To investigate the correlation of serum pentraxin 3 (PTX-3), soluble interleukin-2 receptor (SIL-2R), C-reactive protein (CRP), procalcitonin (PCT) levels, and acute physiology and chronic health evaluation II (APACHE II) scores in patients with severe acute pancreatitis (SAP). A total of 30 patients with SAP from October 2020 to October 2021 were selected as the SAP group, and 42 patients with mild acute pancreatitis (MAP) or moderate-severe acute pancreatitis (MSAP) was selected as the control group. The serum levels of PTX-3, SIL-2R, CRP, PCT, and APACHE II scores were evaluated. The serum levels of PTX-3, SIL-2R, CRP, PCT, and APACHE II scores at admission in the SAP group were significantly higher than those in the control group (all P < .05). Spearman analysis showed that serum PTX-3, SIL-2R, CRP, and PCT levels were positively correlated with APACHE II scores (all P < .05). The mortality rate within 28 days was 26.7% in the SAP group; moreover, the serum PTX-3, SIL-2R, CRP, and PCT levels and APACHE II scores at admission in the death group were significantly higher than those in the survival group (all P < .05). The receiver operating curve showed that the combined prediction value of all indicators (PTX-3 + SIL-2R + CRP + PCT + APACHE II) was superior to the single indicators, and the diagnostic sensitivity and specificity were 90.9% and 84.2%, respectively. Serum PTX-3, SIL-2R, CRP, and PCT levels and APACHE II scores have high guiding significance in early diagnosis and prognostic evaluation of SAP patients.

目的 探讨小肠梗阻患者治疗方式选择的影响因素.方法 回顾性分析2017年1月至2018年10月于本科治疗的153例小肠梗阻患者的临床资料,排除急诊手术及放弃治疗患者29例,其余124例患者根据保守治疗是否有效分为手术组(n=50)、非手术组(n=74).对影响治疗方式选择的临床资料进行单因素分析,将单因素分析中有统计学意义的变量进行多因素Logistic回归分析,分析影响小肠梗阻治疗方式选择的影响因素.结果 单因素分析显示,手术组腹腔积液、肠鸣音减弱消失、腹膜刺激征、腹痛加剧发生率及C反应蛋白(CRP)、白细胞介素-6(IL-6)水平均高于非手术组,小肠减压管发生率低于非手术组,首日引流量多于非手术组,差异有统计学意义(P<0.05).多因素Logistic回归分析显示,腹痛加剧、腹腔积液、IL-6是患者保守治疗无效的影响因素,小肠减压管是保守治疗成功的保护因素.结论 应用小肠减压管可提高小肠梗阻保守治疗成功率,腹痛加剧、腹腔积液、IL-6是影响患者治疗方式转变的影响因素,在保守治疗中需密切注意相关指标.

The systemic inflammatory response following global myocardial ischemia/reperfusion (I/R) injury is a critical driver of poor outcomes. Both pyroptosis and necroptosis are involved in the systemic inflammatory response and contribute to regional myocardial I/R injury. This study aimed to explore the effect of necrosulfonamide (NSA) on post-resuscitation myocardial dysfunction in a rat model of cardiac arrest. Sprague-Dawley rats were randomly categorized to Sham, CPR and CPR-NSA groups. For rats in the latter two groups, ventricular fibrillation was induced without treatment for 6 min, with cardiopulmonary resuscitation (CPR) being sustained for 8 min. Rats were injected with NSA (10 mg/kg in DMSO) or vehicle at 5 min following return of spontaneous circulation. Myocardial function was measured by echocardiography, survival and neurological deficit score (NDS) were recorded at 24, 48, and 72 h after ROSC. Western blotting was used to assess pyroptosis- and necroptosis-related protein expression. ELISAs were used to measure levels of inflammatory cytokine. Rats in the CPR-NSA group were found to exhibit superior post-resuscitation myocardial function, and better NDS values in the group of CPR-NSA. Rats in the group of CPR-NSA exhibited median survival duration of 68 ± 8 h as compared to 34 ± 21 h in the CPR group. After treatment with NSA, NOD-like receptor 3 (NLRP3), GSDMD-N, phosphorylated-MLKL, and phosphorylated-RIP3 levels in cardiac tissue were reduced with corresponding reductions in inflammatory cytokine levels. Administration of NSA significantly improved myocardial dysfunction succeeding global myocardial I/R injury and enhanced survival outcomes through protective mechanisms potentially related to inhibition of pyroptosis and necroptosis pathways.

