신장의 허혈 및 재관류 손상방지에 관한 연구

윤성수(Sung Su Yun),신명준(Myeong Jun Shin),송선교(Sun Kyo Song),김홍진(Hong Jin Kim),심민철(Minn Chul Shim),권굉보(Koing Bo Kwun) 대한외과학회 1991 Annals of Surgical Treatment and Research(ASRT) Vol.41 No.5

개심술에 있어서 Low-Dose Aprotinin의 투여효과

박남희,최세영 대한흉부심장혈관외과학회 1996 Journal of Chest Surgery (J Chest Surg) Vol.29 No.9

체외순환을 이용한 개심술후 혈소판기능부전에 의한 비정상적인 출혈은 수술 사망율 및 이환율의 증가를 초래한다. 본 논문에서는 체외순환시 aprotinin을 투여하여 임상적 지혈 및 혈소판기능보존에 대한 효과를 관찰하기 위해 인공판막치 환술을 받은 40명의 환자를 대상으로 low-dose aprotinln 투여군 20명, 대조군 20명으로 나누어 그 효과를 비교 분석하였다. Aprotinin 투여군에서 대조군에 비해 약 40%의 출혈감소(622.0$\pm$ 186m1 versus 1021 $\pm$483.5ml, p<0.01) 및 약 63%의 혈색소 손실(14.7 $\pm$6.8g versus 39.7$\pm$ 16.4g, p<0.01)을 줄일 수 있었으며 약 70%의 수혈감 소(197.7$\pm$ 56.3ml versus 651.2 $\pm$ 147.5ml, p<0.01) 효과를 얻을 수 있었다. 또한 투여 군에서 혈소판 응집 능이 효과적으로 보존되었다(P<0.05). 체외순환중 activated clotting time이 투여 군에서 연장되어 heparin의 항응고작용에 대해 상승효과가 있었으며 aprotinin의 투여와 관련된 합병증은 없었다. 이상의 결과에서 체외순환을 이용한 개심술에 있어서 low-dose aprotinin의 투여는 술후 출혈량 및 혈 액과 혈액제제의 사용감소에 효과가 있으며 이는 혈소판응집능의 효과적 \ulcorner보존에 의한 것으로 사료된다. Excessive blood loss secondary to cardiopulmonary bypass(CPB) may be encountered after open heart surgery and platelet dysfunction appears to be especially responsible for this problem. To evaluate the effect of low-dose aprotinin during hypothermic CPB on platelet aggregation, anticoagulation and clinical hemostasis,.40 patients undergoing valve replacement using hypothermic CPB procedures were randomized to give either a low dose aprotinin(2$\times$ 106 KIU in the CPB priming sol- ution, n=20) or a placebo(n=20). During postoperative 24 hours, blood and hemoglobin loss were lower in the aprotinin group (225.5 $\pm$ 121.9ml, and 11.3$\pm$2.4g) than the control group(572.2$\pm$)35.5ml and 26.3$\pm$9.8g)(P<0.01). The total blood and hemoglobin loss were lower in the aprotinin group (622.0$\pm$ 186m1 and 14.7$\pm$6.8g) than the con- trol group (102.1 $\pm$483.5ml and 39.7$\pm$ 16.4g) (P<0.01). The amonut of packed red cell needed decreased in the aprotinin group: 197.7$\pm$56.3ml vers s 651.2: 147.5ml (P<0.01). Hemoglobin concentration, platelet counts and fibrinogen checked at fixed times perioperatively did not differ between the two groups. Platelet aggregation was induced by ADP, collagen, epinephrine and ristocetin before and after CPB. Maximum platelet aggregation was significantly reduced after CPB in control group (ranging from -31 % to -58% relative to prebypass values). Significant prolongation of activated clotting time(ACT) after 5 minute and 30 minute of hypothermic CPB were observed: 955.9 $\pm$35.1 and 967.5$\pm$32.7sec versus 743.8 $\pm$ 52.1 and 731.2: 54.6sec (P<0.01). There was no complication associated with aprotinin infusion. These results demonstrate that low-dose aprotinin significantly reduces blood loss and blood requirment and provides improved postoperative hemostasis which might be related to protection of platelet aggregation capacity.

