Elimination of 2‐Arachidonoylglycerol Action by Direct Hemoperfusion Through Immobilized Polymyxin B Fibers: An Experimental Study in Conscious Guinea Pigs

Shiga, Naoko; Nemoto, Kayo; Shimada, Yasushi; Nakanowatari, Yuichi; Ninomiya, Norifumi; Yamamoto, Yasuhiro

doi:10.1111/j.1744-9987.2006.00427.x

Cited by 9 publications

(8 citation statements)

References 16 publications

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“…The post‐LPS decreases in intestinal tension and blood pressure have been reported to peak approximately 2 h after LPS administration; this effect has been shown to be mediated by the type 1 cannabinoid (CB 1 ) receptor 18–20 . Lipopolysaccharide acts on macrophages and monocytes through toll‐like receptor 4 (TLR4) 21 .…”

Section: Discussionmentioning

confidence: 99%

“…The post-LPS decreases in intestinal tension and blood pressure have been reported to peak approximately 2 h after LPS administration; this effect has been shown to be mediated by the type 1 cannabinoid (CB 1 ) receptor. [18][19][20] Lipopolysaccharide acts on macrophages and monocytes through toll-like receptor 4 (TLR4). 21 The signals mediated by TLR4 result in the increased synthesis and release of 2-arachidonoyl glycerol, an endocannabinoid, which results in smooth muscle relaxation, specifically of the colon and blood vessels.…”

Section: Discussionmentioning

confidence: 99%

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

Hara¹,

Nemoto²,

Ninomiya³

et al. 2008

Clin Exp Pharma Physio

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1. Sivelestat sodium hydrate (sivelestat), a neutrophil elastase inhibitor, is used to treat acute lung injury associated with systemic inflammatory response syndrome, but its effects have not been described for endotoxaemia. In the present study, we examined the effects of a continuous infusion of sivelestat on intestinal mechanical activity and blood pressure using an endotoxaemic model in conscious, unrestrained guinea-pigs. 2. Guinea-pigs underwent laparotomy while anaesthetized and were implanted with a force transducer sutured onto the taenia caecum. With this transducer, changes in tension in the intestinal longitudinal muscle were measured continuously via telemetry. Catheters were inserted into the carotid artery and jugular vein, were tunnelled subcutaneously and were accessed from the back of the neck. These catheters were connected to a cannula swivel and were used to monitor arterial pressure as well as to administer drugs i.v. in conscious, unrestrained guinea-pigs. Twenty hours after surgery, guinea-pigs received a single dose of lipopolysaccharide (LPS; 0.3 mg/kg, i.p.) 10 min after the start of a continuous 2 h i.v. infusion of sivelestat (30 mg/kg per h) or vehicle (saline). Elastase activity before and after sivelestat or vehicle administration was measured spectrometrically using a specific synthetic substrate. 3. We confirmed that intestinal longitudinal muscle tension decreased 2-3 h after LPS administration in the control group, with a concurrent decline in blood pressure. In guinea-pigs treated with sivelestat, the LPS-induced decreases in muscle tension and blood pressure were significantly reduced. In LPS-treated control guinea-pigs, serum elastase activity was elevated and this increase was significantly attenuated by administration of sivelestat. 4. The findings from the present study suggest that sivelstat can effectively reduce intestinal dysfunction and attenuate LPS-induced decreases in blood pressure in endotoxaemia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Hara¹,

Nemoto²,

Ninomiya³

et al. 2008

Clin Exp Pharma Physio

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“…LPS, which is a ligand for the Toll-like receptor 4 (TLR4), binds to TLR4 on the cell membrane and transmits a signal that results in production of mediators such as endocannabinoids, nitric oxide (NO), and cytokines, which initiate immune reactions 13) . Endogenous cannabinoids have wide-ranging physiological activities, including the relaxation of intestinal smooth muscles [14][15][16] and vascular smooth muscles 2,16) . Both of these reponses are elicited by the CB1-R, but not the CB2-R. LPS is reported to induce the NO-mediated responses of decreased gastrointestinal transit 17) , and decreased ileal muscle contractility 18) and blood vessel relaxation 19) .…”

Section: Discussionmentioning

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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“…For such severe endotoxaemia, PMX treatment was clearly effective and significantly improved survival rates. PMX treatment removes LPS and LPS-induced endocannabinoids 5,12) . Endocannabinoids, particularly 2-arachidonylglycerol (2-AG), are attracting attention as early initial mediators of sepsis 17,18) .…”

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

confidence: 99%

“…have reported that LPS administration induces the production of 2-AG, leading to paralytic ileus mediated by cannabinoid (CB)-1 receptors. It has been shown that the elimination of 2-AG by polymyxin B immobilized fiber-direct hemoperfusion (PMX-DHP) reduces paralytic ileus 5) . In cases of patients with increased blood pressure resulting from PMX-DHP treatment, the plasma concentration of 2-AG was decreased 6,7) .…”

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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Elimination of 2‐Arachidonoylglycerol Action by Direct Hemoperfusion Through Immobilized Polymyxin B Fibers: An Experimental Study in Conscious Guinea Pigs

Cited by 9 publications

References 16 publications

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

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

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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