Lung ischemia-reperfusion injury: implications of oxidative stress and platelet-arteriolar wall interactions

Abstract

Pulmonary ischemia-reperfusion (IR) injury may result from trauma, atherosclerosis, pulmonary embolism, pulmonary thrombosis and surgical procedures such as cardiopulmonary bypass and lung transplantation. IR injury induces oxidative stress characterized by formation of reactive oxygen (ROS) and reactive nitrogen species (RNS). Nitric oxide (NO) overproduction via inducible nitric oxide synthase (iNOS) is an important component in the pathogenesis of IR. Reaction of NO with ROS forms RNS as secondary reactive products, which cause platelet activation and upregulation of adhesion molecules. This mechanism of injury is particularly important during pulmonary IR with increased iNOS activity in the presence of oxidative stress. Platelet-endothelial interactions may play an important role in causing pulmonary arteriolar vasoconstriction and post-ischemic alveolar hypoperfusion. This review discusses the relationship between ROS, RNS, P-selectin, and platelet-arteriolar wall interactions and proposes a hypothesis for their role in microvascular responses during pulmonary IR.

Figure 1

General concept of the early phase of pulmonary ischemia–reperfusion. In the oxidative stress induced by pulmonary ischemia–reperfusion (IR), formation of reactive nitrogen species (RNS) may promote platelet and endothelial cell activation with subsequent platelet adhesion to the arteriolar wall and release of vasoactive substances. We propose that pulmonary IR induces platelet–arteriolar wall interactions via a P-selectin-dependent mechanism and contributes to pulmonary microvascular constriction during reperfusion. Increased P-selectin expression results from elevated inducible nitric oxide synthase (iNOS) activity and subsequent over-production of nitric oxide (NO) and RNS generation.