Abstract

BackgroundNuclear magnetic resonance (NMR) imaging and spectroscopy have been applied to assess skeletal muscle oxidative metabolism. Therefore, in-vivo NMR may enable the characterization of ischemia-reperfusion injury. The goal of this study was to evaluate whether NMR could detect the effects of ischemic preconditioning (IPC) in healthy subjects.MethodsTwenty-three participants were included in two randomized crossover protocols in which the effects of IPC were measured by NMR and muscle force assessments. Leg ischemia was administered for 20 minutes with or without a subsequent impaired reperfusion for 5 minutes (stenosis model). IPC was administered 4 or 48 hours prior to ischemia. Changes in 31phosphate NMR spectroscopy and blood oxygen level-dependent (BOLD) signals were recorded. 3-Tesla NMR data were compared to those obtained for isometric muscular strength.ResultsThe phosphocreatine (PCr) signal decreased robustly during ischemia and recovered rapidly during reperfusion. In contrast to PCr, the recovery of muscular strength was slow. During post-ischemic stenosis, PCr increased only slightly. The BOLD signal intensity decreased during ischemia, ischemic exercise and post-ischemic stenosis but increased during hyperemic reperfusion. IPC 4 hours prior to ischemia significantly increased the maximal PCr reperfusion signal and mitigated the peak BOLD signal during reperfusion.ConclusionsIschemic preconditioning positively influenced muscle metabolism during reperfusion; this resulted in an increase in PCr production and higher oxygen consumption, thereby mitigating the peak BOLD signal. In addition, an impairment of energy replenishment during the low-flow reperfusion was detected in this model. Thus, functional NMR is capable of characterizing changes in reperfusion and in therapeutic interventions in vivo.Trial RegistrationClinicalTrials.gov: NCT00883467

Highlights

  • Nuclear magnetic resonance (NMR) imaging and spectroscopy have been applied to assess skeletal muscle oxidative metabolism

  • There were no changes in blood pressure or in the concentrations of circulating creatine kinase, free hemoglobin or C-reactive protein across the study periods

  • Multi-modal in vivo NMR in ischemiareperfusion injury (IRI) enables the evaluation of mitochondrial oxidative metabolism, muscle metabolic changes and changes in perfusion

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Summary

Introduction

Nuclear magnetic resonance (NMR) imaging and spectroscopy have been applied to assess skeletal muscle oxidative metabolism. In-vivo NMR may enable the characterization of ischemia-reperfusion injury. The goal of this study was to evaluate whether NMR could detect the effects of ischemic preconditioning (IPC) in healthy subjects. Reperfusion itself can result in additional cell damage, which is known as ischemiareperfusion injury (IRI) [1,2]. Ischemic preconditioning (IPC) is an established method to avoid IRI in different vascular beds [3,4,5]. The controlled repeated application of short periods of ischemia preceding a prolonged ischemic episode could protect remote tissue against IRI [6]. Previous data suggest that there is great variation in the amount of protection conferred by this mechanical intervention [6,7,9], and different protocols have been used for IRI attenuation in clinical studies

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