worldwide, approximately 2% of all broiler chickens die of ascites/pulmonary hypertension syndrome, at an estimated cost exceeding $400 million. This research has conclusively demonstrated that broilers are susceptible to PHS/ascites when the capacity of the blood vessels in their lungs is inadequate to accommodate the requisite cardiac output. Research conducted in collaboration with Dr. Howard French (Senior Geneticist, Hubbard ISA, Walpole, NH) evaluated the genetic component of ascites susceptibility. Using the unilateral pulmonary artery occlusion technique, susceptible individuals were eliminated from the genetic stock because they were unable to survive having their entire cardiac output forced to flow through the blood vessels of only one lung. The broilers that thrived in spite of having one pulmonary artery occluded (PHS-Resistant line), subsequently produced first generation male and female progeny exhibiting a > 50% reduction in their susceptibility
ascites. Growth performance was minimally affected. A second generation of selection within the PHS-Resistant line achieved an additional 25% reduction in ascites susceptibility with a minimal impact on growth performance. The dramatic improvement in ascites resistance within two generations of selection demonstrates that, with appropriately focused and sufficiently rigorous selection pressures, major advances can be accomplished in reducing the frequency of undefined but clearly dominant genes responsible for ascites susceptibility in commercial broilers.
Impacts
This research conclusively demonstrated that broilers are susceptible to PHS when the capacity of the blood vessels in the lungs is inadequate to accommodate the cardiac output required to support the metabolism of modern fast-growing broilers exposed to cool temperatures. The gene or genes involved in ascites susceptibility appear to be dominant, indicating that ongoing proactive exposure and elimination of susceptible individuals will be necessary to achieve an overall improvement in ascites resistance.
Publications
- Ruiz-Feria, C. A., Beers, K. W., Kidd, M. T., and Wideman, R. F. 1999. Plasma taurine levels in broilers with pulmonary hypertension syndrome induced by unilateral pulmonary artery occlusion. Poultry Science 78:1627-1633.
- Forman, M. F., and Wideman, R. F. 1999. Renal responses of normal and preascitic broilers to systemic hypotension induced by unilateral pulmonary artery occlusion. Poultry Science 78:(in press).
- Wideman, R. F., and French, H. 1999. Ascites resistance of progeny from broiler breeders selected for two generations using chronic unilateral pulmonary artery occlusion. Poultry Science 78:(in press).
- Kirby, Y. K., Anthony, N. B., Hughes, J. D., McNew, R. W., Kirby, J. D., and Wideman, R. F. 1999. Electrocardiographic and genetic evaluation of giant jungle fowl, broilers, and their reciprocal crosses following unilateral bronchus occlusion. Poultry Science 78:125-134.
- Kirby, Y. K., McNew, R. W., Anthony, N. B., Marson, N. E., Hughes, J. D., Kirby, J. D., and Wideman, R. F. 1999. Electrocardiographic evaluation of broilers following unilateral occlusion of an extrapulmonary primary bronchus. Poultry Science 78:242-254.
- Wideman, R. F. 1999. Cardiac Output in 4, 5 and 6 week old broilers, and hemodynamic responses to intravenous injections of epinephrine. Poultry Science 78:392-403.
- Wideman, R. F., and French, H. 1999. Broiler breeder survivors of chronic unilateral pulmonary artery occlusion produce progeny resistant to pulmonary hypertension syndrome (ascites) induced by cool temperatures. Poultry Science 78:404-411.
- Wideman, R. F., Maynard, P., and Bottje, W. G. 1999. Thromboxane mimics the pulmonary but not systemic vascular responses to bolus HCl injections in broiler chickens. Poultry Science 78:714-721.
- Roberts, J. R., Ford, B. C., and Wideman, R. F. 1999. Blood flow to the avian kidney: the use of transit-time ultrasonic flow probes. J. Exp. Zool. 284:15-22.
- Wideman, R. F., Maynard, P., and Bottje, W. G. 1999. Venous blood pressure in broilers during acute inhalation of five percent carbon dioxide or unilateral pulmonary artery occlusion. Poultry Science 78:1443-1451.
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Progress 01/01/98 to 12/31/98
Outputs
Broilers from three consecutive hatches were exposed to 16 C to amplify the incidence of pulmonary hypertension syndrome (PHS, ascites). The largest apparently healthy individuals on Day 42 were evaluated using minimally invasive diagnostic indices (percentage saturation of hemoglobin with oxygen, hematocrit [HCT], heart rate, electrocardiogram [ECG] Lead II, body weight), then they were subjected to the ongoing pressures of fast growth and cool temperatures to determine which of these indices are predictive of the subsequent onset of PHS. Body weights, heart rates, and percentage saturation of hemoglobin with oxygen were lower on Day 42 for susceptible (preascitic) than for resistant males. The ECG Lead II S wave amplitudes were more negative in susceptible males and females than in resistant males and females. The necropsy results support a primary role for pulmonary hypertension but not cardiomyopathy in the pathogenesis of ascites triggered by cool temperatures.
