Nitroprusside가 고양이 뇌저동맥의 이완효과에 미치는 연구

Abstract

[한글]

뇌혈관의 연축현상(cerebral vasospasm)은 뇌동맥류의 파열후에 잘 나타나며 환자의 예후에 매우 나쁜 영향을 미치고 때로는 사망의 주요 원인이 되고 있다. 뇌혈관의 연축 발생기전은 현재까지 확실히 밟혀지지 않았으나 두 가지 설을 들고 있다. 첫째는 지주막하

출혈로 인해서 뇌실질과 혈소판에서 혈관 수축 물질이 유리되어 뇌혈관 연축을 유발시킨다는 설 (Brawley등, 1965; Echlin, 1968: Robertson, 1974)과 둘째는 감수체 반응기전(sensitive receptor mechanism)을 들고 있다(Fraser등, 1970; Peerless와 Yasargil, 1971;

Sundt등, 1973).

동물실험에서 뇌혈관 연축에 대한 여러 약물의 이완효과를 보고한 실험은 많으나, 임상적으로 그 효과가 인정되어 인체에 투여해 본 것은 isoproterenol, lidocaine, papaverine 등 몇개를 제외하고는 없을 정도이다(Odom, 1975). 최근 Allen(1976)과 Allen및 Gross(

1976)는 개의 뇌저동맥을 적출하여 serotonin으로 유발시킨 연축현상을 nitroprusside가 이완시키는 효과가 있음을 관찰 보고하였고 또한 nitroprusside와 phenylephrine을 뇌동

맥 연축이 있는 환자들에 사용하여 nitroprusside가 뇌혈관 연축의 이완에 도움이 될 것 이라는 가능성을 제시한 바 있다.

Nitroprusside의 작용기전에 관해서는 아직 확실히 밝혀지지 않았지만 최근 Kreye등(1975)은 nitroprusside가 혈관 평활근의 activator calcium을 차단함으로써 이완시킨다고 설명하고 있다.

본 실험에서 nitroprusside를 정맥주입 또는 국소도포하여 고양이의 뇌저동맥에 미치는 이완효과를 수술현미경하에서 직접 관찰하고 다음과 같은 결론을 얻었다.

1. 실험동물 자가 혈액 국소도포에 의한 뇌저동맥 연축은 5분까지 현저하였으며 이후부터 연축 정도가 점차 감소하였으나 60분까지 유지되었다.

2. Nitroprusside 정맥주입(5μg/kg/min)으로 정상 뇌저동맥과 연축 뇌저동맥이 이환 되었다.

3. Nitroprusside 국소도포(5x10**-5 %)로서 정상 뇌저동맥과 연축 뇌저동맥이 현저히 이완되었다.

4. Nitroprusside 정맥주입 (5μg/kg/min)으로 혈압은 주입후 5분에 주입전보다 33% 떨어져서 이 상태로 지속되었고 주입중지후 5분에 주입전 상태로 회복되었다. 심박수의 변동은 없었다.

5. Nitroprusside 국소도포(5x10**-5 %로서 혈압 및 심박수의 변동은 없었다.

이상의 실험성적에서 고양이 뇌저동맥 연축은 nitroprusside 국소도포 또는 정맥주입으로 현저한 이완 효과를 나타냄을 알 수 있었다.

Spasmelytlc Effects of Nitroprusside on the Feline Basilar Artery

Hun Hwa Jung, M.D.

Department of Medical Science, The Graduate School, Yonsei University

(Directed by Prof. Hun Jae Lee, M.D.)

Cerebral vasospasm fellowing the rupture of an intracranial aneurysm is still one

of the most baffling problems confronting the neurosurgeon. Cerebral arterial spasm

usually occurs in association with bloody subarachnoid fluid in the patient with a

ruptured intracranial aneurysm. It occurs less frequently after traumatic injuries

of the cerebrum and fellowing operations for lesions around the circle of Willis

(Allock and Drake, 1965: Echlin, 1968; Ransohoff et al, 1972; Robertson, 1974).

Presently, two major theories are in vogue about the cause of cerebral vasospasm.

One of these argues that a vasospastic substance is elaborated from platlets and

brain as a result of subarachnoid blood (Echlin, 1968; Brawley et al, 1968;

Robertson, 1974). The second theory is based on the theoretical "sensitive receptor

mechanism"(Fraser et al, 1970; Peerless and Yasargil, 1971; Sundt et al, 1973).

Numerous investigators have reported extensive laboratory studios but despite all

efforts, etiology and pathogenesis have net been established nor has any form of

therapy proven successful in the relief of cerebral vasospasm in humans. Recently

Allen(1976) reported that nitroprusside is effective in relaxing canine basilar

artery segments which are contracted by serotonin in vitro. Additionally he

reported the treatment of three patients with delayed cerebral arterial spasm with

simultaneous intravenous infusion of nitroprusside and phenylephrine.

