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
Experimental

Abstract

Background

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.

Design

Controlled, block-randomized study.

Setting

University research laboratory.

Subject

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

Interventions

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.

Conclusions

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.

Keywords

Antioxidant Nitric oxide Heart Swine Newborn 

Abbreviations

CI

Cardiac index

FiO2

Fractional inspired oxygen concentration

H-R

Hypoxia-reoxygenation

I-R

Ischemia-reperfusion

L-NMMA

NG-monomethyl-l-arginine

MAP

Mean arterial pressure

NAC

N-Acetyl-l-cysteine

NO

Nitric oxide

NOx

Nitrate/nitrite

PAP

Pulmonary arterial pressure

ROS

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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