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Biomedical Science Letters 2017, 23(3): 208~214 https://doi.org/10.15616/bsl.2017.23.3.208 eissn : 2288-7415 Original Article Acute Variation of Hematological Parameters during 622 km Ultra-Marathon Kyung-A Shin 1 and Young-Joo Kim 2, 1 Department of Clinical Laboratory Science, Shinsung University, Chungnam 31801, Korea 2 Department of Exercise Rehabilitaion Welfare, Sungshin University, Seoul 02844, Korea To investigate the effects of strenuous physical exercise on commonly used hematological markers in subjects the intensive long running. Blood samples were obtained from nineteen participants in a 622 km ultra-marathon race before, 300 km and immediately after completion of the 622 km ultra-marathon. Samples were analyzed for total white cell count (WBC) and differential, total red cell count (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelets, mean platelets volume (MPV), platelets distribution width (PDW). Significant increases were found in WBC, neutrophil and platelets at 622 km compared to the pre-race. RBC, hemoglobin and hematocrit decreased statistically significantly the race at 300 km and 622 km compared to pre-race. A wide range of hematological perturbations occur during 622 km ultra-marathon running but it was physiological changes within a reference range. The 622 km ultramarathon is less likely to cause clinically significant hematologic changes in athletes. Key Words: Ultra-marathon, Hematological markers, Physiological changes 서론규칙적인신체활동은다양한생리적반응에의한긍정적효과가있지만, 격렬한운동은저나트륨혈증, 골격근과간세포손상, 염증반응, 빈혈, 면역기능저하등생화학및면역학적변화를일으킬수있다고보고된다 (Peters, 1997; Shin and Kim, 2012; Waśkiewicz et al., 2012; Drygas et al., 2014). 검사실에서시행하는혈액학적검사는임상및항도핑 (antidoping) 목적으로스포츠의학분야에서주목받고있다 (Lippi et al., 2010). 운동에의한혈액학적변화를조사하는것은데이터의오역을방지하고임상적유용성을향상시키기위해필요하지만, 인체에미치는잠재적 영향에대한정보는부족하다 (Banfi and Dolci, 2003). 지금까지운동상황에서관찰된혈액학적변화는 21 km 하프마라톤후일시적인백혈구, 호중구, 단구의증가와급성호산구감소증을유발하며, 24시간이내에안정상태로회복된다고보고된다 (Lippi et al., 2010). Fallon 등 (1999) 은 1,600 km 울트라마라톤직후백혈구는증가하나헤모글로빈, 적혈구용적백분율 (packed cell volume, PCV), 림프구및단구비율은감소한다고보고하였다. 장시간고강도운동에의한혈액학적변화는기계적외상으로인한혈관내용혈, 적혈구삼투압및산화적손상, 잠혈에의한혈액손실의가능성, 염증반응등을고려해야한다 (Smith, 1995; Shin and Kim, 2012). 42.195 km의마라톤과비교해장거리를달리는울트라 * Received: June 11, 2017 / Revised: August 7, 2017 / Accepted: August 7, 2017 Corresponding author: Young-Joo Kim. Department of Exercise Rehabilitaion Welfare Soojung Campus, Sungshin University, 2 Bomun-Ro 34Da-Gil, Seongbuk-Gu, Seoul 02844, Korea. Tel: +82-2-920-7942, Fax: +82-2-920-7942, e-mail: kyj87@sungshin.ac.kr C The Korean Society for Biomedical Laboratory Sciences. All rights reserved. CC This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. - 208 -

