Intensive Care Medicine

, Volume 35, Issue 9, pp 1628–1635 | Cite as

Post-resuscitation NOS inhibition does not improve hemodynamic recovery of hypoxic newborn pigs

  • Tze-fun Lee
  • Corinne N. Tymafichuk
  • Richard Schulz
  • Po-Yin Cheung



Significant improvement in myocardial recovery has been shown previously with interventions to decrease reactive oxygen species after ischemia/hypoxia. We investigated whether co-administration of N-acetylcysteine (NAC, a scavenger for reactive oxygen species) and NG-monomethyl-l-arginine (L-NMMA, a non-selective nitric oxide synthase inhibitor) results in better hemodynamic recovery.


Controlled, block-randomized study.


University research laboratory.


Mixed breed piglets (1-4d, 1.6–2.4 kg).


Acutely instrumented piglets received normocapnic alveolar hypoxia (10–15% oxygen) for 2 h followed by reoxygenation with 100% oxygen (1 h) then 21% oxygen (3 h). After reoxygenation, hypoxic-reoxygenated piglets were given either saline (controls), NAC [30 mg/kg bolus + 20 mg/(kg h) infusion], NMMA [0.1 mg/kg bolus + 0.1 mg/(kg h) infusion] or NAC + L-NMMA via intravenous infusion in a blinded, randomized fashion (n = 8/group). Sham-operated piglets had no hypoxia-reoxygenation (n = 5).

Measurements and results

Both cardiac index and stroke volume of hypoxia-reoxygenation controls remained depressed during reoxygenation (vs. normoxic baseline, p < 0.05). Post-resuscitation treatment with L-NMMA alone did not improve systemic hemodynamic recovery, but caused pulmonary hypertension (vs. controls). In contrast, treating the piglets with either NAC or NAC + L-NMMA improved cardiac index and stroke volume, with no effect on heart rate and blood pressure (vs. controls). These treatments also decreased various oxidative stress markers in myocardial tissues (vs. controls). However, there was no significant difference between NAC- and NAC + L-NMMA groups in all examined parameters.


Post-resuscitation administration of NAC improved cardiac function and reduced oxidative stress in newborn pigs with hypoxia-reoxygenation insult. Low-dose, non-selective inhibitor of nitric oxide synthase activity did not provide any further beneficial effect.


Antioxidant Nitric oxide Heart Swine Newborn 



Cardiac index


Fractional inspired oxygen concentration








Mean arterial pressure




Nitric oxide




Pulmonary arterial pressure


Reactive oxygen species


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Tze-fun Lee
    • 1
  • Corinne N. Tymafichuk
    • 1
  • Richard Schulz
    • 1
    • 2
    • 3
  • Po-Yin Cheung
    • 1
    • 2
    • 3
  1. 1.Department of PediatricsUniversity of AlbertaEdmontonCanada
  2. 2.PharmacologyUniversity of AlbertaEdmontonCanada
  3. 3.Cardiovascular Research CentreUniversity of AlbertaEdmontonCanada

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