Inhibition of heparin/protamine complex-induced complement activation by Compstatin in baboons

Complement activation products are major components of the inflammatory response induced by cardiac surgery and cardiopulmonary bypass which contribute to postoperative organ dysfunction, fluid accumulation, and morbidity. Activation of the complement system occurs during extracorporeal circulation, during reperfusion of ischemic tissue, and after the formation of heparin-protamine complexes. In this study we examine the efficacy of Compstatin, a recently discovered peptide inhibitor of complement, in preventing heparin/protamine-induced complement activation in baboons. The study was performed in baboons because Compstatin binds to baboon C3 and is resistant to proteolytic cleavage in baboon blood (similar to humans); Compstatin inhibits only the activation of primates' complement system. After testing various doses and administration regimens, Compstatin produced complete inhibition at a total dose of 21 mg/kg when given as a combination of bolus injection and infusion. Compstatin completely inhibited in vivo heparin/protamine-induced complement activation without adverse effects on heart rate or systemic arterial, central venous, and pulmonary arterial pressures. This study indicates that Compstatin is a safe and effective complement inhibitor that has the potential to prevent complement activation during and after clinical cardiac surgery. Furthermore, Compstatin can serve as the prototype for designing an orally administrated drug.     

Fatty acid synthesis in the arrested rabbit heart during ischemia

In rabbit hearts arrested by a carnosine-buffered cardioplegic solution the incorporation of [1-¹⁴C]acetate into lipids was investigated. After 10–20 and 60 min of ischemia the radioactivities of phospholipids, mono-, di-, and triacylglycerols, acyl-CoA, acylcarnitine, and free fatty acids were determined. In the first period of ischemia mainly acylcarnitine was labelled (ca. 50%) and only 25% of [¹⁴C]-activity was found in phospholipids which showed the lowest specific activity of all lipid classes. After 60 min of ischemia the percentage of total radioactivity of acylcarnitine and phospholipids was decreased, whereas that of neutral lipids was increased to more than 50%. During the increase of total radioactivity the relative specific activity of all lipids decreased except that of triacylglycerols. Only fatty acids up to chain lengths of 16 carbon atoms were labelled. Lauric and myristic acid had high specific activities. These results indicated de novo synthesis of fatty acids accumulating in triacylglycerols during ischemia of the arrested heart.     

Cell cycle arrest of human gingival fibroblasts and periodontal ligament cells by Actinobacillus actinomycetemcomitans: involvement of the cytolethal distending toxin

The cytolethal distending toxin (Cdt) is produced by several Gram-negative bacterial species and causes growth arrest and morphological alterations in mammalian cells. Actinobacillus actinomycetemcomitans, which is involved in the pathogenesis of localized aggressive periodontitis, also produces a Cdt that affects periodontal connective tissue cells. The aim of this study was to investigate in which phase of the cell cycle these cells are arrested and enlarged when challenged with A. actinomycetemcomitans, and to evaluate the involvement of its Cdt. Human gingival fibroblasts and periodontal ligament cells were challenged with A. actinomycetemcomitans extract, or with purified Cdt, and cell cycle analysis was performed by propidium iodide staining and flow cytometry. Cells exposed to an A. actinomycetemcomitans wild-type strain, or to purified Cdt, were arrested in both G1 and G2/M phases, and appeared enlarged compared to the corresponding controls. The cellular enlargement occurred in both G1 and G2/M arrested cells. In contrast, cells exposed to an A. actinomycetemcomitans cdt-knockout mutant strain showed cell cycle phase distribution and size similar to the controls. In conclusion, A. actinomycetemcomitans causes a combined G1 and G2/M growth arrest and enlargement in periodontal connective tissue cells, which is attributed to its Cdt.     

线粒体ATP敏感性钾通道参与超极化停搏的心肌保护作用

目的：探讨线粒体ATP敏感性钾通道（mitoKATP）开放在超极化停搏心肌保护中的作用机制。方法:将SD大鼠随机分为对照组（Control）、去极化停搏组（D）、超极化停搏组（H）、5-羟葵酸(5-HD) +去极化停搏组（5HD+D）、5-HD+超极化停搏组（5HD+H），每组8例。建立Langendorff灌注模型，平衡20 min，以不同方式停搏40 min，再灌注30 min，对比观察：(1)不同时间血流动力学变化；(2)再灌注末取心肌并分离、制备线粒体，电镜观察超微结构的变化。(3)平衡末、再灌注末线粒体活性氧的产生。结果: (1)各组再灌注末大鼠心脏功能明显低于平衡末, 心肌线粒体超微结构均遭受不同程度损伤，左室发展压（LVDP）、左室舒张末压（LVEDP）、率压双乘积（DP）、冠脉流量（CF）有显著差异（P<0.01）；（2）超极化停博组再灌注末心脏功能指标LVDP、LVEDP、DP、CF明显优于去极化停博组、5-HD+超极化停搏组、5-HD+去极化停搏组、对照组（P<0.01），电镜示：心肌、线粒体超微结构遭受的损伤较轻; (3)超极化停博组再灌注末心肌线粒体活性氧产生率低于对照组与其它3组（P<0.01）。结论:(1)超极化停搏能明显改善再灌注后心功能，保护心肌、线粒体超微结构，减少活性氧生成；(2)mitoKATP的早期开放参与超极化停搏，其作用可能通过保护再灌注后的线粒体呼吸功能，减轻线粒体的氧化损伤，为再灌注心肌提供较好的能量供应，从而使缺血再灌注后的心脏收缩功能得到一定恢复。     

Hypotensive brain stem necrosis in a stillborn

Summary Hypotensive brain stem necrosis is reported in a stillborn. Additional postmortem findings included evidence of intrauterine distress, shock, and a pure blood culture of group B -hemolytic streptococci. These findings suggest group B -hemolytic streptococcal sepsis in utero, with a subsequent episode of transitory circulatory failure prior to intrauterine demise.     