마라톤은 100 km 이상을달리는경기로규정되며, 622 km 국토종단울트라마라톤은우리나라에서진행되는가장긴코스의경기로본연구는인간능력의한계를탐구하려는특별한시도이다. 본연구는 622 km 울트라마라톤대회에출전한주자들을대상으로경기전, 300 km, 경기종료직후에혈액학적지표변화를통해잠재적인의학적합병증의평가와치료에도움이되고자하였다. 재료및방법 622 km 울트라마라톤대회이연구는 2015년 7월 5일 06시부터 7월 11일 12시까지총 150시간동안대한울트라마라톤연맹주관하에시행한 622 km 울트라마라톤에참여한주자들을대상으로하였다. 대회출발지는전남해남땅끝기념탑이며, 도착지는강원도고성출입국관리소였다. 울트라마라톤출발시기온은 29, 습도는 70% 였다. 622 km 울트라마라톤참가자격은한반도횡단대회 308 km를완주한자, 제주일주 200 km를완주한자, 622 km 울트라마라톤을중도포기하였으나 200 km 이상을제한시간내에주파한자, 308 km 울트라마라톤을중도포기하였으나 200 km 이상을제한시간내에주파한자, 대회일기준으로최근 2년내대한울트라마라톤연맹에서공인한대회에 200 km 이상완주한자이다. 622 km 울트라마라톤주자들은 50 km 단위를제한시간내에통과하여야하며, 통과한주자는대회조직위원, 가족및지인이준비한텐트, 음식, 마사지등을제공받을수있었다. 그러나차량탑승은부정행위로간주하였다. 대회 3개월전대한울트라마라톤연맹회장에게실험방법및절차에대해설명을한후대회홈페이지에서인터넷상으로지원자를모집하였다. 참가의향을밝힌자들을선별하여개인메일로연구목적과절차에대해설명하였으며, 동의서를받은후대회 1개월전부터출발 1주일전까지운동부하검사를실시하였다. 이연구는인제대학교상계백병원에서 IRB 심의를받은후시행되었다 (2015년 5월 6일, SGPAIK 2015-04-003-001). 연구대상자본연구대상자는연구에자발적으로지원한남성총 28명중에서 622 km 울트라마라톤을완주한 19명을최종연구대상자로선정하였다. 연구대상자에서제외되는기준은 622 km 울트라마라톤완주에실패한자, 경기규정시간내에완주하지못한자, 안정시혈압이 140/90 mmhg 이상인자, 협심증이나심근경색증, 심장수술의과거력이있는심혈관계질환자, 당뇨, 신장질환, 간질환자, 고혈압으로약물복용중인자는제외하였다. 혈액검사연구대상자들의혈액학적지표를분석하기위하여대회출발전, 경기중반지점인 300 km, 경기종료지점인 622 km에서채혈을시행하였다. K2-EDTA tube (BD Vacutainer, USA) 에채혈한전혈검체로 LH 750 (Beckman Coulter, Miami, FL, USA) 자동화장비를이용하여적혈구 (red blood cell, RBC), 헤모글로빈 (hemoglobin, Hb), 헤마토크리트 (hematocrit, Hct), 적혈구분포계수 (red cell distribution width, RDW), 백혈구 (white blood cell, WBC), 백혈구백분율 (WBC differential count), 혈소판 (platelet), 혈소판용적치 (plateletcrit, PCT), 평균혈소판용적 (mean platelet volume, MPV), 혈소판분포계수 (platelet volume distribution width, PDW) 를측정하였으며, Hb과 Hct를이용하여평균적혈구용적 (mean corpuscular volume, MCV), 평균적혈구혈색소 (mean corpuscular hemoglobin, MCH), 평균적혈구혈색소농도 (mean corpuscular hemoglobin concentration, MCHC) 를산출하였다. MCV는적혈구한개당평균용적을나타내는지수로 (hematocrit %)/(RBC 10 6 /μl) 10으로, MCH는적혈구한개당혈색소량으로 (hemoglobin g/dl)/(rbc 10 6 /μl) 10으로, MCHC는적혈구한개당평균혈색소농도로 hemoglobin / hematocrit 100으로계산하였다. 운동부하검사연구대상자들의유산소성운동능력을측정하기위하여트레드밀운동부하검사 (Quintion Co, U.S.A) 는 3분마다속도와경사도를증가시키는 Bruce Protocol로시행하였으며, Medtrack ST 55 (Quinton Instrument Co., Boston, USA) 트레드밀장비를사용하여측정하였다. 운동부하검사종료시점은심박수가더이상증가하지않고운동자각도 (RPE; rating of perceived exertion, Borg's Scale) 가 17 이상일경우로하였으며, 미국심장학회 (America College of Cardiology, ACC) 및미국심장협회 (American Heart Association, AHA) 의지침에따라검사하였다 (Gibbons et al., 2002). 모든피험자는검사전의자에앉아안정을취한후안정시심박수와혈압을측정하였으며, 혈압은수은혈압계로측정하였다. 운동중운동자각도와혈압은매 stage와테스트직후및회복기동안에측정하였다. 운동부하검사를통해안정시심박수 (resting heart rate, RHR). 최대심박수 (maximum - 209 -