目的 联合多个芯片筛选小肠克罗恩病相关致病基因,并分析其诊断效能,以便从分子水平探索疾病的调控机制.方法 通过GEO数据库检索并下载相关芯片数据集.利用GEO在线分析工具筛选差异表达的miRNA、R语言筛选差异表达的mRNA,构建miRNA-mRNA调控网络.差异表达的mRNA通过R语言进行GO富集和KEGG通路富集分析,运用String数据库构建蛋白互作网络(PPI)、Cytoscape软件筛选关键基因,应用ROC曲线进行诊断效能分析.结果 GSE102127数据集中共筛选出15个差异表达的miRNA,GSE20881、GSE75214、GSE102133数据集融合后筛选出273个差异mRNA,构建38个miRNA-mRNA调控关系对.差异mRNA GO富集在白细胞迁移、中性粒细胞迁移等生物过程;KEGG富集注释表明差异基因主要参与IL-17、肿瘤坏死因子等信号通路.Cytoscape软件的cytoHubba模块下基于"Degree"、"MCC"、"Betweenness"算法筛选排名前10的关键基因,取交集后得到IL-6、IL-1β、MMP9及ICAM14个关键基因.ROC曲线分析发现仅MMP9可用于诊断小肠克罗恩病,其P值为0.025,AUC为0.361,敏感性100％,特异性31％.结论 多芯片联合成功筛选出小肠克罗恩病致病基因,并构建了miRNA-mRNA调控网络,致病基因尚无法作为小肠克罗恩病早期诊断的分子标志物.

Post-resuscitation cerebral ischemia-reperfusion injury (IRI) is a vital contributor to poor neurological prognosis. Exploring novel therapeutics that attenuate cerebral IRI is of great significance. Inflammation plays a role in the development of cerebral IRI after successful cardiopulmonary resuscitation (CPR). Monoacylglycerol lipase (MAGL) is an enzyme that is predominantly responsible for the metabolism of endocannabinoid 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA) metabolites, which are associated with inflammation. Therefore, we investigated the efficacy of the MAGL inhibitor, JZL184, on cerebral IRI and further compared the effects to therapeutic hypothermia (TH). Thirty-six rats were randomized into three groups: 1) JZL184; 2) Control; 3) TH (N = 12 for each group). Animals underwent 6 min of ventricular fibrillation (VF) followed with 8 min of CPR. After return of spontaneous circulation (ROSC), rats received an intraperitoneal injection of JZL184 (16 mg/kg) or DMSO (20 mg/ml) or body cooling was initiated. Cerebral microcirculation, brain edema, blood brain barrier (BBB) permeability, serum neuron-specific enolase (NSE), S-100β, interleukin-6 (IL-6) and interleukin-10 (IL-10) were quantified at 6 h post ROSC. Compared to control, treatment with JZL184 or TH was associated with significantly ameliorated cerebral microcirculation, mitigated brain edema, attenuated BBB permeability, decreased serum levels of NSE, S-100β and IL-6, and increased serum IL-10 levels (p < 0.05). There was no significant difference in the above measurements between JZL184 and TH. JZL184 has comparable neuroprotective effects to therapeutic hypothermia on global cerebral IRI in a rat model of cardiac arrest (CA).

