Ischaemia-reperfusion injury and hyperbaric oxygen pathways: a review of cellular mechanisms

Abstract

Ischaemia-induced tissue injury has wide-ranging clinical implications including myocardial infarction, stroke, compartment syndrome, ischaemic renal failure and replantation and revascularization. However, the restoration of blood flow produces a 'second hit' phenomenon, the effect of which is greater than the initial ischaemic event and characterizes ischaemia-reperfusion (IR) injury. Some examples of potential settings of IR injury include: following thrombolytic therapy for stroke, invasive cardiovascular procedures, solid organ transplantation, and major trauma resuscitation. Pathophysiological events of IR injury are the result of reactive oxygen species (ROS) production, microvascular vasoconstriction, and ultimately endothelial cell-neutrophil adhesion with subsequent neutrophil infiltration of the affected tissue. Initially thought to increase the amount of free radical oxygen in the system, hyperbaric oxygen (HBO) has demonstrated a protective effect on tissues by influencing the same mechanisms responsible for IR injury. Consequently, HBO has tremendous therapeutic value. We review the biochemical mechanisms of ischaemia-reperfusion injury and the effects of HBO following ischaemia-reperfusion.

Keywords: Free radicals; Hyperoxia; Hypoxia; Ischaemic preconditioning; Nitric oxide; Reperfusion injury; Review article.

Figure 1

Mediators of ischaemia-reperfusion injury; oxidative stress, microvascular dysfunction, and the neutrophil-endothelial cell interaction produce changes in cellular physiology that increase cell damage and tissue death; CAM – cellular adhesion molecule; EC – endothelial cell; PMN – polymorphonuclear neutrophil; ROS – reactive oxygen species

Figure 2

Physiologic effects following hyperbaric oxygen therapy for ischaemia-reperfusion; hyperbaric oxygen results in interference with neutrophil-endothelial cell interactions, promotes arteriolar vasodilation, and ameliorates cellular damage; solid arrows represent stimulatory pathways; dotted arrows represent inhibitory pathways; ECM − extracellular matrix; eNOS − endothelial nitric oxide synthase; HBO − hyperbaric oxygen; ICAM − intercellular adhesion molecule; iNOS − inducible nitric oxide synthase; NO − nitric oxide; PMN − polymorphonuclear neutrophil; ROS − reactive oxygen species; SOD − superoxide dismutase;tPA − tissue plasminogen activator; uPA − urinokinase-like plasminogen activator; VEGF− vascular endothelial growth factor