Combination of Fibrin Glue with Growth Hormone Augments Healing of Incomplete Intestinal Anastomoses in a Rat Model of Intra-Abdominal Sepsis: A Dynamic Study

This study was devised to investigate whether fibrin glue (FG) in combination with growth hormone (GH) could have a beneficial effect at a late period (14 days) after injury. Male Wistar rats, with abdominal sepsis induced by an incomplete anastomosis, were divided into three groups. In the control group, the rats got incomplete anastomoses sutured alone; in the FG and FG/GH groups, anastomoses protection was performed with application of FG alone or in combination with GH. The anastomotic bursting pressure (ABP) was significantly higher in the FG/GH group than that of the FG group on postoperative day (POD) 5 (p <. 01), while it could not be measured from POD 7 to POD 14 because of intestinal dehiscence. There was no difference between FG and FG/GH group on POD 3 and POD 5 in anastomotic tensile strength, which was significantly higher in the FG/GH group than that of the FG group from POD 7 to POD 14 (p <. 001). Hydroxyproline content of the FG/GH group was significantly higher than that of the control from POD 3 and that of the FG group from POD 5 (p <. 05). Combination of FG with GH had a synergistic effect to improve intestinal anastomotic healing over a limited 14-day course of observation.     

Effect of 5-Fluorouracil plus Interferon on the Integrity of Colonic Anastomoses Covering with Fibrin Glue

Background It has been well established that the immediate postoperative intraperitoneal administration of chemotherapeutic agents such as 5-fluorouracil (5-FU) after curative colon resection for colon cancer destroys disseminated cancer cells and inhibits micrometastases but also inhibits anastomotic healing. On the other hand, the application of fibrin glue constitutes a physical barrier around the anastomosis and may prevent anastomotic leakage. The purpose of this experimental study was to determine the effect of 5-FU plus interferon (IFN)-α-2a on the integrity of colonic anastomoses covered with fibrin glue when injected intraperitoneally immediately after colon resection. Materials and Methods Sixty rats were randomized to one of four groups. After resection of a 1-cm segment of the transverse colon, an end-to-end sutured anastomosis was performed. Rats of the control and the fibrin glue groups were injected with 6 ml of 0.9% sodium chloride (NaCl) solution intraperitoneally. Rats in the 5-FU + IFN and the 5-FU + IFN + fibrin glue groups received 5-FU plus IFN intraperitoneally. The colonic anastomoses of the rats in the fibrin glue and in the 5-FU + IFN + fibrin glue groups were covered with fibrin glue. All rats were sacrificed on the 8th postoperative day, and the anastomoses were examined macroscopically. The bursting pressure measurements were recorded, and the anastomoses were graded histologically. Results Only the 5-FU + IFN group had anastomoses rupture, and the rupture rate (33%) in this group was significantly greater than in the other groups, where there were no ruptures (P = 0.015). The adhesion formations score was, on average, significantly higher in rats of the 5-FU + IFN group compared with the control group (P = 0.006) and the 5-FU + IFN + fibrin glue group (P = 0.010). Bursting pressures were significantly lower in the control group when compared to the fibrin glue and 5-FU + IFN + fibrin glue group (P < 0.001). Rats in the 5-FU + IFN + fibrin glue group developed significantly more marked neoangiogenesis than rats in the other groups. Inflammatory cell infiltration, collagen deposition, and fibroblast activity did not differ significantly among the four groups (P = 0.856, P = 0.192 and P = 0.243, respectively). Conclusion The immediate postoperative intraperitoneal administration of 5-FU plus IFN impairs colonic healing. However, when the colonic anastomoses were covered with fibrin glue, the injection of 5-FU plus IFN had no adverse effects on the integrity of the anastomoses.     