Background:Previous studies have demonstrated that inflammation and impaired microcirculation are key factors in post-resuscitation syndromes. Here, we investigated whether methylprednisolone (MP) could improve myocardial function and microcirculation by suppressing the systemic inflammatory response following cardiopulmonary resuscitation (CPR) in a rat model of cardiac arrest (CA).Methods:Sprague-Dawley rats were randomly assigned to (1) sham, (2) control, and (3) drug groups. Ventricular fibrillation was induced and then followed by CPR. The rats were infused with either MP or vehicle at the start of CPR. Myocardial function and microcirculation were assessed at baseline and after the restoration of spontaneous circulation. Blood samples were drawn at baseline and 60-min post-resuscitation to assess serum cytokine (TNF-α, IL-1β, and IL-6) levels.Results:Myocardial function [estimated by the ejection fraction (EF), myocardial performance index (MPI), and cardiac output (CO)] improved post-ROSC in the MP group compared with those in the control group (p < 0.05). MP decreased the levels of the aforementioned pro-inflammatory cytokines and alleviated cerebral, sublingual, and intestinal microcirculation compared with the control (p < 0.05). A negative correlation emerged between the cytokine profile and microcirculatory blood flow.Conclusion:MP treatment reduced post-resuscitation myocardial dysfunction, inhibited pro-inflammatory cytokines, and improved microcirculation in the initial recovery phase in a CA and resuscitation animal model. Therefore, MP could be a potential clinical target for CA patients in the early phase after CPR to alleviate myocardial dysfunction and improve prognosis.

To investigate the effects of the selective NLRP3 inflammasome inhibitor MCC950 on post-resuscitation myocardial function and survival in a rat model of cardiopulmonary resuscitation (CPR). Thirty-six Sprague Dawley rats were randomized into three groups: (1) MCC950, (2) control, and (3) sham. Each group consisted of a 6 h non-survival subgroup (n = 6) and a 48 h survival subgroup (n = 6). Ventricular fibrillation (VF) was induced and untreated for 6 min. CPR was initiated and continued for 8 min. Resuscitation was attempted with a 4 J defibrillation. MCC950 (10 mg/kg) or vehicle was administered via intraperitoneal injection immediately after the return of spontaneous circulation (ROSC). Myocardial function and sublingual microcirculation were measured after ROSC in the non-survival subgroups. Plasma levels of interleukin Iβ (IL-1β) and cardiac troponin I (cTnI) were measured at baseline and 6 h in the non-survival subgroups. Heart tissue was harvested to measure the NLRP3 inflammasome constituents, including NLRP3, apoptosis-associated speck-like protein (ASC), Caspase-1, and IL-1β. Survival duration and neurologic deficit score (NDS) were recorded and evaluated among survival groups. Post-resuscitation myocardial function and sublingual microcirculation were improved in MCC950 compared with control (p < 0.05). IL-1β and cTnI were decreased in MCC950 compared to control (p < 0.01). The MCC950 treated groups showed significantly reduced ASC, caspase-1, and IL-1β compared with the control group (p < 0.05). Survival at 48 h after ROSC was greater in MCC950 (p < 0.05) with improved NDS (p < 0.05). Administration of MCC950 following ROSC mitigates post-resuscitation myocardial dysfunction and improves survival.

Cardiac arrest (CA) remains a major public health issue. Inflammatory responses with overproduction of interleukin-1β regulated by NLRP3 inflammasome activation play a crucial role in cerebral ischemia/reperfusion injury. We investigated the effects of the selective NLRP3-inflammasome inhibitor MCC950 on post-resuscitation cerebral function and neurologic outcome in a rat model of cardiac arrest. Thirty-six male rats were randomized into the MCC950 group, the control group, or the sham group (N = 12 of each group). Each group was divided into a 6 h non-survival subgroup (N = 6) and a 24 h survival subgroup (N = 6). Ventricular fibrillation (VF) was electrically induced and untreated for 6 min, followed by 8 min of precordial compressions and mechanical ventilation. Resuscitation was attempted with a 4J defibrillation. Either MCC950 (10 mg/kg) or vehicle was injected intraperitoneally immediately after the return of spontaneous circulation (ROSC). Rats in the sham group underwent the same surgical procedures without VF and CPR. Brain edema, cerebral microcirculation, plasma interleukin Iβ (IL-1β), and neuron-specific enolase (NSE) concentration were measured at 6 h post-ROSC of non-survival subgroups, while 24 h survival rate, neurological deficits were measured at 24 h post-ROSC of survival subgroups. Post-resuscitation brain edema was significantly reduced in animals treated with MCC950 (p < 0.05). Cerebral perfused vessel density (PVD) and microcirculatory flow index (MFI) values were significantly higher in the MCC950 group compared with the control group (p < 0.05). The plasma concentrations of IL-1β and NSE were significantly decreased in animals treated with MCC950 compared with the control group (p < 0.05). 24 h-survival rate and neurological deficits score (NDS) was also significantly improved in the MCC950 group compared with the control group (p < 0.05). NLRP3 inflammasome blockade with MCC950 at ROSC reduces the circulatory level of IL-1β, preserves cerebral microcirculation, mitigates cerebral edema, improves the 24 h-survival rate, and neurological deficits.

