Abstract
To compare the effects of the sustained exposure to inhaled nitric oxide(NO) on pulmonary gas exchange, cardiovascular function and lung mechanics in newborn lambs with pulmonary hypertension induced by tracheal instillation of meconium. Fifteen newborn lambs (<6 d old) were studied in three groups(n = 5): control, and pulmonary hypertension (5 mL·kg-1 of a 20% meconium solution) with or without inhaled NO(20 ppm) exposure. Heart rate, systemic and pulmonary arterial pressures, arterial pH and blood gases, cardiac output, and pulmonary mechanics were measured. The exposure to inhaled NO in lambs with pulmonary hypertension, induced by experimental meconium aspiration, produced a transient response. There were a transient improvement in gas exchange, a decrease in pulmonary arterial pressure and airway resistance, without changes in cardiovascular profile. The transient and incomplete response to inhaled NO in experimental MAS might be related to the fact that hypoxemia is not only due to pulmonary vasoconstriction but also to parenchymal lung disease. We hypothesize that this poor and transient response could probably be avoided if strategies that increase lung recruitment, were applied before inhaled NO exposure.
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Abbreviations
- F102:
-
fraction of inspired O2
- MAS:
-
meconium aspiration syndrome
- NO:
-
nitric oxide
- PAP:
-
pulmonary artery pressure
- Paco2:
-
partial pressure of arterial CO2
- Pao2:
-
partial pressure of arterial O2
- PPH:
-
persistent pulmonary hypertension
- PVR:
-
pulmonary vascular resistance
- Sao2:
-
arterial O2 saturation
- SAP:
-
systemic arterial pressure
- V/Q :
-
ventilation/perfusion ratio
- IPPV:
-
intermittent positive pressure ventilation
- CI:
-
cardiac index
References
Katz VL, Bowes WA 1992 Meconium aspiration syndrome: reflections on a murky subject. Am J Obstet Gynecol 166: 171–183.
Sun B, Curstedt T, Robertson B 1993 Surfactant inhibition in experimental meconium aspiration. Acta Pediatr 82: 182–189.
Carter MJM, Gerstmann DR, Clark MRH, Snyder MG, Cornish JD, Null DM, deLemos RA 1990 High-frequency oscillatory ventilation and extracorporeal membrane oxygenation for the treatment of acute neonatal respiratory failure. Pediatrics 85: 159–164.
Fineman JR, Wong J, Soifer SJ 1993 Hyperoxia and alkalosis produce pulmonary vasodilation independent of endothelium-derived nitric oxide in newborn lambs. Pediatr Res 33: 341–346.
Curtis J, O'Neill T, Pettett G 1993 Endotracheal administration of tolazoline in hypoxia-induced pulmonary hypertension. Pediatrics 92: 403–408.
Zobel G, Dacar D, Rödl S, Friehs I 1995 Inhaled nitric oxide versus inhaled prostacyclin and intravenous versus inhaled prostacyclin in acute respiratory failure with pulmonary hypertension in piglets. Pediatr Res 38: 198–204.
Wiswell TE, Peabody SS, Davis JM, Slayter MV, Bent RC, Merrit TA 1994 Surfactant therapy and high-frequency jet ventilation in the management of a piglet model of the meconium aspiration syndrome. Pediatr Res 36: 494–500.
Turbow R, Waffarn F, Yang L, Sills J, Hallman M 1995 Variable oxigenation response to inhaled nitric oxide in severe persistent pulmonary hypertension of the newborn. Acta Pediatr 84: 1305–1308.
Sun B, Curstedt T, Song GW, Robertson B 1993 Surfactant improves lung function and morphology in newborn rabbits with meconium aspiration. Biol Neonate 63: 96–104.
Shaffer TH, Lowe CA, Bhutani VK, Douglas PR 1984 Liquid ventilation: effects on pulmonary function in distressed meconium-stained lambs. Pediatr Res 18: 47–52.
Moncada S, Palmer RM, Higgs EA 1991 Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43: 109–142.
Roberts JD, Polaner DM, Lang P, Zapol WM 1992 Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 340: 818–819.
Kinsella JP, Neish SR, Shaffer E, Abman SH 1992 Low-dose inhalational nitric oxide in persistent pulmonary hypertension of the newborn. Lancet 340: 819–820.
Kinsella JP, Ivy DD, Abman SH 1994 Inhaled nitric oxide improves gas exchange and lowers pulmonary vascular resistance en severe experimental hyaline membrane disease. Pediatr Res 36: 402–408.
Roberts JD, Chen TY, Kawai N, Wain J, Dupuy P, Shimouchi A, Bloch K, Zapol WM 1993 Inhaled nitric oxide reverses pulmonary vasoconstriction in the hypoxic and acidotic newborn lambs. Circ Res 72: 246–254.
Zayek M, Wild L, Roberts JD, Morin FC 1993 Effect of nitric oxide on the survival rate and incidence of lung injury in newborn lambs with persistent pulmonary hypertension. J Pediatr 123: 947–952.
Kinsella JP, Neish SR, Ivy DD, Shaffer E, Abman SH 1993 Clinical responses to prolonged treatment of persistent pulmonary hypertension of the newborn with low doses of inhaled nitric oxide. J Pediatr 123: 103–108.
