Temporal Association Between Ischemic Muscle Perfusion Recovery and the Restoration of Muscle Contractile Function After Hindlimb Ischemia

We examined this relationship in BALB/cJ mice (N=24) following unilateral hindlimb ischemia (HLI). Specifically, we examined this relationship in two phenotypically distinct muscles (i.e. ‘oxidative’ soleus - Sol and ‘glycolytic’ extensor digitorum longus - EDL) 14- or 56-days after HLI. Although overall limb blood flow (LDPI) reached its’ recovery peak (48% of control) by HLI d14, the capillary networks in both the Sol and EDL (whole mount confocal imaging) were disrupted and competent muscle capillary perfusion (perfused lectin+ μm2 / muscle μm2) remained reduced. Interestingly, both Sol and EDL muscles recovered their distinct capillary structures and perfusion (Con Sol; 0.056 ± 0.02 lectin+μm2/ muscle μm2, and Con EDL; 0.039 ± 0.005 lectin+μm2/ muscle μm2) by HLI d56 (Sol; 0.062 ± 0.011 lectin+μm2/ muscle μm2 and EDL; 0.0035 ± 0.005 lectin+μm2/ muscle μm2) despite no further improvement in limb blood flow (LDPI). Both muscles suffered severe myopathy, indicated by loss of dystrophin positive immunostaining and the absence of stimulation induced isometric force production at HLI d14. Dystrophin immunofluorescence returned at HLI d56, although neither myofiber CSA (μm2) nor isometric force production (58% and 28% sustained deficits, Sol and EDL respectively) recovered completely in either muscle. In summary, we reveal that the temporal relationship between the restoration of muscle capillary perfusion and functional ischemic muscle regeneration favo...

Source: Frontiers in Physiology - June 27, 2019 Category: Physiology Source Type: research