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

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.

• Authors: Marek Nalos, Damian Vassilev, Antje Pittner, Pierre Asfar, Uwe Bernd Brückner, Elisabeth Marion Schneider, Michael Georgieff, Peter Radermacher, Gebhard Froeba
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 19 Issue 6 Pg. 526-32 (Jun 2003) ISSN: 1073-2322 [Print] United States
• PMID: 12785007 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Isoprostanes
• Lactates
• Lipopolysaccharides
• Metalloporphyrins
• tin mesoporphyrin
• Heme Oxygenase (Decyclizing)
• Glutathione

Topics

• Animals
• Blood Volume (drug effects)
• Chronic Disease
• Disease Models, Animal
• Endotoxemia (blood, drug therapy, physiopathology)
• Enzyme Inhibitors (pharmacology)
• Glutathione (blood)
• Heme Oxygenase (Decyclizing) (antagonists & inhibitors)
• Hemodynamics (drug effects, physiology)
• Hydrogen-Ion Concentration
• Isoprostanes (blood)
• Lactates (metabolism)
• Lipopolysaccharides (toxicity)
• Lung (drug effects, physiopathology)
• Metalloporphyrins (pharmacology)
• Oxygen Consumption (drug effects)
• Pulmonary Artery (drug effects, physiopathology)
• Swine
• Time Factors