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Dexamethasone의 국소도포가 연축된 고양이 뇌저동맥에 미치는 이완효과에 관한 연구

Other Titles
 Spasmolytic effects of topically applied dexamethasone on the spasm of feline basilar artery 
Issue Date
1976
Description
의학과/박사
Abstract
[한글] 뇌혈관의 연축현상(vasospasm)은 지주막하출혈, 두개강내 염증성 질환 및 두뇌외상 등에서 관찰되며 특히 뇌동맥류의 파열시 생기는 주요 사망원인의 하나로 잘 알려져 있다. Florey(1925)가 최초로 동물실험에서 연뇌막동맥(pial artery)의 연축을 관찰한 이래 Echlin(1965)은 수술현미경을 사용하여 고양이 뇌동맥에서 실험동물의 자가혈액 도포, 기계적 및 전기적 자극 등으로 뇌혈관 연축에 대한 실험을 시행하였다. 혈액에 의한 뇌혈관 연축은 혈액내 혈관수축성 물질에 의한다고 알려져 왔으나 Raynor등(1961)은 serotonin과 angiotensin이 그 원인물질이라고 보고 하였다. 이후 Wilkins등(1967)은 혈소판 및 뇌조직 내에 존재하는 prostaglandin F^^2α도 원인물질중의 하나라고 말하고 있다. 혈액에 의한 뇌동맥 연축은 기계적 및 전기적 자극에 의한 연축에 비하여 그 정도는 다소 약하나 지속성이 있으므로 약물을 이용한 동물실험에 많이 이용되고 있으며 실험동물 중에서는 고양이가 뇌혈관 연축현상이 가장 민감한 것으로 보고 되었다(Gurdjian과 Thomas, 1969). 연축된 뇌혈관을 이완시키는 문제가 신경외과 영역에서 큰 과제로 되고 있으며 지금까지 많은 약물이 실험적으로 시도되었ㅇ나 현재까지 치료제로서 papaverine을 제외하고는 인정될만한 것이 없다해도 과언이 아니다. Dexamethasone의 투여가 뇌부종의 치료 목적으로 흔히 사용하고 있으나 이것을 직접 연축된 뇌혈관에 도포해서 이완작용이 있는지는 전혀 알려지지 않고 있다. 저자는 수술현미경을 사용해서 25배 확대된 시야하에서 고양이의 뇌저동맥을 손상을 주지 않고 노출시키고 실험동물의 자가혈액을 채취해서 뇌저동맥 위에 도포하여 연축을 유발시켰으며 이어서 연축된 동맥 위에 dexamethasone을 국소도포하여 이 약물의 이완효과를 현미경사진상에 담아 측정하고 다음과 같은 결과를 얻었다. 1. 실험동물 자가 혈액에 의한 뇌저동맥 연축은 5분까지 가장 현저하였으며 이후부터는 연축정도가 점차 감소하여 90분 이상 지속하였다. 2. 혈액으로 일으킨 뇌저동맥 연축은 dexamethasone(0.5%) 국소도포로 현저한 이완효과를 나타냈으며 도포후 20분에는 연축시에 배해 혈관직경이 81±5.5% 이완되었다. 3. 이상이 실험성적으로 미루어 보아 고양이의 연축된 뇌저동맥에 국소도포한 dexamethasone의 이완효과는 인정되나 그 작용기전을 규명하기 위해서는 앞으로 더 실험적 추구가 필요할 것으로 생각된다. Spasmolytic effects of topically applied dexamethasone on the spasm of feline basilar artery Joong Uhn Choi, M.D. Department of Medical Science, The Graduate School, Yonsei University (Directed by Prof. Hun Jae Lee, M.D.) Cerebral vasospasm is frequently concomitant with reptured aneurysms but may also accompany trauma of the head and meningeal infection. And it is well known that ischemia of the brain, secondary to arterial spasm is one of the principal caused of morbidity and mortality in patient with subarachnoid hemorrhage, and spasm is the single problem in aneurysm surgery today. In early, Florey(1925) reported mechanically produced vasospasm in pial vessels over convexity of cerebral hemisphere in cats. Echlin(1942) confirmed the findings of Florey with photographic technique and extended them to include the basilar artery at the base of the brain. From the work of others we know that cerebral arteries constrict in response to mechanical, electrical stimulation and the topical application of autogeous blood(Lende, 1960; Echlin, 1965). It is generally admitted that fresh blood contains vasoactive substances. When the blood has clotted, its vasoconstrictor properties are lost (Echlin, 1965; Gurdjian and Thomas, 1969). Several workers have attempted to isolate the agent or agents in blood responsible for the production of spasm. The consensus favors serotonin, angiotensin or some other heat-stable component of blood which is different from serotonin or angiotensin (Raynor et al, 1961; Kapp et al, 1968). Wilkins et al(1967) reported the role of prostaglandin F^^2α which is present in brain tissue and platelet. The presence of adrenergic and cholinergic nerve fibers within the walls of cerebral vessels has been known for many years, but their functional role has only begun to be appreciated(Arutiunov et al, 1970; Fraser et al, 1970). Cerebral vasoconstriction appears to be mediated principally by vascular musculature but intrinsic neurogenic reflex activity may also play a part(Pool, 1958; Fraser et al, 1970). The possibility that dexamethasone may have intracranial vasodilatory effects combating vasospasm has received only fleeting mention in literature(Fox and Yasargil, 1975). The clinical value of dexamethasone to reduce cerbral edema associate with brain neoplasms is well established(Galicich et al, 1961). Our review of literature has failed to reveal any experimental study seriously evaluating the value of dexamethasone as agents effective in reducing intracranial arterial spasm. Accordingly the following investigation with dexamethasone was taken. In cats the basilar artery was exposed transclivally using operating microscope and spasm was induced by topical application of autogenous blood. Dexamethasone was applied topically on spastic basilar artery and its spasmolytic effects were evaluated with microphotographic technique. The result of study are summarized as follows: 1. Induced spasm of basilar artery by autogenous blood was remarkable within 5 minutes and decreased gradually after 10 minutes. But spasm persisted for over 90 minutes. 