Invited commentary

Abstract

So you successfully re-establish blood supply to a 70-year-old woman with atrial fibrillation who experienced a right common femoral artery embolus 6 hours prior. Even with four-quadrant fasciotomy, the muscle swelling is tremendous, and some of the anterior compartment muscle appears greyish on initial inspection. You have anticoagulation to prevent recurrent thrombus formation and hydration to aid in managing some of the metabolic consequences but little to actually salvage ongoing muscle damage associated with reperfusion injury. A successful treatment that could be easily provided at the time of reperfusion to ameliorate the associated injury would be a highly desirable addition to our clinical toolbox. Reperfusion injury and its potential treatment is not a new concept. Reperfusion injury is a complex event involving reactive oxygen species, activated neutrophils that release potentially toxic intracellular granules, complement activation, and cytokines that signal activated leukocyte adhesion and transmigration. This, in essence, describes inflammation as a major component of this injury event as it is being recognized for many such events. Attempts at ameliorating the effects of these negative factors have to date not be entirely effective or transferable to the clinical arena. This study recognizes the anti-inflammatory and microvascular perfusion protection properties of carbon monoxide (CO) but the downside of exogenously inhaled CO due to its increased carboxyhemoglobin generation. With the availability of transitional metal carbonyls, CO-releasing molecules that can be delivered intravascularly without carboxyhemoglobin production, a potential therapeutic option became available to test. Such agents do appear to protect myocardium during reperfusion and reduce the overall inflammatory response in other animal models. This study demonstrates a similar protective effect in a skeletal muscle model with improved microvascular perfusion, inhibition of inflammation, and attenuation of cellular damage on skeletal muscle when a CO-releasing molecule is delivered at the time of reperfusion. The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. Systemic application of carbon monoxide-releasing molecule 3 protects skeletal muscle from ischemia-reperfusion injuryJournal of Vascular SurgeryVol. 66Issue 6PreviewIschemia-reperfusion (IR) is a limb- and life-threatening complication of acute limb ischemia and musculoskeletal trauma. Carbon monoxide-releasing molecules (CORMs) have recently been shown to protect microvascular perfusion and to reduce inflammation and injury in various ischemic animal models. The purpose of this study was to examine the effects of water-soluble CORM-3 on the extent of IR-induced muscle injury. Full-Text PDF Open Archive