TY - JOUR
T1 - In utero placement of aortopulmonary shunts
T2 - A model of postnatal pulmonary hypertension with increased pulmonary blood flow in lambs
AU - Reddy, V. Mohan
AU - Meyrick, Barbara
AU - Wong, Jackson
AU - Khoor, Andras
AU - Liddicoat, John R.
AU - Hanley, Frank L.
AU - Fineman, Jeffrey R.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 1995/8/1
Y1 - 1995/8/1
N2 - Background: The development of pulmonary hypertension and its associated increased vascular reactivity is a common accompaniment of congenital heart disease with increased pulmonary blood flow. Although the morphology of the pulmonary vascular changes is well described, the mechanisms of vascular remodeling and increased reactivity remain incompletely understood. Methods and Results: To elucidate these mechanisms, we established an accurate and reliable experimental model of pulmonary hypertension with increased pulmonary blood flow. An aortopulmonary shunt was created with an 8.0 mm expanded polytetrafluoroethylene vascular graft in 11 late gestation fetal lambs. At 1 month of age, shunted lambs had a pulmonary to systemic blood flow ratio of 2.2±1.2. Compared with 11 age-matched control lambs, mean pulmonary arterial pressure (44.8±11.7 versus 16.2±2.9 mm Hg) and the ratio of pulmonary to systemic arterial pressure were significantly increased (P<.05). Pulmonary vascular resistance was not significantly increased. The pulmonary vasoconstricting response to the infusion of U46619 (a thromboxane A2 mimic) or acute alveolar hypoxia also was augmented in the shunted lambs. Morphometric analysis of the barium-filled pulmonary artery bed revealed medial hypertrophy, abnormal extension of muscle distally into the walls of the intra-acinar arteries, and increased numbers of barium-filled intra- acinar arteries. Conclusions: In utero placement of aortopulmonary shunts reproduces the aberrant hemodynamic state of children with congenital heart disease with left-to-right shunts; postnatal pulmonary hypertension, increased pulmonary blood flow, and vascular remodeling. In addition, the lambs have a unique paradoxical increase in pulmonary vascular volume that attenuates an increase in pulmonary vascular resistance. This experimental preparation provides a useful and consistent model for the study of the pathogenesis of pulmonary hypertension.
AB - Background: The development of pulmonary hypertension and its associated increased vascular reactivity is a common accompaniment of congenital heart disease with increased pulmonary blood flow. Although the morphology of the pulmonary vascular changes is well described, the mechanisms of vascular remodeling and increased reactivity remain incompletely understood. Methods and Results: To elucidate these mechanisms, we established an accurate and reliable experimental model of pulmonary hypertension with increased pulmonary blood flow. An aortopulmonary shunt was created with an 8.0 mm expanded polytetrafluoroethylene vascular graft in 11 late gestation fetal lambs. At 1 month of age, shunted lambs had a pulmonary to systemic blood flow ratio of 2.2±1.2. Compared with 11 age-matched control lambs, mean pulmonary arterial pressure (44.8±11.7 versus 16.2±2.9 mm Hg) and the ratio of pulmonary to systemic arterial pressure were significantly increased (P<.05). Pulmonary vascular resistance was not significantly increased. The pulmonary vasoconstricting response to the infusion of U46619 (a thromboxane A2 mimic) or acute alveolar hypoxia also was augmented in the shunted lambs. Morphometric analysis of the barium-filled pulmonary artery bed revealed medial hypertrophy, abnormal extension of muscle distally into the walls of the intra-acinar arteries, and increased numbers of barium-filled intra- acinar arteries. Conclusions: In utero placement of aortopulmonary shunts reproduces the aberrant hemodynamic state of children with congenital heart disease with left-to-right shunts; postnatal pulmonary hypertension, increased pulmonary blood flow, and vascular remodeling. In addition, the lambs have a unique paradoxical increase in pulmonary vascular volume that attenuates an increase in pulmonary vascular resistance. This experimental preparation provides a useful and consistent model for the study of the pathogenesis of pulmonary hypertension.
KW - heart defects, congenital
KW - hypertension, pulmonary
KW - pulmonary heart disease
UR - http://www.scopus.com/inward/record.url?scp=0029160781&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029160781&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.92.3.606
DO - 10.1161/01.CIR.92.3.606
M3 - Article
C2 - 7634475
AN - SCOPUS:0029160781
SN - 0009-7322
VL - 92
SP - 606
EP - 613
JO - Circulation
JF - Circulation
IS - 3
ER -