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1 J. Exp. Biomed. Sci. 10 (2004) Cerebral Blood Flow Velocity of Young People in Their Twenties Seok-Cheol Choi, Heun-Young Kwon, Tae-Un Kim and Jai-Young Kim Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan , Korea Transcranial Doppler sonography (TCD) is a useful diagnostic method to measure cerebral blood flow velocity in various cerebral disorders. However, we haven't data enough to be available for young persons, especially in the twenties in Korea. This study was performed to collect the basic data of the cerebral blood flow velocity and to understand the cerebral physiology in the twenties. We determined the mean velocities of middle, anterior, and posterior cerebral artery, and vertebral and basilar artery (MCA-V, ACA-V, PCA-V, VA-V, and BA-V, respectively) in eighty-two healthy volunteers. For evaluating cerebral autoregulation, only the MCA-V was measured under various conditions such as stable, apnea, and hyperventilation state. Right and left MCA-V were 80.66±14.03 and 83.22±14.40 cm/sec at stable state, 90.13±17.47 and 90.26±16.38 cm/sec at apnea, and 54.83±11.09 and 55.33±10.74 cm/sec at hyperventilation. Right and left ACA-V were 49.11±15.71 and 48.19±13.75 cm/sec. Right and left PCA-V were 39.44±9.12 and ±6.74 cm/sec. Right and left VA-V were 33.65±9.26 and 36.18±10.39 cm/sec. BA-V was 48.49±11.16 cm/sec. Right and left MCA-V, VA-V, and right ACA-V and PCA-V in women were higher than those of men (P<0.05). No significant differences were found between men and women in the others. These findings indicate that cerebral hemodynamics and autoregulation were normal in young people in their twenties. The velocities of MCA, ACA, PCA, and BA were high values in women as compared with men. Key Words: Transcranial Doppler (TCD), Young people, Cerebral blood flow velocity, Cerebral autoregulation 서 초음파를이용한말초혈관내혈류속도측정은 1959년 Satomura에의해최초로시행된이래경동맥혈류평가검사에널리이용되어뇌혈관관련질환의진단에유용하게사용되었다. 그러나이방법은 5~10 MHz의탐촉자를사용하기때문에두개강내뇌혈관의혈류속도측정은불가능하여그적용범위에한계가있었다. 1982년 Aaslid (Aaslid et al., 1982) 가뼈와연조직투과시감쇠가적은저주파수 (2 MHz) 의탐촉자를개발함으로써두개골중가장얇은측두골부분을통해 Willis환동맥들의혈류속도측정이가능해졌다. 경두개초음파검사 (Transcranial Doppler, TCD) 라불리우는이검사법은측정의용이함과함께비혈관적, 비침습적, 반복적인실시간값의측정이라는매우큰장점을가지고있어현재임상에서 론 * 논문접수 : 2004 년 9 월 9 일수정재접수 : 2004 년 10 월 26 일 교신저자 : 최석철, ( 우 ) , 부산광역시금정구부곡 3 동 9, 부산가톨릭대학교보건과학대학임상병리학과 Tel: , Fax: scchoi@cup.ac.kr 널리이용되고있는유용한방법이다 (Lindegaard et al., 1985; Seiler et al., 1986). 최근식생활의서구화와다양한사회적요인에의해한국인의뇌혈관질환발생률이급격히증가함에따라 TCD의임상적유용성은더욱강조되고있다. 그러나연구보고의대부분은임상적사례에관한내용이기때문에실제건강인에대한 TCD자료가상대적으로축적되어있지않고특히젊은연령층에대해참고할만한국내자료가절대부족한실정이다. 저자들은 20대연령층을대상으로 TCD 를이용한뇌혈류속도측정을통해젊은이들의뇌혈류역학및생리에대한이해와향후관련연구를위한기초자료로활용하기위해이연구를시행하게되었다. 대상및방법 1. 대상저자들은부산시소재 P대학교에재학중인 20대연령층 ( 범위 20~24세, 평균 22.0±1.75세 ) 대학생들중뇌혈관질환, 심혈관질환, 고혈압, 당뇨병등과같은질환의병력이없고신경학적이상소견이없는건강한젊은이들을대상으로연구하였다. 대상자들중특정약물을복용중인사람들은연구

Table 1. Demographic characteristics in study population Variable Mean SD Age (year) 21.02 1.75 Height (cm) 164.4 9.35 Weight (kg) 55.0 9.35 BP (mmhg) a 118.48/77.34 11.42/9.55 Mean BP (mmhg) 91.05 9.