Values obtained for minimally invasive diagnostic indices on Day 42 established predictive thresholds that can be used to evaluate the PHS susceptibility of large and apparently healthy male and female broilers. In another experiment, we tested the hypothesis that a distended gastrointestinal tract (and thus compressed caudal air sacs) in full-fed broilers may result in an abnormally low tidal volume and minute ventilation that could lead to pulmonary hypoxia, pulmonary arterial vasoconstriction, right ventricular failure, and ascites. Tidal volume was not abnormally low in hypoxemic (preascitic) broilers compared with relatively normoxemic broilers. Blood oxygenation improved after 3 hr of fasting, despite a reduction in minute ventilation and no reduction in oxygen consumption. Feed deprivation improved blood oxygenation by reducing a ventilation/ perfusion mismatch in the lungs of preascitic broilers, not by increasing gas intake.
Impacts
(N/A)
Publications
- Wideman, R. F., Kirby, Y. K., Forman, M. F., Marson, N., McNew, R. W., and Owen, R. L. 1998. The infusion rate dependent influence of acute metabolic acidosis on pulmonary vascular resistance in broilers. Poultry Sci. 77:309-321.
- Wideman, R. F., Forman, M. F., Hughes, J. D., Kirby, Y. K., Marson, N., and Anthony, N. B. 1998. Flow-dependent pulmonary vasodilation during acute unilateral pulmonary artery occlusion in jungle fowl. Poultry Sci. 77:615-626.
- Wideman, R. F., Wing, T., Kirby, Y. K., Forman, M. F., Marson, N., Tackett, C. D., and Ruiz-Feria, C. A. 1998. Evaluation of minimally invasive indices for predicting ascites susceptibility in three successive hatches of broilers exposed to cool temperatures. Poultry Sci. 77:1565-1573.
- Fedde, M. R., Weigle, G. E., and Wideman, R. F. 1998. Influence of feed deprivation on ventilation and gas exchange in broilers: relationship to pulmonary hypertension syndrome. Poultry Sci. 77:1704-1710.
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Progress 01/01/97 to 12/31/97
Outputs
The incidence of pulmonary hypertension syndrome (PHS, ASCITES) was evaluated in broilers subjected to sham surgery (SHAM), surgical obstruction of an extrapulmonary primary bronchus (B-CLAMP),or obstruction of a pulmonary artery (PA-CLAMP). Compared with the Sham group, the B-CLAMP and PA-CLAMP groups exhibited intermediate and high incidences of PHS, respectively, thereby conclusively demonstrating the primary role of inadequate pulmonary capacity in the susceptibility of broilers to PHS. Survivors of subsequent PA-CLAMP surgeries are serving as the foundation stock for PHS-resistant genetic lines. Three statistical methodologies (logistic regression, linear regression, probabilistic neural network) were used to evaluate the relative contribution of various diagnostic indices for predicting the susceptibility of broilers to PHS. These studies demonstrated that seemingly independent challenges known to induce PHS in susceptible broilers (cold exposure, PA-Clamp,
B-Clamp) initiate a similar pathophysiological progression which can be characterized with a high degree of accuracy using a variety of diagnostic indices. The pulmonary vascular responses of clinically healthy male broilers were evaluated during acute metabolic acidosis induces by bolus intravenous injections or constant intravenous infusions of HCL. Bolus acid injections caused pulmonary hypertension secondary to an increase in pulmonary vascular resistance that apparently was mediated by intravascular thromboxane release.
Impacts
(N/A)
Publications
- WIDEMAN, R. F., KIRBY, Y. K., OWEN, R. L., AND FRENCH, H. CHRONIC UNILATERAL OCCLUSION OF AN EXTRAPULMONARY PRIMARY BRONCHUS INITIATES PULMONARY HYPERTENSION SYNDROME (ASCITES) IN MALE AND FEMALE BROILERS. POULTRY SCIENCE 76:400-404, 1997.
