Alterations in endogenous nitric oxide production after cardiopulmonary bypass in lambs with normal and increased pulmonary blood flow

D. Michael McMullan, Janine M. Bekker, Andrew J. Parry, Michael J. Johengen, Alexander Kon, R. Scott Heidersbach, Stephen Matthew Black, Jeffrey R. Fineman

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background - After cardiopulmonary bypass (CPB), altered vascular reactivity is a major source of complications, particularly for children with increased pulmonary blood flow. Although changes in agonist-induced NO activity are well described after CPB, potential changes in basal NO production and their role in post-CPB pulmonary hypertension remain unclear. By using aortopulmonary vascular graft placement in the fetal lamb (shunt lambs), we established a unique model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. The objective of the present study was to investigate potential alterations in endogenous NO production after CPB in lambs with normal and increased pulmonary blood flow. Methods and Results - Vascular pressures and blood flows were monitored in 1-month-old lambs (n=7) with increased pulmonary blood flow and 6 age-matched control lambs. After shunt closure, hypothermic CPB (25°C) was performed for 2 hours. The hemodynamic variables were monitored for 4 hours after CPB. Before, during, and after CPB, peripheral lung biopsies were performed to determine tissue NO, nitrite, nitrate, and cGMP concentrations; total NO synthase (NOS) activity; and endothelial NOS protein levels. Hypothermic CPB increased both mean pulmonary arterial pressure and left pulmonary vascular resistance (P<0.05). The increase in pulmonary arterial pressure induced in shunt lambs was greater than that induced in control lambs (P<0.05). Four hours after CPB, tissue concentrations of NO, nitrite, nitrate, and cGMP were decreased to ≃70% of pre-CPB levels in both control and shunt lambs (P<0.05). Total NOS activity and endothelial NOS protein levels were unchanged. Conclusions - Modest decreases in basal NO production, the inability to increase NO production, or both may play a role in the altered pulmonary vascular reactivity after CPB. The decrease in NO is independent of gene expression. However, other mechanisms for this decrease, such as substrate or cofactor availability, warrant further study.

Original languageEnglish (US)
JournalCirculation
Volume102
Issue number19
StatePublished - Nov 7 2000

Fingerprint

Cardiopulmonary Bypass
Nitric Oxide
Lung
Nitric Oxide Synthase
Blood Vessels
Nitrites
Pulmonary Hypertension
Nitrates
Arterial Pressure
Vascular Resistance
Heart Diseases
Proteins
Hemodynamics
Blood Pressure
Transplants
Biopsy
Gene Expression

Keywords

  • Cardiopulmonary bypass
  • Endothelium
  • Hypertension
  • Lungs
  • Nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

McMullan, D. M., Bekker, J. M., Parry, A. J., Johengen, M. J., Kon, A., Heidersbach, R. S., ... Fineman, J. R. (2000). Alterations in endogenous nitric oxide production after cardiopulmonary bypass in lambs with normal and increased pulmonary blood flow. Circulation, 102(19).

Alterations in endogenous nitric oxide production after cardiopulmonary bypass in lambs with normal and increased pulmonary blood flow. / McMullan, D. Michael; Bekker, Janine M.; Parry, Andrew J.; Johengen, Michael J.; Kon, Alexander; Heidersbach, R. Scott; Black, Stephen Matthew; Fineman, Jeffrey R.

In: Circulation, Vol. 102, No. 19, 07.11.2000.

Research output: Contribution to journalArticle

McMullan, DM, Bekker, JM, Parry, AJ, Johengen, MJ, Kon, A, Heidersbach, RS, Black, SM & Fineman, JR 2000, 'Alterations in endogenous nitric oxide production after cardiopulmonary bypass in lambs with normal and increased pulmonary blood flow', Circulation, vol. 102, no. 19.
McMullan DM, Bekker JM, Parry AJ, Johengen MJ, Kon A, Heidersbach RS et al. Alterations in endogenous nitric oxide production after cardiopulmonary bypass in lambs with normal and increased pulmonary blood flow. Circulation. 2000 Nov 7;102(19).
McMullan, D. Michael ; Bekker, Janine M. ; Parry, Andrew J. ; Johengen, Michael J. ; Kon, Alexander ; Heidersbach, R. Scott ; Black, Stephen Matthew ; Fineman, Jeffrey R. / Alterations in endogenous nitric oxide production after cardiopulmonary bypass in lambs with normal and increased pulmonary blood flow. In: Circulation. 2000 ; Vol. 102, No. 19.
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abstract = "Background - After cardiopulmonary bypass (CPB), altered vascular reactivity is a major source of complications, particularly for children with increased pulmonary blood flow. Although changes in agonist-induced NO activity are well described after CPB, potential changes in basal NO production and their role in post-CPB pulmonary hypertension remain unclear. By using aortopulmonary vascular graft placement in the fetal lamb (shunt lambs), we established a unique model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. The objective of the present study was to investigate potential alterations in endogenous NO production after CPB in lambs with normal and increased pulmonary blood flow. Methods and Results - Vascular pressures and blood flows were monitored in 1-month-old lambs (n=7) with increased pulmonary blood flow and 6 age-matched control lambs. After shunt closure, hypothermic CPB (25°C) was performed for 2 hours. The hemodynamic variables were monitored for 4 hours after CPB. Before, during, and after CPB, peripheral lung biopsies were performed to determine tissue NO, nitrite, nitrate, and cGMP concentrations; total NO synthase (NOS) activity; and endothelial NOS protein levels. Hypothermic CPB increased both mean pulmonary arterial pressure and left pulmonary vascular resistance (P<0.05). The increase in pulmonary arterial pressure induced in shunt lambs was greater than that induced in control lambs (P<0.05). Four hours after CPB, tissue concentrations of NO, nitrite, nitrate, and cGMP were decreased to ≃70{\%} of pre-CPB levels in both control and shunt lambs (P<0.05). Total NOS activity and endothelial NOS protein levels were unchanged. Conclusions - Modest decreases in basal NO production, the inability to increase NO production, or both may play a role in the altered pulmonary vascular reactivity after CPB. The decrease in NO is independent of gene expression. However, other mechanisms for this decrease, such as substrate or cofactor availability, warrant further study.",
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AU - McMullan, D. Michael

