Ischaemia/Reperfusion Injury of Skeletal Muscle: Mechanisms, Morphology, Treatment Strategies, and Clinical Applications

Abstract

Summary: Background: Any surgical manoeuvre that involves cessation of blood supply to an organ with subsequent re‐establishment of blood flow can result in ischaemia/reperfusion (I/R) injury. The consequences of such injury are local and remote tissue destruction. Methods: I/R is characterized by ‘no reflow phenomenon’ and interstitial oedema formation. Changes in the production of nitric oxide (NO) and superoxide play an important role in the development of I/R. Overproduction of reactive oxygen‐derived free radicals (OFR) leads to a consumption and depletion of endogenous scavenging antioxidants. Results: Direct NO measurements showed a production of large concentrations of NO from cNOS at the beginning of ischaemia. Intracellular influx of Ca2+ after onset of ischaemia activates cNOS, leading to local depletion of L‐arginine and subsequently to disarrangement of cNOS, which produces superoxide instead of NO. Microvascular constriction during ‘no reflow’ reflects deficiency in vasodilator NO due to its consumption by vasoconstrictor oxygen free radicals. Stimulated production of thromboxane A2 and endothelin release may also promote ‘no reflow’. Conclusions: At least two major strategies are viable for preventing I/R injury: (a) treatment with L‐arginine and their analogues, or BH4, thus preventing L‐arginine and H4B deficient conditions, so that cNOS will not produce excessive O2–; (b) scavenging O2– already produced by cNOS and other potential sources of O2– by using large concentrations of free radical scavengers. Further research on oxidant/antioxidant biochemistry and its clinical application is needed.

Study of Warm Ischemia Followed by Reperfusion on a Lower Limb Model in Rats: Effect of Allopurinol and Streptokinase

“…These alterations to mi-crocirculation constitute the no-reflow phenomenon. 3,[5][6][7][8][9] Obstruction is progressive, with thrombus formation in the microcirculation, platelet aggregation, and tissue edema. Irreversible damage and loss of limb or of microsurgical flap can result.…”

“…Irreversible damage and loss of limb or of microsurgical flap can result. 2,8,10,11 The possible role of oxygen free radicals in the pathogenesis of tissue lesions after reperfusion has been studied, as has the use of pharmacological agents to prevent this phenomenon. 12,13 Encouraging results have been obtained using antioxidants , as well as a number of other drugs and agents in different tissues.…”

Effect of Mailuoning injection on 8-iso-prostaglandin F2 alpha and superoxide dismutase in rabbits with extremity ischemia–reperfusion injury

“…The consequences of IR injury are tissue and cell damage and even destruction. IR injury is a serious and common problem that leads to various diseases and, occasionally, life-threatening complications [1,2]. Although the mechanisms of IR injury have not been fully understood, many studies have suggested that oxidative stress induced by reactive oxygen species plays an important role [3e5].…”

Intestinal ischemia-reperfusion leads to early systemic micro-rheological and multiorgan microcirculatory alterations in the rat

“…Intestinal ischemia-reperfusion injury may occur due to several clinical conditions, such as acute 27 mesenteric ischemia, trauma, cardiopulmonary disease, shock, intestinal transplant rejection, volvulus 28 and necrotizing enterocolitis in newborns [1,2,12]. Mortality and morbidity remained high during the 29 last decades [19,39].…”