heart rate, MHR), 안정시수축기혈압 (resting systolic blood pressure, RSBP) 및이완기혈압 (resting diastolic blood pressure, RDBP), 최대수축기혈압 (maximum systolic blood pressure, MSBP) 및이완기혈압 (maximum diastolic blood pressure, MDBP) 을기록하였다. 운동부하검사용심전도검사기 Q4500 (Quinton Instrument Co., Boston, USA) 및호흡가스분석기 QMC (Quinton Instrument Co., Boston, USA) 를이용하여최대산소섭취량 (maximum oxygen consumption, VO 2 max) 을측정하였으며, 체질량지수 (body mass index, BMI) (kg/m 2 ) 는몸무게 (kg)/[ 신장 (m 2 )] 으로계산하였다. 은 65.47±6.80 bpm이었으며, 운동부하검사시평균 MHR 은 177.00±5.93 bpm이었다. 평균 RSBP와 RDBP는각각 126.05±8.78 mmhg, 80.21±5.82 mmhg 이었다. 운동부하검사시평균 MSBP와 MDBP는각각 219.89±17.37 mmhg, 78.32±8.31 mmhg이었다. 평균최대산소섭취량은 49.65 ±5.76 ml/kg/min이었으며, 평균경기시간은 8,110.26± 1,312.05분이었다. 622 km 울트라마라톤구간별백혈구관련지표의변화 622 km 울트라마라톤대회에출전한주자들을대상으로 자료처리방법 본연구의통계분석은 SPSS Windows 21.0 (IBM, Armonk, USA) 프로그램을이용하였다. 622 km 울트라마라톤경기전, 300 km 지점, 622 km 종료시점에서의구간별기술통계치 ( 평균, 표준편차 ) 를구하였다. 3구간에서시기별혈액학적지표의차이를비교하기위해단일변량반복측정분산분석 (one way repeated measures ANOVA) 을실시하였으며, 사후검정방법으로 Bonferroni를적용하였다. 본연구의통계학적유의수준은 P<0.05로설정하였다. 결과 622 km 울트라마라톤참가자의특성 622 km 울트라마라톤대회에출전한주자들의특성은 Table 1에제시된바와같이평균연령은 53.00±4.36세, 평균신장은 171.32±3.83 cm, 평균체중은 69.63±3.89 kg, 평균체질량지수는 23.65±1.32 kg/m 2 이었다. 평균 RHR Variables Table 1. Subject characteristics (N=19) Mean ± SD Age (year) 53.00±4.36 Height (cm) 171.32±3.83 Weight (kg) 69.63±3.89 BMI (kg/m 2 ) 23.65±1.32 RHR (bpm) 65.47±6.80 MHR (bpm) 177.00±5.93 RSBP (mmhg) 126.05±8.78 RDBP (mmhg) 80.21±5.82 MSBP (mmhg) 219.89±17.37 MDBP (mmhg) 78.32±8.31 VO 2 max (ml/kg/min) 49.65±5.76 Race time (min) 8,110.26±1,312.05 Abbreviations: BMI, body mass index; RHR, resting heart rate; MHR, maximum heart rate; RSBP, resting systolic blood pressure; RDBP, resting diastolic blood pressure; MSBP, maximum systolic blood pressure; MDBP, maximum diastolic blood pressure. Table 2. Changes in WBC parameters during the 622 km ultra-marathon Variables Pre-race 300 km 622 km P-value WBC ( 10 3 cells/μl) 6.20±0.99 9.79±2.06 * 8.95±2.29 * <0.001 WBC differential count Neutrophil (%) 51.31±10.09 71.20±7.90 * 72.77±6.53 * <0.001 Lymphocyte (%) 38.40±8.76 19.43±6.52 * 17.66±5.26 * <0.001 Monocyte (%) 6.46±1.27 7.58±1.64 7.42±2.03 0.053 Eosinophil (%) 3.21±2.50 1.49±1.17 * 1.83±1.54 0.042 Basophil (%) 0.60±0.25 0.27±0.13 * 0.28±0.14 * <0.001 Calculated by one way repeated measures ANOVA and Bonferroni test. Values are presented as mean ± SD. Abbreviations: WBC, white blood cell. *; Significantly different from Pre-race at P<0.05. - 210 -