AU - Bekker, Janine M.

AU - Parry, Andrew J.

AU - Johengen, Michael J.

AU - Kon, Alexander

AU - Heidersbach, R. Scott

AU - Black, Stephen Matthew

AU - Fineman, Jeffrey R.

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N2 - Background - After cardiopulmonary bypass (CPB), altered vascular reactivity is a major source of complications, particularly for children with increased pulmonary blood flow. Although changes in agonist-induced NO activity are well described after CPB, potential changes in basal NO production and their role in post-CPB pulmonary hypertension remain unclear. By using aortopulmonary vascular graft placement in the fetal lamb (shunt lambs), we established a unique model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. The objective of the present study was to investigate potential alterations in endogenous NO production after CPB in lambs with normal and increased pulmonary blood flow. Methods and Results - Vascular pressures and blood flows were monitored in 1-month-old lambs (n=7) with increased pulmonary blood flow and 6 age-matched control lambs. After shunt closure, hypothermic CPB (25°C) was performed for 2 hours. The hemodynamic variables were monitored for 4 hours after CPB. Before, during, and after CPB, peripheral lung biopsies were performed to determine tissue NO, nitrite, nitrate, and cGMP concentrations; total NO synthase (NOS) activity; and endothelial NOS protein levels. Hypothermic CPB increased both mean pulmonary arterial pressure and left pulmonary vascular resistance (P<0.05). The increase in pulmonary arterial pressure induced in shunt lambs was greater than that induced in control lambs (P<0.05). Four hours after CPB, tissue concentrations of NO, nitrite, nitrate, and cGMP were decreased to ≃70% of pre-CPB levels in both control and shunt lambs (P<0.05). Total NOS activity and endothelial NOS protein levels were unchanged. Conclusions - Modest decreases in basal NO production, the inability to increase NO production, or both may play a role in the altered pulmonary vascular reactivity after CPB. The decrease in NO is independent of gene expression. However, other mechanisms for this decrease, such as substrate or cofactor availability, warrant further study.

AB - Background - After cardiopulmonary bypass (CPB), altered vascular reactivity is a major source of complications, particularly for children with increased pulmonary blood flow. Although changes in agonist-induced NO activity are well described after CPB, potential changes in basal NO production and their role in post-CPB pulmonary hypertension remain unclear. By using aortopulmonary vascular graft placement in the fetal lamb (shunt lambs), we established a unique model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. The objective of the present study was to investigate potential alterations in endogenous NO production after CPB in lambs with normal and increased pulmonary blood flow. Methods and Results - Vascular pressures and blood flows were monitored in 1-month-old lambs (n=7) with increased pulmonary blood flow and 6 age-matched control lambs. After shunt closure, hypothermic CPB (25°C) was performed for 2 hours. The hemodynamic variables were monitored for 4 hours after CPB. Before, during, and after CPB, peripheral lung biopsies were performed to determine tissue NO, nitrite, nitrate, and cGMP concentrations; total NO synthase (NOS) activity; and endothelial NOS protein levels. Hypothermic CPB increased both mean pulmonary arterial pressure and left pulmonary vascular resistance (P<0.05). The increase in pulmonary arterial pressure induced in shunt lambs was greater than that induced in control lambs (P<0.05). Four hours after CPB, tissue concentrations of NO, nitrite, nitrate, and cGMP were decreased to ≃70% of pre-CPB levels in both control and shunt lambs (P<0.05). Total NOS activity and endothelial NOS protein levels were unchanged. Conclusions - Modest decreases in basal NO production, the inability to increase NO production, or both may play a role in the altered pulmonary vascular reactivity after CPB. The decrease in NO is independent of gene expression. However, other mechanisms for this decrease, such as substrate or cofactor availability, warrant further study.

KW - Cardiopulmonary bypass

KW - Endothelium

KW - Hypertension

KW - Lungs

KW - Nitric oxide

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