2. Definite vasodiltory effects of feline basilar artery and small visible branches were found with topical application 0.5% dexamethasone. 3. The experimental experience obtained with dexamethosone indicate that further studies with this drug are necessary to determine effectiveness in human cerebral vasospasm and to find out the mechanism of action as spasmolytic agent.
[영문] Cerebral vasospasm is frequently concomitant with reptured aneurysms but may also accompany trauma of the head and meningeal infection. And it is well known that ischemia of the brain, secondary to arterial spasm is one of the principal caused of morbidity and mortality in patient with subarachnoid hemorrhage, and spasm is the single problem in aneurysm surgery today. In early, Florey(1925) reported mechanically produced vasospasm in pial vessels over convexity of cerebral hemisphere in cats. Echlin(1942) confirmed the findings of Florey with photographic technique and extended them to include the basilar artery at the base of the brain. From the work of others we know that cerebral arteries constrict in response to mechanical, electrical stimulation and the topical application of autogeous blood(Lende, 1960; Echlin, 1965). It is generally admitted that fresh blood contains vasoactive substances. When the blood has clotted, its vasoconstrictor properties are lost (Echlin, 1965; Gurdjian and Thomas, 1969). Several workers have attempted to isolate the agent or agents in blood responsible for the production of spasm. The consensus favors serotonin, angiotensin or some other heat-stable component of blood which is different from serotonin or angiotensin (Raynor et al, 1961; Kapp et al, 1968). Wilkins et al(1967) reported the role of prostaglandin F^^2α which is present in brain tissue and platelet. The presence of adrenergic and cholinergic nerve fibers within the walls of cerebral vessels has been known for many years, but their functional role has only begun to be appreciated(Arutiunov et al, 1970; Fraser et al, 1970). Cerebral vasoconstriction appears to be mediated principally by vascular musculature but intrinsic neurogenic reflex activity may also play a part(Pool,1958; Fraser et al, 1970). The possibility that dexamethasone may have intracranial vasodilatory effects combating vasospasm has received only fleeting mention in literature(Fox and Yasargil, 1975). The clinical value of dexamethasone to reduce cerbral edema associate with brain neoplasms is well established(Galicich et al, 1961). Our review of literature has failed to reveal any experimental study seriously evaluating the value of dexamethasone as agents effective in reducing intracranial arterial spasm. Accordingly the following investigation with dexamethasone was taken. In cats the basilar artery was exposed transclivally using operating microscope and spasm was induced by topical application of autogenous blood. Dexamethasone was applied topically on spastic basilar artery and its spasmolytic effects were evaluated with microphotographic technique. The result of study are summarized as follows: 1. Induced spasm of basilar artery by autogenous blood was remarkable within 5 minutes and decreased gradually after 10 minutes. But spasm persisted for over 90 minutes. 2. Definite vasodiltory effects of feline basilar artery and small visible branches were found with topical application 0.5% dexamethasone. 3. The experimental experience obtained with dexamethosone indicate that further studies with this drug are necessary to determine effectiveness in human cerebral vasospasm and to find out the mechanism of action as spasmolytic agent.
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http://ir.ymlib.yonsei.ac.kr/handle/22282913/117253
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2. 학위논문 > 1. College of Medicine (의과대학) > 박사
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