13 research outputs found
Study Protocol of a Prospective Multicenter Observational Study Evaluating Acute Lower Limb Ischemia
Subclavian artery rupture in a young man during excessive weight lifting
We report a 19-year-old man with rupture of the right subclavian artery after an excessive exercise of weight lifting. Imaging showed a hematothorax and hematomediastinum, a pseudoaneurysm with a maximum diameter of 4 cm, and a dissection of the right vertebral artery. As an emergency procedure an interposition graft was performed for reconstruction of the right subclavian artery. The patient's postoperative course was uneventful, and he was symptom free except for regressive hoarseness due to a paresis of the right recurrent laryngeal nerve
Study protocol of a Prospective Multicentre Observational Study Evaluating Acute Lower Limb Ischemia
eine Pilotstudie
Introduction: 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.
Methods: 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.
Results: 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. Conclusion: 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.Einleitung: Bei der peripheren arteriellen Verschlusskrankheit (pAVK) kommt es
in Folge von hämodynamisch relevanten atherosklerotisch bedingten Stenosen
oder Verschlüssen zu einer Minderversorgung von betroffenen Muskelabschnitten
mit Sauerstoff. Als Symptomatik berichten Patienten über belastungsabhängige
Schmerzen in den betroffenen Muskeln, welche sich nach einer Ruhepause
bessern. Diese sich immer wiederholende Ischämie-Reperfusions-Situation führt
zu histomorphologischen und metabolischen Veränderungen des betroffenen
Muskels und Mitochondrien spielen bei diesem Mechanismus eine entscheidende
Rolle. Ziel der Studie ist es, den Mitochondriengehalt sowie die
Mitochondrienfunktion in betroffenen Muskelabschnitten von pAVK Patienten
sowie die Regenerationsfähigkeit nach erfolgreicher Revaskularisation von
Mitochondrien zu untersuchen. Methodik: Es wurden 10 Patienten im Stadium IIB
– IV einer pAVK, mit isolierten Pathologien der Arteria femoralis
superficialis sowie geplanter Revaskularisation in die Studiengruppe und 10
gesunde Probanden in die Kontrollgruppe eingeschlossen. Muskelbiospien wurden
aus dem Musculus gastrocnemius entnommen, in der Studiengruppe unmittelbar vor
sowie 6 Wochen nach erfolgreicher Revaskularisation, in der Kontrollgruppe
erfolgte die Probenentnahme einmalig. Zur Beurteilung des
Mitochondriengehaltes erfolgte die Messung der Citrat-Synthase Aktivität
(CSA), die mitochondriale Respiration wurde anhand von hochauflösender
Respirometrie bestimmt. Durch Korrelation der Werte der Respiration auf die
Werte der CSA Messung erfolgte die Bestimmung der Mitochondrienfunktion.
Ergebnisse: Die demographischen Daten der Patienten der Studiengruppe und der
Probanden der Kontrollgruppe zeigten keine statistisch signifikanten
Unterschiede. Bei der Bestimmung der CSA zeigte sich nach erfolgreicher
Revaskularisation ein signifikanter Anstieg der Werte wobei dies einer
Adaptierung an die Werte der Kontrollgruppe entsprach. Bei der Komplex I und
Komplex I+II abhängigen Respiration normalisiert auf die CSA zeigte sich vor
Revaskularisation eine signifikant erhöhte Mitochondrienfunktion mit
postoperativer Angleichung der Werte an die Kontrollgruppe. Schlussfolgerung:
Es konnte gezeigt werden, dass es in betroffenen Muskelabschnitten von pAVK
Patienten zu einer Reduktion der Mitochondrienzahl und einer kompensatorischen
Zunahme der Mitochondrienfunktion kommt. Nach erfolgreicher Revaskularisation
zeigte sich mit der Zunahme der Mitochondrienzahl und der Abnahme der
Mitochondrienfunktion eine Angleichung an die untersuchten gesunden Probanden
und somit konnte eine Regerationsfähigkeit der Mitochondrien nachgewiesen
werden. Die hochauflösende Respirometrie in Kombination mit der Bestimmung der
CSA bieten somit eine gute Möglichkeit zur Untersuchung von mitochondrialen
Veränderungen bei pAVK Patienten und ermöglichen ein besseres Verständnis der
pathophysiologischen Veränderungen der mit dieser Erkrankung verbundenen
Myopathie
Acute ischemia of the extremities
Die akute Extremitätenischämie ist der häufigste gefäßchirurgische Notfall und bedarf
je nach Schweregrad der akuten bis subakuten Versorgung, um den Extremitätenerhalt
sicherzustellen. Dieser Artikel bietet eine Übersicht zu Definition, Pathophysiologie
und Versorgungslage sowie zur Vielzahl an offen-chirurgischen und endovaskulären
Versorgungsmöglichkeiten. Insbesondere die Anzahl an voroperierten Patienten und
damit komplexerer Verschlusspathologien nimmt stetig zu. Damit steigt die Bedeutung
moderner endovaskulärer Therapien (z. B. Katheterlyse oder perkutane Thrombektomie)
sowie der Zu- und Abstromverbesserung mittels Ballonangioplastie oder Stents im
Rahmen von Hybrideingriffen. Eine abschließende Bewertung der Verfahren aus