Demographic characteristics of male and female groups Variable Male Gender Female Sample size (number) 30 52 Age (year) 22.27±2.74 21.45±2.54 Height (cm) 173.70±5.28 * 161.47±3.86 Weight (kg) 67.0±6.

2 Table 1. Demographic characteristics in study population Variable Mean SD Age (year) Height (cm) Weight (kg) BP (mmhg) a / /9.55 Mean BP (mmhg) HR (beat/min) b Data were expressed as mean ± standard deviation (SD). a, systolic blood pressure/diastolic blood pressure; b, heart rate A Table 2. Demographic characteristics of male and female groups Variable Male Gender Female Sample size (number) Age (year) 22.27± ±2.54 Height (cm) ±5.28 * ±3.86 Weight (kg) 67.0±6.35 * 51.09±5.71 S-BP (mmhg) a ±12.64 * ±10.82 D-BP (mmhg) b 79.22± ±10.93 M-BP (mmhg) c 95.70±11.58 * 89.63±10.27 HR (beat/min) d 75± ±11.84 Data were expressed as mean ± SD. *, P<0.05 (compared with female group). a, systolic blood pressure; b, diastolic blood pressure; c, mean blood pressure; d, heart rate A B ACA C ACA at a depth of insonation of 70 mm B C VA at a depth of insonation of 65 mm MCA D PCA MCA at a depth of insonation of 50 mm BA E PCA at a depth of insonation of 65 mm D BA at a depth of insonation of 100 mm VA Fig. 1. The temporal window (A, B) allows the insonation of the anterior (ACA, C), middle (MCA, D), and posterior (PCA, E) cerebral arteries through the thin temporal bone. The diagram depicts the sampling volume For Doppler recording (cylinder). (BA=basilar artery; VA=vertebral artery). Fig. 2. The suboccipital window (A, B) allows the insonation of the vertebral (VA, C) and basilar (BA, D) arteries through the foramen magnum. 에서제외시켰다. 각측정값들은전체대상자들에대한평균값을구하여분석하였고남녀성별로분류하여주요측정변수들을비교분석하였다 (Table 1, 2). 2. 방법 1) 뇌혈류속도뇌혈류속도는 Remed TCD (ReMed Co., Israel) 와 2 MHz pulsed probe를이용하여아래의부위와조건에서측정하였고각값은평균수치 (mean velocity) 를기록하였다. 