Ischemia–reperfusion injury pathophysiology, part I

Objective: To review the current scientific literature on ischemia–reperfusion (IR) injury in both human and veterinary medicine. To describe the normal antioxidant defense mechanisms, the pathophysiology of IR injury, and the role of neutrophils in IR injury. Data sources: Data sources include scientific reviews and original research publications in both human and veterinary medicine. Summary: IR injury is a complex pathophysiological process involving numerous pathways and body systems. Normal antioxidant defense mechanisms function to limit oxidative injury during times of health. Ischemia is the period that occurs before oxygenated blood is re‐introduced and the severity of injury has been shown to correlate with the magnitude and length of ischemia in dogs. During ischemia, there is a buildup of substances (i.e., xanthine oxidase, hypoxanthine, etc.) that, upon re‐introduction of oxygen, form reactive oxygen species (ROS). ROS, produced in large part upon reperfusion, can cause extensive damage to DNA, proteins, carbohydrates, and lipids. Although mammalian systems are endowed with abundant antioxidant defenses, the generation of large amounts of ROS can overwhelm these mechanisms leading to cell dysfunction and death. Neutrophils play a critical role in IR injury and may mediate the majority of mucosal and microvascular injury that occurs by releasing ROS and proteolytic enzymes. Although experimental studies have been carried out on cats, dogs, and horses there are few clinical studies on companion animals. Conclusions: The pathophysiology of IR injury is complex and involves damage by ROS to all biological membranes. Neutrophils play a major role in IR injury and initiate and propogate much of the damage. This article is intended as a review of the pathophysiology of IR injury.