実験的虚血脳における血圧上昇の影響

EFFECT OF ACUTE ARTERIAL HYPERTENSION ON ISCHEMIC BRAIN : AN EXPERIMENTAL STUDY

I．はじめに

　脳血管閉塞症および脳動脈瘤破裂後の血管攣縮などの虚血性病態の急性期において，虚血からいかに脳をまもるか，すなわち脳梗塞を最小限におさえ，かつ随伴する脳浮腫をいかにくい止めるかは重要な課題である。それに関して多くの基礎的ならびに臨床的研究がなされ，脳血管攣縮時の脳梗塞の予防に対して高血圧療法が行なわれ，その有効性も論じられている^{4,11,13,18）}。また，この人為的高血圧は，血行再建術の適応決定の一手段としても用いられており，Itoら^10）は脳機能の可逆性のパラメーターとして血圧上昇時の局所脳血流量（r-CBF）および体性感覚誘発電位（SEP）の変化をその指標としている。しかし，一方臨床的にも高血圧性脳症が存在し，人為的高血圧による血液脳関門（BBB）の透過性の亢進・破綻^1,5,6,12），脳軟膜細動脈の形態学的変化^2,12,15），auto—regulationの破綻^7,9,17）など，高血圧が脳におよぼす悪影響についても報告されている。われわれは，虚血脳における人為的高血圧の影響を，脳微小循環およびBBBの破綻という立場より検討し，その結果，適度の高血圧は微小循環を改善させるが，その程度や持続時間によつては，BBBの破綻を伴うという結論を得た。

Effect of induced arterial hypertension on the ischemic brain is studied with special reference to cerebral microcirculation and blood-brain barrier disturbance. A right middle cerebral artery is occluded by transorbital approach in 40 cats. Im-mediately after r-MCA occlusion, acute hyperten-sion is produced in 30 animals by intravenous injection of Angiotensin-II. Systemic arterial blood pressure is maintained at the level that the percentage increase of systolic perssure is 50% above the original value. In 10 animals, no hyper-tensive insult is produced. According to the duration of hypertension, 30 animals were devided into three groups, 3 hours hypertension group, 6 hours hypertension group and 12 hours hyperten-sion group. In all animals, time course of arterial occlusion is 12 hours. Before sacrifice, sodium fluorescein was given intravenously for BBB-tracer and carbon perfusion was performed for detection of microcirculation. Extent of impaired carbon filling and that of fluorescein staining were studiedand compared at the same coronal sections. His-tological study was also added.

Infarcted area identified by the extent of impaired carbon filling is variable from animal to animal even in control group. For adequate comparison, grade was set up as follows. Grade I is the smallest, Grade IV is the largest. Grade II and III are the intermediate size. According to the above grade, extent of impaired carbon filling is smaller in hypertension group than in control group. This tendency is closely related to the duration of hypertension, that is, the longer the duration, the smaller the extent. As to fluorescein staining there is no particular relation among four groups. Each case was studied from both points of view at once (grade of impaired carbon filling and grade of fluorescein staining) in each group. In control group, both grade is high. In 3 hours hypertension group, carbon filling is remarkably improved and fluorescein staining also becomes smaller. In 6 hours hypertension group, grade of impaired carbon filling tends to become the same value as grade of fluorescein staining. In 12 hours hypertension group, instead of marked improvement of carbon filling, fluorescein staining aggravated remarkably.

Summarizing the above results, microcirculation indicated by carbon filling becomes improved by acute hypertension. On the other hand, BBB dis-turbance indicated by fluorescein staining becomes aggravated by hypertensive insult.

Induced hypertension therapy may be applicable treatment for acute ischemic brain damage case if profound consideration is payed to degree of hy-pertension, duration of hypertension, and timing of the start of treatment.