生长激素减轻梗阻性黄疸时肠菌及内毒素移位的实验研究

目的　探讨生长激素减轻梗阻性黄疸时肠细菌及内毒素移位的作用及其机理。方法　将 60只大鼠随机均分为假手术组 (SO组 )、梗阻性黄疸组 (OJ组 )及生长激素组 (rhGH组 ) ,rhGH组每天皮下注射Saizen 0 .75u/kg ,SO组及OJ组则用等量生理盐水作对照。检测各组血内毒素水平 ,并取腹水、血及肠系膜淋巴结、肝脏、肾脏和脾脏作细菌培养 ,同时测定末段回肠之粘膜厚度及绒毛高度。结果　OJ组血内毒素值为 (0 .77± 0 .0 3 )u/ml,较rhGH组的 (0 .40±0 .0 2 )u/ml明显增高 (P <0 .0 1) ,rhGH组接近SO组的 (0 .3 3± 0 .0 3 )u/ml水平。OJ组细菌移位率为 5 8.8% ,较rhGH组 (10 .0 % )明显增高 (P<0 .0 1) ,rhGH组与SO组 (0 )比较 ,P>0 .0 5。rhGH组绒毛高度为 (2 3 7.5 2± 13 .65 ) μm ,较OJ组的(183 .3 9± 11.0 9) μm明显增高 (P<0 .0 1) ;rhGH组粘膜厚度为 (3 2 0 .81± 14 .3 4) μm ,较OJ组的 (2 5 5 .62± 16.5 8) μm增厚(P <0 .0 1)。结论　生长激素对肠粘膜屏障具有明显的保护作用 ,可有效减轻梗阻性黄疸时肠菌及内毒素的移位。     

Repair of the Aortic Arch with Fibrin Glue in Type A Aortic Dissection

Location of the intimal tear in the aortic arch in type A aortic dissection is for many authors an indication for replacement of the aortic arch, but this operation has a high in-hos-pitai mortality rate: 20% to 40%. Instead, we suggest repairing the aortic arch by injecting fibrin glue, which contains a human sealer protein concentrate, between the two dissected layers under circulatory arrest while replacing the ascending aorta. To evaluate this technique, we reviewed 45 successive patients operated on for type A acute aortic dissection between January 1989 and July 1993, of which 6 had the intimal tear located on or extending into the aortic arch. Mean age was 71 ± 4.2 years (range 68 to 74). After proximal supracoronary anastomosis with a collagen-impregnated graft, aortic arch repair was achieved by injecting fibrin glue between the two layers, using circulatory arrest at a mean temperature of 22°C, with a mean duration of 24 minutes. This obliterated the dissection in the arch and also the intimal flap. The distal part of the graft was then anastomosed to the proximal portion of the aortic arch at the origin of the innominate artery under circulatory arrest. There were no early or late deaths. All patients were asymptomatic at a mean follow-up of 2.6 years. Follow-up angloscan showed obliteration of the dissection in the aortic arch in all patients; there were two patients with dilatation of the distal aortic arch of 40 and 45 mm. These results suggest that repair of the aortic arch with fibrin glue facilitates surgery, reduces operative time, and has a lower mortality rate than aortic arch replacement. The risk of possible reoperatlon for arch replacement Is largely balanced by the good immediate and late results reported here. (J Card Surg 1994;9:734–739)     

Experimental Study on the Viscosity and Adhesive Performance of Exogenous Liquid Fibrin Glue

Exogenous fibrin glue (FG) is highly suitable for neurosurgical procedures, because of its viscosity and adhesive properties. Several FGs are commercially available, but only few reports detail their differences. In the present study, we investigated the viscosity and adhesive performance of two types of FG: one is derived from blood donated in Europe and the United States (CSL Behring''s Beriplast^®, BP) and the other is derived from blood donated in Japan (the Chemo-Sero-Therapeutic Research Institute''s Bolheal^®, BH). The viscosity test that measured fibrinogen viscosity revealed that BP had significantly higher viscosity than BH. Similarly, the dripping test showed that BP traveled a significantly shorter drip distance in the vertical direction than BH, although the transverse diameter of the coagulated FG did not differ statistically significantly. In the tensile strength test, BP showed superior adhesion performance over BH. The histological study of the hematoxylin-eosin-stained specimens in both groups showed favorable adhesion. Although further studies are required on its manufacturing and usage methods, FG shows differences in viscosity and adhesive performance according to the blood from which it is derived. We conclude that it is desirable to select the type and usage method of FG according to the characteristics of the surgical operation in question. Our findings suggest that FG produced from the blood donated in Europe and the United States might be more suitable for use in surgical procedures that demand an especially high degree of viscosity and rapid adhesive performance.     

