RESUMEN
Current anesthetic theory is mostly based on neurons and/or neuronal circuits. A role for astrocytes also has been shown in promoting recovery from volatile anesthesia, while the exact modulatory mechanism and/or the molecular target in astrocytes is still unknown. In this study by animal models in male mice and electrophysiological recordings in vivo and in vitro, we found that activating astrocytes of the paraventricular thalamus (PVT) and/or knocking down PVT astrocytic Kir4.1 promoted the consciousness recovery from sevoflurane anesthesia. Single-cell RNA sequencing of the PVT reveals two distinct cellular subtypes of glutamatergic neurons: PVT GRM and PVT ChAT neurons. Patch-clamp recording results proved astrocytic Kir4.1-mediated modulation of sevoflurane on the PVT mainly worked on PVT ChAT neurons, which projected mainly to the mPFC. In summary, our findings support the novel conception that there is a specific PVTâprefrontal cortex projection involved in consciousness recovery from sevoflurane anesthesia, which is mediated by the inhibition of sevoflurane on PVT astrocytic Kir4.1 conductance.
Asunto(s)
Astrocitos , Estado de Conciencia , Núcleos Talámicos de la Línea Media , Canales de Potasio de Rectificación Interna , Sevoflurano , Animales , Astrocitos/fisiología , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Masculino , Ratones , Sevoflurano/farmacología , Estado de Conciencia/fisiología , Estado de Conciencia/efectos de los fármacos , Núcleos Talámicos de la Línea Media/fisiología , Núcleos Talámicos de la Línea Media/efectos de los fármacos , Núcleos Talámicos de la Línea Media/citología , Canales de Potasio de Rectificación Interna/metabolismo , Ratones Endogámicos C57BL , Anestésicos por Inhalación/farmacología , Vías Nerviosas/fisiología , Vías Nerviosas/efectos de los fármacos , Neuronas/fisiología , Neuronas/efectos de los fármacos , Corteza Prefrontal/fisiología , Corteza Prefrontal/efectos de los fármacos , Lóbulo Frontal/fisiología , Lóbulo Frontal/efectos de los fármacos , Periodo de Recuperación de la AnestesiaRESUMEN
INTRODUCTION: The number of elderly patients who require surgery as their primary treatment has increased rapidly in recent years. Among 300 million people globally who underwent surgery every year, patients aged 65 years and over accounted for more than 30% of cases. Despite medical advances, older patients remain at higher risk of postoperative complications. Early diagnosis and effective prediction are essential requirements for preventing serious postoperative complications. In this study, we aim to provide new biomarker combinations to predict the incidence of postoperative intensive care unit (ICU) admissions > 24 h in elderly patients. METHODS: This investigation was conducted as a nested case-control study, incorporating 413 participants aged ≥ 65 years who underwent non-cardiac, non-urological elective surgeries. These individuals underwent a 30-day postoperative follow-up. Before surgery, peripheral venous blood was collected for analyzing serum creatinine (Scr), procalcitonin (PCT), C-reactive protein (CRP), and high-sensitivity CRP (hsCRP). The efficacy of these biomarkers in predicting postoperative complications was evaluated using receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) values. RESULTS: Postoperatively, 10 patients (2.42%) required ICU admission. Regarding ICU admissions, the AUCs with 95% confidence intervals (CIs) for the biomarker combinations of Scr × PCT and Scr × CRP were 0.750 (0.655-0.845, P = 0.007) and 0.724 (0.567-0.882, P = 0.015), respectively. Furthermore, cardiovascular events were observed in 14 patients (3.39%). The AUC with a 95% CI for the combination of Scr × CRP in predicting cardiovascular events was 0.688 (0.560-0.817, P = 0.017). CONCLUSION: The innovative combinations of biomarkers (Scr × PCT and Scr × CRP) demonstrated efficacy as predictors for postoperative ICU admissions in elderly patients. Additionally, the Scr × CRP also had a moderate predictive value for postoperative cardiovascular events. TRIAL REGISTRATION: China Clinical Trial Registry, ChiCTR1900026223.
Asunto(s)
Biomarcadores , Proteína C-Reactiva , Creatinina , Unidades de Cuidados Intensivos , Complicaciones Posoperatorias , Humanos , Anciano , Masculino , Biomarcadores/sangre , Femenino , Unidades de Cuidados Intensivos/estadística & datos numéricos , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/diagnóstico , Proteína C-Reactiva/análisis , Creatinina/sangre , Estudios de Casos y Controles , Polipéptido alfa Relacionado con Calcitonina/sangre , Anciano de 80 o más Años , Curva ROC , Valor Predictivo de las PruebasRESUMEN
Background: Postoperative complications in aging patients remain a significant cause of increased costs, hospital length of stay, and patient distress. Although alterations in energy metabolism have been closely linked to aging process and surgery, it is still unclear whether metabolic changes during surgery is associated with postoperative complications in elderly patients. This study was conducted to investigate whether metabolic changes during surgery predicts postoperative complications in elderly patients. Methods: We conducted a prospective single-center observational cohort study. 244 adults (aged ≥65 years) who were scheduled for elective major non-cardiac surgery were recruited. Blood samples for each patient were taken before and after surgery. All patients were randomly divided into two groups (122 in each group), then oxygen consumption rate (OCR) or extracellular acidification rate (ECAR) was measured on isolated monocytes in each group. Results: 14 of 110 (12.7%) patients went through OCR measurement and 15 of 122 patients (12.3%) went through ECAR measurement experienced moderate to severe complications. Overall, there was an intensification of glycolysis in monocytes after surgery. Among all variables, only the change (preoperative -postoperative) of glycolytic reserve (GR)/glycolysis (G) and GR/non-glycolytic acidification (NG) were predictors of moderate to severe complications (AUC = 0.70; 95% CI, 0.56-0.81; P = 0.019 and AUC = 0.67; 95% CI, 0.55-0.80; P = 0.031). Decreased postoperative GR/G were associated with worse postoperative complications (RR = 9.08; 95% CI, 1.23-66.81; P = 0.024). Conclusions: Compared with mitochondria function, the change of glycolytic function in monocyte was more valuable in predicting postoperative complications after major abdominal surgery. Our study gave us a new insight into identifying patients at high risk in aging patients.