- KIRBY, Y. K., KIRBY, J. D., MCNEW, R. W., AND WIDEMAN, R. F. EVALUATION OF LOGISTIC VERSUS LINEAR REGRESSION MODELS FOR PREDICTING PULMONARY HYPERTENSION SYNDROME (ASCITES) USING COLD STRESS OR PULMONARY ARTERY CLAMP MODELS IN BROILERS. POULTRY SCIENCE
- ROUSH, W. B., T. L. CRAVENER, Y. KOCHERA KIRBY, AND R. F. WIDEMAN. PROBABILISTIC NEURAL NETWORK PREDICTION OF ASCITES IN BROILERS BASED ON MINIMALLY INVASIVE PHYSIOLOGICAL FACTORS. POULTRY SCIENCE
- WIDEMAN, R. F., KIRBY, Y. K., FORMAN, M. F., MARSON, N., MCNEW, R. W., AND OWEN, R. L. THE INFUSION RATE DEPENDENT INFLUENCE OF ACUTE METABOLIC ACIDOSIS ON PULMONARY VASCULAR RESISTANCE IN BROILERS.
- WIDEMAN, R. F., FORMAN, M. F., HUGHES, J. D., KIRBY, Y. K., MARSON, N., AND ANTHONY, N. B. FLOW-DEPENDENT PULMONARY VASODILATION DURING ACUTE UNILATERAL PULMONARY ARTERY OCCLUSION IN JUNGLE FOWL. POULTRY
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Progress 01/01/96 to 12/30/96
Outputs
Electrocardiography was evaluated as a noninvasive method for detecting right ventricular hypertrophy associated with pulmonary hypertension syndrome (PHS, ASCITES) in broiler chickens. An increasingly negative lead II "S" wave amplitude and an increasing mean resultant vector were strongly correlated with the right: total ventricular weight ratio (RV:TV), thus constituting accurate, noninvasive predictive criteria suitable for detecting the onset of PHS. An artificial neural network was trained to accurately predict the presence or absence of ascites in broiler chickens based on invasive and noninvasive criteria. Comparisons of the blood from normal and ascitic broilers revealed no difference in relative viscosity and thus no difference in deformability characteristics of erythrocytes. Increasing the packed cell volume (PCV) equally increased the apparent viscosity of blood from both normal and ascitic broilers, indicating an elevated PCV can contribute to an
elevated pulmonary vascular resistance. Tightening a snare on the left pulmonary artery shunted the entire cardiac output through the right lung and caused an acute decrease in the oxygen content of systemic arterial blood (HYPOXEMIA); simultaneously tightening a snare around the left bronchus directed the entire respiratory minute volume to the right lung but did not attenuate the hypoxemia, indicating broiler lungs are highly susceptible to hypoxemia induced by elevations in cardiac output. Detailed evaluations of cardiac output, pulmon.
Impacts
(N/A)
Publications
- INDEPENDENT AND SIMULTANEOUS UNILATERAL OCCLUSION OF THEPULMONARY ARTERY AND EXTRA-PULMONARY PRIMARY BRONCHUS IN BROILERS. POULTRY SCIENC ROUSH, W. B., KIRBY, Y. K., CRAVENER, T. L., AND WIDEMAN, R. F., 1996. ARTIFICIAL NEURAL NETWORK PREDICTION OF ASCITES IN BROILERS. POULTRY SCIENCE 75:1479-1487.
- WIDEMAN, R. F., KIRBY, Y. K., TACKETT, C. T., MARSON, N. E., AND MCNEW, R. W., 1996. CARDIO- PULMONARY FUNCTION DURING ACUTE UNILATERAL OCCLUSION OF THE PULMONARY ARTERY IN BROILERS FED DIETS CONTAINING NORMAL OR HIGH LEVELS OF ARGININE-HCL KIRBY, Y. K., KIRBY, J. D., MCNEW, R. W., AND WIDEMAN, R. F., (IN PRESS). EVALUATION OF LOGISTIC VS. LINEAR REGRESSION MODELS FOR PREDICTING PULMONARY HYPERTENSION SYNDROME (ASCITES) USING COLD STRESS OR PULMONARY ARTERY CLAMP MODELS IN BRO.
- WIDEMAN, R. F., AND KIRBY, Y. K., 1996. ELECTROCARDIOGRAPHIC EVALUATION OF BROILERS DURING THE ONSET OF PULMONARY HYPERTENSION INITIATED BY UNILATERAL PULMONARY ARTERY OCCLUSION. POULTRY SCIENCE 75:407-416.
- FEDDE, M. R., AND WIDEMAN, R. F., 1996. BLOOD VISCOSITY IN BROILERS: INFLUENCE OF PULMONARY HYPERTENSION SYNDROME (ASCITES). POULTRY SCIENCE 75:1261-1267.
- WIDEMAN, R. F., KIRBY, Y. K., TACKETT, C. D., MARSON, N. E., TRESSLER, C. J., AND MCNEW, R. W., 1996.