Efficacy of a Pedicled Pericardial Fat Pad Fixed with Fibrin Glue on Postoperative Alveolar Air Leakage

The purpose of this randomized trail was to investigate the effect of using a pedicled pericardial fat pad fixed with fibrin glue on postoperative alveolar air leakage. Thirty consecutive patients with lung cancer, who had moderate alveolar air leaks after pulmonary resection, were randomized into two groups: in group A fibrin glue was applied onto the surface of the leaking raw lung and in group B, after applying fibrin glue in the same manner as in group A, a pedicled pericardial fat pad was immediately fixed to the leaking lung surface with fibrin glue. The duration of the postoperative air leakage and chest tube drainage was recorded. In 6 of 15 patients in group B the air leakage ceased within the first 24 h after pulmonary resection, while in group A only 1 of 15 patients showed a cessation of the air leakage, and a significant difference was noticed between the two groups (P = 0.0309). The duration of the postoperative air leakage was 4.8 ± 4.6 days in group A and 3.6 ± 3.4 days in group B. The pedicled pericardial fat pad fixed onto the surface of the leaking raw lung using fibrin glue was found to reduce alveolar air leakage after pulmonary resection. Received: January 11, 2001 / Accepted: September 11, 2001     

生物蛋白胶预防鸡趾鞘管区屈肌腱粘连的实验研究

目的 研究生物蛋白胶预防鸡趾鞘管区屈肌腱粘连的作用。方法 种禽褐鸡60只，随机分为生物蛋白胶组（FG）和生理盐水组（NS），每组各30只动物。将第三、四趾趾深屈肌腱切断，作改良Kessler法缝合，不修复腱鞘，然后在腱鞘内肌腱周围及皮下按分组注入相应药物。术后第2、4、6周取材，分别进行大体观察、组织学检查、生物力学测定。结果 术后2、4、6周，组织学检查示两组动物肌腱吻合处的炎症细胞浸润情况及肌腱的愈合进程无明显差别。缝合处粘连半定量评分、将肌腱拉出鞘管所需最大力量、耗功，FG组与NS组相比，差异均无显性意义（P＞0．05）。结论 局部应用FG不能有效预防术后肌腱粘连，但不影响肌腱的愈合进程，也不引起额外的炎症反应。     

Effect of Peritoneal Lavage with Taurolidine on Primary Colonic Anastomosis in a Rat Model of Secondary Peritonitis

Purpose The reported antibacterial, antiendotoxic, and antiadhesive effects of taurolidine prompted us to study the benefits of intraperitoneal lavage with taurolidine on primary colonic anastomosis in a rat model of secondary peritonitis. Methods We induced peritonitis in 40 rats by injecting Escherichia coli isolate intraperitoneally. We performed colonic resection and primary anastomosis 5 h later, after lavage with either taurolidine or saline solution. After the rats were killed, on postoperative day (POD) 3 (n = 10) or 7 (n = 10), we measured the bursting pressures and hydroxyproline levels, then examined the resected specimens histologically. Results Bursting pressures and tissue hydroxyproline levels were significantly higher in the taurolidine group than in the control group on PODs 3 and 7 (P < 0.05). Histopathological examination revealed significantly higher fibroblastic activity in the taurolidine group. Conclusions The higher bursting pressures and tissue hydroxyproline levels in the rats given taurolidine showed the positive effect of taurolidine on anastomotic strength in secondary peritonitis. Taurolidine is a novel antibiotic with both antibacterial and antiendotoxic effects. Intraperitoneal lavage with taurolidine solution may reduce the risks associated with performing primary colonic anastomosis in patients with secondary peritonitis.     

Intestinal and Cerebral Oxygenation during Severe Isovolemic Hemodilution and Subsequent Hyperoxic Ventilation in a Pig Model

Background: During severe isovolemic hemodilution, determination of critical hematocrit levels for the microvascular oxygenation of different organs might provide more insight into the effect of the redistribution of blood flow and oxygen delivery on the oxygenation of different organs. The effect of an increased amount of dissolved oxygen on tissue oxygenation during severely decreased hematocrit levels is not clear.

