Continuous Infusion of Sivelestat Sodium Hydrate Prevents Lipopolysaccharide‐induced Intestinal Paralysis and Hypotension in Conscious Guinea‐pigs

Hara, Shoko; Nemoto, Kayo; Ninomiya, Norifumi; Kubota, Minoru; Kuno, Miyuki; Yamamoto, Yasuhiro

doi:10.1111/j.1440-1681.2008.04921.x

Cited by 7 publications

(10 citation statements)

References 26 publications

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“…Vasospasm, involving sustained, abnormal contraction of arteries, plays important roles in a wide variety of ischemic diseases such as vasospasm after subarachnoid hemorrhage, nonocclusive mesenteric ischemia (NOMI) [4], coronary vasospasm, and other diseases. Various therapeutic agents are available to treat the vasospasm associated with these diseases.…”

Section: Introductionmentioning

confidence: 99%

Sivelestat relaxes vascular smooth muscle contraction in human gastric arteries

et al. 2011

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Sivelestat sodium hydrate (sivelestat) is a novel synthetic drug and specific inhibitor of neutrophil elastase that has been approved in Japan as a treatment for acute lung injury associated with systemic inflammatory response syndrome. It is important to determine how sivelestat affects hemodynamics and the regulatory mechanisms of vascular smooth muscle (VSM). We recently found that sivelestat relaxes porcine coronary artery VSM via selective inhibition of Ca(2+) sensitization induced by a receptor agonist without affecting the normal Ca(2+)-induced contraction. Although sivelestat relaxes porcine artery, its effects on human artery are unknown; therefore, the purpose of the present study was to assess the effects of sivelestat on human artery. In the present study, sivelestat induced concentration-dependent (1 × 10(-6) to 3 × 10(-4) M) vasorelaxation in U46619 (1 nM) and sphingosylphosphorylcholine (SPC) (30 mM)-precontracted human gastric artery with or without endothelium, but sivelestat did not induce vasorelaxation in conditions of high K(+) (40 mM) depolarization. Sivelestat inhibited VSM contraction by an agonist and SPC, and it did not affect Ca(2+)-induced normal physiologic contraction.

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Section: Introductionmentioning

confidence: 99%

Sivelestat relaxes vascular smooth muscle contraction in human gastric arteries

et al. 2011

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“…Animals were allowed free access to tap water and laboratory animal diet, and housed in a temperature-and humidity-controlled room with a 12-h light/dark cycle. They were acclimated to the environmental conditions for at least 7 d. §Surgical procedures A previously described protocol was used with modifications 10) . After guinea pigs were anesthetized with sodium pentobarbital (30 mg/kg, i.p.…”

Section: Materials and Methods §Animal Preparationmentioning

confidence: 99%

“…LPS has prebiously been shown to affect the intestinal tone, not the intestinal movement. Intermittent blood sampling via the arterial cannula allows the measurement of inflammatory mediators in the blood at various stages of endotoxemia 10) . We used conscious, nonrestrained, free-moving guinea pigs to measure physiological intestinal tension and blood pressure, and found LPS-induced conditions were more accurately assessed without anesthesia, than with anesthesia.…”

Section: Introductionmentioning

confidence: 99%

Rimonabant, a specific antagonist of the cannabinoid CB1-receptor, prevents lipopolysaccharide-induced endotoxemia in awake guinea pigs

