TY - JOUR
T1 - Effects of lack of pulsatility on pulmonary endothelial function in the Fontan circulation
AU - Henaine, Roland
AU - Vergnat, Mathieu
AU - Bacha, Emile A.
AU - Baudet, Bruno
AU - Lambert, Virginie
AU - Belli, Emre
AU - Serraf, Alain
PY - 2013/9
Y1 - 2013/9
N2 - Objectives: Continuous flow in the Fontan circulation results in impairment of pulmonary artery endothelial function, increased pulmonary arterial resistance, and, potentially, late failure of Fontan circulation. We investigated the mechanisms of vascular remodeling and altered vascular reactivity associated with chronic privation of pulsatility on pulmonary vasculature. Methods: A total of 30 pigs were evenly distributed in 3 groups: 10 underwent a sham procedure (group I) and 20 underwent a cavopulmonary shunt between the superior vena cava and right pulmonary artery - 10 with complete ligation of the proximal right pulmonary artery (group II, nonpulsatile) and 10 with partial ligation (group III, micropulsatile). At 3 months postoperatively, the in vivo hemodynamics, in vitro vasomotricity (concentration response curves on pulmonary artery isolated rings), and endothelial nitric oxide synthase protein level were assessed. A comparison between group and between the right and left lung in each group was performed. Results: Group II developed right pulmonary hypertension and increased right pulmonary resistance. Endothelial function was altered in group II, as reflected by a decrease in the vasodilation response to acetylcholine and ionophoric calcium but preservation of the nonendothelial-dependent response to sodium nitroprusside. Group III micropulsatility attenuated pulmonary hypertension but did not prevent impairment of the endothelial-dependant relaxation response. Right lung Western blotting revealed decreased endothelial nitric oxide synthase in group II (0.941 ± 0.149 vs sham 1.536 ± 0.222, P =.045) that was preserved in group III (1.275 ± 0.236, P =.39). Conclusions: In a chronic model of unilateral cavopulmonary shunt, pulsatility loss resulted in an altered endothelial-dependant vasorelaxation response of the pulmonary arteries. Micropulsatility limited the effects of pulsatility loss. These results are of importance for potential therapies against pulmonary hypertension in the nonpulsatile Fontan circulation, by retaining accessory pulmonary flow or pharmaceutical modulation of nonendothelial-dependant pulmonary vasorelaxation.
AB - Objectives: Continuous flow in the Fontan circulation results in impairment of pulmonary artery endothelial function, increased pulmonary arterial resistance, and, potentially, late failure of Fontan circulation. We investigated the mechanisms of vascular remodeling and altered vascular reactivity associated with chronic privation of pulsatility on pulmonary vasculature. Methods: A total of 30 pigs were evenly distributed in 3 groups: 10 underwent a sham procedure (group I) and 20 underwent a cavopulmonary shunt between the superior vena cava and right pulmonary artery - 10 with complete ligation of the proximal right pulmonary artery (group II, nonpulsatile) and 10 with partial ligation (group III, micropulsatile). At 3 months postoperatively, the in vivo hemodynamics, in vitro vasomotricity (concentration response curves on pulmonary artery isolated rings), and endothelial nitric oxide synthase protein level were assessed. A comparison between group and between the right and left lung in each group was performed. Results: Group II developed right pulmonary hypertension and increased right pulmonary resistance. Endothelial function was altered in group II, as reflected by a decrease in the vasodilation response to acetylcholine and ionophoric calcium but preservation of the nonendothelial-dependent response to sodium nitroprusside. Group III micropulsatility attenuated pulmonary hypertension but did not prevent impairment of the endothelial-dependant relaxation response. Right lung Western blotting revealed decreased endothelial nitric oxide synthase in group II (0.941 ± 0.149 vs sham 1.536 ± 0.222, P =.045) that was preserved in group III (1.275 ± 0.236, P =.39). Conclusions: In a chronic model of unilateral cavopulmonary shunt, pulsatility loss resulted in an altered endothelial-dependant vasorelaxation response of the pulmonary arteries. Micropulsatility limited the effects of pulsatility loss. These results are of importance for potential therapies against pulmonary hypertension in the nonpulsatile Fontan circulation, by retaining accessory pulmonary flow or pharmaceutical modulation of nonendothelial-dependant pulmonary vasorelaxation.
KW - 50% of the maximal response
KW - EC
KW - Emax
KW - NO
KW - PA
KW - PAP
KW - PVP
KW - PVR
KW - SVC
KW - eNOS
KW - endothelial nitric oxide synthase
KW - maximal response
KW - nitric oxide
KW - pulmonary artery
KW - pulmonary artery pressure
KW - pulmonary vascular resistance
KW - pulmonary vein pressure
KW - superior vena cava
UR - http://www.scopus.com/inward/record.url?scp=84881615612&partnerID=8YFLogxK
U2 - 10.1016/j.jtcvs.2012.11.031
DO - 10.1016/j.jtcvs.2012.11.031
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C2 - 23219498
AN - SCOPUS:84881615612
SN - 0022-5223
VL - 146
SP - 522
EP - 529
JO - Journal of Thoracic and Cardiovascular Surgery
JF - Journal of Thoracic and Cardiovascular Surgery
IS - 3
ER -