2) 측정부위및조건모든대상자들에대해앙와위의안정상태에서좌측및우 측의전대뇌동맥, 중대뇌동맥, 후대뇌동맥, 추골동맥의평균혈류속도를각각측정하였고기저동맥의평균혈류속도도함께측정하였다 ( 이하 Rt or Lt ACA-V, MCA-V, PCA-V, VA-V 그리고 BA-V로각각표시 ). ACA-V, MCA-V, PCA-V는관골궁바로위쪽의측두창 (temporal window) 을통해탐촉자의각도를변화시켜가면서각해당혈관의혈류속도를측정하였고 (Fig. 1) BA-V와 VA-V 는후두와창 (suboccipital middle line) 과유양돌기의 2 cm뒷쪽 (paramedian line) 에서각각측정하였다 (Fig. 2). 각측정부위의초음파발사깊이는 ACA의경우 60~70 mm, MCA의경우 50~60 mm, PCA의경우 60~75 mm,

3 Table 3. Mean velocity in the intracranial vessels at stable condition MCA-V (cm/s) ACA-V (cm/s) PCA-V (cm/s) VA-V (cm/s) Right Left Right Left Right Left Right Left BA (cm/s) Mean SD Data were expressed as the mean ± SD Table 4. Comparison of mean velocity of MCA at stable state to those at apnea and hyperventilation condition Position Condition Stable Apnea Hyperventilation Rt-MCA (cm/s) 80.66± ±17.4 * 54.83±11.09 * Lt-MCA (cm/s) 83.22± ±17.4 * 55.33±10.74 * Data were expressed as mean ± SD. *, P<0.01 (compared with stable condition) VA의경우 60~70 mm, BA의경우 80~110 mm였다. 또한환경변화에따른뇌의자동조절기전의변화유무를조사하기위해 30초간의무호흡상태에서, 그리고 30초간과호흡상태 (50~ 55회 / 분 ) 에서각각 MCA-V를측정하여안정상태의측정치와비교하였다. 3) 혈압및심장박동수자동혈압측정기를이용하여전체대상자들의수축기혈압, 확장기혈압, 평균혈압, 심장박동수를각각측정하였다. 4) 자료분석및통계처리모든연구대상자들의안정상태의각부위별뇌혈류속도의좌우비교와혈압및심장박동수의각측정치의남녀간비교에는 unpaired t-test를적용하였고, 안정상태의 MCA-V와무호흡혹은과호흡상태의 MCA-V 간의비교에는 paired t-test를적용하였다. 가능한모든값은평균 ± 표준편차로나타내었다. 자료처리에사용한통계분석프로그램은 SPSS 10.0이었고 P< 0.05일때통계적으로유의한차이가있는것으로판단하였다. 결 과 1. 안정상태의평균뇌혈류속도 도플러상뇌혈류의방향은중대뇌동맥과후대뇌동맥은상향, 전대뇌동맥, 뇌기저동맥, 추골동맥은하향을보였다 (Fig. 3). 안정상태의평균뇌혈류속도는중대뇌동맥의경우상향파로서 80.66±14.30 및 83.22±14.40 cm/sec ( 우측과좌측 ), 전대뇌동맥의경우하향파로서 49.11±15.71 및 48.19±13.75 cm/sec, 후대뇌동맥의경우상향파로서 39.24±9.12 및 37.91±6.74 cm/ sec, 추골동맥의경우하향파로서 33.65±9.26 및 36.18±10.39 cm/sec, 뇌기저동맥의경우하향파로서 48.49±11.16 cm/sec였고우측과좌측동맥간유의한차이는없었다 (P>0.05, Table 3). 뇌혈관별평균혈류속도는중대뇌동맥, 전대뇌동맥, 뇌기저 동맥, 후대뇌동맥, 추골동맥의순으로점차낮았다. 2. 무호흡및과호흡상태의뇌혈류속도우측및좌측의중대뇌동맥평균뇌혈류속도는안정상태에비해무호흡시유의하게상승하였으나 (P=0.0006, P=0.011) 과호흡시에는유의하게감소하였다 (P=0.007, P=0.0033, Table 4). 3. 