| 摘要: | 肺氣栓塞(Pulmonary air embolism)會造成呼吸型態的改變(Breathing pattern change)和肺組織病理病徵(Lung tissue injury)。C纖維(C fiber nerve endings)和快適應性受器(Rapidly adapting receptors)具有預先偵測肺組織病變徵兆的兩大類肺迷走感覺神經受器,而且刺激這兩類受器皆會產生共同性的淺快呼吸。誘發肺氣栓塞已證實會刺激肺C纖維和快適應性受器。然而到目前為止,肺氣栓塞是否會引發淺快呼吸?何種肺迷走感覺神經受器在此呼吸型態改變的神經機轉(Neural pathways)中扮演重要的角色?皆仍不清楚。已知肺氣栓塞會導致一些肺介質的釋放,譬如前列腺素及血栓素等環氧化酵素產物(Cyclooxygenase productors)、以及氫氧自由基(OH？)。又根據我們最近研究的結果顯示這些肺介質會參與在肺氣栓塞所活化的C纖維和快適應性受器之中。然而到目前為止,肺氣栓塞活化的肺迷走神經受器,所產生呼吸型態改變的化學性機轉(Chemical pathways),是否藉由這些肺介質的釋放?亦有待研究。本計畫的目的是去探討:(一).肺氣栓塞是否會引發呼吸型態的改變?(二).肺氣栓塞產生呼吸型態改變的神經路徑,是藉由何種迷走感覺神經受器的傳導?(三).環氧化酵素的產物和OH？等肺介質是否參與在肺氣栓塞引發呼吸型態的改變中?本計畫的基礎呼吸型態的長期觀察。 本計畫以成年犬為實驗動物,麻醉後,施以股動脈、股靜脈、氣管插管。其目的分別是測量動脈壓、給予補助麻醉劑、及測量一些呼吸性的參數(Respiratory parameters)。此些參數分別為潮氣容積(Tidal volume)、氣流(Airflow)、氣道內壓(Airway pressure)。藉這些參數可觀察呼吸型態的變化。以注射空氣進入肺循環來誘發肺氣栓塞。本計畫的實驗設計為研究一(n=5),基礎呼吸型態的長期觀察。研究二(n=8),觀察肺氣栓塞所引發的呼吸型態。在迷走感覺神經無損的情況下,即給予等張性生理食鹽水,誘發重複肺氣栓塞。研究三(n=8)在阻斷C-纖維的情況下,即運用兩側頸迷走神經周圍辣椒素處理法,誘發重複肺氣栓塞。研究四(n=8),採用異丁苯丙酸(Ibuprofen)處理來抑制環氧化酵素的產物,誘發重複肺氣栓塞。研究五(n=8),採用雙甲基硫尿(Dimethylthiourea)處理來清除OH？,誘發重覆肺氣栓塞。 根據實驗結果顯示,在自發性呼吸的狗上,給予肺氣栓塞後,便引發淺快呼吸反射反應。在辣椒素塗抹頸迷走神經處理後,淺快呼吸的反應被消除。誘發重複肺氣栓塞可引發加成性的淺快呼吸;相反的,此反應可被異丁苯丙酸、或雙甲基硫尿處理所減弱。綜合先期實驗的結果,我們發現:肺氣栓塞會引發呼吸淺快的反應,其間的機轉可能是藉由環氧化酵素產物以及OH？的釋放來活化C-纖維,而非快適應性受器,進而引發呼吸型態的改變。另一方面,由於肺氣栓塞會釋放環氧化酵素產物以及OH？,進而引發肺組織病理病徵。表示肺氣栓塞在出現病徵之前,動物體內都應有C-纖維傳導訊號至中樞且立即造成淺快呼吸,使動物警覺本身正處於不正常狀態。而本計畫之研究成果可為進一步探討肺氣栓塞發生後,呼吸系統如何防禦以及此防禦機轉如何失控而造成病理性的傷害的長期計畫的研究基礎。
We investigated the vagal and mediator mechanisms underlying the tachypnea caused by pulmonary air embolism (PAE) in anesthetized and spontaneous breathing dogs. PAE was induced by infusion of air into the right atrium (0.2ml kg/sup -1/ min/sup -1/for 10 min). The first PAE induction caused an increase in respiratory frequency accompanied by a decrease in tidal volume in each of the 30 animals studied. Subsequently, animals were evenly divided into five groups and a second PAE induction was repeated following various experimental interventions. The tachypneic response to PAE was not significantly altered by pretreatment with a saline vehicle, but was largely attenuated by either perivagal capsaicin treatment (a technique that selectively blocks the conduction of unmyelinated C-fibers), pretreatment with ibuprofen (a cyclooxygenase inhibitor), or pretreatment with dimenthylthiourea (a hydroxy radical scavenger). Ultimately, the tachypneic response was nearly abolished by a bilateral cervical vagotomy. These results suggest that 1) both lung vagal unmyelinated C-fiber afferents and myelinated afferents are responsible for evoking the reflex tachypneic response to PAE, although the former afferents play a predominant role, and 2) both cyclooxygenase products and hydroxyl radical are important in eliciting this response. |