The Application of Creatine Supplementation in Medical Rehabilitation

Numerous health conditions affecting the musculoskeletal, cardiopulmonary, and nervous systems can result in physical dysfunction, impaired performance, muscle weakness, and disuse-induced atrophy. Due to its well-documented anabolic potential, creatine monohydrate has been investigated as a supplemental agent to mitigate the loss of muscle mass and function in a variety of acute and chronic conditions. A review of the literature was conducted to assess the current state of knowledge regarding the effects of creatine supplementation on rehabilitation from immobilization and injury, neurodegenerative diseases, cardiopulmonary disease, and other muscular disorders. Several of the findings are encouraging, showcasing creatine’s potential efficacy as a supplemental agent via preservation of muscle mass, strength, and physical function; however, the results are not consistent. For multiple diseases, only a few creatine studies with small sample sizes have been published, making it difficult to draw definitive conclusions. Rationale for discordant findings is further complicated by differences in disease pathologies, intervention protocols, creatine dosing and duration, and patient population. While creatine supplementation demonstrates promise as a therapeutic aid, more research is needed to fill gaps in knowledge within medical rehabilitation.     

体外循环心内直视手术后左室破裂抢救成功4例

目的：报告4例体外循环心内直视手术后左室破裂修补成功病例,方法：4例心内直视手术后发生左室自发性破裂,再次体外循环阻断主动脉,两条长涤纶补片距裂口10mm处全层修补后,加用组织生物胶和止血纱布覆盖创面,其中1例加用自身心包补片修补。结果：4例病人均修补止血成功,3例康复出院,1例水后第10天因肾功能衰竭而死亡。结论：左室破裂是心脏手术后的严重的并发症,用长涤纶补片距裂口10mm处修补,外盖自身心包补片加固,并加用组织生物胶,止血纱布粘固是一种有效的修补方法。     

Potent antioxidative potential of propofol during cardiopulmonary bypass in the adult

Summary The potent antioxidative potential of propofol during cardiopulmonary bypass (CPB) in adults was investigated. The selected 30 patients receiving open heart surgery under CPB were randomly divided into group A and group B. The patients in the group A and group B were given propofol (0. 1 mg. kg⁻¹, min⁻¹ and fentanyl (5 μg. kg⁻¹, min⁻¹) respectively to maintain anesthesia after aorta was cross-clamped. Blood samples were drawn pre-anesthesia, pre-CPB, at 30 min of CPB, at the end of CPB, at 1 h after CPB, at the end of operation, at 12 and 24 h postoperatively. RBC suspension was prepared and erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) and phosphofructokinase (PFK) activities, total erythrocyte reduced glutathione (GSH) and oxidized GSH (GSSG) were assayed and GSH/GSSG ratio was calculated. In the group A, G-6-PD and PFK activities and GSH/GSSG ratio were almost uneventfully during CPB and postoperatively. In the group B, G-6-PD activity was increased and PFK activity and GSH/GSSG ratio decreased significantly from 30 min of CPB until 12 h postoperatively. It was demonstrated that propofol could obviously attenuate free radical activity during CPB, while fentanyl has no effect on free radical reduction. Propofol could be beneficial as an anesthetic in patients presenting pathologies associated with free radical reactions during CPB. This project was supported partly by a grant from National Natural Sciences Foundation of China (No. 39270660).     

体外循环时心肌细胞上ICAM-1的变化及抑肽酶对其表达的影响

为观察心脏瓣膜置换术病人在CPB前后心肌上ICAM-1的表达,并探讨抑肽酶对其表达的影响,选择择期心脏瓣膜替换术病人20例,随机分为抑肽酶组和对照组,各10例。分别于手术开始及结束时取右心房心肌标本,采用免疫组化法检测心肌细胞及心肌血管内皮细胞上ICAM-1的表达,以测得ICAM-1积分光密度值（IOD值）进行分析。结果心脏瓣膜替换术病人CPB后心肌细胞上ICAM-1的表达较术前有明显增加（P<0.05）,而在抑肽酶组则无明显变化。组间比较,差异具有显著意义,P<0.05。在对照组,心肌血管EC上ICAM-1在CPB后表达明显增加（P<0.05）,而抑肽酶组,差异无显著性。组间比较,P<0.05。认为CPB时心肌细胞及心肌血管EC上ICAM-1的表达增高,ICAM-1可能参与CPB时心肌的炎症损伤,抑肽酶可以通过抑制ICAM-1的表达而减轻CPB所致的炎症反应。     

Surgical management of a pulsatile chest wall mass secondary to an ascending aortic aneurysm in a patient with bovine arch

Ascending aortic pseudoaneurysms are rare, but life‐threatening conditions, that often require intervention. While endovascular techniques have advanced significantly, the majority of these clinical scenarios preclude endovascular options and the primary treatment modality remains open surgical repair. Repair of an aortic pseudoaneurysm eroding through the sternum resulting in a pulsatile chest wall mass is technically challenging. We report the successful repair of a large ascending aortic pseudoaneurysm in a 62‐year‐old male with bovine arch anatomy and prior Type A dissection repair, presenting with contained rupture and a pulsatile chest wall mass.