Angiographically, there was a dramatic increase in the caliber of their cerebral

vessels after treatment.

The mechanism of action of nitroprusside has not been extensively studied and is

not well understood. More recently it has been postulated that nitroprusside blocks

the activator calcium of vascular smooth muscle(Kreye et al, 1975).

In this report, nitroprusside was tested to determine its effects on the response

of the feline basilar artery. The vasodilatory effects of nitroprusside were

studied in normal basilar arteries and autogenous blood induced contracted arteries

in cats by intravenous infusion and topical application of nitroprusside. The

changes of vessel diameter were evaluated with microphotographic technique.

The result of this study are summarized as follows;

1. Feline basilar arterial spasm that was induced by autogenous blood was

remarkable within 5 minutes, was decreased after 10 minutes, but persisted for a

total of 60 minutes.

2. Intravenous infusion of nitroprusside(5 μg/kg/min) produced vasodilation on

normal feline basilar arteries and feline basilar arteries contracted by autogenous

blood.

3. Topical application of nitroprusside(5x10**-5 %) showed potent vasodilatory

effects on physiologic state and spastic state of feline basilar arteries.

4. Within 5 minutes after start of nitroprusside intravenous infusion, blood

pressure was reduced to 67% of that of the control state. The reduced blond

pressure persisted during systemic infusion of nitroprusside, but the blood

pressure returned to its control level within 5 minutes after the infusion of

nitroprusside was stopped. During intravenous infusion of nitroprusside, there were

no significant changes of heart rate.

5. Topical application of nitroprusside on feline basilar arteries produced no

significant changes of blood pressure or heart rate.

In this study, nitroprusside revealed prominent vasodilatory effects on the

contracted feline basilar arteries by topical or systemic administration.

[영문]

Cerebral vasospasm fellowing the rupture of an intracranial aneurysm is still one of the most baffling problems confronting the neurosurgeon. Cerebral arterial spasm usually occurs in association with bloody subarachnoid fluid in the patient with a

ruptured intracranial aneurysm. It occurs less frequently after traumatic injuries of the cerebrum and fellowing operations for lesions around the circle of Willis (Allock and Drake, 1965: Echlin, 1968; Ransohoff et al, 1972; Robertson, 1974).

Presently, two major theories are in vogue about the cause of cerebral vasospasm.

One of these argues that a vasospastic substance is elaborated from platlets and brain as a result of subarachnoid blood (Echlin, 1968; Brawley et al, 1968; Robertson, 1974). The second theory is based on the theoretical "sensitive receptor

mechanism"(Fraser et al, 1970; Peerless and Yasargil, 1971; Sundt et al, 1973).

Numerous investigators have reported extensive laboratory studios but despite all efforts, etiology and pathogenesis have net been established nor has any form of therapy proven successful in the relief of cerebral vasospasm in humans. Recently Allen(1976) reported that nitroprusside is effective in relaxing canine basilar artery segments which are contracted by serotonin in vitro. Additionally he reported the treatment of three patients with delayed cerebral arterial spasm with

simultaneous intravenous infusion of nitroprusside and phenylephrine.

Angiographically, there was a dramatic increase in the caliber of their cerebral vessels after treatment.

The mechanism of action of nitroprusside has not been extensively studied and is not well understood. More recently it has been postulated that nitroprusside blocks the activator calcium of vascular smooth muscle(Kreye et al, 1975).

In this report, nitroprusside was tested to determine its effects on the response of the feline basilar artery. The vasodilatory effects of nitroprusside were studied in normal basilar arteries and autogenous blood induced contracted arteries

in cats by intravenous infusion and topical application of nitroprusside. The changes of vessel diameter were evaluated with microphotographic technique.

The result of this study are summarized as follows;

1. Feline basilar arterial spasm that was induced by autogenous blood was remarkable within 5 minutes, was decreased after 10 minutes, but persisted for a total of 60 minutes.

2. Intravenous infusion of nitroprusside(5 μg/kg/min) produced vasodilation on normal feline basilar arteries and feline basilar arteries contracted by autogenous blood.

3. Topical application of nitroprusside(5x10**-5 %) showed potent vasodilatory effects on physiologic state and spastic state of feline basilar arteries.

4. Within 5 minutes after start of nitroprusside intravenous infusion, blood pressure was reduced to 67% of that of the control state. The reduced blond pressure persisted during systemic infusion of nitroprusside, but the blood

pressure returned to its control level within 5 minutes after the infusion of nitroprusside was stopped. During intravenous infusion of nitroprusside, there were no significant changes of heart rate.

5. Topical application of nitroprusside on feline basilar arteries produced no significant changes of blood pressure or heart rate.

In this study, nitroprusside revealed prominent vasodilatory effects on the contracted feline basilar arteries by topical or systemic administration.