Part I: Acute Lower Limb Ischemia-Reperfusion Injury: Pathophysiology and Experimental Interventions

Background: Ischemia-reperfusion injury (IRI) secondary to acute limb ischemia is a complex clinical phenomenon induced by a variety of pathologies, including arterial embolization, arterial thrombosis, vascular trauma, advanced peripheral vascular disease, traumatic crush injuries, and/or prolonged tourniquet application. The restoration of blood flow and oxygen to the limb after an ischemic period, while necessary, is ultimately the driving force of IRI. The exaggerated inflammation, oxidative stress, and tissue damage caused by IRI often lead to limb dysfunction, limb loss, multi-organ failure, and/or death. While no gold-standard therapy currently exists, various in vitro and in vivo models have been developed to explore potential therapeutic strategies. Currently, pharmacological agents with anti-inflammatory and/or antioxidant properties, as well as non-pharmacological strategies, have been investigated, and some agents show promise in mitigating the effects of lower extremity ischemia-reperfusion injury (IRI). Purpose: In this review article, we provide a comprehensive overview of the pathophysiology of IRI, discuss the local and systemic effects of IRI, and examine the experimental models used to investigate IRI. We also outline the current in vitro and in vivo pharmacological and non-pharmacological interventions studied to reduce IRI.