Brain mitochondria are more sensitive to global ischemia compared to heart mitochondria. Complex I in the electron transport chain (ETC) is sensitive to ischemic injury and is a major control point of the rate of ADP stimulated oxygen consumption. The purpose of this study was to explore whether changes in cerebral and myocardial mitochondria differ after cardiac arrest. Animals were randomized into 4 groups (n = 6): 1) Sham 2) VF 3) VF+CPR 4) ROSC 1hr. Ventricular Fibrillation (VF) was induced through a guide wire advanced from the right jugular vein into the ventricle and untreated for 8 min. Resuscitation was attempted with a 4J defibrillation after 8 min of cardiopulmonary resuscitation (CPR). Brain mitochondria and cardiac mitochondrial subpopulations were isolated. Calcium retention capacity was measured to assess susceptibility to mitochondrial permeability transition pore opening. ADP stimulated oxygen consumption and ETC activity assays were performed. Brain mitochondria are far more sensitive to injury during cardiac arrest and resuscitation compared to cardiac mitochondria. Complex I is highly sensitive to injury in brain mitochondria. With markedly decreased calcium retention capacity, mitochondria contribute to cerebral reperfusion injury. Therapeutic preservation of cerebral mitochondrial activity and mitochondrial function during cardiac arrest may improve post-resuscitation neurologic function.

背景与目的:创伤性肠破裂(TE)患者术后常可能伴发急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS),危及生命,因此,选择合适的早期预测及病情严重程度评估指标具有重要意义.本研究探讨外周血肺表面活性蛋白D(SP-D)、肺表面活性蛋白A(SP-A)、白细胞介素1β(IL-1β)动态监测对TE术后伴发ALI/ARDS的早期预测及病情评估价值.方法:回顾性分析2019年8月-2020年12月收治的78例TE患者的临床资料,其中52例术后未发生肺损伤组(对照组),15例术后发生ALI(ALI组),11例术后发生ARDS(ARDS组),分析三组患者的临床指标与外周血SP-D、SP-A、IL-1β水平的动态变化.通过受试者工作曲线(ROC)及相关性分析评判各观察指标对TE术后伴发ALI/ARDS的早期预测价值及病情严重程度评估效能.结果:各组患者年龄、性别、BMI、致伤因素、损伤部位、手术方式、手术时长及术中出血量差异无统计学意义(均P＞0.05),而机械通气时长、降钙素原(PCT)水平、肺损伤预测评分(LIPS)及肺损伤评分(LIS)在对照组、ALI组、ARDS组依次增加,而氧合指数在对照组、ALI组、ARDS组依次降低,差异均有统计学意义(均P＜0.05).术前及术后1、4、7d的SP-D、SP-A、IL-1β水平在ALI组、ARDS组依次且持续增高,除ALI组与ARDS组术后7d的SP-A水平差异无统计学意义外(P＞0.05),其余差异均有统计学意义(均P＜0.05).ROC曲线分析显示,SP-D、SP-A、IL-1β水平早期预测ALI/ARDS的曲线下面积(0.800、0.919、0.755/0.902、0.931、0.957)均高于 PCT(0.739/0.721)及 LIPS 评分(0.851/0.788),三者联合进行平行试验可提高预测ALI/ARDS的灵敏度至0.997/0.988,三者联合进行系列试验可提高预测ALI/ARDS的特异度至0.999/0.997.相关性分析提示,SP-D、SP-A、IL-1β三项指标与氧合指数均呈明显负相关(r=-0.504、-0.657、-0.717,均P＜0.01)、与LIS评分呈明显正相关(r=0.471、0.654、0.634,均 P＜0.01).结论:血清SP-D、SP-A、IL-1β检测对预测TE术后患者伴发ALI/ARDS及严重程度评估均具有一定价值,且三者联合应用预测和评估效能更高.

