Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
-
Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) can easily lead to supranormal oxygenation. The impact of hyperoxygenation beyond the early VA-ECMO support phase is unexplored. We sought to investigate its association with short- and long-term mortality. ⋯ Multivariable Cox regression analyses for in-hospital, 90-day, and 1-year mortality showed a significant association of the T3 compared with the T2 and the T1 of PaO2 to mortality across all endpoints. Conclusion: Hyperoxygenation during VA-ECMO might be associated with increased all-cause mortality. The results of our study further document the known toxicity of hyperoxygenation in general critical care patients and mark the need to focus specifically on VA-ECMO patients.
-
CircKlhl2 knockdown alleviates acute lung injury by regulating miR-29b-3p-mediated ROCK1 expression.
Background: Acute lung injury (ALI) induced by sepsis is distinguished by an inflammatory progression. Herein, we investigated the action of circular RNA kelch like family member 2 (circKlhl2) in sepsis-induced ALI. Methods: The animal or cell model of sepsis ALI was established by LPS stimulation. ⋯ MiR-29b-3p inhibition abrogated circKlhl2 knockdown-mediated effects on MPVECs injury. Moreover, miR-29b-3p overexpression promoted cell proliferation and inhibited apoptosis and inflammation in LPS-treated MPVECs, while ROCK1 enhancement reversed these effects. Conclusion: CircKlhl2 expedited the sepsis-induced ALI by adjusting miR-29b-3p/ROCK1 axis.
-
Ischemic postconditioning (I/Post) reduces I/R injury by activating endogenous cardioprotection mechanisms, such as the JAK/signal transducer and activator of transcription 3 (STAT3) and PI3K/Akt pathways, which offer a traditional approach to myocardial protection. According to a previous study, cardioprotection by I/Post may be lost in aged mice, and in our previous research, hypoxic postconditioning (H/Post) lacked a protective effect in senescent cardiomyocytes, which was associated with low expression of long noncoding RNA H19. The N6-methyladenosine (m 6 A) modification is a dynamic and reversible process that has been confirmed to play a role in cardiovascular diseases. ⋯ Furthermore, ALKBH5 knockdown exacerbated injury following H/Post in senescent cardiomyocytes. In addition, ALKBH5 regulated STAT3 expression by mediating its m 6 A modification and long noncoding RNA H19/miR-124-3p. ALKBH5 also alleviated the H/Post injury induced by the low expression of STAT3 in senescent cardiomyocytes.
-
The original guidelines of cardiopulmonary resuscitation focused on the establishment of an airway and rescue breathing before restoration of circulation through cardiopulmonary resuscitation. As a result, the airway-breathing-circulation approach became the central guiding principle of resuscitation. Despite new guidelines by the American Heart Association for a circulation-first approach, Advanced Trauma Life Support guidelines continue to advocate for the airway-breathing-circulation sequence. ⋯ In severely injured patients, a paradigm shift should be considered, which prioritizes restoration of circulation before ETI and positive pressure ventilation while maintaining a focus on basic airway assessment and noninvasive airway interventions. For this patient population, the most reasonable current strategy may be to target a simultaneous resuscitation approach, with immediate efforts to control hemorrhage and provide basic airway interventions while prioritizing volume resuscitation with blood products and deferring ETI until adequate systemic perfusion has been attained. We believe that a circulation-first sequence will improve both survival and neurologic outcomes for a traumatically injured patient and will continue to advocate this approach, as additional clinical evidence is generated to inform how to best tailor circulation-first resuscitation for varied injury patterns and patient populations.
-
The pathophysiology of acute respiratory distress syndrome (ARDS) involves cytokine storms, alveolar-capillary barrier destruction, and fibrotic progression. Pulmonary interstitial fibrosis is an important factor affecting the prognosis of ARDS patients. Endothelial-to-mesenchymal transition (EndMT) plays an important role in the development of fibrotic diseases, and the occurrence of EndMT has been observed in experimental models of LPS-induced acute lung injury (ALI). ⋯ However, apelin-13 treatment significantly attenuated these changes. Our findings suggest that apelin-13 may be a novel biomarker in patients with sepsis-associated ARDS. These results demonstrate that apelin-13 ameliorates LPS-induced EndMT and post-ALI pulmonary fibrosis by suppressing transforming growth factor β1 signaling.