Ischemia-reperfusion injury: evidences for translational research

First used in the early nineteenth century, the term ischemia refers to impaired blood supply to tissues caused by reduced or obstructed arterial inflow. Restoration of blood flow at the earliest remains the cornerstone of all current treatment options to ischemia, nevertheless reperfusion may paradoxically induce and worsen ischemic tissue damage, leading to ischemia-reperfusion injury (IRI). IRI contributes to pathology in a wide range of conditions, such as single organ infarction and revascularization (stroke; myocardial, renal, intestinal infarction), multiple organ ischemia-reperfusion (trauma, circulatory arrest, sickle cell disease, sleep apnea), organ transplantation or surgery (1). The mechanisms underlying IRI development have not been completely defined yet, and include: (I) reduced ATP levels and intracellular pH as a result of anaerobic metabolism and lactate accumulation, followed by dysfunctional ATPase-dependent ion transport mechanisms, intracellular and mitochondrial calcium overload, cell swelling and rupture, and cell death by necrotic, apoptotic and autophagic mechanisms during prolonged ischemia; (II) generation of reactive oxygen and nitrogen species (ROS, RNS) and tissue infiltration by proinflammatory neutrophils upon reperfusion; (III) opening of the mitochondrial permeability transition pore as a common end-effector of the pathologic events triggered by ischemia-reperfusion (2). In spite of the progress achieved into the pathophysiology of ischemia and reperfusion, the complete knowledge of IRI mechanisms and the introduction of new treatments represent main challenges. In fact, research in this field continues to be afflicted by the failure to translate the results to clinically effective therapies. Dissecting the complex pathways involved in clinically relevant animal models of IRI is needed to provide the rationale for novel therapeutic agents. However, a great deal of work is needed to translate our current know-how from bench to bedside in the continuing effort to enhance the overall success of clinical IRI management