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Copyright © 2009 International Society for Heart and Lung Transplantation Published by Elsevier Inc.

Abstract

135: Combined Administration of Gas and Carbon Monoxide Is a Superior Strategy for Ameliorating Cardiac Cold Ischemia/Reperfusion Injury in Rats Hydrogen

^a Heart, Lung and Esophageal Surgery Institute, University of Pittsburgh, Pittsburgh, PA

COMBINED ADMINISTRATION OF HYDROGEN AND CARBON MONOXIDE IS ASUPERIORSTRATEGY FOR AMELIORATIONG CARDIAC COLD ISCHEMIA/REPERFUSION INJURY

Atsunori Nakao, David J Kaczorowski, Ryujiro Sugimoto, Jianghua Zhan, Yinna Wang, Kenneth R McCurry

Thomas E Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh

Department of Surgery, University of Pittsburgh

Background : Hydroxyl radicals, generated during ischemia/reperfusion injury (IRI), play a critical role in graft injury. Recently, it has been reported that hydrogen (H ₂) gas alleviates oxidative injury by selectively neutralizing hydroxyl radicals. In this study, we evaluated the combined effects of H ₂ with carbon monoxide (CO), a molecule known to have anti-inflammatory and anti-apoptotic properties. 

Methods : Syngeneic, heterotopic HTx (LEW rats) was performed with 18 hrs of cold ischemia time. In the H ₂or CO treated group, both donor and recipients were treated with H ₂(2%) or CO (250 ppm) in air 1 hr before and 1 hr after reperfusion.

Results : In control (air) recipients, serum troponin I (TnI) and CPK levels increased within 3 hrs, but were significantly attenuated with H ₂treatment. Cardiomyocyte apoptosis, prevalent in control grafts at 6 hrs, was also significantly attenuated with H ₂.  H ₂treatment resulted in significantly reduced MDA levels after transplant, demonstrating attenuated lipid peroxidation, and also reduced serum high-mobility group box-1 (HMGB1) levels. CO had marginal effects on preventing lipid peroxidation and myocardial oxidative injury. However, CO suppressed inflammatory responses, reducing graft mRNA levels for TNFα and serum IL-6, whereas H ₂did not. These results suggest that H ₂does not possess direct anti-inflammatory effects, but CO does. Conversely, while H ₂has potent anti-oxidant properties, CO has marginal effects in scavenging radicals. Dual therapy with CO and H₂demonstrated both anti-oxidant and anti-inflammatory effects. 

Conclusion : Mixed gas therapy with CO and H ₂is a novel, safe and potent approach for preventing cardiac cold IRI.

Table. The effects of CO and hydrogen for cardiac cold I/R injury (*p<0.05 vs HTx/air)

具體內容可以參考其一綜述:

J Clin Biochem Nutr.  Links2009 Jan;44(1):1-13. Epub 2008 Dec 27. 

Available online 24 January 2009. 

Article Outline

Purpose

Methods and Materials

Results

Conclusions

A. Nakao ^* , a , DJ Kaczorowski ^a , R. Sugimoto ^a , J. Zhan ^a , Y. Wang ^a and KR McCurry ^a

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