Therapeutic approaches for clinical ischemia and reperfusion injury.

Recent clinical applications of strategies derived from microcirculation and shock research directed at preventing the sequelae of ischemia and reperfusion syndromes are successfully decreasing mortality in a variety of human diseases. The most commonly applied principle remains early reperfusion, which has been most successfully applied in the treatment of myocardial infarction with balloon angioplasty and employed with moderate success in the recent treatment of stroke with fibrinolytic agents. This strategy is designed to prevent reperfusion injury before it occurs and has limited applicability. A more commonly used principle to clinically treat the reperfusion injury component of ischemia and reperfusion syndromes is controlled reperfusion, which is now routinely applied in transplant and experimentally applied in the treatment of peripheral artery occlusion, stroke, and myocardial infarction. Strategies to control the microcirculatory environment during ischemia are employed successfully in transplantation and cardiopulmonary bypass. These techniques have been recently modified for use in a combined fashion with controlled reperfusion in experimental clinical studies in heart surgery, limb ischemia, and transplantation. Future strategies that have indirect support but have not yet been tested in clinical studies include anticytokine therapy and ischemic preconditioning. In conclusion, the successes in the treatment of ischemia reperfusion injury in experimental animals have slowly been integrated into clinical practice. Marked gains have been made in the treatment of myocardial infarction, peripheral artery occlusion, and transplantation. On the other hand, in areas such as stroke and hemorrhagic shock, we have a long way to go.