Table 3. Changes in RBC and RBC indices during the 622 km ultra-marathon Variables Pre-race 300 km 622 km P-value RBC ( 10 6 cells/μl) 4.60±0.42 4.28±0.36 * 4.13±0.34 * <0.001 Hb (g/dl) 14.10±1.54 13.05±1.44 * 12.52±1.35 * <0.001 Hct (%) 40.12±3.50 37.80±3.36 * 36.96±3.40 * <0.001 MCV (fl) 87.38±6.01 88.36±6.23 * 89.63±6.33 * <0.001 MCH (pg) 30.69±2.71 30.49±2.66 * 30.35±2.64 * <0.001 MCHC (g/dl) 35.07±1.25 34.45±1.20 * 33.82±1.07 * <0.001 RDW (%) 13.06±1.46 13.19±1.49 13.36±1.97 0.144 Calculated by one way repeated measures ANOVA and Bonferroni test. Values are presented as mean ± SD. Abbreviations: RBC, red blood cell; Hb, hemoglobin; Hct, hematocrit; MCV, mean corpuscular volume; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; RDW, red cell distribution width. *; Significantly different from Pre-race at P<0.05, ; Significantly different from 300 km at P<0.05. Table 4. Changes in platelet parameters during the 622 km ultra-marathon Variables Pre-race 300 km 622 km P-value Platelet ( 10 3 cells/μl) 225.78±53.12 225.31±47.78 240.26±48.66 * 0.011 PCT (%) 0.23±0.05 0.23±0.04 0.26±0.04 * <0.001 MPV (fl) 10.44±0.92 10.53±0.81 11.00±0.86 * <0.001 PDW (fl) 12.51±2.19 12.48±1.78 12.82±1.67 0.144 Calculated by one way repeated measures ANOVA and Bonferroni test. Values are presented as mean ± SD. Abbreviations: PCT, plateletcrit; MPV, mean platelet volume, PDW, platelet distribution width. *; Significantly different from Pre-race at P<0.05, ; Significantly different from 300 km at P<0.05. 경기전, 300 km 지점, 622 km 경기종료직후의혈액학적지표의변화를알아보고자하였으며, 그결과구간별백혈구관련지표의변화는 Table 2에제시된바와같다. 백혈구는경기전보다 300 km 지점과 622 km 지점에서유의하게높았다 (P<0.001). 백혈구수백분율에서호중구는경기전보다 300 km 지점과 622 km 지점에서유의하게높았으며 (P<0.001), 림프구와호염기구는경기전보다 300 km 지점과 622 km 지점에서유의하게낮았다 ( 각각 P<0.001). 또한호산구는경기전보다 300 km 지점에서유의하게낮았으나 (P=0.042), 단구는마라톤구간별유의한차이가없었다. 622 km 울트라마라톤구간별적혈구관련지표의변화적혈구와 Hb은경기전보다 300 km 지점과 622 km 지점에서낮았으며, 622 km는 300 km 지점보다낮았다 ( 각각 P<0.001). Hct는경기전보다 300 km 지점과 622 km 지점에서낮게나타났다 (P<0.001). MCV는경기전보다 300 km 지점과 622 km 지점에서높았으며, 622 km 지점은 300 km 지점보다높았다 (P<0.001). 그러나 MCHC는경기보다 300 km와 622 km 지점에서낮았으며, 622 km 지점은 300 km 지점보다낮게나타났다 (P<0.001). 또한 MCH는경기전보다 300 km와 622 km 지점에서통계적으로유의하게낮았으나 (P<0.001), RDW는마라톤구간별차이가없었다 (Table 3). 622 km 울트라마라톤구간별혈소판관련지표의변화혈소판수 (P=0.011) 와 PCT (P<0.001), MPV (P<0.001) 는경기전보다 622 km 지점에서높았으며, 300 km 지점보다도 622 km 지점에서높게나타났다. 그러나 PDW는구간별유의한차이가없었다 (Table 4). - 211 -

