Current Mechanistic Concepts in Ischemia and Reperfusion Injury

Abstract

Ischemia-reperfusion injury is associated with serious clinical manifestations, including myocardial hibernation, acute heart failure, cerebral dysfunction, gastrointestinal dysfunction, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Ischemia-reperfusion injury is a critical medical condition that poses an important therapeutic challenge for physicians. In this review article, we present recent advances focusing on the basic pathophysiology of ischemia-reperfusion injury, especially the involvement of reactive oxygen species and cell death pathways. The involvement of the NADPH oxidase system, nitric oxide synthase system, and xanthine oxidase system are also described. When the blood supply is re-established after prolonged ischemia, local inflammation and ROS production increase, leading to secondary injury. Cell damage induced by prolonged ischemia-reperfusion injury may lead to apoptosis, autophagy, necrosis, and necroptosis. We highlight the latest mechanistic insights into reperfusion-injury-induced cell death via these different processes. The interlinked signaling pathways of cell death could offer new targets for therapeutic approaches. Treatment approaches for ischemia-reperfusion injury are also reviewed. We believe that understanding the pathophysiology ischemia-reperfusion injury will enable the development of novel treatment interventions.

Ferroptotic cell death and TLR4/Trif signaling initiate neutrophil recruitment after heart transplantation

“…TLR activation initiates signaling via the adaptor proteins MyD88 or Trif. Our current understanding is that, following IRI, cells die through a combination of apoptosis and nonapoptotic forms of programmed cell death (6). It is further postulated that nonapoptotic forms of programmed cell death such as necroptosis or ferroptosis result in the release of DAMPs that ultimately result in the initiation of inflammation, referred to as necroinflammation (7).…”

Monitoring of the influence of long‐term oxidative stress and ischemia on the condition of kidneys using solid‐phase microextraction chemical biopsy coupled with liquid chromatography–high‐resolution mass spectrometry

“…During the first 4 h of kidney preservation, increased levels of metabolites related to various metabolic pathways involved in reactive oxygen species (ROS) production, especially alterations in purine metabolism, were observed; among them, upregulated levels of purine derivatives such as adenosine monophosphate (AMP), adenosine, inosine, hypoxanthine, and xanthine. In a hypoxic state, mitochondrial ATP generation is disrupted, triggering anaerobic metabolism pathways [27]. The decrease of ATP and ADP levels is related to an increased level of AMP due to enzymatic conversion by ectonucleoside‐triphosphate‐diphosphorylase‐1.…”

Fibroblast Growth Factor 2 Attenuates Renal Ischemia-Reperfusion Injury via Inhibition of Endoplasmic Reticulum Stress

“…Currently, many clinical and experimental studies have investigated renal I/R injury. However, the pathogenesis of AKI caused by I/R injury is not yet fully understood (Chertow et al, 2005;Wu et al, 2018). The pathologic mechanism of AKI is complicated and may involve inflammation, microvascular dysfunction, autophagy, apoptosis, oxidative stress, mitochondrial damage, and maladaptive endoplasmic reticulum (ER) stress (Bonventre and Yang, 2011).…”