Endogenous nitric oxide and pulmonary vascular tone in the neonate

Evan C. Lipsitz, Samuel Weinstein, Arthur J. Smerling, Charles J H Stolar

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Purpose: In newborns, inhaled nitric oxide (NO) has been shown to ameliorate increased pulmonary vascular resistance (PVR) precipitated by hypoxia. The role of endogenous NO production in this response is not clear. The contribution of endogenous NO to resting PVR in normoxic newborns also has not been well studied. The authors used an isolated, in situ, neonatal piglet lung-perfusion model, devoid of systemic detractors in which endogenous NO could be selectively inhibited, to determine whether (1) endogenous NO plays a role in the maintenance of PVR with normoxia, (2) endogenous NO plays a role in the response to hypoxia, and (c) inhaled NO can reverse changes induced by inhibition of endogenous NO. Methods: Sixteen neonatal piglets underwent occlusive tracheostomy and pressure-cycled ventilation. After heparinization and ligation of the ductus arteriosus, left atrial and pulmonary arterial cannulation were performed, without ischemia, via a median sternotomy. The aorta was ligated, and lung perfusion was set at 80 mL/kg/min via an extracorporeal membrane oxygenation circuit. Hematocrit (40% to 45%), pH (7.37 to 7.44), PCO2 (35 to 40 mm Hg), and peak inspiratory pressures (20 mm Hg) were constant. Pulmonary artery pressure (P(PA)), left atrial pressure (P(LA)), and circuit flow (Q(PA)) were recorded continuously. PVR calculated as follows: PVR[(dynes x seconds x cm-5) x 1,000] = [(P(PA) - P(LA))/(Q(PA) x 1,000/60)] x 1,332. The experimental animals were ventilated with normoxic gas (FIO2, 0.21), followed by hypoxic gas (FIO2, 0.07), returned to normoxia, and then divided into two groups of eight animals each. One group remained normoxemic (FIO2, 0.21; S(PA)O2, 100%) while the other group was made hypoxemic by ventilation with hypoxic gas (FIO2, 0.07; S(PA)O2, 50%). Endogenous NO was suppressed with L-arginine- N-omega methyl ester (L-NAME) at 40 mg/kg in both groups. Inhaled NO was given at 40 ppm in both groups. Analysis of variance for repeated measures was used to test for statistical significance. Results: Baseline normoxic PVR (3,403 ± 1,169) was increased significantly by hypoxia (6,524 ± 1,018, P < .01) and was fully restored to baseline by normoxia (3,497 ± 1,079; P = NS). In normoxic animals, inhibition of endogenous NO production by L-NAME increased PVR to levels similar to those seen during hypoxic stress (6,345 ± 1,441, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to normoxic baseline values (3,986 ± 1,363, P = NS). In hypoxic animals, inhibition of endogenous NO production by L-NAME also increased PVR from hypoxic baseline (9,655 ± 1,642, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to hypoxic baseline (6,450 ± 1,796, P = NS). Conclusion: In this piglet model, endogenous NO is important in the regulation of pulmonary vascular tone during both normoxia and hypoxia. Inhaled NO completely reversed the elevations in PVR caused by inhibition of endogenous NO and may normalize PVR in diseases in which the production of endogenous NO is compromised.

Original languageEnglish (US)
Pages (from-to)137-140
Number of pages4
JournalJournal of Pediatric Surgery
Volume31
Issue number1
DOIs
StatePublished - Jan 1996
Externally publishedYes

Fingerprint

Blood Vessels
Nitric Oxide
Lung
Vascular Resistance
Arginine
Esters
Gases
Pressure
Ventilation
Perfusion
Ductus Arteriosus
Extracorporeal Membrane Oxygenation
Atrial Pressure
Sternotomy
Tracheostomy
Hematocrit
Catheterization
Pulmonary Artery
Ligation

Keywords

  • L-NAME, extracorporeal membrane oxygenation
  • Nitric oxide, endogenous, neonate
  • pulmonary hypertension
  • pulmonary vascular resistance

ASJC Scopus subject areas

  • Surgery

Cite this

Endogenous nitric oxide and pulmonary vascular tone in the neonate. / Lipsitz, Evan C.; Weinstein, Samuel; Smerling, Arthur J.; Stolar, Charles J H.

In: Journal of Pediatric Surgery, Vol. 31, No. 1, 01.1996, p. 137-140.