Background Epinephrine increases the rate of return of spontaneous circulation. However, it increases severity of postresuscitation myocardial and cerebral dysfunction and reduces duration of survival. We investigated the effects of aortic infused polyethylene glycol, 20 000 molecular weight (PEG‐20k) during cardiopulmonary resuscitation on coronary perfusion pressure, postresuscitation myocardial and cerebral function, and duration of survival in a rat model of cardiac arrest. Methods and Results Twenty‐four male rats were randomized into 4 groups: (1) PEG‐20k, (2) epinephrine, (3) saline control–intravenous, and (4) saline control–intra‐aortic. Cardiopulmonary resuscitation was initiated after 6 minutes of untreated ventricular fibrillation. In PEG‐20k and Saline‐A, either PEG‐20k (10% weight/volume in 10% estimated blood volume infused over 3 minutes) or saline was administered intra‐aortically after 4 minutes of precordial compression. In epinephrine and placebo groups, either epinephrine (20 μg/kg) or saline placebo was administered intravenously after 4 minutes of precordial compression. Resuscitation was attempted after 8 minutes of cardiopulmonary resuscitation. Sublingual microcirculation was measured at baseline and 1, 3, and 5 hours after return of spontaneous circulation. Myocardial function was measured at baseline and 2, 4, and 6 hours after return of spontaneous circulation. Neurologic deficit scores were recorded at 24, 48, and 72 hours after return of spontaneous circulation. Aortic infusion of PEG‐20k increased coronary perfusion pressure to the same extent as epinephrine. Postresuscitation sublingual microcirculation, myocardial and cerebral function, and duration of survival were improved in PEG‐20k (P<0.05) compared with epinephrine (P<0.05). Conclusions Aortic infusion of PEG‐20k during cardiopulmonary resuscitation increases coronary perfusion pressure to the same extent as epinephrine, improves postresuscitation myocardial and cerebral function, and increases duration of survival in a rat model of cardiac arrest.

基于中国急诊和临床学相关专业充分运用的模拟人教学模式,文章对模拟人教学产生的影响进行深入研讨,并以此来优化教学质量.将60名本校临床医学专业学生随机分为两组.对照组继续使用传统的教学模式也就是课堂教学,试验组选择新型模拟人的教学模式.试验后,对参与的学生发放了问卷调查.对两组的结论及反馈进行归纳,得出以下几点:一是激发学生的学习兴趣,二是提升学生的逻辑思维能力,三是解决问题能力,四是提升对基础知识的理解和应用.对教学模式的满意度评价,试验组明显高于对照组,两者差异具有统计学意义.

Bradley, Jennifer1; Ji, Xianfei2; Zheng, Guanghui1; Ge, Weiwei3; Xu, Jing3; Hu, Juntao3; He, Fenglian4; Peberdy, Mary5; Ornato, Joseph6; Chen, Qun7; Lesnefsky, Edward8; Tang, Wanchun9 Author Information

Tang, Wanchun; Zheng, Guanghui; He, Fenglian; Xu, Jing; Hu, Juntao; Ge, Weiwei; Ji, Xianfei; Mai, Helen; Bradley, Jennifer; Peberdy, Mary; Ornato, Joseph; Jiang, Longyuan; Wang, Tong; Toldo, Stefano Author Information