성별에따른차이안정상태에서각혈관부위별평균혈류속도는남녀간전반적으로차이를보였는데, 여자군의좌측및우측중대뇌동맥, 우측전대뇌동맥, 우측후대뇌동맥, 좌측및우측추골동맥의혈류속도가남자군의경우보다유의하게더높았다 (P<0.05, Table 5). 나머지혈관의평균뇌혈류속도는남녀간에유의한차이가없었다. 혈압의경우남자군이여자군보다수축기및평균혈압은유의하게더높았고확장기혈압과심장박동수는차이가없었다 (Table 2). 고찰 1843년 Christian Doppler에의해도플러효과 (Doppler effect) 가발표된이래 1959년 Satomura가도플러방법을이용하여말초혈관의혈류속도를비침습적이고경피적으로측정함으로써도플러의임상적이용시대를열었다. 그후 1982년노르웨이의물리학자이자인공두뇌학자인 Aaslid가저주파 (2 MHz) 의탐촉자를사용하여측두골을통한두개강내혈관의혈류속도를측정하는방법을개발함으로써폐쇄성혈관질환뿐만아니라지주막하출혈후혈관연축의확인에유용한검사로제시되었다. 오늘날 TCD는뇌혈류역학변화를평가하기위한필수장비로활용되고있다. 한편그동안국내에서도몇몇연구자들에의해 TCD를이용하여경두개뇌혈관혈류속도의정상치에대한보고가있었으나연구대상이 20대에서 70대사이의광범위한연령층이였던까닭에특정연령대에대한뇌혈류역학의이해자료로는다소부족함이있었다. 저자들은이연구에서 20대연령층의젊은이들만을연구대상으로한정시켜이연령대의뇌혈류역학에대한좀더깊은이해와자료의축적을시도하였다. 우리의연구에서뇌혈관별평균혈류속도의빠르기는중대뇌동맥, 전대뇌동맥, 후대뇌

Fig. 3. Summary figure displays the arterial segments investigated and wave forms recorded in a normal transcranial Doppler ultrasonographic examination.

cerebral artery; LVA=left vertebral artery; RVA= right vertebral artery; BA=basilar artery. Table 5.

4 Fig. 3. Summary figure displays the arterial segments investigated and wave forms recorded in a normal transcranial Doppler ultrasonographic examination. LMCA=left middle cerebral artery; RMCA=right middle cerebral artery; LACA=anterior cerebral artery; RACA= right anterior cerebral artery; LPCA=left posterior cerebral artery; RPCA=right posterior cerebral artery; LVA=left vertebral artery; RVA= right vertebral artery; BA=basilar artery. Table 5. Comparison between male and female group in the velocity at stable condition MCA-V (cm/s) ACA-V (cm/s) PCA-V (cm/s) VA-V (cm/s) Right Left Right Left Right Left Right Left BA (cm/s) M a F b * 87.0 * * * * * *, P<0.05 (compared with male group). a, male group; b, female group 동맥의순서로서선행연구보고들 (Kwun et al., 1989; Ahn et al., 1991; Kim et al., 1995; Krejza et al., 1999; Szydlik et al., 2000) 과일치하였고전체연구대상자들중혈관별뇌혈류속도가이순서를벗어나는사례는거의없었다. 또한각혈관별좌측과우측의값에의미있는차이를보이는경우가없으므로연구대상자모두의뇌혈류역학이정상상태를유지함을알수있었다. 