Inhalation of hydrogen (H-2) gas has been demonstrated to limit the infarct volume of brain and liver by reducing ischemia-reperfusion injury in rodents. When translated into clinical practice, this therapy must be most frequently applied in the treatment of patients with acute myocardial infarction, since angioplastic recanalization of infarct-related occluded coronary artery is routinely performed. Therefore, we investigate whether H-2 gas confers cardioprotection against ischemia-reperfusion injury in rats. In isolated perfused hearts, H-2 gas enhances the recovery of left ventricular function following anoxia-reoxygenation. Inhaled H-2 gas is rapidly transported and can reach 'at risk' ischemic myocardium before coronary blood flow of the occluded infarct-related artery is reestablished. Inhalation of H-2 gas at incombustible levels during ischemia and reperfusion reduces infarct size without altering hemodynamic parameters, thereby preventing deleterious left ventricular remodeling. Thus, inhalation of H-2 gas is promising strategy to alleviate ischemia-reperfusion injury coincident with recanalization of coronary artery. (C) 2008 Elsevier Inc. All rights reserved.