Aprotinin을 투여한 개심술 환자에서 Kaolin과 Celite Activator를 이용한 Activated Coagulation Time(ACT) 측정의 비교

김정택,선경,이춘수,백완기,조상록,김현태,김혜숙,박현희,김광호,Kim, Joung-Taek,Sun, Kyung,Lee, Choon-Soo,Baik, Wan-Ki,Cho, Sang-Rock,Kim, Hyun-Tae,Kim, Hea-Sook,Park, Hyun-Hee,Kim, Kwang-Ho 대한흉부심장혈관외과학회 1998 Journal of Chest Surgery (J Chest Surg) Vol.31 No.9

개심수술에서 Aprotinin에 의한 ACT가 연장되는가를 알아보기 위해 서로 다른 표면 촉매제인 kaolin (K-ACT)과 celite(C-ACT)를 이용하여 동시에 측정 비교하였다. 개심수술을 받은 22명의 성인을 대상으로 하여 Hemocron 8000 system을 이용하여 동시에 ACT를 측정 하였는데 aprotinin과 heparin 투여 전(Phase I), Aprotinin투여 후 heparin 투여 전(Phase II), heparin투여 5분 후(Phase III), haparin투여 30분 후(Phase IV), heparin투여 60분 후(Phase V), heparin투여 90분 후(Phase VI), protamin투여 30분 후(Phase VII)에 각각 측정하였다. Phase I, II, III에 두 군간에 차이가 없었으나 heparin투여 30분 후에는 C-ACT가 928$\pm$400초 K-ACT가 572$\pm$159초였고 60분 후에는 C-ACT가 888$\pm$254초 K-ACT가 535$\pm$186초 90분 후에는 C-ACT가 686$\pm$141초 K-ACT가 484$\pm$54초로 K-ACT에 비해 C-ACT가 통계학적으로 의의있게 증가하였다. 그러나 protamin투여 후에는 C-ACT가 137$\pm$26초 K-ACT가 139$\pm$28초로 두군간에 차이가 없었다. 이상의 결과에서 aprotinin투여 후 ACT는 연장이 되는 것이 아니라 activator로 celite를 사용했기 때문인 것으로 생각된다. 결론적으로 aprotinin을 투여한 개심수술에서 정확한 ACT수준을 측정하기 위하여 celite activator보다 kaolin activator를 사용해야 하며 heparin은 보통용량을 투입하여야 할 것으로 생각된다. Background: High-dose aprotinin has been reported to enhance the anticoagulant effects of heparin during cardiopulmonary bypass ; hence, som authors have advocated reducing the dose of heparin in patients treated with aprotinin. Material and Method: The ACT was measured before, during and after cardiopulmonary bypass, with Hemochron 801 system using two activators of celite(C-ACT) and kaolin(K- ACT) as surface activator. From June, 1996 to February, 1997, 22 adult patients who were scheduled for elective operation were enrolled in this study. Result: The ACT without heparin did not differ between C-ACT and K-ACT. At 30 minutes after anticoagulation with heparin and cardiopulmonary bypass, the average C-ACT was 928${\pm}$400 s; K-ACT was 572${\pm}$159s(p<0.05). After administration of protamine, C-ACT was 137${\pm}$26 s; K-ACT was 139${\pm}$28s, which were not statistically significant. Conclusion: Our results showed that the significant increase in the ACT during heparin- induced anticoagulation in the presence of aprotinin was due to the use of celite as surface activator, rather than due to enhanced anticoagulation of heparin by aprotinin. We conclude that the ACT measured with kaolin provides better monitoring of cardiac surgical patients treated with high dose aprotinin than does the ACT measured with celite. The patients treated with aprotinin should receive the usual doses of heparin.

