Alexandra Gratl1,2, Dominik Pesta3,4,5,6, Leonhard Gruber7, Fiona Speichinger1, Ben Raude1, Safwan Omran1, Andreas Greiner1, Jan Paul Frese8. 1. Department of Vascular Surgery, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany. 2. Department of Vascular Surgery, Medical University of Innsbruck, Innsbruck, Austria. 3. Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany. 4. German Center for Diabetes Research (DZD), München-Neuherberg, Germany. 5. Department of Sports Science, Medical Section, Innsbruck, Austria. 6. German Aerospace Center, Institute of Aerospace Medicine, Cologne, Germany. 7. Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria. 8. Department of Vascular Surgery, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany. jan-paul-bernhard.frese@charite.de.
Abstract
BACKGROUND: Peripheral arterial disease (PAD) is accompanied by myopathy characterized by mitochondrial dysfunction. The aim of this experimental study was to investigate the effect of revascularization procedures on mitochondrial function in ischemic and non-ischemic muscle. METHODS: Muscle biopsies from patients with symptomatic stage IIB/III PAD caused by isolated pathologies of the superficial femoral artery were obtained from muscle regions within the chronic ischemic muscle (gastrocnemius) and from non-ischemic muscle (vastus lateralis) before and 6 weeks after invasive revascularization. High-resolution respirometry was used to investigate mitochondrial function and results were normalized to citrate synthase activity (CSA). Results are given in absolute values and fold over basal (FOB). RESULTS: Respiratory states (OXPHOS (P) and electron transfer (E) capacity) normalized to CSA decreased while CSA was increased in chronic ischemic muscle after revascularization. There were no changes in in non-ischemic muscle. The FOB of chronic ischemic muscle was significantly higher for CSA (chronic ischemic 1.37 (IQR 1.10-1.64) vs. non-ischemic 0.93 (IQR 0.69-1.16) p = 0.020) and significantly lower for respiratory states normalized to CSA when compared to the non-ischemic muscle (P per CSA chronic ischemic 0.64 (IQR 0.46-0.82) vs non-ischemic 1.16 (IQR 0.77-1.54) p = 0.011; E per CSA chronic ischemic 0.61 (IQR 0.47-0.76) vs. non-ischemic 1.02 (IQR 0.64-1.40) p = 0.010). CONCLUSIONS: Regeneration of mitochondrial content and function following revascularization procedures only occur in muscle regions affected by malperfusion. This indicates that the restoration of blood and oxygen supply are important mediators aiding mitochondrial recovery.
BACKGROUND:Peripheral arterial disease (PAD) is accompanied by myopathy characterized by mitochondrial dysfunction. The aim of this experimental study was to investigate the effect of revascularization procedures on mitochondrial function in ischemic and non-ischemic muscle. METHODS: Muscle biopsies from patients with symptomatic stage IIB/III PAD caused by isolated pathologies of the superficial femoral artery were obtained from muscle regions within the chronic ischemic muscle (gastrocnemius) and from non-ischemic muscle (vastus lateralis) before and 6 weeks after invasive revascularization. High-resolution respirometry was used to investigate mitochondrial function and results were normalized to citrate synthase activity (CSA). Results are given in absolute values and fold over basal (FOB). RESULTS: Respiratory states (OXPHOS (P) and electron transfer (E) capacity) normalized to CSA decreased while CSA was increased in chronic ischemic muscle after revascularization. There were no changes in in non-ischemic muscle. The FOB of chronic ischemic muscle was significantly higher for CSA (chronic ischemic 1.37 (IQR 1.10-1.64) vs. non-ischemic 0.93 (IQR 0.69-1.16) p = 0.020) and significantly lower for respiratory states normalized to CSA when compared to the non-ischemic muscle (P per CSA chronic ischemic 0.64 (IQR 0.46-0.82) vs non-ischemic 1.16 (IQR 0.77-1.54) p = 0.011; E per CSA chronic ischemic 0.61 (IQR 0.47-0.76) vs. non-ischemic 1.02 (IQR 0.64-1.40) p = 0.010). CONCLUSIONS: Regeneration of mitochondrial content and function following revascularization procedures only occur in muscle regions affected by malperfusion. This indicates that the restoration of blood and oxygen supply are important mediators aiding mitochondrial recovery.
Authors: Ahmed Ismaeel; Emma Fletcher; Dimitrios Miserlis; Marissa Wechsler; Evlampia Papoutsi; Gleb Haynatzki; Robert S Smith; William T Bohannon; Panagiotis Koutakis Journal: Transl Res Date: 2022-03-12 Impact factor: 10.171
Authors: Larissa Schawe; Ben Raude; Jan Christoph Carstens; Irene Hinterseher; Raphael Donatus Hein; Safwan Omran; Gilles Berger; Nina A Hering; Matthias Buerger; Andreas Greiner; Jan Paul Frese Journal: Biomedicines Date: 2022-02-17