Pleiotropic effects of cardiac drugs on healing post-MI. The good, bad, and ugly

Healing after myocardial infarction (MI) is a well-orchestrated time-dependent process that involves inflammation, tissue repair with extracellular collagen matrix (ECCM) deposition and scar formation, and remodeling of myocardial structure, matrix, vasculature, and function. Rapid early ECCM degradation followed by slow ECCM replacement and maturation during post-MI healing results in a prolonged window of enhanced vulnerability to adverse remodeling. Decreased ECCM results in adverse ventricular remodeling, dysfunction, and rupture. Inflammation, a critical factor in normal healing, if impaired results in adverse remodeling and rupture. Several therapeutic drugs prescribed after MI exert pleiotropic effects that suppress ECCM and inflammation during healing and may have good, bad, or ugly consequences. This article reviews the potential impact of pleiotropic effects of some prototypic cardiac drugs such as renin-angiotensin-aldosterone system (RAAS) inhibitors, statins, and thrombolytics during healing post-ST-segment-elevation MI (STEMI), with special focus on inflammation, ECCM and remodeling, and implications in the elderly.     

Healing of colonic anastomoses after immediate postoperative intraperitoneal administration of oxaliplatin

Aim  The aim of this experimental study was to investigate the effect of intraperitoneal administration of oxaliplatin on the healing of colonic anastomoses when injected immediately after colon resection. Materials and methods  Thirty male Wistar rats were used. During the operation, the rats were randomized to two groups of 15 rats each. Immediately after colonic anastomoses were performed, the rats were injected intraperitoneally with either 3 ml of 0.9% NaCl solution or oxaliplatin (2.4 mg/kg body weight) depending on their group. All rats were killed on the eighth postoperative day. The anastomoses were examined macroscopically. The anastomotic bursting pressures were recorded, the anastomoses graded histologically, and the hydroxyproline tissue contents determined. Results  Anastomotic leakage was noted in four rats (26.7%) of the oxaliplatin group, whereas no anastomotic dehiscence was detected among rats of the control group (p = 0.016). The adhesion formation at the anastomotic sites and the inflammatory cell infiltration were significantly higher in the oxaliplatin group than in the control group (p = 0.001). The bursting pressures (p = 0.001), the hydroxyproline tissue content (p = 0.001), the neoangiogenesis (p = 0.033), the fibroblast activity (p = 0.001), and the collagen deposition (p = 0.001) were significantly lower in the oxaliplatin group in comparison to the control group. Conclusion  The immediate postoperative intraperitoneal administration of oxaliplatin seems to impair healing of colonic anastomoses in rats.     

不同皮质骨厚度区域的加载正畸微种植体骨整合的组织形态学和生物力学分析

目的研究皮质骨厚度(CBT)对正畸微种植体骨整合的影响。方法选择四川大学实验动物中心的健康雄性成年Beagle犬12只,依据种植钉植入区皮质骨厚度分为厚CBT组与薄CBT组,将48枚微种植体植入12只Beagle犬两侧胫骨,厚CBT组与薄CBT组微种植体分别在距近中干骺端4 cm和2 cm处植入。术后1、3、5、7周处死,作力学拉拔测试和组织形态学研究。结果薄CBT组和厚CBT组1、3、5、7周CBT比较差异均有统计学意义(P<0.05);在第1、3、5周,厚CBT组骨整合、皮质骨体积密度(骨体积/总体积)、相交表面(与骨表面接触的微种植体)均显著高于薄CBT组,第7周时两组间差异无统计学意义;厚CBT组最大拉拔力在1周达顶峰,3周降到最低点,薄CBT组则随时间延长持续上升。结论较大CBT对微种植体初期稳定性有益,而较薄皮质骨更有利于二期稳定性的获得。     

New experimental procedures to evaluate the biomechanical properties of healing canine medial collateral ligaments

Both clinical and animal studies have indicated that early mobilization and exercise may improve the healing of injured medial collateral ligaments (MCLs). To investigate these effects, transected canine MCLs were subjected to three different treatment regimens: (a) no surgical repair with 6 weeks mobilization; (b) surgical repair with 3 weeks immobilization followed by 3 weeks remobilization; and (c) surgical repair with 6 weeks immobilization. After sacrifice, knee laxity was measured in a newly designed varus-valgus (V-V) laxity device. Each knee was tested subsequently in tension to determine the structural properties of the femur-MCL-tibia complex (FMTC) and the mechanical properties of the healing MCL substance. It was found that the V-V laxity increased for all experimental knees, but that early mobilization enhanced joint stability. The structural properties of the FMTC and the mechanical properties of the MCL substance were also lower than the contralateral controls. Again, the early mobilization groups had better results.     