Finer NN, Etches PC, Kamstra B, Tierney AJ, Peilowski A, Ryan A 1994 Inhaled nitric oxide in infants referred for extracorporeal membrane oxygenation: dose response. J Pediatr 124: 302–308.
Bührer C, Merker G, Falke K, Versmold H, Obladen M 1995 Dose-response to inhaled nitric oxide in acute hypoxemic respiratory failure of newborn infants: a preliminary report. Pediatr Pulmonol 19: 291–298.
Barrington KJ, Finer NN, Peilowski A, Etches PC, Graham AJ, Chan WKY 1995 Inhaled nitric oxide improves oxygenation in piglets with meconium aspiration. Pediatr Pulmonol 20: 27–33.
Fernandez-Martorell P, Bahrami KR, Rivera O, Short BL 1995 Use of nitric oxide in meconium aspiration syndrome (MAS): lack of response. Pediatr Res 37: 331A
Foust R, Tran NN, Cox C, Miller TF Jr, Greenspan JS, Wolfson MR, Shaffer TH 1996 Liquid assisted ventilation: an alternative ventilatory strategy for acute meconium aspiration injury. Pediatr Pulmonol 21: 316–322.
Segerer H, van Gelder W, Angenent FWM, van Woerkens LJPM, Curstedt T, Obladen M, Lachmann B 1993 Pulmonary distribution and efficacy of exogenous surfactant in lung-lavaged rabbits are influenced by the instillation technique. Pediatr Res 34: 490–494.
Etches PC, Finer NN, Barrington KJ, Graham AJ, Chan WKY 1994 Nitric oxide reverses acute hypoxic pulmonary hypertension in the newborn piglet. Pediatr Res 35: 15–19.
Gaston B, Drazen JM, Loscalzo J, Stamler JS 1994 The biology of nitrogen oxides in the airways. Am J Respir Crit Care Med 149: 538–551.
Kinsella JP, Abman SH 1993 Inhalational nitric oxide therapy for persistent pulmonary hypertension of the newborn. Pediatrics 91: 997–998.
Skimming JW, DeMarco VG, Cassin S 1994 The effects of nitric oxide inhalation on the pulmonary circulation of preterm lambs. Pediatr Res 37: 35–40.
Kinsella JP, Abman SH 1995 Recent developments in the pathophysiology and treatment of persistent pulmonary hypertension of the newborn. J Pediatr 126: 853–864.
Kinsella JP, Truog WE, Walsh WE, Goldberg RN, Bancalari E, Clark RH, Mayock DE, Redding GJ, deLemos RA, Sardesai S, McCurnin DC, Yoder BA, Moreland SG, Cutter GR, Abman SH 1996 Randomized, multicenter trial of inhaled nitric oxide and high frequency oscillatory ventilation in severe persistent pulmonary hypertension of the newborn (PPHN). Pediatr Res 39: 222A
Singh AJ, Barrington KJ, Etches PC, Finer NN 1996 Effects of partial liquid ventilation and inhaled nitric oxide in piglets with meconium aspiration. Pediatr Res 39: 245A
Potter FC, Dreshaj IA, Haxhiu MA, Stork EK, Chatburn RL, Martin RJ 1997 Effect of exogenous and endogenous nitric oxide on the airway ant tissue component of lung resistance in the newborn piglet. Pediatr Res 41: 886–891.
Putensen C, Räsänen J, López FA 1995 Improvement in V/Q distributions during inhalation of nitric oxide in pigs with methacholine-induced bronchoconstriction. Am J Respir Crit Care Med 151: 116–122.
Dupuy PM, Shore SA, Drazen JM, Frostell C, Hill WA, Zapol WM 1992 Bronchodilator action of inhaled nitric oxide in guinea pigs. J Clin Invest 90: 421–428.
Abman SH, Kinsella JP 1995 Inhaled nitric oxide for persistent pulmonary hypertension of the newborn: the physiology matters. Pediatrics 96: 1153–1155.
Kinsella JP, Truog WE, Walsh WF, Goldberg RN, Bancalari E, Mayock DE, Redding GJ, deLemos RA, Sardesai S, McCurnin DC, Moreland SG, Cutter GR, Abman SH 1997 Randomized, multicenter trial of inhaled nitric oxide and high frequency-oscillatory ventilation in severe, persistent pulmonary hypertension in the newborn. J Pediatr 131: 55–62.
Acknowledgements
The authors are grateful to Ricardo Corres for his excellent technical assistance in the lung processing and meconium distribution studies, and to Prof. Rodríguez Soriano for his critical advice.
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Supported in part by the Foundation for Investigation of the Spanish Ministry of Health (FIS), Grants 95/1348 and 95/1332, and Department of Education of the Basque Government BFI 93.046.
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Cuesta, E., Díaz, F., Renedo, A. et al. Transient Response to Inhaled Nitric Oxide in Meconium Aspiration in Newborn Lambs. Pediatr Res 43, 198–202 (1998). https://doi.org/10.1203/00006450-199802000-00007
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DOI: https://doi.org/10.1203/00006450-199802000-00007