Objective: Previous studies have shown that abnormal expression of microRNA-184 leads to a variety of cancers, including pancreatic ductal adenocarcinoma, suggesting microRNA-184 as a new treatment target for pancreatic ductal adenocarcinoma. However, the molecular mechanism of microRNA-184 in pancreatic ductal adenocarcinoma remains unclear. It is important to investigate the effect and role of microRNA-184 in pancreatic ductal adenocarcinoma. Methods: The clinical and laboratory inspection data of 120 patients with pancreatic cancer admitted to the First Affiliated Hospital of Anhui Medical University were compared. MicroRNA-184 expression in tumor tissues and cells was evaluated using reverse transcription polymerase chain reaction. Flow cytometry and Annexin V/propidium iodide staining were performed to examine cell cycle and apoptosis. Western blotting analysis was conducted to measure the protein expression of p-PI3K, p-AKT, JNK1, C-Myc, C-Jun, caspase-9, and caspase-3. Results: MicroRNA-184 expression was low in patients with pancreatic ductal adenocarcinoma. Survival curve showed that patients with lower expression of microRNA-184 in tumor tissues had a worse prognosis and shorter survival time ( P < .05), and the multivariate analysis identified that microRNA-184 was an independent prognostic indicator ( P < .05). In vitro studies showed that microRNA-184 overexpression induced apoptosis and suppressed cell cycle transition from G1 to S and G2 phases in pancreatic ductal adenocarcinoma cells. Furthermore, molecular studies revealed that inhibition of microRNA-184 promoted the gene expression of p-PI3K, p-AKT, JNK1, C-Myc, and C-Jun compared with the control group. Overexpression of microRNA-184 led to significantly increased expression of caspase-9 and caspase-3 and significantly decreased expression of Bcl-2. Conclusion: This study suggests that microRNA-184 inhibits the proliferation and promotes the apoptosis of pancreatic ductal adenocarcinoma cells by downregulating the expression of C-Myc, C-Jun, and Bcl-2. Our verification of the role of microRNA-184 may provide a novel biomarker for the diagnosis, therapy, and prognosis of pancreatic ductal adenocarcinoma.

Tang, Wanchun; He, Fenglian; Ge, Weiwei; Zheng, Guanghui; Hu, Juntao; Liang, Lian; Li, Hui; Cheng, Cheng; Zhang, Liuzhi; Preetham, Devi; Moore, Christine; Bradley, Jennifer; Peberdy, Mary; Ornato, Joseph Author Information

Background: Sepsis is a systemic inflammatory response syndrome caused by severe infections. LDK378, a second-generation ALK inhibitor, exhibits a potential anti-inflammatory function against sepsis. Micro- and macro-circulatory dysfunctions are pivotal elements of the pathogenesis of severe sepsis and septic shock. We hypothesized that LDK378 can improve micro- and macro-circulation of septic rats, therefore improving the outcome of survival via blocking the ALK-STING pathway to attenuate inflammatory injuries. Methods: A septic rat model was established by the cecal ligation and puncture (CLP) method. A total of 60 rats were randomized into three groups: a sham group, CLP group, and CLP + LDK378 group (n = 20 in each group). Five rats were randomly selected from each group for the mechanism study; the remaining 15 rats in each group were involved in a survival curve examination. A sidestream dark field video microscope was used to record sublingual microcirculation and mean arterial pressure (MAP) and levels of inflammatory cytokine secretion were examined at 6 h, 30 h, and 54 h after CLP surgery. Expressions of TANK binding kinase 1 (TBK1) and its downstream targets were determined, and histological alterations to the heart, lungs, and kidneys were examined at 54 h after CLP surgery. Results: We found the group that received LDK378 treatment showed increased MAP levels compared to the CLP group at 30 h and 54 h. Meanwhile, LDK378 ameliorated the perfused small vessel density and microvascular flow index, decreased the expression of TNF-a and IL-6, and upregulated the expression of IL-10 in comparison with the CLP group. LDK378 injections also downregulated the expression of TBK1 and its downstream targets. Furthermore, LDK378 treatment significantly reduced sepsis-induced organ injuries, therefore improving survival rates. Conclusions: These findings demonstrate that LDK378 treatment can improve microcirculation and reduce organ injuries in CLP-induced septic rats via the regulation of inflammatory cytokine secretion and the downstream signaling components of the ALK-STING pathway.