wissenschaftlicher Sicht ist aufgrund der aktuellen Datenlage oft nicht möglich, aber
dringend nötig. Bis dahin bleibt die Entscheidung über die geeignetste Therapie oft der
Erfahrung und den technischen Möglichkeiten des Behandlers vorbehalten
The Role of Mitochondrial Function in Peripheral Arterial Disease: Insights from Translational Studies
Recent evidence demonstrates an involvement of impaired mitochondrial function in peripheral arterial disease (PAD) development. Specific impairments have been assessed by different methodological in-vivo (near-infrared spectroscopy, P-31 magnetic resonance spectroscopy), as well as in-vitro approaches (Western blotting of mitochondrial proteins and enzymes, assays of mitochondrial function and content). While effects differ with regard to disease severity, chronic malperfusion impacts subcellular energy homeostasis, and repeating cycles of ischemia and reperfusion contribute to PAD disease progression by increasing mitochondrial reactive oxygen species production and impairing mitochondrial function. With the leading clinical symptom of decreased walking capacity due to intermittent claudication, PAD patients suffer from a subsequent reduction of quality of life. Different treatment modalities, such as physical activity and revascularization procedures, can aid mitochondrial recovery. While the relevance of these modalities for mitochondrial functional recovery is still a matter of debate, recent research indicates the importance of revascularization procedures, with increased physical activity levels being a subordinate contributor, at least during mild stages of PAD. With an additional focus on the role of revascularization procedures on mitochondria and the identification of suitable mitochondrial markers in PAD, this review aims to critically evaluate the relevance of mitochondrial function in PAD development and progression
Neuronal Pre- and Postconditioning via Toll-like Receptor 3 Agonist or Extracorporeal Shock Wave Therapy as New Treatment Strategies for Spinal Cord Ischemia: An In Vitro Study
Spinal cord ischemia (SCI) is a devastating and unpredictable complication of thoracoabdominal aortic repair. Postischemic Toll-like receptor 3 (TLR3) activation through either direct agonists or shock wave therapy (SWT) has been previously shown to ameliorate damage in SCI models. Whether the same applies for pre- or postconditioning remains unclear. In a model of cultured SHSY-5Y cells, preconditioning with either poly(I:C), a TLR3 agonist, or SWT was performed before induction of hypoxia, whereas postconditioning treatment was performed after termination of hypoxia. We measured cytokine expression via RT-PCR and utilized Western blot analysis for the analysis of signaling and apoptosis. TLR3 activation via poly(I:C) significantly reduced apoptotic markers in both pre- and postconditioning, the former yielding more favorable results through an additional suppression of TLR4 and its downstream signaling. On the contrary, SWT showed slightly more favorable effects in the setting of postconditioning with significantly reduced markers of apoptosis. Pre- and post-ischemic direct TLR3 activation as well as post-ischemic SWT can decrease apoptosis and proinflammatory cytokine expression significantly in vitro and might therefore pose possible new treatment strategies for ischemic spinal cord injury
A Modified Run-Off Resistance Score from Cross-Sectional Imaging Discriminates Chronic Critical Limb Ischemia from Intermittent Claudication in Peripheral Arterial Disease
Atherosclerotic peripheral arterial disease (PAD) leads to intermittent claudication (IC) and may progress into chronic limb-threatening ischemia (CLTI). Scoring systems to determine the atherosclerotic burden of a diseased extremity have been developed. This study aimed to evaluate a modification of the run-off resistance (mROR) score for its usability in cross-sectional imaging. The mROR was determined from preoperative imaging of patients undergoing revascularization for PAD. A total of 20 patients with IC and 20 patients with CLTI were consecutively included. A subgroup analysis for diabetic patients was conducted. The mROR was evaluated for its correlation with disease severity and clinical covariates. Patients with CLTI were older; cardiovascular risk factors, diabetes, and ASA 4 were more frequent. The mROR scores were higher in CLTI than in IC. In diabetic patients, no difference was detected between CLTI and IC. In CLTI, non-diabetic patients had a higher mROR. The mROR score is positively correlated with the severity of PAD and can discriminate CLTI from IC. In diabetic patients with CLTI, the mROR is lower than in non-diabetic patients. The mROR score can be determined from cross-sectional imaging angiographies. It may be useful for clinicians helping with vascular case planning, as well as for scientific purposes