Hydrogen-enriched preservation protects the isogeneic intestinal graft and amends recipient gastric function during transplantation

Bettina M. Buchholz, Kosuke Masutani, Tomohiro Kawamura, Ximei Peng, Yoshiya Toyoda, Timothy R. Billiar, Anthony J. Bauer, Atsunori Nakao

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

BACKGROUND.: Inhaled hydrogen gas exerts antioxidant and anti-inflammatory effects in rat intestinal transplantation. Here, we investigated whether ex vivo donor organ treatment with dissolved hydrogen would prevent intestinal graft injury. METHODS.: Isogeneic intestinal transplantation was performed in Lewis rats with vascular flush, luminal preservation, and cold graft storage in nitrogen-bubbled (SITxN2) or hydrogen-bubbled (SITxH2) preservation solution. Lactated Ringer's solution and 3-hr cold ischemia time were used for mechanistic investigations, whereas survival experiments were performed with University of Wisconsin solution and 6-hr cold ischemia time. RESULTS.: During the early phase of ischemia-reperfusion injury, hydrogen-enriched solution significantly preserved mucosal graft morphology, diminished graft malondialdehyde levels demonstrating substantial reduction potential and blunted proinflammatory molecular responses (early growth response gene [EGR-1], interleukin [IL]-6, IL-1ß, and inducible nitric oxide synthase) within the reperfused intestinal graft muscularis. During the late phase of ischemia-reperfusion injury, circulating IL-6 protein and lactate dehydrogenase levels were significantly ameliorated in SITxH2 animals, which were associated with a favorable functional outcome in in vivo liquid gastrointestinal transit and recipient solid gastric emptying of chrome steel balls, and marked prevention of the posttransplant associated suppression of in vitro muscarinic jejunal contractility. Reflecting improved graft preservation, hydrogen preloading of grafts increased recipient survival rates from 41% to 80%. Anti-inflammatory and antiapoptotic heme oxygenase-1 was significantly upregulated in the hydrogen-treated graft muscularis but not mucosa before reperfusion. CONCLUSIONS.: Graft preloading with hydrogen demonstrated superior morphologic and functional graft protection in rodent intestinal transplantation, ultimately facilitating recipient survival. Antioxidant capacity and muscularis heme oxygenase-1 upregulation are possible protective mechanisms.

Original languageEnglish
Pages (from-to)985-992
Number of pages8
JournalTransplantation
Volume92
Issue number9
DOIs
Publication statusPublished - Nov 15 2011

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Hydrogen
Stomach
Transplantation
Transplants
Cold Ischemia
Heme Oxygenase-1
Reperfusion Injury
Interleukin-6
Anti-Inflammatory Agents
Antioxidants
Isogeneic Transplantation
Gastrointestinal Transit
Gastric Emptying
Steel
Nitric Oxide Synthase Type II
Malondialdehyde
Interleukin-1
L-Lactate Dehydrogenase
Cholinergic Agents
Reperfusion

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Hydrogen-enriched preservation protects the isogeneic intestinal graft and amends recipient gastric function during transplantation. / Buchholz, Bettina M.; Masutani, Kosuke; Kawamura, Tomohiro; Peng, Ximei; Toyoda, Yoshiya; Billiar, Timothy R.; Bauer, Anthony J.; Nakao, Atsunori.

In: Transplantation, Vol. 92, No. 9, 15.11.2011, p. 985-992.

Research output: Contribution to journalArticle

Buchholz, BM, Masutani, K, Kawamura, T, Peng, X, Toyoda, Y, Billiar, TR, Bauer, AJ & Nakao, A 2011, 'Hydrogen-enriched preservation protects the isogeneic intestinal graft and amends recipient gastric function during transplantation', Transplantation, vol. 92, no. 9, pp. 985-992. https://doi.org/10.1097/TP.0b013e318230159d
Buchholz, Bettina M. ; Masutani, Kosuke ; Kawamura, Tomohiro ; Peng, Ximei ; Toyoda, Yoshiya ; Billiar, Timothy R. ; Bauer, Anthony J. ; Nakao, Atsunori. / Hydrogen-enriched preservation protects the isogeneic intestinal graft and amends recipient gastric function during transplantation. In: Transplantation. 2011 ; Vol. 92, No. 9. pp. 985-992.
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AU - Buchholz, Bettina M.