중대뇌동맥은뇌분포혈관중가장내경이크고대뇌반구로공급하는전체뇌혈류량의 80% 를담당하는혈관인까닭에평균뇌혈류속도가가장높다. 따라서저자들의연구에서측정조건의변화에따른뇌자동조절기전의정상적반응을조사하기위해중대뇌동맥의평균뇌혈류속도만을측정하여평가지표로활용하였다. 뇌자동조절기전의정상적반응을평가하기위해이연구에서채택한방법은연구대상자로하여금무호흡상태와빈호흡상태를일정시간동안유지하여동맥혈액의이산화탄소분압 (PCO 2 ) 레벨을변화시키는방법이었다. 동맥혈액의 PCO 2 레벨변화 는뇌혈류에영향을미치게된다. 뇌혈관의 CO 2 반응성은혈중이산화탄소가혈관내피세포하의뇌-혈관문 (brain-vessel barrier) 을통과하여세포간산성도를저하시켜뇌혈관의근섬유를수축시킴으로써나타나게된다 (Wade et al, 1988; Widder, 1989). 동맥혈액의 PCO 2 가변화하면뇌의연막혈관은 20초후에변화가일어나는데 (Auer, 1978), 과호흡에따른저탄산혈증에대한변화는상대적으로빨리나타나고 (Severinghaus. et al., 1967) 무호흡으로인한고탄산혈증시에는상대적으로느리게나타나며만성적인노출시그반응성은저하된다 (Levasseur et al., 1979). PCO 2 반응성은외상 (Saunders et al., 1979), 두개내수술 (Haggendal et al., 1965), 동맥경화 (Lindegaard et al., 1987), 뇌지주막하출혈 (Jakubowski et al., 1982) 등의경우저하되고특히뇌대사가저하된혼수상태의환자에서현저히저하된다 (Ingvar et al., 1964). 대개동맥혈액의 PCO 2 가 25~57 mmhg 사이에서는 PCO 2 가 1 mmhg 감소또는증가되면뇌혈류는 2~6% ( 평균 4%) 감소또는증가되며이때변

5 화된 PCO 2 레벨에대해뇌기저큰동맥들의반경은변화가없고미세동맥의반경변화로뇌혈류의변화가일어난다고한다 (Kety et al., 1948; Huber et al., 1967). 혈중 PCO 2 변화에따라연막의소동맥들의내경이변화되면그부위를공급하는뇌기저동맥에이변화가반영되며이는 TCD를이용하여시간에따른평균뇌혈류속도의변화로환산할수있다. 한편 Markwalder 등 (Markwalder et al., 1984) 은정상적인경우동맥혈액의 PCO 2 1 mmhg 변화시중대뇌동맥의혈류속도는 3~4% 변화된다고보고한바있다. 저자들의연구에서도모든연구대상자들이무호흡상태에서는중대뇌동맥의평균뇌혈류속도가안정시보다유의하게증가하였고과호흡시에는유의한감소를보였으며, 그변화양상이과호흡의경우가무호흡의경우보다빠른변화를보임으로써기존의연구저자들이보고한결과들과거의일치하였다. 이러한결과들은저자들의연구에서대상이된 20대연령층의젊은이들이지극히정상적인뇌혈류역학및대사를유지하고있음을보여주는증거라할수있다. 그러나저자들의연구에서측정된중대뇌동맥의평균혈류속도와국내의선행연구결과사이에는차이를보였다. 저자들의결과는 cm/sec ( 우측 ) 와 cm/sec ( 좌측 ) 로써권등 (Kwun et al., 1989) 의 61 cm/sec, 안등 (Ahn et al., 1991) 의 55.9 cm/sec, 김등 (Kim et al., 1995) 의 49 cm/sec ( 남자군 ) 와 57 cm/sec ( 여자군 ) 와는현저한차이가있었다. 연구간의이러한차이가무엇때문에발생하였는지에관해향후지속적연구를통한규명이필요하겠지만현재의관점에서는연구대상간의특성적차이에기인한것으로판단된다. 저자들의경우 20대연령층의젊은이들만을연구대상화한데비해전술한국내타연구저자들은 20대뿐만아니라 30대에서 70대에걸친고연령층이다수포함된대상을연구함으로써중대뇌동맥의평균혈류속도결과가상대적으로낮은값으로통계처리된것으로생각된다. 연령의증가는뇌혈류속도의감소를가져오는데 20대에서 70대사이의연령에서평균뇌혈류속도는약 15~24% 정도감소된다 (Arnolds et al., 1986; Vriens et al., 1989). Grolimund 등 (Grolimund et al., 1988) 은연령 1세의증가시중대뇌동맥의평균혈류속도는약 0.51% 감소한다고보고하였다. 