Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs

Franz Ploner, Peter Radermacher, Marc Theisen, Ilyas F. Tugtekin, Martin Matejovic, Alexander Stehr, Csaba Szabo, Garry J. Southan, Michael Georgieff, Uwe B. Brückner, Karl Träger

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

We investigated the effect of mercaptoethylguanidine (MEG, 3 mg kg-1h-1), a combined selective inducible nitric oxide synthase (iNOS) inhibitor, a peroxynitrite and oxygen free radical scavenger with cyclooxygenase-inhibitor properties on intestinal and hepatic perfusion, O2 exchange, and metabolism during long-term hyperdynamic porcine endotoxemia. MEG was started 12 h after onset of endotoxemia. At baseline and after 12, 18, and 24 h of endotoxemia, hepatic arterial and portal venous blood flow, ileal mucosal-arterial PCO2 gap, portal and hepatic venous lactate/pyruvate ratio, free glutathione (GSH), and 8-isoprostanes were measured. Expired NO and plasma nitrate levels were assessed as well. MEG blunted the endotoxin-induced increase in expired NO and prevented the progressive fall in blood pressure without affecting cardiac output. It attenuated both systemic and regional venous acidosis without influencing the impairment of hepatosplanchnic metabolism nor counteracting the increase in GSH levels. In our model MEG failed to beneficially affect variables of oxidative stress.

Original languageEnglish (US)
Pages (from-to)130-136
Number of pages7
JournalShock
Volume16
Issue number2
StatePublished - Aug 2001
Externally publishedYes

Fingerprint

Peroxynitrous Acid
Endotoxemia
Nitric Oxide Synthase Type II
8-epi-prostaglandin F2alpha
Swine
Liver
Free Radical Scavengers
Cyclooxygenase Inhibitors
Acidosis
Pyruvic Acid
Endotoxins
Cardiac Output
Nitrates
Glutathione
Lactic Acid
Reactive Oxygen Species
Oxidative Stress
Perfusion
Blood Pressure

Keywords

  • Cyclooxygenase
  • Eicosanoids
  • Endotoxin
  • Glutathione
  • Lactate
  • Liver blood flow
  • Mercaptoethylguanidine
  • Nitrate
  • Nitric oxide synthase
  • Tonometry

ASJC Scopus subject areas

  • Physiology
  • Critical Care and Intensive Care Medicine

Cite this

Ploner, F., Radermacher, P., Theisen, M., Tugtekin, I. F., Matejovic, M., Stehr, A., ... Träger, K. (2001). Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs. Shock, 16(2), 130-136.

Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs. / Ploner, Franz; Radermacher, Peter; Theisen, Marc; Tugtekin, Ilyas F.; Matejovic, Martin; Stehr, Alexander; Szabo, Csaba; Southan, Garry J.; Georgieff, Michael; Brückner, Uwe B.; Träger, Karl.

In: Shock, Vol. 16, No. 2, 08.2001, p. 130-136.

Research output: Contribution to journalArticle

Ploner, F, Radermacher, P, Theisen, M, Tugtekin, IF, Matejovic, M, Stehr, A, Szabo, C, Southan, GJ, Georgieff, M, Brückner, UB & Träger, K 2001, 'Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs', Shock, vol. 16, no. 2, pp. 130-136.
Ploner F, Radermacher P, Theisen M, Tugtekin IF, Matejovic M, Stehr A et al. Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs. Shock. 2001 Aug;16(2):130-136.
Ploner, Franz ; Radermacher, Peter ; Theisen, Marc ; Tugtekin, Ilyas F. ; Matejovic, Martin ; Stehr, Alexander ; Szabo, Csaba ; Southan, Garry J. ; Georgieff, Michael ; Brückner, Uwe B. ; Träger, Karl. / Effects of combined selective iNOS inhibition and peroxynitrite blockade during endotoxemia in pigs. In: Shock. 2001 ; Vol. 16, No. 2. pp. 130-136.
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