고찰마라톤은인체에과도한부담을주어선수의 2~8% 정도는경기중또는경기후에전해질불균형, 근골격계상해및심폐기능합병증등으로의료진의진료를받는것으로보고된다 (Crouse and Beattie, 1996; Roberts, 2000; Sanchez et al., 2006; Mohseni et al., 2011). 또한마라톤경기에의해백혈구증가와혈소판, 적혈구, Hb, Hct 등의다양한혈액학적변화를보이지만, 이러한지표는주자들의특성, 채혈시점, 경기수행능력및거리, 운동강도, 환경적요인등으로인해다양한결과를나타낸다 (Kratz et al., 2002; Spiropoulos and Trakada, 2003; Traiperm et al., 2013; Lippi et al., 2014; Martin et al., 2015). 본연구에서는우리나라에서시행되는가장긴코스의 622 km 국토종단울트라마라톤이혈액학적지표변화에미치는영향을알아보고자하였다. 그결과경기전보다 300 km 지점과경기직후에호중구증가및림프구감소에따른백혈구수증가를보였다. 울트라마라톤은넓은범위의혈액학적지표변화를나타내는데, 특히백혈구상승은대부분호중구증가증 (neutrophilia) 에의한것으로일시적인면역기능저하가나타난것으로생각된다 (Pyne, 1994; Natale et al., 2003; Smith et al., 2004). 이는운동에의한생체부하및스트레스로유발된정상적인급성기반응으로감염이나질환의지표와혼돈해서는안될것으로생각된다 (Fallon et al., 1999). 운동에의한호중구증가는국소적으로손상된조직에서분비되는카테콜아민, 코티졸과같은호르몬이나체온변화및혈류증가에따른염증반응에의해유발되는것으로제시된다 (Pyne, 1994; Natale et al., 2003; Nieman, 2007; Lippi et al., 2010). 본연구에서 622 km 울트라마라톤직후 4명의대상자에게서백혈구수가참고범위를벗어났으나, 감염의징후는없었다. Wu 등 (2004) 은 24시간울트라마라톤직후빈혈지표인적혈구, Hb, Hct는정상이었으나, 경기이틀후에감소한다고보고하였다. 또한적혈구와 Hb은탈수와혈장용적감소로마라톤초기에는상승하다가적혈구손상에의해경기종료후감소하는것으로보고되며 (Martin et al., 2015), 이러한현상을스포츠빈혈이라한다 (Eichner, 1986). 스포츠빈혈은만성적희석상태 (chronic dilutional state) 로써물리적외상에의한혈관내용혈뿐만아니라적혈구의산화적손상때문에유발된다 (Eichner, 1986; Smith, 1995). 본연구결과적혈구와 Hb은경기전보다달리는거리 가길어질수록낮아졌으며, Hct는경기전보다 300 km 지점과 622 km 지점에서낮았다. 정상적으로적혈구의평균수명은 120일로매일약 1% 씩새로운세포로교체된다 (Wu et al., 2004). 마라톤과같은지구력운동에의한지속적인발바닥충격 (foot strike) 은용혈의원인이되어적혈구교체율 (turnover rate) 을증가시키지만, 새로운적혈구는오래된적혈구보다산소운반에더효율적일수있다고보고된다 (Smith, 1995; Jordan et al., 1998). 한편, Lippe 등 (2010) 은하프마라톤종반에적혈구의크기를의미하는 MCV의유의한증가를보고하였으나, 24시간울트라마라톤경기전후에 MCV의차이가없다는결과도보고된다 (Wu et al., 2004). 본연구에서는주행거리가길어질수록 MCV와 MCHC는비례하여증가하였으며, MCH는경기전보다 300 km와경기직후유의한증가를보여스포츠빈혈에적혈구크기및헤모글로빈양이원인인것으로보인다. 그러나적혈구용혈과관련된 haptoglobin, 망상적혈구수, 철분관련검사가요구되며, 향후 622 km 울트라마라톤에서혈액학적변인들의회복기반응에관한연구가필요하리라생각된다. 마라톤과같은고강도지구력운동에의해혈소판과 MPV의증가가보고되며 (Wu et al., 2004; Lippi et al., 2014), 본연구결과에서도 622 km 울트라마라톤직후혈소판과 MPV가증가하였다. 전통적으로 MPV의증가는혈소판과반응성 (platelet hyperreactivity) 을반영하는데, 최근메타분석에서급성심근경색, 심근경색후사망률및관상동맥혈관성형술후재협착과의관련성이확인되었다 (Chu et al., 2010; Gasparyan et al., 2011). 그러나 Lippi 등은혈소판과 MPV가경기이후 3시간의회복기동안에안정시수치로회복됨을보고하여혈소판용적증가가지속적운동에의한생리학적변동임을유추할수있으나, 응고장애와관련된추가검사가필요하겠다 (Lippi et al., 2014). 결론적으로 622 km 울트라마라톤은호중구증가에의한백혈구수증가와적혈구및 Hb의감소, 혈소판증가를유발하였다. 이러한결과는참고범위내에서의생리학적변화로 622 km 울트라마라톤이선수들에게임상적으로중요한혈액학적변화를일으킬위험은낮은것으로나타났다. CONFLICT OF INTEREST The authors have no conflicts of interest to disclose. - 212 -

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