Effect of ischemic preconditioning in skeletal muscle measured by functional magnetic resonance imaging and spectroscopy: a randomized crossover trial

Abstract

Background: Nuclear 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.

Methods: Twenty-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.

Results: The 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.

Conclusions: Ischemic 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 registration: ClinicalTrials.gov: NCT00883467.

Figure 1

Schema of NMR data acquisition. Time course was equal for ³¹P spectroscopy and BOLD imaging. The first line shows the baseline day without low flow, the second line the day with low flow but without ischemic preconditioning (IPC) and the third line represents the two days with IPC.

Figure 2

³¹P time course. Time course of phosphocreatine (PCr) at baseline, during ischemia and reperfusion, and in the presence of post-ischemic stenosis with or without mechanical preconditioning four hours before ischemia. The data represent the means ± SEM (n=8).

Figure 3

BOLD time course. Time course of the BOLD signal in the gastrocnemius, soleus, and tibialis anterior muscles at baseline, during ischemia and reperfusion, and in the presence of post-ischemic stenosis with or without mechanical preconditioning four hours prior to ischemia. The data represent the means ± SEM (n=8).

Figure 4

Echoplanar images for the BOLD signal analysis. The images are representative of the BOLD source data. An image for every 4^th minute of data collection is shown.

Figure 5

Muscle strength time course. Ankle plantar flexion and dorsiflexion strength before and during ischemia and after reperfusion with or without post-ischemic stenosis. The data represent the means ± SEM (n=7).