체외순환후 혈중 Thromboxane $B_2$와 Endothelin-1 농도 변화에 미치는 Aprotinin의 효과

임청,윤태진,김연승,김승후,이재담,노준량,송명근,Lim, Cheong,Yun, Tae-jin,Kim, Yeon-seung,Kim, Seung-hoo,Lee, Jae-dam,Rho, Joon-Ryang,Song, Meong-Gun 대한흉부심장혈관외과학회 2000 Journal of Chest Surgery (J Chest Surg) Vol.33 No.3

Background: Thromboxane A2 and endothelin-1 are the potent vasoconstrictors affecting pulmonary pathophysiology in response to whole body inflammatin following CPB. Aprotinin, as an antiiflammatory agent, may decrease the release of such vasoactive substance from pulmonary tissues, preventing pulmonary hypertension after cardiopulmonary bypass. Material and Method: Ten mongrel dogs(Bwt. ac. 20kg) were subjected to cardioupulmonary bypass for 2 hours and postbypass pulmonary vascular resistance(0, 1, 2, 3 hours) were compared with prebypass level. The dogs were divided into 2 groups; control group(n-5) and aprotinin group(n=5). In the aprotinin group, aprotinin was administered as follows; 50,000 KIU/kg mixed in pump priming solution, 50,000 KIU/kg prebypass intravenous infusion over 30 minutes, 10,000 KIU/kg/hour postbypass continuous infusion. Prebypass and postbypass 0, 1, 2, 3 hour pulmonary vascular resistance were measured. At prebypass and postbypass 0, 90, 180 minutes, blood samples were obtained from pulmonary arterial and left atrial catherers for the assay of plasma thromboxane B2 a stable metabolite of thromboxane A2, and endothelin-1 concentrations. Result: The ratios of pustbypass over prebypass pulmonary vascular at postbypass 0, 1, 2, 3 hours were 1.28$\pm$0.20, 1.82$\pm$0.23, 1.90$\pm$0.19, 2.14$\pm$0.18 in control group, 1.58$\pm$0.18, 1.73$\pm$0.01, 1.66$\pm$0.10, 1.50$\pm$0.08 in aprotinin group ; the ratios gradually increased in control group while decreased or fluctuated after postbypass 1 hour in aprotinin group. There was statistically significant difference between control group and aprotinin group at postbypass 3 hours(P=0.014). Pulmonary arterial plasma concentration of thromboxane B2(pg/ml) at prebypass, postbypass 0, 90, 180 minutes were 346.4$\pm$61.9, 529.3$\pm$197.6, 578.3$\pm$255.8, 493.3$\pm$171.3 in control group, 323.8$\pm$118.0, 422.6$\pm$75.6, 412.3$\pm$59.9, 394.5$\pm$154.0 in aprotinin group. Left atrial concentrations were 339.3$\pm$89.2, 667.0$\pm$65.7, 731.2$\pm$192.7, 607.5$\pm$165.9 in control group, 330.0$\pm$111.2, 468.4$\pm$190.3, 425.4$\pm$193.6, 4.7.3$\pm$142.8 in aprotinin group. These results showed decrement of pulmonary thromboxane A2 generation in aprotinin group. Pulmonary arterial concentrations of endothelin-1(fmol/ml) at the same time sequence were 7.84$\pm$0.31, 13.2$\pm$0.51, 15.0$\pm$1.22, 16.3$\pm$1.73 in control group, 7.76$\pm$0.12, 15.3$\pm$0.71, 22.6$\pm$6.62, 14.9$\pm$1.11 in aprotinin group. Left atrial concentrations were 7.61$\pm$17.2, 57.1$\pm$28.4, 18.9$\pm$18.2, 31.5$\pm$20.5 in control group, 5.61$\pm$7.61, 37.0$\pm$26.2, 28.6$\pm$21.7, 37.8$\pm$30.6 in aprotinin group. These results showed that aprotinin had no effect on plasma endothelin-1 concentration after cardiopulmonary bypass. Conclusion: Administration of aprotinin during cardiopulmonary bypass could attenuate the increase in pulmonary vascular resistance after bypass. Inhibition of pulmonary thromboxane A2 generation was thought to be one of the mechanism of this effect. Aprotinin had no effect on postbypass endothelin-1 concentration.

