Tin-mesoporphyrin for inhibition of heme oxygenase during long-term hyperdynamic porcine endotoxemia.
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.
Nalos
Marek
M
Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Ulm, Germany.
Vassilev
Damian
D
Pittner
Antje
A
Asfar
Pierre
P
Brückner
Uwe Bernd
UB
Schneider
Elisabeth Marion
EM
Georgieff
Michael
M
Radermacher
Peter
P
Froeba
Gebhard
G
D000818:Animals; D001810:Blood Volume / Q000187:drug effects; D002908:Chronic Disease; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000097:blood; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D028421:Isoprostanes / Q000097:blood; D007773:Lactates / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008665:Metalloporphyrins / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D013552:Swine; D013997:Time Factors
D004791:Enzyme Inhibitors; D028421:Isoprostanes; D007773:Lactates; D008070:Lipopolysaccharides; D008665:Metalloporphyrins; C055421:tin mesoporphyrin; D006419:Heme Oxygenase (Decyclizing); D005978:Glutathione