第一型抗組織胺對於皮瓣重建之影響

H1 Receptor Antagonist and Initiation of Flap Necrosis in Vascular Anastomosis in Rats

張進芳(Chin-Fang Chang)

指導教授 ： 周明智

中山醫學大學/醫學院/醫學研究所/碩士(2014年)

https://doi.org/10.6834/CSMU.2014.00114

摘要

研究目的： 惡性腫瘤切除手術後，立即以游離皮瓣來重建，可獲得最佳的組織披覆，成功率可達95%以上，然而仍有許多的因素會造成游離皮瓣的失敗，例如局部血管栓塞、感染或血管痙攣，可能會需要再進行通血管手術或是血管須重新接合。往往使患者產生嚴重的憂慮、恐懼及悲觀情緒，對二次手術喪失信心。本研究旨在利用動物實驗觀察抗組織胺是否有與劑量相關的血管收縮動作。其實驗發現大多數抗組織胺（H1和H2受體阻斷劑）是否可直接影響對血管平滑肌作用。
研究方法及資料：本研究係以20隻大鼠接受血管吻合手術，在接受手術後第三天進行實驗以腹腔內注射之方式給藥，於注射完藥物後於注射完藥物後放置回籠子內直到手術後的第七天，期間觀察其外觀、攝食及行動能力。於七日後以二氧化碳將大鼠犧牲，固定於手術板上把腹股溝的傷口打開，觀察血管吻合處傷口復原之情形並取出吻合處的血管以福馬林浸泡，後由病理科醫師進行冷凍切片。
研究結果：所有接受手術的大鼠，吻合處之傷口皆維持良好，没有皮膚壞死、皮下血腫或肢體無力之情形。在腹股溝部位內之血管如股動靜脈及下腹動靜脈皆由皮下脂肪包覆，無明顯黏連現象。在血管的流通性方面，於一週時之標本顯示此時血管吻合端皆已完全密合且血液流通順暢，沒有發現血管阻塞的現象，血管管徑雖然有縮小，但血流依然順暢。在組織病理切片中以免疫化學染色法對 α-smooth muscle actin 染色以觀察血管平滑肌細胞的活動，發現在注入低劑量Chlorpheniramine Maleate (0.1 ml) 的大鼠血管並未明顯發現平滑肌細胞活動之情形，但在注入高劑量Chlorpheniramine Maleate (1.0 ml) 的大鼠血管切片中的確有發現到平滑肌細胞匯聚之情形我們實驗之藥物的確會對血管造成收縮的影響。
結論：本實驗的結果並未完全驗證我們所提出的假說。雖然我們成功的在大鼠的股動脈模擬了血管吻合的狀況，但我們不論在施打抗組織胺或生理食鹽水之大鼠身上並未發現有任何皮膚壞死、皮下血腫、肢體無力之情形或其他證明吻合失敗之跡象。雖然在施打高濃度抗組織胺的大鼠血管有看見平滑肌收縮的情況，但血管的切面仍顯示血管管徑並未因此而縮小太多。在本動物實驗之設計模式所提供的環境下，抗組織胺的給予並未造成血管管徑的極度收縮進而引起血管吻合的失敗。
本研究在手術中做了許多處置來減少血管吻合失敗，如運用簡單縫合 (simple suture) 的方式而非連續縫合 (continue suture) 來減少血管徑的縮小程度、盡量保留血管的分枝減少因為血管內皮細胞受傷釋出物質影響血管癒合以及縮短手術時間以及末梢血管幾乎沒有缺血時間 (ischemia time) 來保持血管細胞活性，術後大鼠們也都沒有出現感染的問題，這些動作得到的結果都呼應了之前許多前輩們的臨床研究，證明影響皮瓣修補最主要的原因為手術者的技術以及經驗，在小心減少手術中的失誤及對血管的傷害後皮瓣手術的成功率原則上是非常高的。

關鍵字

自由皮瓣修補 ； 血管吻合 ； 顯微手術

並列摘要

Background: The treatment of head and neck cancer is mainly operation, including primary cancer wide excision and neck dissection; further adjunctive radiotherapy with or without chemotherapy is considered if the cancer advanced . If the oral leision is smaller, we can only suture the defect after wide excision. However, in most patients in taiwan, staging is already advanced when the cancer is found. Therefore, wider range of tumor excision is needed. When the defect could not be directly sutued after tumor excision, or when simple wound suture would cause oral dysfunction, free flap woud be needed to reconstruct the defect.
Materials and Methods: Twenty male SD rats weight were used in this experiment. Operationing under the micrscope, we separated the femoral artery from the inguinal area and the distal branch. Then the cutted end of the femoral artery is sutued end to end with 9-0 nylone and the Skin wound is sutured with 4-0 nylone. All of the rat are placed separately in the cage after the operation for three days , and their vital signs , including feeding and activity are all recorded. On the third day after the operation, they are given medication with intra-abdominal injection and released back to the cage until the seventh day. Seven days later, the rat is sacrificed with carbon dioxided. The blood vessels ‘s anastomosis area were examined for their healing status ,and then removed and soak with formaldehyde solution, they are later made into cryostat section by pathologist.
Results: All of the rat survived after the opertaion till the second operation for tissue specimen retrival. Their outer experience, feeding and activity showed no abnormality. All anastomosis wounds were in good condition without skin necrosis, subcutaneous hematoma or limb paralysis. No blood vessel obstruction was found in spite that the blood vessel’s diameter had shrunk. Histopathologically, smooth muscle accumulation was noted under immunochemical stain.
Conclusion: In the experiment, the study found that rat’s healing ability is very stunning, comparing to the human. When observing during the operation and after the anastomosis operation, we can find that aside from better blood coagulation function , a layer of coagulation connective tissue was formed aournd the blood vessels anastomosis end. Comparing to mammals, rodent’s healing ability is very strong, so rodent may not be the most suitable choice in this kind of experiment. Perhaps in the future the study can use other mammals , such as canine, as experimental specimen to reduce inter species diffentiality.
The rats did not have infection after the operation, which proved that, alike the clinical researches from other predecessor , the determinant factor of flap repair is the skill and experience of the operator.If this study can carefully reduce the errors and the damage to blood vessels during operation, the success rate of flap surgey is very high.

並列關鍵字

free flap ； anastomosis ； microsurgery

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