흰쥐의 비장손상에 의한 조절되지 않는 복강 내 출혈모델에서 aprotinin의 효과에 대한 연구

성원영,임형우,조병준,이장영,양희범,양영모,홍성엽 대한응급의학회 2007 大韓應急醫學會誌 Vol.18 No.5

Purpose: We investigated the effect of the protease inhibitor, aprotinin, on mean arterial pressure (MAP), hematocrit (Hct), blood loss, and survival rate in rats with experimental splenic injury. Methods: We created an experimental splenic injury model in anesthetized rats by cutting the splenic parenchyma into three fragments. We analyzed the effect of aprotinin on three different treatment groups. The aprotinin treatment group received a single dose of 30,000 U/kg of aprotinin in 10 ml/kg normal saline, the tranexamic acid group was treated with a single dose of 100 mg/kg of tranexamic acid in 10ml/kg normal saline, and the saline control group was treated with only 10 ml/kg normal saline. In addition, a sham-operated group (laparotomy without splenectomy) was treated with 10 ml/kg normal saline. Results: MAP was higher in the sham-operated group and the aprotinin group than in the other groups. There were no significant differences for hematocrit except that the saline group exhibited a lower level than the other groups at the six-hour time point. The amount of intraperitoneal blood loss in the sham-operated and aprotinin groups due to splenic injury was significantly lower than in the tranexamic acid and saline groups. The survival rate in the aprotinin group was similar to the tranexamic acid group, but, the survival rate of the aprotinin-treated group was statistically higher than that of the saline control group. Conclusion: Hemodynamic changes resulting from splenic injury can be diminished by aprotinin treatment. Aprotinin could be considered in preference to other drugs as a first line treatment in hemodynamically unstable splenic injury patients.

Glucagon 검사시 Aprotinin 첨가와 Plastic tube 사용이 미치는 영향

조윤교,최삼규,서소연,신용환,Cho, Youn-Kyo,Choi, Sam-Kyu,Seo, So-Yeon,Shin, Yong-Hwan 대한핵의학기술학회 2011 핵의학 기술 Vol.15 No.1