Research output: Contribution to journalArticle

Lipsitz, Evan C. ; Weinstein, Samuel ; Smerling, Arthur J. ; Stolar, Charles J H. / Endogenous nitric oxide and pulmonary vascular tone in the neonate. In: Journal of Pediatric Surgery. 1996 ; Vol. 31, No. 1. pp. 137-140.
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abstract = "Purpose: In newborns, inhaled nitric oxide (NO) has been shown to ameliorate increased pulmonary vascular resistance (PVR) precipitated by hypoxia. The role of endogenous NO production in this response is not clear. The contribution of endogenous NO to resting PVR in normoxic newborns also has not been well studied. The authors used an isolated, in situ, neonatal piglet lung-perfusion model, devoid of systemic detractors in which endogenous NO could be selectively inhibited, to determine whether (1) endogenous NO plays a role in the maintenance of PVR with normoxia, (2) endogenous NO plays a role in the response to hypoxia, and (c) inhaled NO can reverse changes induced by inhibition of endogenous NO. Methods: Sixteen neonatal piglets underwent occlusive tracheostomy and pressure-cycled ventilation. After heparinization and ligation of the ductus arteriosus, left atrial and pulmonary arterial cannulation were performed, without ischemia, via a median sternotomy. The aorta was ligated, and lung perfusion was set at 80 mL/kg/min via an extracorporeal membrane oxygenation circuit. Hematocrit (40{\%} to 45{\%}), pH (7.37 to 7.44), PCO2 (35 to 40 mm Hg), and peak inspiratory pressures (20 mm Hg) were constant. Pulmonary artery pressure (P(PA)), left atrial pressure (P(LA)), and circuit flow (Q(PA)) were recorded continuously. PVR calculated as follows: PVR[(dynes x seconds x cm-5) x 1,000] = [(P(PA) - P(LA))/(Q(PA) x 1,000/60)] x 1,332. The experimental animals were ventilated with normoxic gas (FIO2, 0.21), followed by hypoxic gas (FIO2, 0.07), returned to normoxia, and then divided into two groups of eight animals each. One group remained normoxemic (FIO2, 0.21; S(PA)O2, 100{\%}) while the other group was made hypoxemic by ventilation with hypoxic gas (FIO2, 0.07; S(PA)O2, 50{\%}). Endogenous NO was suppressed with L-arginine- N-omega methyl ester (L-NAME) at 40 mg/kg in both groups. Inhaled NO was given at 40 ppm in both groups. Analysis of variance for repeated measures was used to test for statistical significance. Results: Baseline normoxic PVR (3,403 ± 1,169) was increased significantly by hypoxia (6,524 ± 1,018, P < .01) and was fully restored to baseline by normoxia (3,497 ± 1,079; P = NS). In normoxic animals, inhibition of endogenous NO production by L-NAME increased PVR to levels similar to those seen during hypoxic stress (6,345 ± 1,441, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to normoxic baseline values (3,986 ± 1,363, P = NS). In hypoxic animals, inhibition of endogenous NO production by L-NAME also increased PVR from hypoxic baseline (9,655 ± 1,642, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to hypoxic baseline (6,450 ± 1,796, P = NS). Conclusion: In this piglet model, endogenous NO is important in the regulation of pulmonary vascular tone during both normoxia and hypoxia. Inhaled NO completely reversed the elevations in PVR caused by inhibition of endogenous NO and may normalize PVR in diseases in which the production of endogenous NO is compromised.",
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T1 - Endogenous nitric oxide and pulmonary vascular tone in the neonate

AU - Lipsitz, Evan C.

AU - Weinstein, Samuel

AU - Smerling, Arthur J.

