Gratl 2018 Thesis

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Gratl A (2018) High-resolution respirometry for measurement of mitochondrial function in PAD patients before and after revascularisation. PhD Thesis 69.

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Gratl A (2018) PhD Thesis

Abstract: Peripheral arterial disease (PAD) is characterized by hemodynamically relevant atherosclerotic lesions with subsequent low blood supply to affected muscle regions. Patients who are suffering from symptomatic PAD report a pain induced by walking in affected muscles with relief of symptoms after resting. This repeating ischemia-reperfusion situation leads to histomorphological and metabolic changes in affected muscle regions. Mitochondria are known to play a crucial role in this pathophysiological mechanism. The aim of this study is the evaluation of mitochondrial content and function in affected muscles of symptomatic PAD patients and the potential of mitochondrial regeneration six weeks after successful revascularisation.

Ten patients suffering from PAD grade IIB – IV with isolated pathologies of the superficial femoral artery with planned revascularisation have been recruited into the study group. Ten participants known to be vascularly healthy have been included into the control group. Muscle biopsies of the medial belly of the gastrocnemius muscle have been obtained just before and six weeks after successful revascularisation in the study group, whereas within the control group biopsies have been taken at one instance. High- resolution respirometry has been performed to evaluate mitochondrial respiration and citrate synthase activity (CSA) has been measured to determine mitochondrial content. By correlation of values from high-resolution respirometry to values from CSA, mitochondrial function has been investigated.

Demographic data of the study group and the control group showed no statistically significant difference. CSA measurements in the study group showed a statistically significant increase of mitochondrial content after successful revascularisation coming close to those of healthy control subjects. Complex I- and complex I+II-related respiration normalized to CSA showed a statistically significant reduction of mitochondrial function six weeks after successful revascularisation compared to preoperative values. These results show increasing correspondence with the results of healthy control subjects.

This study showed that mitochondria in PAD patients are reduced in number but they compensate with increased function ability. After successful revascularisation, mitochondrial content and function approach that of healthy control subjects. Demonstrating a regeneration of initially impaired mitochondria. High-resolution respirometry in combination with measurement of CSA seems therefore useful for determining mitochondrial impairments and may be used for investigating pathophysiology of PAD related myopathy.

Keywords: Mitochondrial function, Peripheral arterial disease, Respirometry Bioblast editor: Plangger M


Labels: MiParea: Respiration, Patients  Pathology: Cardiovascular  Stress:Ischemia-reperfusion  Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 


Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, NS, ROX  HRR: Oxygraph-2k 

Labels, 2019-01