연령의증가에따른뇌혈류속도의저하는큰뇌동맥의직경변화보다는작은뇌혈관의저항증가와더관련이있을것으로생각된다 (Kim et al., 1995). 최근 Krejza 등 (Kre- jza et al., 1999) 과 Szydlik 등 (Szydlik et al., 2000) 은 20대연령층의중대뇌동맥의평균혈류속도가약 81 cm/sec라고보고함으로써저자들의연구결과와거의일치하였다. 그외나머지뇌혈관별혈류속도는타연구들과유의한차이를보이지않았다. 한편성별에따른안정상태시뇌혈류속도의비교결과는전반적으로여자군이남자군보다높은것으로나타났다. 이러한성별에따른뇌혈류속도의차이에대해이등 (Lee et al., 2001) 은여성의경우 estrogen 호르몬이분비됨으로써남자보다뇌혈류속도가약 3~5% 정도빠르다고설명한바있고, Grolimund 등 (Grolimund et al., 1988) 과 Vriens 등 (Vriens et al., 1989) 은헤마토크리트 (hematocrit) 의차이에기인한것으로설명하고있다. 이들은여성이남성보다헤마토크리트수치가낮으므로더높은뇌혈류속도를보였다고주장하였다. Brass 등 (Brass et al., 1988) 은헤마토크리트수치와뇌혈류속도사이에유의하게높은음의상관성이있다고설명한바있다. 저자들의연구에서도비록결과에서제시하지는않았지만뇌혈류검사시채혈을통해측정한헤마토크리트치가여자군의경우평균 35.89%, 남자군의경우평균 44.37% 를보임으로써여자군이유의하게더낮았다. TCD검사시함께측정한수축기혈압과평균혈압역시여자군이남자군보다유의하게낮았는데이러한혈압의차이가남녀간의뇌혈류속도의차이에영향을미친것으로는판단되지않는다. 그이유는고혈압이나뇌혈관질환이없는사람의경우평균혈압이 50~150 mmhg 사이로유지되면뇌혈류는특별한변화없이일정한상태를유지할수있기때문이다 (Schell et al., 1993). 결국저자들의연구에서나타난여자군의상대적으로더높은뇌혈류속도는전술한에스트로겐및헤마토크리트의차이에기인한것으로사료된다. 그러나권등 (Kwun et al., 1989), 안등 (Ahn et al., 1991), 김등 (Kim et al., 1995) 의경우남녀간의중대뇌동맥의뇌혈류속도에유의한차이가없다고보고함으로써저자들의연구결과와상치되었다. 이러한차이는이미전술한연구대상의차이에따른결과로판단된다. Vriens 등 (Vriens et al., 1989) 과 Bode 등 (Bode et al., 1988) 은성별에따른뇌혈류속도의차이는 20~60대연령층과어린아이군에서는유의한차이를보이지만 70대이상의연령층에서는남녀간의차이가유의하지않다고보고한바있다. 따라서국내타연구들의경우 60대이상의고연령층이연구대상에포함됨으로써남녀간의차이를상쇄시킨것으로사료되나향후좀더큰연구집단을대상으로한지속적연구가필요할것으로판단된다. 결론적으로, 저자들의연구에있어기왕의질병이없는 20 대연령층의뇌혈류역학및자동조절기전은정상적이었고여자군이남자군에비해뇌혈류속도가상대적으로더높았다. 향후더많은건강인을대상으로한다양한조건 ( 예를들어음주전후, 흡연, 자세의다양한변화 ) 에서의뇌혈역학및뇌생리에대한연구를실시하여좀더폭넓고깊이있는데이터수집이지속되어야할것으로생각된다. REFERENCES Aaslid R, Markwalder TM, Nornes H. Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cere

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(01) hwp Journal of Life Science 2013 Vol. 23. No. 2. 157~166 ISSN (Print) 1225-9918 ISSN (Online) 2287-3406 DOI : http://dx.doi.org/10.5352/jls.2013.23.2.157 α μ δ κ 158 생명과학회지 2013, Vol. 23. No. 2 Journal of