AU - Stolar, Charles J H

PY - 1996/1

Y1 - 1996/1

N2 - Purpose: In newborns, inhaled nitric oxide (NO) has been shown to ameliorate increased pulmonary vascular resistance (PVR) precipitated by hypoxia. The role of endogenous NO production in this response is not clear. The contribution of endogenous NO to resting PVR in normoxic newborns also has not been well studied. The authors used an isolated, in situ, neonatal piglet lung-perfusion model, devoid of systemic detractors in which endogenous NO could be selectively inhibited, to determine whether (1) endogenous NO plays a role in the maintenance of PVR with normoxia, (2) endogenous NO plays a role in the response to hypoxia, and (c) inhaled NO can reverse changes induced by inhibition of endogenous NO. Methods: Sixteen neonatal piglets underwent occlusive tracheostomy and pressure-cycled ventilation. After heparinization and ligation of the ductus arteriosus, left atrial and pulmonary arterial cannulation were performed, without ischemia, via a median sternotomy. The aorta was ligated, and lung perfusion was set at 80 mL/kg/min via an extracorporeal membrane oxygenation circuit. Hematocrit (40% to 45%), pH (7.37 to 7.44), PCO2 (35 to 40 mm Hg), and peak inspiratory pressures (20 mm Hg) were constant. Pulmonary artery pressure (P(PA)), left atrial pressure (P(LA)), and circuit flow (Q(PA)) were recorded continuously. PVR calculated as follows: PVR[(dynes x seconds x cm-5) x 1,000] = [(P(PA) - P(LA))/(Q(PA) x 1,000/60)] x 1,332. The experimental animals were ventilated with normoxic gas (FIO2, 0.21), followed by hypoxic gas (FIO2, 0.07), returned to normoxia, and then divided into two groups of eight animals each. One group remained normoxemic (FIO2, 0.21; S(PA)O2, 100%) while the other group was made hypoxemic by ventilation with hypoxic gas (FIO2, 0.07; S(PA)O2, 50%). Endogenous NO was suppressed with L-arginine- N-omega methyl ester (L-NAME) at 40 mg/kg in both groups. Inhaled NO was given at 40 ppm in both groups. Analysis of variance for repeated measures was used to test for statistical significance. Results: Baseline normoxic PVR (3,403 ± 1,169) was increased significantly by hypoxia (6,524 ± 1,018, P < .01) and was fully restored to baseline by normoxia (3,497 ± 1,079; P = NS). In normoxic animals, inhibition of endogenous NO production by L-NAME increased PVR to levels similar to those seen during hypoxic stress (6,345 ± 1,441, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to normoxic baseline values (3,986 ± 1,363, P = NS). In hypoxic animals, inhibition of endogenous NO production by L-NAME also increased PVR from hypoxic baseline (9,655 ± 1,642, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to hypoxic baseline (6,450 ± 1,796, P = NS). Conclusion: In this piglet model, endogenous NO is important in the regulation of pulmonary vascular tone during both normoxia and hypoxia. Inhaled NO completely reversed the elevations in PVR caused by inhibition of endogenous NO and may normalize PVR in diseases in which the production of endogenous NO is compromised.

AB - Purpose: In newborns, inhaled nitric oxide (NO) has been shown to ameliorate increased pulmonary vascular resistance (PVR) precipitated by hypoxia. The role of endogenous NO production in this response is not clear. The contribution of endogenous NO to resting PVR in normoxic newborns also has not been well studied. The authors used an isolated, in situ, neonatal piglet lung-perfusion model, devoid of systemic detractors in which endogenous NO could be selectively inhibited, to determine whether (1) endogenous NO plays a role in the maintenance of PVR with normoxia, (2) endogenous NO plays a role in the response to hypoxia, and (c) inhaled NO can reverse changes induced by inhibition of endogenous NO. Methods: Sixteen neonatal piglets underwent occlusive tracheostomy and pressure-cycled ventilation. After heparinization and ligation of the ductus arteriosus, left atrial and pulmonary arterial cannulation were performed, without ischemia, via a median sternotomy. The aorta was ligated, and lung perfusion was set at 80 mL/kg/min via an extracorporeal membrane oxygenation circuit. Hematocrit (40% to 45%), pH (7.37 to 7.44), PCO2 (35 to 40 mm Hg), and peak inspiratory pressures (20 mm Hg) were constant. Pulmonary artery pressure (P(PA)), left atrial pressure (P(LA)), and circuit flow (Q(PA)) were recorded continuously. PVR calculated as follows: PVR[(dynes x seconds x cm-5) x 1,000] = [(P(PA) - P(LA))/(Q(PA) x 1,000/60)] x 1,332. The experimental animals were ventilated with normoxic gas (FIO2, 0.21), followed by hypoxic gas (FIO2, 0.07), returned to normoxia, and then divided into two groups of eight animals each. One group remained normoxemic (FIO2, 0.21; S(PA)O2, 100%) while the other group was made hypoxemic by ventilation with hypoxic gas (FIO2, 0.07; S(PA)O2, 50%). Endogenous NO was suppressed with L-arginine- N-omega methyl ester (L-NAME) at 40 mg/kg in both groups. Inhaled NO was given at 40 ppm in both groups. Analysis of variance for repeated measures was used to test for statistical significance. Results: Baseline normoxic PVR (3,403 ± 1,169) was increased significantly by hypoxia (6,524 ± 1,018, P < .01) and was fully restored to baseline by normoxia (3,497 ± 1,079; P = NS). In normoxic animals, inhibition of endogenous NO production by L-NAME increased PVR to levels similar to those seen during hypoxic stress (6,345 ± 1,441, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to normoxic baseline values (3,986 ± 1,363, P = NS). In hypoxic animals, inhibition of endogenous NO production by L-NAME also increased PVR from hypoxic baseline (9,655 ± 1,642, P < .01). Replacement of endogenous NO by inhaled NO reversed PVR to hypoxic baseline (6,450 ± 1,796, P = NS). Conclusion: In this piglet model, endogenous NO is important in the regulation of pulmonary vascular tone during both normoxia and hypoxia. Inhaled NO completely reversed the elevations in PVR caused by inhibition of endogenous NO and may normalize PVR in diseases in which the production of endogenous NO is compromised.

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KW - Nitric oxide, endogenous, neonate

KW - pulmonary hypertension

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