A Novel Experimental Method for the Study of Intestinal Paralysis due to Endotoxicosis

Ninomiya, Norifumi; Nemoto, Kayo; Okamura, Tadao; Suzuki, Hidenori; Yamamoto, Yasuhiro

doi:10.3893/jjaam.14.241

Cited by 11 publications

(13 citation statements)

References 12 publications

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“…We have previously published work on intestinal paralysis associated with endotoxaemia using the lipopolysaccharide (LPS)‐induced intestinal paralysis model 15 . In the present study, we examined the effects of the continuous administration of sivelestat on LPS‐induced intestinal paralysis and LPS‐induced hypotension in guinea‐pigs.…”

Section: Introductionmentioning

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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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: Introductionmentioning

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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“…Administration of LPS at 10 mg/kg, i.v. showed the maximum reaction and resulted in death of all subjects in a previous study 11) . For such severe endotoxaemia, PMX treatment was clearly effective and significantly improved survival rates.…”

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

confidence: 82%

“…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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“…We have maintained our interest in the decline of CMT in endotoxemia since previously observing this dose‐dependent change in conscious guinea pigs given LPS concentration (10). The present study is the first where CMT and MAP were measured simultaneously in conscious, freely moving guinea pigs.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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Direct hemoperfusion through a network of immobilized polymyxin B fibers is used for the treatment of septic shock, but the mechanism underlying the clinical benefits remains unclear. The aims of the present study were to assess the actions of direct hemoperfusion through immobilized polymyxin B fibers on effects of exogenous endotoxin or 2-arachidonoylglycerol in conscious guinea pigs; and to examine the underlying mechanisms. In the present study, colonic motion was monitored continuously by telemetry using a force transducer attached to the taenia caecum, while blood pressure was monitored with a carotid artery catheter. To establish a hemoperfusion circuit in a freely moving, conscious guinea pig, catheters were implanted in the carotid artery and the jugular vein, tunneled subcutaneously, exteriorized at the back of the neck in contact with a lightweight tethering spring, and attached to a swivel device at the top of the cage. On the day after the operation, lipopolysaccharide (Escherichia coli, O111:B4; 1 mg/kg) or 2-arachidonoylglycerol (1 mg/kg) was given intraperitoneally (i.p.) and direct hemoperfusion through immobilized polymyxin B fibers was carried out for 2 h. The results showed that in guinea pigs treated with direct hemoperfusion through immobilized polymyxin B fibers, relaxation of colonic longitudinal muscle caused by lipopolysaccharide or 2-arachidonoylglycerol was significantly suppressed, as were decreases in blood pressure. We conclude that the actions following exogenous administration of 2-arachidonoylglycerol were eliminated by direct hemoperfusion through immobilized polymyxin B fibers. These results suggest that effectiveness of direct hemoperfusion through immobilized polymyxin B fibers in endotoxemia involves elimination of 2-arachidonoylglycerol action.

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A Novel Experimental Method for the Study of Intestinal Paralysis due to Endotoxicosis

Cited by 11 publications

References 12 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

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

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

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