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Sevoflurane Improves Hemorrhagic Shock and Resuscitation-Induced Cognitive Impairments and Mitochondrial Dysfunctions through SIRT1-Mediated Autophagy.

ABSTRACT: Cerebral ischemia reperfusion injury (IRI) induced by hemorrhagic shock and reperfusion (HSR) is the main cause of death following trauma. Previous studies indicated the neuroprotective effect of sevoflurane postconditioning (SP) in cerebral IRI. However, the mechanisms still remain elusive. Cerebral IRI models with SP were established by using HSR with C57BL/6 mice (male, 3-month-old) in vivo and by using oxygen glucose deprivation and reoxygenation (OGD/R) with HT22 cells in vitro. Postoperative cognition was evaluated by the Morris water maze, novel object recognition, and elevated plus maze tests. The role of SIRT1 was determined by using siRNA, a sensitive inhibitor (EX527), or an overexpression shRNA-GFP lentivirus. IRI caused significant disabilities of spatial learning and memory associated with enhanced cerebral infarct and neuronal apoptosis, which were effectively attenuated by SP. IRI also made a significant decrease of SIRT1 accompanied by oxidative stress, mitochondria dysfunction, and inactivated autophagy. SP or genetically overexpressing SIRT1 significantly suppressed defective autophagy, mitochondrial oxidative injury, and neuronal death caused by HSR or OGD/R. However, genetic suppression or pharmacological inhibition of SIRT1 significantly reversed the impact of SP treatment on mitochondrial DNA transcription ability and autophagy. Our results demonstrate that the loss of SIRT1 causes a sequential chain of mitochondrial dysfunction, defective autophagy, and neuronal apoptosis after IRI in the preclinical stroke models. Sevoflurane postconditioning treatment could effectively attenuate pathophysiological signatures induced by noxious stimuli, which maybe mediated by SIRT1.

SUBMITTER: Shu J

PROVIDER: S-EPMC9068312 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Sevoflurane Improves Hemorrhagic Shock and Resuscitation-Induced Cognitive Impairments and Mitochondrial Dysfunctions through SIRT1-Mediated Autophagy.

Shu Jianwei J Huang Xiaotong X Liao Qizhi Q Wang Jianan J Zhou Yuqi Y Chen Yihuan Y Chen Ming M Qian Cheng C Zhang Ye Y Hu Xianwen X Huang Chunxia C

Oxidative medicine and cellular longevity 20220311

Cerebral ischemia reperfusion injury (IRI) induced by hemorrhagic shock and reperfusion (HSR) is the main cause of death following trauma. Previous studies indicated the neuroprotective effect of sevoflurane postconditioning (SP) in cerebral IRI. However, the mechanisms still remain elusive. Cerebral IRI models with SP were established by using HSR with C57BL/6 mice (male, 3-month-old) <i>in vivo</i> and by using oxygen glucose deprivation and reoxygenation (OGD/R) with HT22 cells <i>in vitro</i ...[more]

PMID: 35528522

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Project description:BackgroundFluid resuscitation is important for correcting hypovolemia. Isotonic crystalloids are the preferred solution for the initial clinical management of patients with multiple traumas. Bicarbonated Ringer's solution (BRS), offering physiological levels of bicarbonate ions and electrolyte ions, can be used for supplementing missing extracellular fluid and correcting metabolic acidosis. We here investigated the effects of BRS on the resuscitation of hemorrhagic shock models and compared the resuscitation performance of three crystalloids, including BRS, acetated Ringer's solution (ARS), and normal saline.MethodsThirty adult male New Zealand rabbits were randomly divided into five groups (n=6): a sham operation group (Sham group), an operation without fluid therapy group (Shock group), a BRS group, an ARS group, and a normal saline group (Saline group). The New Zealand rabbits experienced rapid bloodletting to shock status and maintained for 20 minutes except Sham group. The status of shock was maintained in the Shock group. The fluid was infused at a rate of 60 mL/kg per hour for 1.5 hours in three fluid therapy group. Measurement of vital signs, arterial blood gas tests, blood biochemistry, hematoxylin and eosin (HE) staining of lung tissue, TUNEL staining of the liver and kidney tissues, and analysis of intestinal flora were performed.ResultsThe reduction in both base excess (BE) and bicarbonate ion (HCO3 -) caused by acidosis in rabbits with hemorrhagic shock was significantly improved in the BRS group when compared with the Saline group at infusion for 30 minutes (T3) and 30 minutes after infusion (T5) (BRS group vs. Saline group, BE: at T3, -4.83±3.60 vs. -12.50±3.27 mmol/L, P<0.01; at T5, -3.67±4.37 vs. -11.00±2.76 mmol/L, P<0.01; HCO3 -: at T3, 22.15±2.63 vs. 15.42±3.03 mmol/L, P<0.01; at T5, 23.15±2.9 vs. 16.23±3.07 mmol/L, P<0.01). Compared with Shock group, liver cell apoptosis due to hemorrhagic shock was relieved in both the BRS group and ARS group (BRS group vs. Shock group: 19.1±3.3 vs. 28.1±6.1, P<0.05; ARS group vs. Shock group: 19.8±5.4 vs. 28.1±6.1, P<0.05).ConclusionsDuring resuscitation of hemorrhagic shock, BRS, a novel perioperative balanced crystalloid, is more effective than normal saline in maintaining acid-base balance and in protecting tissues and organs.