Glucagon은 췌장 Langerhans섬 ${\alpha}$-세포에서 합성 분비되며, 기능으로는 간 당원분해, 지방분해, 인슐린분비 촉진 작용 등이 있다. Glucagon의 측정은 Glucagon 과잉증에 의한 당뇨병, 특발성 Glucagon 결손증, 불안정 당뇨병에서 저혈당의 진단을 하기위해 실시된다. Glucagon 측정시 세 가지 주의를 요하는데, 첫째, Aprotinin이 첨가된 EDTA tube에 채혈해야 하고 둘째, Plasma를 분리하여 Glass tube에 냉동 보관하여야 하고, 마지막으로 검사시에도 Glass tube에서 측정을 해야 한다. 이에 우리는 EDTA tube에 Aprotinin의 유무에 따른 결과 비교, 검체 보관 용기의 차이에 따른 비교(Plastic tube/ Glass tube), 측정용기에 따른 비교(Plastic tube/Glass tube)를 하여, 세 가지가 결과에 미치는 영향을 알아보고자 한다. 성별 구분 없이 건강검진에서 정상 소견을 보인 성인 40명을 대상으로 실험하여 대조군과 세가지 다른 실험군의 Glucagon 결과를 비교하였다. Aprotinin첨가한 EDTA 용기에 채혈 후, 검체를 Glass tube에 3일 냉동 보관하여 Glass tube에서 실험(대조군)한 결과와 Aprotinin첨가하지 않은 EDTA 용기에 채혈한 결과(실험군1), Plastic tube에 3일 냉동 보관한 후의 결과(실험군2), Plastic tube에서 실험(실험군3)한 결과를 비교하였다. 통계적인 분석은 SPSS를 이용한 paired t-test와 단순선형회귀분석을 실시하였고 시약은 상품화된 Siemens사의 Glucagon RIA kit를 사용하였다. Aprotinin이 첨가된 EDTA 용기에 채혈하여 실험한 결과와 Aprotinin이 첨가되지 않은 EDTA용기에 채혈하여 실험한 상관계수는 r=0.783(p=0.064)를 보였다. 검체 분리 후 Plastic tube에서 3일 냉동 보관하여 실험한 결과는 Glass tube의 결과에 비해서 유의하게 낮게 나타났다(r=0.979, p=0.005). 또 측정 시 Plastic tube를 사용한 결과도 Glass tube에서 실험한 결과보다 유의하게 낮게 나타났다(r=0.754, p<0.001). Glucagon 검사 시에는 단백 분해효소 억제제인 Aprotinin이 첨가된 EDTA tube 사용이 권장되며, Plastic tube 사용 시 환자의 결과가 유의하게 낮게 나타나므로 검체는 분리 후 Glass tube에 냉동 보관하고 Glass tube에서 실험하여야 한다. Purpose: There are 3 warnings for Glucagon tests. First, EDTA tubes that already contain Aprotinin must be used for plasma collection. Second, for freezer storage of centrifuged plasma, glass tubes must be used. Last, glass tubes must be used for testing procedure. So we compared the glucagon results of next 3 situation to those of control group. First, We compared to results by tubes without Aprotinin and with aprotinin. Second, we compared to results by tubes(plastic vs glass) for plasma storage. Third, we compared to results by tubes(plastic vs glass) for testing. We tried to evaluate the results of the 3 different condition. Materials and Methods: 40 healthy adults were studied with normal results on the general medical check up and laboratory tests. We compared the results of 3 different condition belows: Blood were collected in EDTA tube containing aprotinin and plasma was stored in the glass tube for 3 days in a freezer and results were obtained by tests in the glass tubes. Results from EDTA plasma without aprotinin, results from platic tubes for freezer stroage, results from plastic tube when testing. Simple linear regression analysis and paired t-test using SPSS were done for statistical analysis. Commercial glucagon kit(RIA-method)which made by Siemens company were used. Results: Correlation coefficient between results of EDTA tubes with Aprotinin vs without Aprotinin was r=0.783 (p=0.064). Result of specimen in plastic tubes stored 3 days in a freezer showed lower value compared to those in glass tube(r=0.979, p=0.005). Also, results of testing in plastic tubes showed lower values than those testing in glass tubes. (r=0.754, p<0.001). Conclusion: It is recommended for glucagon determination to use EDTA tube with Aprotinin which is a inhibitor of protein breakdown enzyme. Results of plastic tube when storage and testing showed lower value than those of glass tubes, so it is recommended to store and test in glass tubes.