Methods: Fifteen anesthetized pigs were randomized between an experimental group (n = 10), in which severe isovolemic hemodilution was performed with 6% hydroxyethylstarch (1:1), and a time-matched control group (n = 5). Systemic, intestinal, and cerebral hemodynamic and oxygenation parameters were monitored. Microvascular oxygen partial pressure ([mu]Po2) was measured in the cerebral cortex and the intestinal serosa and mucosa, using the oxygen-dependent quenching of Pd-porphyrin phosphorescence. In the final phase of the experiment, fraction of inspired oxygen was increased to 1.0.

Results: Hemodilution decreased hematocrit from 25.3 +/- 3.0 to 7.6 +/- 1.2% (mean +/- SD). Systemic and intestinal oxygen delivery fell with the onset of hemodilution; intestinal oxygen consumption deceased at a hematocrit of 9.9%, whereas the systemic oxygen consumption decreased at a hematocrit of 7.6%. During hemodilution, the intestinal and cerebral oxygen extraction ratios increased from baseline with 130 and 52%, respectively. Based on the intersection of the two best-fit regression lines, determined by a least sum of squares technique, similar critical hematocrit levels were found for systemic oxygen consumption and the cerebral and intestinal mucosa [mu] Po2; the intestinal serosa [mu]Po2 decreased at an earlier stage (P < 0.05). Hyperoxic ventilation improved the [mu]Po2 values but not systemic or intestinal oxygen consumption.     

Role of Fibrin Glue as a Sealant to Esophageal Anastomosis in Cases of Congenital Esophageal Atresia with Tracheoesophageal Fistula

Objective The aim of this study was to characterize a successful approach for the management of infants with long-gap esophageal atresia (EA) with tracheoesophageal fistula (TEF). The goal was to preserve the native esophagus and minimize the incidence of esophageal anastomotic leaks using fibrin glue as a sealant over the esophageal anastomosis. Method A total of 52 patients were evaluated in this study. Only patients in whom, gap between the two ends of the esophagus was ≥ 2 cm were selected during January 2005 to January 2007. Patients were divided in two groups on the basis of block randomization. Group A comprised the patients in whom fibrin sealant was used as reinforcement on a primary end-to-end esophageal anastomosis; in group B, fibrin glue was not used. The two groups were compared in terms of esophageal anastomotic leak (EL), postoperative esophageal stricture (ES), and mortality. The statistical analysis was done using Fisher’s exact test and the chi-squared test. Result The number of anastomotic leaks in group A (glue group) was about one-fifth that in group B (no glue group). The incidence of ES was almost twice as high in group B as in group A. The mortality rate was almost threefold higher in group B (no-glue group). The higher incidence of EL and ES in group B compared to group A was statistically significant. Conclusion Thus, fibrin glue when used as an adjunct to esophageal anastomosis for primary repair of long-gap EA with TEF appears safe in the clinical setting and may lower the chances of esophageal leak and anastomosis-site strictures. Hence, it can diminish the mortality and morbidity of these patients.     

限制性液体复苏对失血性休克大鼠肠损伤的影响

目的 研究不同剂量液体复苏对失血性休克大鼠肠损伤及肠黏膜通透性的影响。方法 将72只SD大鼠随机分成4组（n=18）：高剂量液体复苏组（HLR组）、中剂量液体复苏组（MLR组）、低剂量液体复苏组（LLR组）及未复苏组（Sham组）,前3组的液体复苏剂量分别为45、30和15 mL / （kg · h）。复苏后检测所有大鼠肠黏膜的通透性。于复苏后24、48及72 h,均分别抽取6只大鼠检测动脉血中乳酸和静脉血中肿瘤坏死因子-α （TNF-α）的水平,测量肠湿/干重比,进行小肠组织病理学检查并评分。结果 复苏后,HLR组的肠黏膜通透性高于其余3组（P＜0.05）。复苏3～8 h内,Sham组的所有大鼠均死亡,而其余3组大鼠均存活。术后24 h时LLR组的乳酸水平低于其余2组（P＜0.05）;HLR组的TNF-α水平在术后24、48及72 h均高于其余2组（P＜0.05）,在48 h时,LLR组低于MLR组（P＜0.05）;术后24 h时,LLR组的肠湿/干重比最低,HLR组最高（P＜0.05）。HE染色结果显示,3组大鼠肠黏膜损伤严重程度均随时间好转,但在48和72 h时,LLR组的肠绒毛基本正常。结论 复苏剂量为15 mL / （kg · h）的限制性液体复苏能降低失血性休克大鼠术后早期酸中毒的程度和TNF-α的释放,降低肠黏膜通透性,减轻对肠道的损伤。     

