Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies

Abstract

Ischemia/reperfusion injury (IRI) permeates a variety of diseases and is a ubiquitous concern in every transplantation proceeding, from whole organs to modest grafts. Given its significance, efforts to evade the damaging effects of both ischemia and reperfusion are abundant in the literature and they consist of several strategies, such as applying pre-ischemic conditioning protocols, improving protection from preservation solutions, thus providing extended cold ischemia time and so on. In this review, we describe many of the latest pharmacological approaches that have been proven effective against IRI, while also revisiting well-established concepts and presenting recent pathophysiological findings in this ever-expanding field. A plethora of promising protocols has emerged in the last few years. They have been showing exciting results regarding protection against IRI by employing drugs that engage several strategies, such as modulating cell-surviving pathways, evading oxidative damage, physically protecting cell membrane integrity, and enhancing cell energetics.

Dissecting Cellular Mechanisms of Long-Chain Acylcarnitines-Driven Cardiotoxicity: Disturbance of Calcium Homeostasis, Activation of Ca2+-Dependent Phospholipases, and Mitochondrial Energetics Collapse

“…In this article, we revisited the role of saturated long-chain acylcarnitines in the control of both cellular Ca 2+ homeostasis and mitochondrial energy metabolism. Most recent reviews devoted to the studies of reperfusion/injury and cardioprotective mechanisms are focused on harmful effects of calcium and reactive oxygen species (ROS) [ 57 , 58 , 59 , 60 ]. The mechanisms of acute lipotoxicity are analyzed separately of Ca 2+ effects and include the inhibition of mitochondrial oxidative phosphorylation and the accumulation of ROS induced by long-chain fatty acids or respective acylcarnitines [ 59 , 60 ].…”

“…Most recent reviews devoted to the studies of reperfusion/injury and cardioprotective mechanisms are focused on harmful effects of calcium and reactive oxygen species (ROS) [ 57 , 58 , 59 , 60 ]. The mechanisms of acute lipotoxicity are analyzed separately of Ca 2+ effects and include the inhibition of mitochondrial oxidative phosphorylation and the accumulation of ROS induced by long-chain fatty acids or respective acylcarnitines [ 59 , 60 ]. It is well established that rapid influx and accumulation of Na + and Ca 2+ in cytoplasm, which generally occurs in I/R, may lead to the accumulation of [Ca 2+ ] i and [Ca 2+ ] m and mitochondrial (mPTP) or mitochondrial-independent cell death [ 57 , 61 ].…”

Hyperbaric oxygen therapy in managing systemic inflammatory response syndrome caused by ischemia-reperfusion injury following hand replantation and long-term outcomes: A report of two cases

“…Nayak et al reported cases of hand replantation involving 6–8 hours of warm ischemia and concluded that arterialization prior to replantation should be performed immediately, in order to delay tissue necrosis and enable limbs to survive after long warm ischemic time [ 10 ]. The replantation technique includes irrigation and debridement, identification, dissection, marking of nerves and blood vessels, bone shortening, internal fixation, extensor tendon grafting, flexor tendon grafting, arterial, vein and nerve grafting, and skin graft (to close the wound) [ 1 , 11 ].…”

“…However, ROS levels are controlled by intracellular antioxidants; when blood flow is returned to hypoxic tissues, oxygen molecules will bind to each other, which—given the absence of a supply of local antioxidants—will cause a surge in ROS. In the end, instead of promoting cell recovery, the excessive amount of ROS can cause cellular damage [ 11 ]. Moreover, prolonged ischemia triggers inflammation and influences the wound healing process.…”

Photoacoustic Imaging in Evaluating Early Intestinal Ischemia and Reperfusion Injury with Rat Models

“…In the process of ischemia and reperfusion, there is a dependence between reperfusion injury and ischemia time, and the ischemia process itself can cause injury, which is also the basis of reperfusion injury [31,32] . The essence of reperfusion injury is to further aggravate or convert the injury in ischemic phase into irreversible injury after blood ow recovery [33] . So the rst thing that affects reperfusion injury is ischemia time [34] .…”