The pathophysiology of acute lung injury following intestinal ischemia-reperfusion.

Abstract

Acute mesenteric ischemia (AMI) is a severe and life-threatening condition with a mortality rate of up to 50%. Its treatment, which depends on the etiology, focuses on preserving intestinal viability through prompt restoration of blood flow. Although it is well established that intestinal ischemia-reperfusion results in significant local tissue damage, it is less recognized that it can also lead to remote tissue injuries, particularly in the lungs. Acute lung injury following intestinal ischemia-reperfusion is a severe complication that affects nearly 30% of patients with acute mesenteric ischemia and significantly contributes to mortality. The underlying pathophysiology of this injury is complex and multifactorial, yet it remains poorly understood. Neutrophil-endothelial interactions, regulated by both systemic and local mediators, play a pivotal role. Among the contributing factors, the intestinal ischemia-reperfusion process itself appears to be the most significant. Reperfusion of the ischemic intestine allows the release of mediators generated during ischemia into the systemic circulation. This triggers a cascade of biological events, including elevated levels of proinflammatory cytokines, overproduction of reactive oxygen species (ROS), nitric oxide imbalance, neutrophil activation, mitochondrial damage, and the initiation of cell death pathways. Here, we review the current knowledge on the various pathophysiological pathways explored in clinical and animal models of acute lung injury induced by intestinal ischemia-reperfusion, with the aim of providing therapeutic insights.