大肠癌合并大肠息肉的外科治疗体会

为探讨大肠癌合并大肠息肉的手术处理方法及疗效,回顾分析56例大肠癌合并大肠息肉病例的诊治资料。结果显示,2004年3月至2009年7月收治的255例大肠癌患者中共发现并存大肠息肉者56例,其中45例行术前息肉摘除手术,7例行术中结肠息肉切除,4例在术后进行结肠息肉摘除。全组无手术并发症发生,息肉切除部位无残留、恶变或癌种植转移。结果表明,术前应用内镜切除是治疗大肠癌合并大肠息肉的主要手段;不宜内镜切除者,尽量采用扩大切除术;远离大肠癌常规切除范围、较分散的息肉和不宜扩大切除的患者,可在内镜定位下行局部切除,如为恶性息肉则行结肠次全或全切除。双镜联合可提高大肠息肉的诊治水平。     

Assessment of the Thrombogenic Effect of Fibrin Sealant Dressing in a Vascular Surgery Model in Rabbits

This study's objective was to investigate the potential thrombogenic effects of thrombin-containing fibrin sealant dressings (FSD) in a vascular repair model. Oval-shaped pieces of the rabbit abdominal aorta and vena cava were excised, the injuries were repaired with FSD, and animals were allowed to recover. Thrombus formation was examined by (1) an infusion of indium-labeled platelets into the rabbits following FSD application and estimation of total number of platelets attached to the wounds at 2, 4, and 6 h later (short-term effect, n = 12); and by (2) morphological and histological examinations of the vessels and dressings on days 1, 3, and 7 after repair operation in another group of rabbits (long-term effect, n = 12). Application of FSD sealed the vascular injures and produced immediate hemostasis that was stable up to 1 week. The highest numbers of platelets (both native and labeled) adhered to the arterial and venous repair sites were 6.5 × 10⁶ and 4.4 × 10⁷, respectively, 6 h after operation. The adhered platelets, however, did not form a visible and clinically significant thrombus. In long-term experiments, no evidence of thrombus was found in the lumens of the repaired vessels or on the dressings, and no microthrombi were detected histologically in other tissues at any time point. Although vena caval injuries showed signs of healing at day 7 postoperatively, the aortic wounds expanded progressively (pseudoaneurysm) and were prone to rupture at later times. Thus, direct exposure of FSD does not cause intravascular thrombosis or thrombotic events in rabbits. The dressing appears to be safe and effective for short-term repair of vascular injuries. It may also allow healing of minor venous defects, but cannot replace conventional surgical techniques (suturing) for permanent repair of arterial damages.     

生长激素对化疗大鼠机体状态和骨髓功能的影响

目的探讨人生长激素（hGH）对化疗大鼠机体状态和造血功能的影响。方法实验选用健康成年SD大鼠136只,体重（200&#177;50）g,标准喂养,采用随机数字表法随机分为5组：正常对照组（空白组,n=8）、生理盐水对照组（NS组,n=32）、生长激素组（hGH组,n=32）、化疗组（CT组,n=32）及CT＋hGH组（n=32）。分别于实验前及给药后第7、14、21及28天称量大鼠体重,采用骨髓涂片、病理切片及免疫组化法（增殖细胞核抗原检测）检测大鼠骨髓造血功能。结果给药后第7天CT＋hGH组大鼠体重下降程度较CT组明显减轻（P〈0.05）;CT组和CT＋hGH组骨髓增生极度低下或明显减低（P〈0.05）。第14天CT＋hGH组大鼠体重已为正增长,而CT组仍表现为体重丢失;CT＋hGH组骨髓增生极度活跃,骨髓有核细胞总数较CT组明显增加（P〈0.05）。第7、14及21天CT组增殖细胞核抗原阳性细胞数均明显低于hGH组和CT＋hGH组（P〈0.05）。给药后第7天hGH组大鼠体重较空白组明显增加（P〈0.05）,其他不同时间点空白组、NS组与hGH组各指标检测结果差异均无统计学意义（P〉0.05）。结论hGH能减少化疗大鼠的体重丢失,对化疗大鼠的骨髓抑制有一定的保护作用。