Tin-mesoporphyrin for inhibition of heme oxygenase during long-term hyperdynamic porcine endotoxemia.

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Nalos M, Vassilev D, Pittner A, Asfar P, Bruckner UB, Schneider EM, Georgieff M, Radermacher P, Froeba G

Tin-mesoporphyrin for inhibition of heme oxygenase during long-term hyperdynamic porcine endotoxemia.

Shock. 2003 Jun;19(6):526-32.

PubMed ID

12785007 [ View in PubMed

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Abstract

Heme oxygenase (HO) has both deleterious and protective effects in various shock models. Most of these data have been derived from experiments with hypodynamic shock states associated with depressed cardiac output. Therefore we studied the role of HO during long-term porcine hyperdynamic endotoxemia characterized by a sustained increase in cardiac output resulting from colloid resuscitation to maintain mean arterial pressure > 60 mmHg. Systemic, pulmonary, and hepatosplanchnic hemodynamic and metabolic effects of the HO-inhibitor tin-mesoporphyrin (SnMP) were assessed in anesthetized and mechanically ventilated animals. After 12 h of continuous intravenous lipopolysaccharide (LPS), animals received either vehicle (n = 6) or SnMP (n = 8; 6 micromol kg(-1) i.v. over 30 min at 12 and 18 h of LPS). Measurements were performed before LPS, before SnMP infusion, and at 24 h of LPS. SnMP did not influence systemic hemodynamics but significantly increased mean pulmonary artery pressure. Although liver blood flow was not affected, SnMP markedly impaired liver lactate clearance. HO inhibition was associated with increased plasma nitrate levels likely the result of increased NO production. Our results suggest a protective role of HO activation during hyperdynamic porcine endotoxemia possibly as a result of an interaction with the LPS-induced increase in NO formation.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Stannsoporfin	Heme oxygenase 1	Protein	Humans	Unknown	Not Available	Details
Stannsoporfin	Heme oxygenase 2	Protein	Humans	Unknown	Not Available	Details