Perioperative Glycine Treatment Attenuates Ischemia/Reperfusion Injury and Ameliorates Smooth Muscle Dysfunction in Intestinal Transplantation

Schaefer, Nico; Tahara, Kazunori; Schuchtrup, S.; Websky, Martin von; Overhaus, Marcus; Schmidt, Joachim; Wirz, Stefan; Abu‐Elmagd, Kareem; Kalff, Jörg C.; Hirner, A.; Türler, Andreas

doi:10.1097/tp.0b013e31816c576f

Cited by 21 publications

(25 citation statements)

References 54 publications

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“…This finding was highly consistent with the observed amount of cell infiltration as illustrated in Figures 3-5. Previous studies clarified the key role of resident macrophages in the setting of intestinal transplantation and their activation as response to IRI and acute rejection (11,17,22,23,42). Postoperative graft motility, as a main cause for postoperative translocation and subsequent sepsis improved significantly with infliximab treatment in the early phase after transplantation.…”

Section: Discussionmentioning

confidence: 99%

Perioperative Infliximab Application Ameliorates Acute Rejection Associated Inflammation After Intestinal Transplantation

Pech

Finger

Fujishiro

et al. 2010

American Journal of Transplantation

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As we have shown in the past, acute rejection-related TNF-a upregulation in resident macrophages in the tunica muscularis after small bowel transplantation (SBTx) results in local amplification of inflammation, decisively contributing to graft dysmotility. Therefore, the aim of this study is to investigate the effectiveness of the chimeric-monoclonal-anti-TNF-a antibody infliximab as perioperative single shot treatment addressing inflammatory processes during acute rejection early after transplantation. Orthotopic, isogenic and allogenic SBTx was performed in rats (

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Section: Discussionmentioning

confidence: 99%

Perioperative Infliximab Application Ameliorates Acute Rejection Associated Inflammation After Intestinal Transplantation

Pech

Finger

Fujishiro

et al. 2010

American Journal of Transplantation

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“…Protection from I/R injury by glycine has also been described in the intestine. Inclusion of the amino acid in the storage solution decreased intestinal hypothermic preservation injury in an in situ reperfusion model in dogs [16], and perioperative glycine treatment attenuated injury of the cold-stored graft in a rat small bowel transplantation model [17]. Likewise, warm I/R injury of the intestine was attenuated by either enteral or parenteral (intravenous or local intra-arterial) application of glycine to mice and rats, respectively [18,19,20,21,22].…”

Section: Introductionmentioning

confidence: 99%

Protection from Glycine at Low Doses in Ischemia-Reperfusion Injury of the Rat Small Intestine

Petrat¹,

Drowatzky²,

Boengler³

et al. 2011

Eur Surg Res

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Background: Glycine at high doses is known to protect the small intestine against ischemia-reperfusion (I/R) injury. Here, we studied whether glycine at low clinically applicable doses has a protective effect. Methods: In series 1, intestinal I/R was induced in male Wistar rats by occlusion (90 min)/reopening (120 min) of the superior mesenteric artery. Glycine was intravenously infused for 30 min before ischemia (pre-ischemic infusion), and once again from 30 min before until 60 min after reperfusion. Total glycine doses applied over the 120-min infusion were 5, 10, 20, and 75 mg glycine/kg. In series 2, pre-ischemic blood plasma glycine concentrations were determined under the conditions of series 1. Results: In series 1, attenuation of I/R injury was comparable at 10, 20, and 75 mg glycine/kg, but less at 5 mg/kg (as indicated by less intestinal hemorrhages and better preserved mean arterial blood pressure, among other signs). In series 2, pre-ischemic blood plasma glycine concentrations increased with increasing glycine doses from 280 to 330, 340, 380, and 680 µM, respectively. Conclusion: These results demonstrate that even at a dose 50 times lower than previously applied – and at only slightly elevated plasma concentrations – glycine provides full protection against I/R injury of the small intestine.

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“…Syngeneic orthotopic SBTx was performed in Lewis rats as previously described under isoflurane inhalation anesthesia [15]. The mean operation time did not differ significantly between all transplant groups.…”

Section: Methodsmentioning

confidence: 99%

A Natural Tetrahydropyrimidine, Ectoine, Ameliorates Ischemia Reperfusion Injury after Intestinal Transplantation in Rats

Pech¹,

Ohsawa²,

Praktiknjo³

et al. 2012

Pathobiology

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Background/Aims: Ischemia reperfusion (I/R) injury after small bowel transplantation leads to inflammatory reactions and loss of structural integrity with subsequent graft contractile dysfunction in the early postoperative phase. The natural tetrahydropyrimidine ectoine (1-,4-,5-,6-tetrahydro-2-methyl-4-pyrimidine carboxylic acid; THP) protects the ileal mucosa and muscularis against effects of I/R injury in an experimental model of isolated graft reperfusion. The effects of THP treatment were evaluated in an established experimental intestinal transplant model. Methods: Isogenic, orthotopic small bowel transplantation was performed in Lewis rats (6 h cold ischemia time). Perioperative THP treatment (intraluminal/intravascular) groups were compared to vehicle-treated animals (after 3 and 24 h) and non-transplanted controls (n = 5/group). Park’s score defined the effects of I/R injury. The infiltration of neutrophils, monocytes and macrophages, mRNA expression of IL-6 and TNF-α, serum levels of IL-6 and NO and smooth muscle contractility were evaluated. Results: Improved graft outcome after intraluminal and intravascular THP treatment was defined by considerably ameliorated neutrophil infiltration and less histological signs of I/R injury (p ≤ 0.05). In the presence of THP, mRNA expression of IL-6 and TNF-α and IL-6 and NO serum levels were reduced and smooth muscle function was improved. Conclusion: THP treatment offers protection against the effects of I/R injury in intestinal transplantation in vivo, however, only as supplementary treatment option.

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Perioperative Glycine Treatment Attenuates Ischemia/Reperfusion Injury and Ameliorates Smooth Muscle Dysfunction in Intestinal Transplantation

Cited by 21 publications

References 54 publications

Perioperative Infliximab Application Ameliorates Acute Rejection Associated Inflammation After Intestinal Transplantation

Perioperative Infliximab Application Ameliorates Acute Rejection Associated Inflammation After Intestinal Transplantation

Protection from Glycine at Low Doses in Ischemia-Reperfusion Injury of the Rat Small Intestine

A Natural Tetrahydropyrimidine, Ectoine, Ameliorates Ischemia Reperfusion Injury after Intestinal Transplantation in Rats

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