심장수술시 심폐기 충전액에 첨가된 저용량 aprotinin의 효과

문성민,최석철,Moon, Seong-Min,Choi, Seok-Cheol 한국생명과학회 2007 생명과학회지 Vol.17 No.4

Serine protease 억제약물인 aprotinin은 체외순환을 동반한 심장수술 후 필연적으로 발생하는 혈액성분 손상을 포함한 유해한 합병증을 감소시키기 위해 사용한다. 그러나 이 약물의 용량이나 사용법에 대해 여전히 논란의 여지가 있다. 본 연구자들은 심장수술 동안 심폐기 충전액에 저 용량의 aprotinin을 투여하여 그 효과를 연구하였다. 30명의 성인 심장수술 환자들을 대상으로 aprotinin 투여군(n=15)과 대조군(n=15)으로 나눈 뒤 수술 전, 동안, 후의 시기에 혈액학적 및 생화학적 변수들, 사이토카인 및 심장 표지자, 수술 후 각종 임상결과들을 비교분석 하였다. 혈소판수와 activated partial thromboplastin time은 수술 후 24시간 때 아프로티닌군이 대조군 보다 유의하게 높았다. Troponin-I 농도와 수술 후 출혈량은 아프로티닌군이 대조군보다 유의하게 낮았다. 이러한 결과들을 볼 때 심장수술시 저 용량의 aprotinin을 심폐기 충전액에 첨가하는 방법은 혈소판의 파괴를 줄여줘 수술 후 출혈량의 감소를 제공해주며 심근보호 효과가 있는 것으로 판단된다. 향후 더 많은 성인 환자군과 소아환자에 대한 다양한 연구가 더 많이 수행되어야 할 것으로 사료된다. Aprotinin, a serine protease inhibitor, has been used to ameliorate the inevitable consequences, including blood component injury after cardiac surgery with cardiopulmonary bypass (CPB). However, there are many arguments on its dosage or usage. We assessed whether administration of low dose of aprotinin in only priming solution has any beneficial effect or reduces its side effects on cardiac surgery. Thirty patients scheduled for elective cardiac surgery were randomly assigned to aprotinin group (n=15) which received aprotinin in priming solution (two million kallikrein inhibitory unit, KIU) and added one million KIU at 1 hour after the beginning of CPB or control group (n=15) which did not receive it. Hematological and biochemical variables, cytokines and cardiac marker levels, and postoperative outcomes were compared between two groups at before, during or after operation. Platelet count in aprotinin group was higher than that of control group at postoperative 24 hr. Activated partial thromboplastin time in aprotinin group was longer than that of control group at intensive care unit (ICU). Troponin-I level and postoperative blood loss volumes in aprotinin group were lower than those of control group at ICU. There were no significant differences between the two groups on the others. These results showed that low dosage of only priming solution during cardiac surgery with CPB reduced platelet destruction and postoperative bleeding, and attenuates myocardial damage. However, further studies need to be carried out with more population or pediatric patients for evaluating various aprotinin usage.

척추 변형 수술에서 Aprotinin의 출혈량 감소

석세일(Se-Il Suk),김진혁(Jin-Hyok Kim),김성수(Sung-Soo Kim),김정훈(Jung-Hoon Kim),조범철(Beom-Cheol Cho),정락용(Nak-Young Jung) 대한정형외과학회 2007 대한정형외과학회지 Vol.42 No.3

