aHeart, Lung and Esophageal Surgery Institute, University of Pittsburgh, Pittsburgh, PA
COMBINED ADMINISTRATION OF HYDROGEN AND CARBON MONOXIDE IS A
Atsunori Nakao, David J Kaczorowski, Ryujiro Sugimoto, Jianghua Zhan, Yinna Wang, Kenneth R McCurry
Thomas E Starzl Transplantation Institute, Department of Surgery,
Department of Surgery,
Background: Hydroxyl radicals, generated during ischemia/reperfusion injury (IRI), play a critical role in graft injury. Recently, it has been reported that hydrogen (H2) gas alleviates oxidative injury by selectively neutralizing hydroxyl radicals. In this study, we evaluated the combined effects of H2 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 H2 or CO treated group, both donor and recipients were treated with H2 (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 H2 treatment. Cardiomyocyte apoptosis, prevalent in control grafts at 6 hrs, was also significantly attenuated with H2. H2 treatment 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 H2 did not. These results suggest that H2 does not possess direct anti-inflammatory effects, but CO does. Conversely, while H2 has potent anti-oxidant properties, CO has marginal effects in scavenging radicals. Dual therapy with CO and H2 demonstrated both anti-oxidant and anti-inflammatory effects.
Conclusion: Mixed gas therapy with CO and H2 is 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)
|
|
TnI (3h) |
CPK (IU/L, 3h) |
TUNEL (6h) |
MDA (3h) |
HMGB1 (1h) |
Serum IL-6 (3h) |
|
normal |
1.1 |
101 |
7.4 |
0.47 |
0.08 |
21 |
|
HTx (air) |
224.7 |
15312 |
55.4 |
0.85 |
4.3 |
928.1 |
|
HTx (CO) |
160.3 |
9171 |
35.2 |
0.83 |
3.8 |
462* |
|
HTx (H2) |
80.5* |
5458* |
24.3* |
0.65* |
2.6 |
872.1 |
|
HTx (CO/H2) |
47.5* |
4405* |
22.1* |
0.59* |
2.7 |
206.4* |
具体内容可以参考其一综述:
J Clin Biochem Nutr. 2009 Jan;44(1):1-13. Epub 2008 Dec 27.
Therapeutic antioxidant medical gas.
Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Medical gases are pharmaceutical gaseous molecules which offer solutions to medical needs and include traditional gases, such as oxygen and nitrous oxide, as well as gases with recently discovered roles as biological messenger molecules, such as carbon monoxide, nitric oxide and hydrogen sulphide. Medical gas therapy is a relatively unexplored field of medicine; however, a recent increasing in the number of publications on medical gas therapies clearly indicate that there are significant opportunities for use of gases as therapeutic tools for a variety of disease conditions. In this article, we review the recent advances in research on medical gases with antioxidant properties and discuss their clinical applications and therapeutic properties.
PMID: 19177183 [PubMed - in process]
PMCID: PMC2613492
