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Objective

Hypertonic saline (HTS) has potent immune and vascular effects. We assessed recipient pretreatment with HTS on allograft function in a porcine model of heart transplantation and hypothesized that HTS infusion would limit endothelial and left ventricular (LV) dysfunction following transplantation.

Methods

Heart transplants were performed after 6 hours of cold ischemic storage. Recipient pigs were randomized to treatment with or without HTS (7.5% NaCl) before cardiopulmonary bypass (CPB). Using a myograft apparatus, coronary artery endothelial-dependent (Edep) and -independent (Eind) relaxation was assessed. LV performance was determined using pressure-volume loop analysis. Pulmonary interleukin (IL)-2, IL-6, and tumor necrosis factor (TNF)-α expression was measured.

Results

Weaning from CPB and LV performance after transplantation were improved in HTS-treated animals. Successful weaning from CPB was greater in the HTS-treated hearts (8 of 8 vs 2 of 8; P < .05). Mean LV functional recovery was improved in the HTS-treated animals, as assessed by preload recruitable stroke work (65 ± 10% vs 27 ± 10%; P < .001) and end-systolic elastance (55 ± 7% vs 37 ± 4%; P < .001). Treatment with HTS resulted in improved Edep (mean maximum elastance [Emax], 56 ± 5% vs 37 ± 7%; P < .001) and Eind (mean Emax%, 77 ± 6% vs 52 ± 4%; P < .001) vasorelaxation compared with control. Pulmonary expression of IL-2, IL-6, and TNF-α increased following transplantation, whereas HTS therapy attenuated IL production (P < .001). Transplantation increased plasma TNF-α levels and LV TNF-α expression, whereas HTS prevented this up-regulation (P < .001).

Conclusions

Recipient HTS pretreatment preserves allograft vasomotor and LV function, and HTS therapy limits CPB-induced injury. HTS may be a novel recipient intervention to prevent graft dysfunction.  相似文献   
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目的:建立液相色谱-串联质谱法(UPLC-MS/MS)同时测定人血浆中头孢哌酮与舒巴坦的浓度,分析头孢哌酮/舒巴坦血药浓度监测结果,为临床合理用药提供参考。方法:以氯唑沙宗为内标,采用Waters BEHC18柱(2.1 mm×100 mm,1.7 μm)进行分离,通过串联质谱仪,负离子检测模式下,以多反应监测(MRM)方式进行定量测定。对某院2018年以不同给药方案进行治疗的73例住院患者测定的头孢哌酮/舒巴坦血药浓度结果进行分析。结果:头孢哌酮与舒巴坦在测定条件下1~200 mg·L-1范围内线性关系良好,两者日内精密度RSD均<10%,基质效应分别为(72.77±0.99)%与(75.72±0.11)%,提取回收率均>90%。73例患者共监测血药浓度96次,其中不同给药方案2 g,q8 h(43例次);2 g,q12 h(26例次);2 g,q6 h(27例次),各组头孢哌酮血药浓度的中位数分别为34.12 mg·L-1(4.12~177.79 mg·L-1)、31.23 mg·L-1(1.89~251.8 mg·L-1)、59.96 mg·L-1(1.77~140.58 mg·L-1),舒巴坦血药浓度的中位数分别为6.3 mg·L-1(0.61~136.01 mg·L-1)、28.83 mg·L-1(0.5~133.69 mg·L-1)、11.17 mg·L-1(0.73~143.53 mg·L-1)。Mann-Whitney U检验显示,头孢哌酮血药浓度结果无统计学差异(P>0.05),舒巴坦有统计学差异(P<0.05)。结论:本检测方法操作简便、快速、重复性好,可满足临床头孢哌酮与舒巴坦浓度的检测;头孢哌酮/舒巴坦在不同给药方案下血药浓度结果与个体差异相关,有必要开展血药浓度监测并依据结果适时调整用药方案,提高治疗效果减少耐药率的发生。  相似文献   
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This study aimed at evaluating how encapsulation in a regular nanocarrier (NC) (providing extended circulation time) or in a brain-targeting NC (providing prolonged circulation time and increased brain uptake) may influence the therapeutic index compared with the unformulated drug and to explore the key parameters affecting therapeutic performance using a model-based approach. Pharmacokinetic (PK) models were built with chosen PK parameters. For a scenario where central effect depends on area under the unbound brain concentration curve and peripheral toxicity relates to peak unbound plasma concentration, dose-effect and drug-side effect curves were constructed, and the therapeutic index was evaluated. Regular NC improved the therapeutic index compared with the unformulated drug due to reduced peripheral toxicity, while brain-targeting NC enhanced the therapeutic index by lowering peripheral toxicity and increasing central effect. Decreasing drug release rate or systemic clearance of NC with drug still encapsulated could increase the therapeutic index. Also, a drug with shorter half-life would therapeutically benefit more from a NC encapsulation. This work provides insights into how a NC for brain delivery should be optimized to maximize the therapeutic performance and is helpful to predict if and to what extent a drug with certain PK properties would obtain therapeutic benefit from nanoencapsulation.  相似文献   
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目的 分析重症医学科PBL教学法在临床心肺复苏术教学中的应用效果.方法 本次实验的开展基础数据选择2016年9月—2018年7月进入医院重症医学科实习学生64例,按照学生自身意愿以及学校安排将参与实验学生分为均数相同的两个小组(对照组、观察组),每组实验人数均为32例,其中对照组(n=32)采用传统教学方法 ,观察组(n=32)则应用PBL教学法教学,对比两组学生在学期结束后整体的学习质量情况和教学满意率.结果 观察组学生经过测试后理论知识和专业技能得分均对比对照组更高,教学效果更加理想,观察组学生对于教学的满意率评价更高,P<0.05.结论 重症医学科临床心肺复苏术教学中应用PBL教学法,将理论与实践进行结合,对教学方法 进行改进,全面提升学生的思维理解能力,培养良好的动手能力,促进理论教学与实践的结合,为学生以后的职业生涯提供更加理想的条件.  相似文献   
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Serum eye drops (SED) have shown beneficial effects in patients suffering from dry eye syndrome and are manufactured for an increasing number of patients in Australia every year. Previous studies have examined the stability of serum growth factors during storage in either experimental vessels not used as the final packaging system or in eye drop bottles. To ensure the quality and safety of SED product manufactured in Australia, the stability of growth factors in serum packaged into two different systems during storage at different temperatures was examined. Healthy blood donors provided a whole blood donation, from which serum was prepared, diluted to 20% and dispensed into either a tube or a vial packaging system. The stability of growth factors, fibronectin and total protein in tube segments was comparable to matched vials samples during storage at −30 °C, 4 °C, 22 °C and 37 °C, with the exception of EGF and fibronectin in 20% SED stored in tube segments, which were more sensitive to storage conditions at 4 °C and 22 °C when compared to vials. Additionally, the growth factor, fibronectin and total protein concentration in both tube segments and vials was stable during storage at −30 °C for at least 9 months. This study highlights the impact of different manufacturing procedures on serum growth factor stability during storage.  相似文献   
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