Department of Surgery, Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittburgh, Pennsylvania 15213, USA.
J Heart Lung Transplant. 2010 May;29(5):544-53. doi: 10.1016/j.healun.2009.10.011. Epub 2009 Dec 24.
Recent advances in novel medical gases, including hydrogen and carbon monoxide (CO), have demonstrated significant opportunities for therapeutic use. This study was designed to evaluate the effects of inhaled hydrogen or CO, or both, on cold ischemia/reperfusion (I/R) injury of the myocardium.
Syngeneic heterotopic heart transplantation was performed in rats after 6 or 18 hours of cold ischemia in Celsior solution. Survival, morphology, apoptosis and marker gene expression were assessed in the grafts after in vivo inhalation of hydrogen (1% to 3%), CO (50 to 250 ppm), both or neither. Both donors and recipients were treated for 1 hour before and 1 hour after reperfusion.
After 6-hour cold ischemia, inhalation of hydrogen (>2%) or CO (250 ppm) alone attenuated myocardial injury. Prolonged cold ischemia for 18 hours resulted in severe myocardial injury, and treatment with hydrogen or CO alone failed to demonstrate significant protection. Dual treatment with hydrogen and CO significantly attenuated I/R graft injury, reducing the infarcted area and decreasing in serum troponin I and creatine phosphokinase (CPK). Hydrogen treatment alone significantly reduced malondialdehyde levels and serum high-mobility group box 1 protein levels as compared with air-treated controls. In contrast, CO only marginally prevented lipid peroxidation, but it suppressed I/R-induced mRNA upregulation for several pro-inflammatory mediators and reduced graft apoptosis.
Combined therapy with hydrogen and CO demonstrated enhanced therapeutic efficacy via both anti-oxidant and anti-inflammatory mechanisms, and may be a clinically feasible approach for preventing cold I/R injury of the myocardium.
新型医学气体（包括氢气和一氧化碳）的最新进展表明，它们具有很大的治疗应用潜力。本研究旨在评估吸入氢气或一氧化碳，或两者同时吸入对心肌冷缺血再灌注（I/R）损伤的影响。
在 Celsior 溶液中冷缺血 6 或 18 小时后，对大鼠进行同基因异位心脏移植。在体内吸入氢气（1%至 3%）、一氧化碳（50 至 250ppm）、两者或两者都不吸入后，评估移植物的存活、形态、细胞凋亡和标记基因表达。供体和受体均在再灌注前 1 小时和再灌注后 1 小时接受治疗。
在 6 小时冷缺血后，单独吸入氢气（>2%）或一氧化碳（250ppm）可减轻心肌损伤。延长 18 小时冷缺血导致严重的心肌损伤，单独使用氢气或一氧化碳治疗未能显示出显著的保护作用。氢气和一氧化碳的联合治疗可显著减轻 I/R 移植损伤，减少梗死面积，并降低血清肌钙蛋白 I 和肌酸磷酸激酶（CPK）。与空气处理对照组相比，单独使用氢气治疗可显著降低丙二醛水平和血清高迁移率族蛋白 1 蛋白水平。相比之下，一氧化碳仅能轻微防止脂质过氧化，但能抑制 I/R 诱导的几种促炎介质的 mRNA 上调，并减少移植物细胞凋亡。
氢气和一氧化碳联合治疗通过抗氧化和抗炎机制显示出增强的治疗效果，可能是预防心肌冷缺血再灌注损伤的一种临床可行方法。
