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Chlorpromazine이 연축된 고양이 뇌저동맥에 미치는 영향

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 Effects of chlorpromazine on the spastic feline basilar artery 
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[한글]뇌혈관의 연축현상(Vasospasm)은 지주막하출혈과 두뇌외상등에서 관찰되며 이러한 연축현상은 뇌혈관 순환장애를 유발함에 따라 뇌동맥류 파열로 생기는 지주막하 출혈의 예후를 악화시키는 주원인으로 알려져 왔다. 뇌혈관 연축은 기계적, 전기적 자극과 혈액에서 유리되는 여러가지 화학물질에 의한다는 것이 보고되어 왔으며 지금까지 알려진 물질은 serotonin, prostaglandin F^^2α 및 angiotensin등이다(Raynor 등, 1961; Denton 등, 1972; Allen 등, 1974). 뇌혈관 연축현상으로 병발되는 뇌순환장애를 막기 위해 연축된 뇌혈관을 이완시키는 문제가 신경외과 영역의 큰 과제가 되어 왔으며 여러 가지 혈관 이완제가 시도 되었으나 현재까지 임상적으로 만족할만한 효과를 거둔 치료제는 없었다. 저자는 뇌동맥류 파열환자에서 재출혈을 방지하기 위해 혈압강하와 진정목적으로 사용하는 chlorpromazine을 실험약물로 선택하여 연축혈관에 대한 이완효과를 조사하였다. 고양이에서 16배수술 현미경하에서 사대를 경유한 개두술로서 뇌저동맥을 노출한 뒤 자가혈액 및 serotonin에 의해 뇌저동맥연축을 유발하고 chlorpromazine을 국소도포 및 정맥주입하여 그 이완효과를 관찰하고 다음과 같은 결론을 얻었다. 1. 실험동물의 자가혈액에 의한 뇌저동맥 연축은 연축 유발후 5분까지 가장 현저하였으며 이후부터 점차 감소하였으나 90분까지도 지속하였다. Serotonin 국소도포에 의한 뇌저동맥 연축은 자가혈액도포에 의한 연축효과와 유사한 결과였으나 자가혈액에 비해 그 효과는 약했다. 2. 0.05% chlorpromazine(1.4×10**-3 M)을 국소도포한 결과 정상뇌저동맥과 자가혈액 또는 serotonin으로 연축시킨 뇌저동맥에 대한 이완효과는 현저하였다. 3. 자가혈액으로 연축시킨 뇌저동맥에 chlorpromazine을 정맥 주입한 결과 그 이완효과는 경미하였다. 4. Chlorpromazine을 국소도포하여 이완시킨 뇌저동맥에 serotonin도포시 serotonin에 의한 연축효과는 차단되었으나 chlorpromazine을 정맥 주입한 후 serotonin도포시에는 연축효과는 억제되지 않고 그대로 나타났다. 이상의 실험으로 미루어 보아 연축된 뇌저동맥에 국소도포한 chlorpromazine의 이완효과는 인정되었으며 임상응용을 위해서는 앞으로 더 추구되어야 할 것으로 생각된다.
[영문]Cerebral vasospasm is concomitant with raptured aneurysms and head injury. It is well known that cerebral infarction secondary to arterial spasm is one of the principal causes of morbidity and mortality in patients with subarachnoid hemorrhage (Allcock and Drake, 1965; Echlin, 1968). Cerebral vasospasm was known to be produced with mechanical or electrical stimulation and topical application of autogenous blood(Lende, 1960; Echlin, 1965). It is generally admitted that blood contains vasoactive substances and manly workers have attempted to isolate the agents in blood responsible for the production of spasm. The consensus favors serotonin, angiotensin, and oxyhemoglobin etc. (Raynor et at, 1961; Kapp et al, 1968; Osaka, 1977) and Wilkins et al(1968) reported the role of prostaglandin F2^^α which is present in brain tissue and pletelets. Cerebral vasoconstriction appears to be mediated mainly by vascular musculature hut intrinsic reflex activity may also play a Fart (Pool, 1958; Fraser et al, 1970). It has been the major problem in neurosurgery to relieve the cerebral circulatory insufficiency following arterial spasm and many drags have teen attempted to prevent and treat the vasospasm. But none of them were satisfactory for this purpose. This author performed an experimental study using chlorpromazine to evaluate its spasmolytic effect, which has been used for hypotension and sedation to reduce the chances of rebleeding in aneurysm patients. In cats the basilar artery was exposed transclivally using an operating microscope and vasospasm was induced by topical application of autogenous blood or serotonin. Chlorpromazine was applied topically or intravenously and its spasmolytic effect was evaluated with microphotographic technique. The results of the study are summarized as follows; 1. Feline basilar arterial spasm which was induced by autogenous blood was remarkable within 5 minutes, decreased gradually after 10 minutes but persisted for over 90 minutes. Vasospasm induced by topical application of serotonin was similar hut its spasmogenic effect was weaker than that of autogenous blood. 2. Topical application of chlorpromazine(1.4×10**-3 M) showed potent vasodilatory effect on spastic basilar arteries induced by autogenous blood or serotonin as well as on normal arteries. 3. Intravenous injection of chlorpromazine (3mg/kg) produced weak vasodilatory effect on spastic basilar arteries and no effect on normal arteries. 4. Serotonin has no spasmogenic effect on dilated basilar arteries which was treated with topical application of chlorpromazine but spasmogenic effect of serotonin was not inhibited on basilar artery after intravenous injection of chlorpromazine. The experimental experience obtained with chlorpromazine indicates that further studies with this drug are necessary to determine its effectiveness in human cerebral vasospasm.
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