Project description:BackgroundFast and effective treatment of hemorrhagic shock is one of the most important preclinical trauma care tasks e.g., in combat casualties in avoiding severe end-organ damage or death. In scenarios without immediate availability of blood products, alternate regimens of fluid resuscitation represent the only possibility of maintaining sufficient circulation and regaining adequate end-organ oxygen supply. However, the fluid choice alone may affect the extent of the bleeding by interfering with coagulation pathways. This study investigates the impact of hydroxyethyl starch (HES), gelatine-polysuccinate (GP) and balanced electrolyte solution (BES) as commonly used agents for fluid resuscitation on coagulation using a porcine hemorrhagic shock model.MethodsFollowing approval by the State and Institutional Animal Care Committee, life-threatening hemorrhagic shock was induced via arterial blood withdrawal in 24 anesthetized pigs. Isovolumetric fluid resuscitation with either HES, GP or BES (n = 3 × 8) was performed to compensate for the blood loss. Over four hours, hemodynamics, laboratory parameters and rotational thromboelastometry-derived coagulation were analyzed. As secondary endpoint the porcine values were compared to human blood.ResultsAll the agents used for fluid resuscitation significantly affected coagulation. We measured a restriction of laboratory parameters, clot development and clot firmness, particularly in HES- and GP-treated animals. Hemoglobin content dropped in all groups but showed a more pronounced decline in colloid-treated pigs. This effect was not maintained over the four-hour monitoring period.ConclusionHES, GP, and BEL sufficiently stabilized the macrocirculation, but significantly affected coagulation. These effects were most pronounced after colloid and particularly HES administration. Despite suitability for rapid hemodynamic stabilization, colloids have to be chosen with caution, because their molecular properties may affect coagulation directly and as a consequence of pronounced hemodilution. Our comparison of porcine and human coagulation showed increased coagulation activity in pig blood.

Project description:Traumatic brain injury (TBI) is often accompanied by hemorrhage, and treatment of hemorrhagic shock (HS) after TBI is particularly challenging because the two therapeutic treatment strategies for TBI and HS often conflict. Ischemia/reperfusion injury from HS resuscitation can be exaggerated by TBI-induced loss of autoregulation. In HS resuscitation, the goal is to restore lost blood volume, while in the treatment of TBI the priority is focused on maintenance of adequate cerebral perfusion pressure and avoidance of secondary bleeding. In this study, we investigate the responses to resuscitation from severe HS after TBI in rats, using fresh blood, polymerized human hemoglobin (PolyhHb), and lactated Ringer's (LR). Rats were subjected to TBI by pneumatic controlled cortical impact. Shortly after TBI, HS was induced by blood withdrawal to reduce mean arterial pressure (MAP) to 35-40 mmHg for 90 min before resuscitation. Resuscitation fluids were delivered to restore MAP to ~ 65 mmHg and animals were monitored for 120 min. Increased systolic blood pressure variability (SBPV) confirmed TBI-induced loss of autoregulation. MAP after resuscitation was significantly higher in the blood and PolyhHb groups compared to the LR group. Furthermore, blood and PolyhHb restored diastolic pressure, while this remained depressed for the LR group, indicating a loss of vascular tone. Lactate increased in all groups during HS, and only returned to baseline level in the blood reperfused group. The PolyhHb group possessed lower SBPV compared to LR and blood groups. Finally, sympathetic nervous system (SNS) modulation was higher for the LR group and lower for the PolyhHb group compared to the blood group after reperfusion. In conclusion, our results suggest that PolyhHb could be an alternative to blood for resuscitation from HS after TBI when blood is not available, assuming additional testing demonstrate similar favorable results. PolyhHb restored hemodynamics and oxygen delivery, without the logistical constraints of refrigerated blood.

Project description:BackgroundCurrent research suggests that administration of vasopressin to patients with uncontrolled hemorrhagic shock (UHS) can avoid the detrimental effects associated with aggressive fluid resuscitation. However, vasopressin has a short half-life of 10~35 minutes in in vivo use and precludes its use in the pre-hospital setting. To increase the half-life of vasopressin, we proposed to synthesize liposome-encapsulated vasopressin and test it in a rat model of UHS.MethodsThe film hydration method was used to prepare liposomal vasopressin consisting of: Dipalmitoylphosphatidylcholine, cholesterol, and dipalmitoyl phosphatidylethanolamine (20:20:1 mole ratio). 42 rats were subjected to UHS and randomly received 5 different treatments (vasopressin, liposomal vasopressin, lactate ringer (LR), liposome only and sham). Outcome of UHS were measured using 4 common prognostic tests: mean arterial pressure (MAP), serum lactate level, inflammatory profile and pulmonary edema.ResultsThe dynamic light scattering results confirmed that we had prepared a successful liposomal vasopressin complex. Comparing the serum vasopressin concentration of liposomal vasopressin and vasopressin treated animals by ELISA, we found that the concentration of vasopressin for the liposomal vasopressin treated group is higher at 60 minutes. However, there was no significant difference between the MAP profile of rats treated with vasopressin and liposomal vasopressin in UHS. We also observed that animals treated with liposomal vasopressin performed indifferently to vasopressin treated rats in serum lactate level, inflammatory profile and edema profile. For most of our assays, the liposome only control behaves similarly to LR resuscitation in UHS rats.ConclusionWe have synthesized a liposomal vasopressin complex that can prolong the serum concentration of vasopressin in a rat model of UHS. Although UHS rats treated with either liposomal vasopressin or vasopressin showed no statistical differences, it would be worthwhile to repeat the experiments with different liposomal compositions.

Dataset Information

Sevoflurane Improves Hemorrhagic Shock and Resuscitation-Induced Cognitive Impairments and Mitochondrial Dysfunctions through SIRT1-Mediated Autophagy.

Publications

Sevoflurane Improves Hemorrhagic Shock and Resuscitation-Induced Cognitive Impairments and Mitochondrial Dysfunctions through SIRT1-Mediated Autophagy.

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