血管内皮生长因子在骨折修复过程中血管生成的促进作用

目的观察血管内皮生长因子(VEGF)在骨折修复过程中对骨折端微血管密度(MVD)的影响，探讨VEGF在骨折端血管生成中的作用。方法用168只大白鼠制作股骨骨折模型，随机分为VEGF组、拮抗VEGF组、对照组，用免疫组织化学分别测定伤后不同时间骨折端MVD的变化。结果应用外源性VEGF后。骨折端MVD明显增加；拮抗VEGF组，骨折端MVD明显下降；对照组MVD低于VEGF组，但高于拮抗VEGF组。结论VEGF在骨折修复过程中，对血管生成具有重要作用，并可能作为一种重要细胞因子参与和调节了骨折修复过程。     

骨髓间充质干细胞对放创复合伤创面的促愈作用

目的 探讨骨髓间充质干细胞对放创复合伤创面的促愈作用。方法 利用自体骨髓来源的间充质干细胞移植于局部合并放射损伤的创面，采用荧光示踪技术、形态学观察、胶原染色、成纤维细胞和毛细血管计数、羟脯氨酸含量测定等多种指标，观察了间充质干细胞对放创复合伤创面的促愈使用。结果 间充质干细胞能加快创面愈合，促进肉芽组织生长和胶原合成。结论 骨髓间充质干细胞对放创复合伤创面有明显的促愈效应。     

同种异体骨移植后移植愈合的影响因素

同种异体骨目前已成功用于修复因肿瘤、感染、创伤后造成的骨缺损。异体骨的愈合机制也得到广泛的研究。作者对影响异体骨愈合的因素作一综述。     

Effects of topical allicin on second-intention wound healing in dogs (histological aspects)

Alllicin is one of the pharmacologically active garlic sulfur compounds that have antimicrobial (antibacterial, antiviral, antifungal and antiparasitic) and vasodilating effects. Five normal, male, mixed-breed dogs were selected to investigate the effects of allicin (5 mg/ml in methyl cellulose gel) as a topical treatment for full-thickness, excisional wounds. The dogs were approximately 3 years old. The histological aspects of second-intention wound healing were studied. Eight full-thickness skin wounds (20×20 mm) were created on the back of each dog. On days 0, 7, 14 and 21, each dog received two wounds, symmetrically, and were assigned to one of two groups: control (methyl cellulose gel) or test (allicin 5 mg/ml methyl cellulose gel). Wounds were treated once daily for a week. Left-side wounds were treated with allicfin (test group) and right-side wounds were treated with methylcellulose gel (control group). At day 28 (4 weeks) after initial wounding, biopsies were taken from wounds for histological examination. The density of inflammatory cells in the center of the day 7 wounds was significantly lower in test group (P=0.041), but the density of fibrocytes and fibroblasts in the center of day 7 wounds was significantly higher in the test group (P=0.042). No significant differences were observed in the amount of collagen and fibrin between the test and control wounds (P>0.05).     

腱旁组织修复后对肌腱愈合方式影响的实验研究

为了观察腱旁组织对肌腱愈合方式的影响，选用雌性罗曼鸡２０只，取双侧第三趾手术，以鸡趾伸肌腱为模型，随机分为两组，每组１０只２０趾。Ａ组仅缝合趾伸肌腱；Ｂ组缝合趾伸肌腱后再修复腱旁组织。术后３周和６周，分别取标本进行大体形态和组织学观察。结果表明，术后３周，Ａ组粘连广泛，成纤维细胞增生紊乱；Ｂ组修复的肌腱形成规则而光滑的“梭形体”，粘连较轻，成纤维细胞增生有序。术后６周，Ａ组粘连较重，愈合处为瘢痕组织连接，形态不规则，纤维细胞排列紊乱，胶原纤维少而幼稚；Ｂ组粘连基本消失，肌腱及腱旁组织基本恢复正常，增生的纤维细胞及胶原纤维来自肌腱和腱旁组织，排列有序，有腱束形成趋势     

维生素A拮抗氢化可的松延迟大鼠结肠吻合口愈合的作用

结肠吻合口而是结肠手术后重要的并发症和死亡原因。本研究通过动物实验观察到氢化可的松延迟结肠吻合口愈合，而维生素Ａ能促进结肠吻合口愈合，并拮抗氢化可的松的抑制作用。同时探讨了其作用机理。为临床长期应用类固醇制剂而需行结脉手术者，使用维生素Ａ以期降低吻合口漏发生率，提供了初步的实验依据。