Inagaki

Nemoto

Ninomiya

et al. 2010

Nihon Kyukyu Igakukai Zasshi

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2-arachidonoyl glycerol (2-AG), an endogenous cannabinoid, has been drawing much attention as an early stage mediator at the onset of sepsis. In the present study, we investigated weather rimonabant, one of the CB1 antagonists, alleviated the medical conditions during endotoxemia and measured the level of prostaglandin E metabolite (PGEM). A cylindrical electric transmitter was connected to the transducer via a cable embedded beneath the animal's dorsal skin and sutured in place. Signals from the transmitter were detected by a receiver placed directly beneath the cage via telemetry. We monitored arterial pressure via catheter in the carotid artery and administrated drugs via catheter in jugular vein. We separated animals into three groups. The control group received lipopolysaccharide (LPS, 0.3 mg/kg, i.v.) and vehicle i.v. Experimental animals received LPS and rimonabant (1, 3 mg/kg/h) i.v. Ten minutes after the injection of the vehicle or rimonabant, LPS (0.3 mg/kg, i.v.) was administered. The prostaglandin E metabolites (PGEM) levels were measured by EIASA. In the control group, LPS induced intestinal paralysis and the decline in blood pressure peaked 1-3h after administration of LPS. In rimonabant-treated group, rimonabant inhibited LPS-induced intestinal paralysis and hypotension. Levels of PGEM in guinea pig was increased by LPS-administrate, rimonabant inhibits PGEM increase. The results suggest that rimonabant was effective against LPS-induced endotoxemia in guinea pigs. (JJAAM. 2010; 21: 118-25)

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“…We have previously shown that the dose of sivelestat (30 mg/kg/h) used in this in vivo study improved the symptoms of low dose LPS administration (0.3 mg/ kg) 13) . In the previous study, it was shown that early infusion of sivelestat effectively improved outcomes.…”

Section: Effects Of Pmx And/or Sivelestat On Lps-induced Increases Inmentioning

confidence: 99%

“…A synergistic effect is expected due to the different targets and mechanisms of action of each treatment. In this study, we examined the efficacy of simultaneous treatment with PMX-DHP and sivelestat against endotoxemia using an in vivo model developed in our laboratory [11][12][13] . This model is unique in that it does not utilize anesthesia, and can therefore be used to measure levels of resting tension of intestinal smooth muscle and blood pressure, thereby affording greater accuracy than models that require sedation.…”

Section: Introductionmentioning

confidence: 99%

Effects of simultaneous treatment with PMX-DHP and sivelestat on endotoxaemia in conscious guinea pigs

Ishinokami

Nemoto

Ninomiya

et al. 2012

Nihon Kyukyu Igakukai Zasshi

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Using an endotoxaemia model in conscious guinea pigs, we previously reported that polymyxin B immobilized fiber-direct hemoperfusion (PMX-DHP) or administration of sivelestat are effective treatments for sepsis. In the present study, we investigated whether simultaneous treatment with PMX-DHP and sivelestat sodium was more effective than either treatment alone for sepsis. Measurements examined included intestinal paralysis, blood pressure, serum HMGB1 level and survival rate. Colonic motion was monitored continuously by telemetry using a transducer attached to the taenia caecum, while blood pressure was monitored with a carotid artery catheter. The guinea pigs were divided into 4 groups and lipopolysaccharide (LPS) was administered to all animals. The control group received only LPS. The remaining three groups received PMX treatment for 2 hours, sivelestat sodium administration for 2 hours or simultaneous PMX and sivelestat treatment for 2 hours. In the control group, decreased colonic muscle tension and arterial pressure, and increased serum HMGB1 levels were observed and all animals died within 30 hours. In the PMX-DHP treated group, the decreases in colonic tension and arterial pressure were less severe than for the control group and the survival rate was higher than the control group, but serum HMGB1 levels were not significantly different. In the sivelestat group, decreases in colonic tension and arterial pressure were not significantly different with the control group, but serum HMGB1 levels were lower than in the control group. Simultaneous treatment with both PMX-DHP and sivelestat sodium did not exhibit synergistic effects for the treatment of LPS-induced endotoxaemia and mortality. PMX-DHP was effective at treating sepsis induced by administration of a high dose of LPS in guinea pigs, but simultaneous administration of sivelestat sodium did not augment the efficacy of PMX-DHP treatment. (JJAAM. 2012; 23: 12-20)

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Continuous Infusion of Sivelestat Sodium Hydrate Prevents Lipopolysaccharide‐induced Intestinal Paralysis and Hypotension in Conscious Guinea‐pigs

Cited by 7 publications

References 26 publications

Sivelestat relaxes vascular smooth muscle contraction in human gastric arteries

Sivelestat relaxes vascular smooth muscle contraction in human gastric arteries

Rimonabant, a specific antagonist of the cannabinoid CB1-receptor, prevents lipopolysaccharide-induced endotoxemia in awake guinea pigs

Effects of simultaneous treatment with PMX-DHP and sivelestat on endotoxaemia in conscious guinea pigs

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