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.

Lockdown surgery: the impact of coronavirus disease 2019 measures on cardiac cases.

OBJECTIVES: The need to ration medical equipment and interventions during the coronavirus disease 2019 pandemic translated to an ever-lengthening wait list for surgical care. Retrospective analysis of lockdowns is of high importance to learn from the current situation for future pandemics. This monocentric study assessed the impact of lockdown periods on cardiac surgery cases and outcomes. METHODS: The single-centre cross-sectional descriptive observational study was conducted to investigate the first lockdown period and the following post-lockdown period in comparison to the same periods during the previous 3 years at the Department of Cardiac Surgery at the Medical University of Innsbruck. Data were prospectively collected and retrospectively analysed from the department-specific quality management system. The primary objective was to compare the number of open-heart procedures between the prelockdown and the lockdown period. The secondary objectives were to analyse the characteristics and the outcomes of open-heart procedures. RESULTS: There were no differences in patient demographics. A significant decrease of 29% in weekly surgical procedures was observed during the lockdown period. The surgical case-mix was unaffected: The numbers of aortic valve replacements, coronary artery bypass grafts, mitral valve repair or replacement procedures and others remained stable. The urgency of cases increased significantly, and the general health conditions of patients appeared to be worse. However, outcomes were unchanged. CONCLUSIONS: By implementing a rational patient selection process, the quality of open-heart procedures was maintained even though patients who underwent surgery during lockdown were sicker and more symptomatic.

Defining a therapeutic range for regeneration of ischemic myocardium via shock waves.

Shockwave therapy (SWT) represents a promising regenerative treatment option for patients with ischemic cardiomyopathy. Although no side-effects have been described upon SWT, potential cellular damage at therapeutic energies has not been addressed so far. In this work, we aimed to define a therapeutic range for shock wave application for myocardial regeneration. We could demonstrate that SWT does not induce cellular damage beneath energy levels of 0.27 mJ/mm2 total flux density. Endothelial cell proliferation, angiogenic gene expression and phosphorylation of AKT and ERK are enhanced in a dose dependent manner until 0.15 mJ/mm2 energy flux density. SWT induces regeneration of ischemic muscle in vivo via expression of angiogenic gene expression, enhanced neovascularization and improved limb perfusion in a dose-dependent manner. Therefore, we provide evidence for a dose-dependent induction of angiogenesis after SWT, as well as the absence of cellular damage upon SWT within the therapeutic range. These data define for the first time a therapeutic range of SWT, a promising regenerative treatment option for ischemic cardiomyopathy.

Shock waves promote spinal cord repair via TLR3.

Spinal cord injury (SCI) remains a devastating condition with poor prognosis and very limited treatment options. Affected patients are severely restricted in their daily activities. Shock wave therapy (SWT) has shown potent regenerative properties in bone fractures, wounds, and ischemic myocardium via activation of the innate immune receptor TLR3. Here, we report on the efficacy of SWT for regeneration of SCI. SWT improved motor function and decreased lesion size in WT but not Tlr3-/- mice via inhibition of neuronal degeneration and IL6-dependent recruitment and differentiation of neuronal progenitor cells. Both SWT and TLR3 stimulation enhanced neuronal sprouting and improved neuronal survival, even in human spinal cord cultures. We identified tlr3 as crucial enhancer of spinal cord regeneration in zebrafish. Our findings indicate that TLR3 signaling is involved in neuroprotection and spinal cord repair and suggest that TLR3 stimulation via SWT could become a potent regenerative treatment option.