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Jejunal mucosal NO production and substrate dependency during mesenteric hypoperfusion in pigs

Background and aims

Intestinal NO production has been attributed a central role in the maintenance of the intestinal mucosal barrier. Hypofunction of this barrier has been suggested to be one important factor behind the initiation of the multiple organ dysfunction syndrome. Jejunal NO formation, as we previously have reported, has been shown to be impaired during mucosal hypoperfusion [1]. This study was undertaken to investigate if the impaired jejunal NO levels could be due to restricted mucosal availability of NO-synthase substrates, i.e. oxygen and/or L-arginine.

Methods

Chloralose-anesthetized pigs (n = 18) were prepared for jejunal intraluminal perfusion with 150 mM NaCl or 3 mM L-arginine solution and then subjected to cardiac tamponade. Jejunal mucosal NO formation was measured with a tonometric technique. Mesenteric blood flow was measured as portal blood flow and mucosal perfusion was measured by laserdoppler flowmetry. Regional oxygen consumption was calculated from blood samples.

Results

Cardiac tamponade reduced jejunal NO formation (-52%), mesenteric oxygen delivery (-75%), oxygen consumption (-39%) and mucosal laser doppler flow (-43%). Oxygenation of the jejunal intraluminal perfusate completely restored the intestinal NO levels within 30 min. Presence of L-arginine was without effect.

Conclusion

The study indicates that oxygen rather than L-arginine is the rate limiting factor for mucosal NO production during reduced splanchnic perfusion.

References

  1. 1.

    Åneman A, Snygg J, Pettersson A, Johansson B, Holm M, Fändriks L: Detecting gastrointestinal hypoperfusion during cardiac tamponade in pigs: A role for nitric oxide tonometry? Crit Care Med 1998, 26: 1251. 10.1097/00003246-199807000-00030

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Snygg, J., Åneman, A., Pettersson, A. et al. Jejunal mucosal NO production and substrate dependency during mesenteric hypoperfusion in pigs. Crit Care 3, P167 (2000). https://doi.org/10.1186/cc540

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Keywords

  • Cardiac Tamponade
  • Multiple Organ Dysfunction Syndrome
  • Substrate Dependency
  • Portal Blood
  • Doppler Flow