An Inadequate Pulmonary Vascular Capacity and Susceptibility to Pulmonary Arterial Hypertension in Broilers

Abstract

Broilers are susceptible to pulmonary hypertension syndrome (PHS; ascites syndrome) when their pulmonary vascular capacity is anatomically or functionally inadequate to accommodate the requisite cardiac output without an excessive elevation in pulmonary arterial pressure. The consequences of an inadequate pulmonary vascular capacity have been demonstrated experimentally and include elevated pulmonary vascular resistance (PVR) attributable to noncompliant, fully engorged vascular channels; sustained pulmonary arterial hypertension (PAH); systemic hypoxemia and hypercapnia; specific right ventricular hypertrophy, and right atrioventricular valve failure (regurgitation), leading to central venous hypertension and hepatic cirrhosis. Pulmonary vascular capacity is broadly defined to encompass anatomical constraints related to the compliance and effective volume of blood vessels, as well as functional limitations related to the tone (degree of constriction) maintained by the primary resistance vessels (arterioles) within the lungs. Surgical occlusion of 1 pulmonary artery halves the anatomical pulmonary vascular capacity, doubles the PVR, triggers PAH, eliminates PHS-susceptible broilers, and reveals PHS-resistant survivors whose lungs are innately capable of handling sustained increases in pulmonary arterial pressure and cardiac output. We currently are using i.v. microparticle injections to increase the PVR and trigger PAH sufficient in magnitude to eliminate PHS-susceptible individuals while allowing PHS-resistant individuals to survive as progenitors of robust broiler lines. The microparticles obstruct pulmonary arterioles and cause local tissues and responding leukocytes to release vasoactive substances, including the vasodilator NO and the highly effective vasoconstrictors thromboxane A(2) and serotonin [5-hydroxytryptamine (5-HT)]. Nitric oxide is the principal vasodilator responsible for modulating (attenuating) the PAH response and ensuing mortality triggered by i.v. microparticle injections, whereas microparticle-induced increases in PVR can be attributed principally to 5-HT. Our observations support the hypothesis that susceptibility to PHS is a consequence of anatomically inadequate pulmonary vascular capacity combined with the functional predominance of the vasoconstrictor 5-HT over the vasodilator NO. The contribution of TxA(2) remains to be determined. Selecting broiler lines for resistance to PHS depends upon improving both anatomical and functional components of pulmonary vascular capacity.

Pulmonary arterial hypertension (ascites syndrome) in broilers: A review

“…The rate at which venous blood returns to the heart must equal the cardiac output; therefore, during the first 2 mo posthatch the blood vessels in a broiler's lungs must develop the pulmonary vascular capacity to receive and oxygenate a 100-fold increase in venous return. We have defined pulmonary vascular capacity to broadly encompass both anatomical and functional characteristics, including the total number and volume of blood vessels in the lungs, the tone (degree of partial constriction) maintained by the precapillary arterioles that offer the primary resistance to pulmonary blood flow, as well as the compliance (ease of distention) and reserve capacity (availability for recruitment) of the capillaries Wideman, 2000Wideman, , 2001Wideman et al, 2007). Evaluations of cardio-pulmonary hemodynamics indicate broiler lungs possess a very limited capacity to employ key compensatory mechanisms that enable mammalian lungs to readily accommodate increases in the cardiac output, such as flow-dependent dilation of precapillary arterioles, and vascular distention or recruitment of previously underperfused vascular channels.…”

Minimal distensibility of pulmonary capillaries in avian lungs compared with mammalian lungs

“…The etiology of the illness has been studied extensively (Currie, 1999;Wideman et al, 2007) because worldwide it is estimated to cost the broiler industry over a billion dollars each year.…”

Immunohistochemical examination of plexiform-like complex vascular lesions in the lungs of broiler chickens selected for susceptibility to idiopathic pulmonary arterial hypertension

“…Pulmonary arterial pressure (PAP) is elevated beyond the normal level in broiler chickens with IPAH. PAP ]25 mmHg coupled with wedge pressures 515 mmHg are specifically diagnostic for IPAH attributable to elevated arteriole (precapillary) resistance (Wideman et al, 2007). In our previous study, PAP and wedge pressures were recorded from 8-week-old, 12-week-old, 16-week-old, 20-weekold and 24-week-old male and female broilers from a IPAH-susceptible line.…”

“…Approximately 3% of all broiler chickens develop IPAH when reared under conditions that promote rapid growth. Incidences of IPAH exceeding 20% have been induced in broiler chickens by subjecting them to conditions that further increase the cardiac output or pulmonary vascular resistance, including exposure to sub-thermoneutral temperatures, hypobaric hypoxia, poor air quality, respiratory disease, or partial occlusion of the pulmonary vasculature (Wideman, 2000(Wideman, , 2001Wideman et al, 2007). Broilers with IPAH consistently exhibit medial hypertrophy within the 25 to 100 mm diameter inter-parabronchial pulmonary arteries that are homologous to the pre-acinar arteries of mammals (Cueva et al, 1974;Hernandez, 1987;Pan et al, 2005;Tan et al, 2005aTan et al, , 2005b.…”