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Progress 01/01/95 to 12/30/95
Outputs
Experiments were conducted to evaluate the hypothesis that broiler chickens are susceptible to pulmonary hypertension syndrome (ASCITES) when their pulmonary vascular resistance is elevated due either to an inadequate pulmonary vascular capacity or to excessive pulmonary vasoconstriction. Low atmospheric oxygen (HYPOXIA) causes constriction of the pulmonary vasculature and acute hypoxia caused acute, reversible pulmonary hypertension in broilers. Furosemide and Arginine reduce pulmonary vascular resistance by dilating the pulmonary vasculature, and diets supplemented with Furosemide or Arginine significantly reduced the incidence of ascites in broilers exposed to cool environmental temperatures. Pulmonary vascular resistance was directly increased by surgically clamping one pulmonary artery, and over 60% of the broilers with a chronically clamped pulmonary artery developed Ascites. The onset of pulmonary hypertension in broilers coincides with a decrease in the oxygen
content of systemic arterial blood (HYPOXEMIA), suggesting pulmonary hypertension causes blood to flow too rapidly through the pulmonary vasculature to acquire a full load of oxygen. A snare placed around one pulmonary artery permitted acute, reversible shunting of the entire cardiac output through the unobstructed lung of clinically healthy 40 to 49 day old male broilers. Tightening the snare caused an acute, reversible hypoxemia accompanied by an increase in blood carbon dioxide.
Impacts
(N/A)
Publications
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Progress 01/01/94 to 12/30/94
Outputs
A detailed review was published, in which abnormalities in pulmonary vascular capacity and Pulmonary Vascular Resistance (PVR) were hypothesized to be the primary causes of Pulmonary Hypertension Syndrome (PHS, ascites) in broilers. Cold Stress and Pulmonary Artery Clamp models were successfully developed to reliably induce PHS. Experiments confirmed that furosemide and L-arginine, compounds known to act as pulmonary vasodilators, reduced the incidence of PHS when incorporated in the diets of broiler-type chickens exposed to cool temperatures. An excessively elevated PVR was further validated as a primary cause of PHS by chronically placing occlusive clamps on one pulmonary artery in 2 to 3 week old chicks. Chronic unilateral pulmonary artery occlusion triggered 68% and 90% incidences of PHS by 49 days of age in two separate trials, constituting the first direct demonstration that a primary increase in PVR can initiate the pathophysiological progression leading to
terminal ascites. Acutely snaring one pulmonary artery triggered hypoxemia in 40 to 49 day old clinically healthy broilers, providing the first direct emonstration that healthy broilers are extremely susceptible to a entilation/perfusion (V/Q) mismatch. Thus, even a moderate (approximately twofold) increase in cardiac output flowing through the vasculature of the unoccluded lung compromised the pulmonary capacity to fully oxygenate the blood.
Impacts
(N/A)
Publications
- WIDEMAN, R. F., KIRBY, Y. K., ISMAIL, M., BOTTJE, W. G., MOORE, R. W., AND VARDEMAN, R. C. 1995. Supplemental L-Arginine attenuates pulmonary hypertension syndrome (ascites) in broilers. Poultry Science (in-press).
- OWEN, R.L., WIDEMAN, R.F., BARBATO, G.F., COWEN, B.S., FORD, B.C., AND HATTEL, A.L. 1995. Morphometric and pathologic changes in the pulmonary system of broilers raised at simulated high altitude. Avian Pathology (in-press).
- OWEN, R.L., WIDEMAN, R.F., LEACH, R.M., COWEN, B.S., DUNN, P.A., AND FORD, B.C. 1995. Physiologic and electrocardiographic changes occurring in broilers reared at simulated high altitude. Avian Diseases (in-press).
- OWEN, R.L., WIDEMAN, R.F., AND COWEN, B.S. 1995. Changes in pulmonary arterial and femoral arterial blood pressure upon acute exposure to hypobaric hypoxia in.
- Wideman, R. F., and W. G. Bottje, 1993. Current understanding of the ascites o syndrome and future research directions. Pages 1-20 in: Nutrition and Technical Symposium Proceedings. Novus International, Inc., St. Louis, MO. . OWEN, R.L., WIDEMAN, R.F., LEACH, R.M., COWEN, B.S., DUNN, P.A., AND FORD, B.C.f 1994. Effect of age of exposure and dietary acidification or alkalinization on u mortality due to broiler pulmonary hypertension syndrome. J. Appl. Poul
- WIDEMAN, R. F., ISMAIL, M., KIRBY, Y. K., BOTTJE, W. G., MOORE, R. W., AND , VARDEMAN, R. C. 1995. Furosemide reduced the incidence of pulmonary hypertension syndrome (ascites) in broilers exposed to cool environmental temperatures. m
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