AU - Masutani, Kosuke

AU - Kawamura, Tomohiro

AU - Peng, Ximei

AU - Toyoda, Yoshiya

AU - Billiar, Timothy R.

AU - Bauer, Anthony J.

AU - Nakao, Atsunori

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N2 - BACKGROUND.: Inhaled hydrogen gas exerts antioxidant and anti-inflammatory effects in rat intestinal transplantation. Here, we investigated whether ex vivo donor organ treatment with dissolved hydrogen would prevent intestinal graft injury. METHODS.: Isogeneic intestinal transplantation was performed in Lewis rats with vascular flush, luminal preservation, and cold graft storage in nitrogen-bubbled (SITxN2) or hydrogen-bubbled (SITxH2) preservation solution. Lactated Ringer's solution and 3-hr cold ischemia time were used for mechanistic investigations, whereas survival experiments were performed with University of Wisconsin solution and 6-hr cold ischemia time. RESULTS.: During the early phase of ischemia-reperfusion injury, hydrogen-enriched solution significantly preserved mucosal graft morphology, diminished graft malondialdehyde levels demonstrating substantial reduction potential and blunted proinflammatory molecular responses (early growth response gene [EGR-1], interleukin [IL]-6, IL-1ß, and inducible nitric oxide synthase) within the reperfused intestinal graft muscularis. During the late phase of ischemia-reperfusion injury, circulating IL-6 protein and lactate dehydrogenase levels were significantly ameliorated in SITxH2 animals, which were associated with a favorable functional outcome in in vivo liquid gastrointestinal transit and recipient solid gastric emptying of chrome steel balls, and marked prevention of the posttransplant associated suppression of in vitro muscarinic jejunal contractility. Reflecting improved graft preservation, hydrogen preloading of grafts increased recipient survival rates from 41% to 80%. Anti-inflammatory and antiapoptotic heme oxygenase-1 was significantly upregulated in the hydrogen-treated graft muscularis but not mucosa before reperfusion. CONCLUSIONS.: Graft preloading with hydrogen demonstrated superior morphologic and functional graft protection in rodent intestinal transplantation, ultimately facilitating recipient survival. Antioxidant capacity and muscularis heme oxygenase-1 upregulation are possible protective mechanisms.

AB - BACKGROUND.: Inhaled hydrogen gas exerts antioxidant and anti-inflammatory effects in rat intestinal transplantation. Here, we investigated whether ex vivo donor organ treatment with dissolved hydrogen would prevent intestinal graft injury. METHODS.: Isogeneic intestinal transplantation was performed in Lewis rats with vascular flush, luminal preservation, and cold graft storage in nitrogen-bubbled (SITxN2) or hydrogen-bubbled (SITxH2) preservation solution. Lactated Ringer's solution and 3-hr cold ischemia time were used for mechanistic investigations, whereas survival experiments were performed with University of Wisconsin solution and 6-hr cold ischemia time. RESULTS.: During the early phase of ischemia-reperfusion injury, hydrogen-enriched solution significantly preserved mucosal graft morphology, diminished graft malondialdehyde levels demonstrating substantial reduction potential and blunted proinflammatory molecular responses (early growth response gene [EGR-1], interleukin [IL]-6, IL-1ß, and inducible nitric oxide synthase) within the reperfused intestinal graft muscularis. During the late phase of ischemia-reperfusion injury, circulating IL-6 protein and lactate dehydrogenase levels were significantly ameliorated in SITxH2 animals, which were associated with a favorable functional outcome in in vivo liquid gastrointestinal transit and recipient solid gastric emptying of chrome steel balls, and marked prevention of the posttransplant associated suppression of in vitro muscarinic jejunal contractility. Reflecting improved graft preservation, hydrogen preloading of grafts increased recipient survival rates from 41% to 80%. Anti-inflammatory and antiapoptotic heme oxygenase-1 was significantly upregulated in the hydrogen-treated graft muscularis but not mucosa before reperfusion. CONCLUSIONS.: Graft preloading with hydrogen demonstrated superior morphologic and functional graft protection in rodent intestinal transplantation, ultimately facilitating recipient survival. Antioxidant capacity and muscularis heme oxygenase-1 upregulation are possible protective mechanisms.

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