EFFECTS OF COMBINED SELECTIVE iNOS INHIBITION AND PEROXYNITRITE BLOCKADE DURING ENDOTOXEMIA IN PIGS

Ploner, Franz; Radermacher, Peter; Theisen, M.; Tugtekin, I.; Matějovič, Martin; Stehr, A.; Szabó, Csaba; Southan, Garry J.; Georgieff, Michael; Brückner, U. B.; Träger, Karl

doi:10.1097/00024382-200116020-00008

Cited by 20 publications

(20 citation statements)

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“…Hence, the control data reported here have also been described elsewhere (11). The surgical preparation was performed as described previously (12,13). The animals were premedicated with intramuscular atropine (2.5 mg of Atropinsulfat®, Braun, Melsungen, Germany) and azaperone (150-200 mg of Stresnil®, Janssen, Neuss, Germany) followed by cannulation of an ear vein.…”

Section: Animal Preparationmentioning

confidence: 99%

“…Temgesic®, Boehringer, Mannheim, Germany) was added every 4 h and prior to any surgical or noxious stimuli to prevent a rise in heart rate and arterial pressure because of inadequate anesthesia. This approach has been shown to provide adequate anesthesia in previous studies (12,13). Muscle paralysis was achieved with alcuronium (14 mg · h −1 ; Alloferin®, Hoffmann-La Roche, Basel, Switzerland).…”

Section: Animal Preparationmentioning

confidence: 99%

“…As a surrogate of total body NO production NO exhalation was estimated by measuring the mixed expiratory NO concentrations using a chemiluminescence analyzer (NOA TM 280 NO Analyzer, Sievers Medical Instruments, Boulder, CO; Refs. [11][12][13]. The principle of NO measurement using this technique has been described in detail elsewhere (17).…”

Section: Measurements and Calculationsmentioning

confidence: 99%

“…12). Portal and hepatic venous reduced glutathione (GSH) levels were determined using an enzymatic assay (12). The measured isoprostane and GSH concentrations were normalized per g total plasma protein content to correct for any dilutional effects of intravenous (i.v.)…”

Section: Measurements and Calculationsmentioning

confidence: 99%

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TIN???Mesoporphyrin for Inhibition of Heme Oxygenase During Long-Term Hyperdynamic Porcine Endotoxemia

Nalos¹,

Vassilev²,

Pittner³

et al. 2003

Shock

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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.

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Section: Animal Preparationmentioning

confidence: 99%

Section: Animal Preparationmentioning

confidence: 99%

Section: Measurements and Calculationsmentioning

confidence: 99%

Section: Measurements and Calculationsmentioning

confidence: 99%

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TIN???Mesoporphyrin for Inhibition of Heme Oxygenase During Long-Term Hyperdynamic Porcine Endotoxemia

Nalos¹,

Vassilev²,

Pittner³

et al. 2003

Shock

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“…136 In a porcine model of long-term hyperdynamic endotoxemia, it did not affect the endotoxin-related impairment of the hepato-splanchnic metabolism, although it prevented the progressive fall in blood pressure and reduced the development of both systemic and regional acidosis. 137 In addition, GED also prevented the development of diabetes, probably by inhibiting 3-NT formation in the islet b-cells.…”

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confidence: 98%

Drugs modulating the biological effects of peroxynitrite and related nitrogen species

Olmos

Giner

Máñez

2006

Medicinal Research Reviews

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The term "reactive nitrogen species" includes nitrogen monoxide, commonly called nitric oxide, and some other remarkable chemical entities (peroxynitrite, nitrosoperoxycarbonate, etc.) formed mostly from nitrogen monoxide itself in biological environments. Regardless of the specific mechanisms implicated in their effects, however, it is clear that an integrated pharmacological approach to peroxynitrite and related species is only just beginning to take shape. The array of affected chemical and pathological processes is extremely broad. One of the most conspicuous mechanisms observed thus far has been the scavenging of the peroxynitrite anion by molecules endowed with antioxidant activity. This discovery has in turn lent great significance to several naturally occurring and synthetic antioxidants, which usually protect not only against oxidative reactions, but also from nitrating ones, both in vitro and in vivo. This has proven to be beneficial in different tissues, especially within the central nervous system. Taking these results and those of other biochemical investigations into account, many research lines are currently in progress to establish the true potential of reactive nitrogen species deactivators in the therapy of neurological diseases, ischemia-reperfusion damage, renal failure, and lung injury, among others.

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Liver Dysfunction: Nitric Oxide, Carbon Monoxide, and Reactive Oxygen Species

Radermacher

Matějovič

Brückner

2002

Mechanisms of Organ Dysfunction in Critical Illness

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EFFECTS OF COMBINED SELECTIVE iNOS INHIBITION AND PEROXYNITRITE BLOCKADE DURING ENDOTOXEMIA IN PIGS

Cited by 20 publications

References 0 publications

TIN???Mesoporphyrin for Inhibition of Heme Oxygenase During Long-Term Hyperdynamic Porcine Endotoxemia

TIN???Mesoporphyrin for Inhibition of Heme Oxygenase During Long-Term Hyperdynamic Porcine Endotoxemia

Drugs modulating the biological effects of peroxynitrite and related nitrogen species

Liver Dysfunction: Nitric Oxide, Carbon Monoxide, and Reactive Oxygen Species

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