목적: 척추 변형 수술은 마취 시간 및 수술 시간이 길어 대량 출혈로 인한 합병증이 흔히 발생한다. 본 논문의 목적은 척추 변형 수술에서 Aprotinin의 효과를 평가, 비교하고자 한다. 대상 및 방법: 척추 변형 수술을 시행 받은 59명을 조사하였으며, 환자는 Aprotinin 투여 군 32명과 비 투여군 27명을 대조 군으로 설정하여 비교하였다. 수술 전후 혈액학적 지표, 술 중 출혈량, 수술 시간, 수혈량과 술 후 흡입 배액 관으로의 출혈량과 흡입 배액관 유지 기간을 측정하였다. 결과: 술 전 두 군 간의 나이, 성비, 키, 몸무게, 혈액학적 지표 및 술 후 흡입 배액 관으로의 출혈량과 흡입 배액관 유지 기간은 두 군 간에 차이가 없었다. 술 중 출혈량, 수혈량 및 수술 시간은 각각 1,345±425 cc, 1,008±721 cc, 247분과 2,070±1,276 cc, 2,552±2,791 cc, 279분으로 양 군 간에 유의한 차이가 있었다. 수술 후 혈색소와 적혈구 용적 수치 또한 각각 12.9±1 cc, 38.3±3.1%와 1l.9±1.8 cc, 35±5.5%로 양 군 간에 유의한 차이를 보였다. 결론: 척추 변형 수술에서 Aprotinin을 사용하여 의미 있는 술 중 출혈량과 수혈량 감소 및 수술 시간 단축을 얻을 수 있었다. 그러므로 많은 출혈이 예상되는 척추 변형 수술 시 Aprotinin 사용이 적극적으로 권장된다. Purpose: Complications are quite common in surgery to correct spinal deformities due to the long duration under anesthesia and massive blood loss. The aim of this study was to evaluate and compare the effectiveness of Aprotinin in spinal deformity surgery. Materials and Methods: Fifty-nine patients who underwent spinal deformity surgery were analyzed. Thirty-two patients were administered Aprotinin, and 27 control patients were not. The Pre-and Post- operative hemoglobin and hematocrit, blood loss, transfusion requirements, operative time, postoperative blood loss through suction drains and duration of suction drains were measured in both groups. Results: There were no differences in age, gender, height, weight, hemodynamic indices, post-operative blood loss through the suction drains and the duration of the suction drains between the two groups. Intraoperative blood loss, transfusion and operative time were 1,345±425 cc, 1,008±721 cc, and 247 minutes in the Aprotinin (+) group and 2,070±1,276 cc, 2,552±2,791 cc, and 279 minutes in the Aprotinin (-) group, respectively. The postoperative hemoglobin and hematocrit levels Werew also significantly different (12.9±1 cc and 38.3±3.1% in the Aprotinin (+) group, and 11.9±1.8 cc and 35±5.5% in the Aprotinin (-) group, respectively). Conclusion: There was significantly less intraoperative blood loss, transfusion and surgery time in the group administered Aprotinin. Therefore, Aprotinin can be used in spinal deformity surgery that has a high risk of massive blood loss.

개심술에서 Aprotinin이 heparin 사용량 및 ACT에 미치는 영향

이현우,이재웅,박철현,박국양 대한흉부심장혈관외과학회 2000 Journal of Chest Surgery (J Chest Surg) Vol.33 No.7