Introduction: Neurologic and myocardial dysfunction after successful resuscitation is prominent and mitochondrial dysfunction is predicted to be a key determinant of poor outcomes. Mitochondria contribute a critical role as effectors and targets of reperfusion injury. However, the onset and severity of mitochondrial dysfunction during cardiac arrest (CA) is not fully understood. The present study was done to explore whether changes in cerebral and myocardial mitochondria differ after cardiac arrest and cardiopulmonary resuscitation (CPR). Hypothesis: Mitochondrial injury is more severe in the brain compared to the heart during and following cardiac arrest and CPR. Methods: Sprague-Dawley rats weighing between 450 - 550 g were randomized into 4 groups (n=6): 1) sham (surgery, no ventricular fibrillation (VF) or CPR), 2) VF (VF 8 mins, no CPR); 3) VF and CPR (VF 8 mins and CPR 8 mins, no defibrillation); ROSC 1 h (VF 8 mins, CPR 8 mins, defibrillation, and observe 1 h after ROSC). VF was induced through a guide wire advanced from the right jugular vein into the right ventricle. Brain and heart mitochondria were extracted by differential centrifugation and used to measure oxidative phosphorylation and calcium retention capacity (CRC). Results: Compared with sham, brain mitochondrial CRC in VF, VF+CPR and ROSC 1 h were decreased (110±11 vs. 70±13, 62±24, 50±6 nmol Ca 2+ /mg protein, p<0.05). However, the CRC of the heart mitochondria was decreased only 1 h after ROSC compared to sham (1000±150 vs. 1000±84, 993±78, 600±76 nmol Ca 2+ /mg protein). Brain mitochondrial oxidative phosphorylation with complex I substrate glutamate in VF, VF+CPR and ROSC 1 h were all decreased compared to sham (127 + 8 vs 92±17, 84±12, and 92±15, p<0.05). This contrasted myocardial mitochondria oxidative phosphorylation which had no impairment (324±3 vs 338±46, 379±29, and 323±45). Conclusions: Mitochondria in the brain are more sensitive to injury during CA and CPR compared to heart mitochondria. With markedly decreased CRC, mitochondria are likely to contribute to cerebral reperfusion injury during CPR and ROSC. Preservation of cerebral mitochondrial activity and mitochondrial function during cardiac arrest may improve post-resuscitation neurological function.

Introduction: Epinephrine is the primary drug given during cardiopulmonary resuscitation (CPR), when given early, to reverse cardiac arrest (CA) by stimulation of α-adrenergic receptors in vascular smooth muscle. This increases coronary perfusion pressure (CPP) and increases rate of return of spontaneous circulation (ROSC). However, the use of epinephrine is not associated with a significant difference in long-term survival or favorable neurologic outcome when given late after arrest onset. In the present study, we compared the effects of aortic injection of polyethylene glycol-20k (PEG-20k) vs. epinephrine during CPR on CPP and postresuscitation myocardial and cerebral function in a rat model of CA. Hypothesis: Aortic injection of PEG-20k during CPR will increase CPP to the same extent as epinephrine without adversely affecting post-resuscitation myocardial and cerebral function. Methods: Twenty four male Sprague-Dawley rats weighing between 450-550 g were randomized into four groups: 1) PEG-20k 2) epinephrine 3) saline placebo 4) saline-intra-aorta (IA). Eight minutes of CPR was initiated after 6 minutes of untreated ventricular fibrillation. PEG-20k IA (10% est. total blood volume [1.8ml]), saline IA, saline IV or epinephrine IV (20ug/kg) was given after 4 minutes of CPR by continuous infusion over 3 minutes. CPP was recorded continuously and resuscitation was attempted with 4 Joule defibrillation. Myocardial function was measured at baseline, 2, 4, and 6 hours after ROSC by echocardiography and neurologic deficit scores (NDS) were recorded at 24, 48, and 72 hours after ROSC. Results: In both saline groups, CPP did not change. However, aortic injection of PEG-20k increased CPP significantly to the same extent as epinephrine (Fig 1). Post-resuscitation ejection fraction was significantly greater in PEG-20k compared to epinephrine (64 + 1 vs 45 + 3, p<0.05) and NDS was significantly improved in PEG-20k compared to epinephrine (100 + 50 vs 450 + 50, p<0.05).