배경; 아프로티닌(Aprotinin)은 nonspecific serine protease inhibitor로 개심술에서 항염효과와 혈액 응고효과를 갖고 있다. 또한 아프로티닌은 심폐기 작동 중에는 항트롬빈(antithrombin) 효과가 있다. 본 연구는 아프로티닌이 헤파린(heparin)사용 양 및 ACT(activated clotting time) 에 어떠한 영향을 미치는 가를 알아보기 위하여 시행하였다. 대상 및 방법; 1998년 12월 1일부터 1999년 11월 30일 까지 본원에서 개심술을 받은 환자 중 연령이 18세 이상인 82명을 대상으로 연구하였다. 환자들은 아프로티닌을 사용한 군(Group A)과 사용하지 안흥ㄴ 군(Group C)으로 나누어 연구하였다. 모든 환자에서 수술 전 체중, 신장, 체표면적, pump time, ACC time 등을 조사하였다. ACT의 측정 시기는 헤파린 공급 전, 공급 후 20분, 40분, 60qs과 프로타민 공급 후 20분 등이었다. 또한 ACT 변화 정도를 알아보기 위하여 헤파린 공급 전과 공급 후 20분, 공급 후 40분과 20분 사이의 차이를 조사하였다. 결과; 연구 대상 환자들이 굴변 특징에서는 연령, 펌프시간 및 대동맥차단 사간에서 모두 A군에서 증가된 소견을 보였다. (p<0.05). 헤파린 공급 전과 프로타민 공급 후의 ACT는 두 군에서 차이가 없으며 헤파린 공급 후 20분(607$\pm$22.3, 525$\pm$169초), 40분(889$\pm$315, 546$\pm$103초), 60분 (748$\pm$310, 472$\pm$115 초)에 측정한 ACT는 모두 A군에서 증가된 소견을 보였다. (p<0.05), 헤파린 공급 전과 궁급 후 20분 사이의 ACT 차이는 A한 군에서 증가된 소견을 보였고(p<0.05), 헤파린 공급 후 40분과 20분 사이의 ACT의 차이 또한 A군에서 증가된 소견을 보였다. (p<0.05). 두 군간의 총 헤파린 및 프로타민 사용 양에는 차이가 없었다. (p>0.05). 결론; 결론적으로 아프로티닌은 본 연구에서 CPB time을 고려해 볼 때 헤파린사용 양을 의미있게 줄여 줄 수 있을 것으로 생각되며 또한 ACT를 증가시켜 주기 때문에 추가적인 헤파린 감량이 가능할 것으로 생각된다. Background; Aprotinin, which is a nonspecific serine protease inhibitor, has an antiinflammatory and thrombogenic effect. However, it has an antithrombogenic effect during the cardiopulmonary bypass. This study was performed to evaluated the effects of aprotinin on the activated clotting time(ACT) and the total amount of the heparin used during the cardiopulmonary bypass. Marterial and Method; From December 1998 to November 1999, 82 consecutive patients electively underwent open heart surgery at Gachon medical school. The patients were older than 18 years. Eighty two patients were classified into a control group(group C, n=36) and a aprotinin-treated group(group A, n=46). Body weight, height, body surface area(BSA), pump time(PT), aortic cross clamping time(ACCT), and body temperature(BT) were determined. Total amount of heparin and protamine during the CPB were also measured. ACT was determined before heparin administration, at 20, 40 and 60 minutes after heparin administration, and after protamine administration. Result; No significant differences were noted in either group in body weight, height, BSA, BT, and the total amoun of heparin and protamine. Group A demonstrated a significant(p <0.05) increase in age, PT, ACCT, and ACT at 20, 40, and 60 minutes after heparin administration. Conclusion; In summary, the use of aprotinin prime resulted in an increase in ACT. The total amount of heparin in aproinin-treated patient was similar to that of the control group in spite of having the prolonged pump time. Therefore aprotinin may reduce the requirement of heparin.

Heme Oxygenase-l Induced by Aprotinin Inhibits Vascular Smooth Muscle Cell Proliferation Through Cell Cycle Arrest in Hypertensive Rats

Choi, Hyoung-Chul,Lee, Kwang-Youn,Lee, Dong-Hyup,Kang, Young-Jin The Korean Society of Pharmacology 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.4

Spontaneous hypertensive rats (SHR) are an established model of genetic hypertension. Vascular smooth muscle cells (VSMC) from SHR proliferate faster than those of control rats (Wistar-Kyoto rats; WKY). We tested the hypothesis that induction of heme oxygenase (HO)-1 induced by aprotinin inhibits VSMC proliferation through cell cycle arrest in hypertensive rats. Aprotinin treatment inhibited VSMC proliferation in SHR more than in normotensive rats. These inhibitory effects were associated with cell cycle arrest in the G1 phase. Tin protoporphyrin IX (SnPPIX) reversed the anti-proliferative effect of aprotinin in VSMC from SHR. The level of cyclin D was higher in VSMC of SHR than those of WKY. Aprotinin treatment downregulated the cell cycle regulator, cyclin D, but upregulated the cyclin-dependent kinase inhibitor, p21, in VSMC of SHR. Aprotinin induced HO-1 in VSMC of SHR, but not in those of control rats. Furthermore, aprotinin-induced HO-1 inhibited VSMC proliferation of SHR. Consistently, VSMC proliferation in SHR was significantly inhibited by transfection with the HO-1 gene. These results indicate that induction of HO-1 by aprotinin inhibits VSMC proliferation through cell cycle arrest in hypertensive rats.