: QOL. 10 ml kg min 20 C SCP

323 Vol. 36, pp. 323 333, 2008 : 20 8 20 QOL 1 SCP 20 C 10 ml kg min 20 C SCP 15 20 ml kg min A : n 5 30 ml kg min B : n 5 40 ml kg min C :n 5 3 20 C 120 SCP SEP ph A SEP 5 B 5 1 4 C A SCP SCP B SCP SCP P 0.0007 C SCP P 0.0064 SCP P 0.0318 Hematoxylin-Eosin HE Kluver-Barrera KB glial fibrillary acidic protein GFAP Ionized calcium binding adaptor molecule 1 Iba 1 B C 20 C 120 SCP 20 ml kg min 9.3 16.0 1 4 3 18 41

324 1 3 SCP RCP 2 SCP 5 SCP 18 22 C 10 ml kg min 6 7 8 SCP SCP 20 C 120 SCP 7.5 ml kg min 9 HBD 15 12.5 1.0 kg Pentobarbital sodium 25 mg kg SN-480 4 15mm 300 kg *12 16 mm Two-Stage 28 32Fr HPO-20H-C: HAD-11: 100 ml kg min 700 ml 20 20 ml 7 40 ml 6 meq 3,000 20 C *12 mm 3 10 ml kg min 2 20 ml kg min A 3 30 ml kg min B 4 40 ml kg min C 120 SCP 34 36 C 200 ml 10 200 ml 10 BPM-100 Unique Medical USA UPS-800 PO 2 POG-203 TBF-LN1 ph PT-501 phase 1 phase 2 phase 3 3 phase 3 20 SEP Neuropack II MEB-7102 SEP 5 SEP P1 N1 P2 N2 SEP P1N1 P2N2 10 42

325 Fig. 1. SEP preserved completely preserved incompletely; extended of latency preserved incompletely; reduction of amplitude. Table 1. Recovery Rate of SEP Complete return of SEP was obtained in all dogs in Group A. However, only one of the five dogs in Group B returned completely. No complete return was obtained in Group C. Ionized Calcium Binding Adapter Molecule1 Iba1Iba1: rabbit polyclonal 1: 500 WAKO SEP c 2 P 0.01 PO 2 ph R Hematoxylin-Eosin HE Nissl Kluver-Barrera KB glial fibrillary acidic protein GFAP mouse monoclonal clone: 6 F 12 1: 1000 DAKO Glostrup Denmark 1 SEP A 20 ml kg min 5 B 30 ml kg min 5 1 4 C 40 ml kg min 5 Fig. 1 SEP A Table 1 P1N1P2N2 43

326 2 a. R SCP A B C SCP 100 P 0.0064 SCP A B SCP 20 P 0.0007 C SCP 20 P 0.0031 Fig. 2 b. po 2 ph po 2 ph 3 HE Fig. 3 KB Nissl Fig. 4 GFAP A B C Fig. 5 Fig. 6 Iba 1 Ionized Calcium Binding Adapter Molecule 1 Iba 1 A B C Fig. 7 HCA RCP SCP 3 Griepp HCA 40 45 60 Fig. 2. The cerebral tissue pressure was stable in Group A, it went up significantly in Group B after SCP p 0.00066. In Group C, it went up significantly during SCP p 0.0064, and even higher after SCP p 0.0318. 44

20 ml kg min 30 ml kg min 40 ml kg min Fig. 3. There was no significant di#erence among the three groups in pathological findings of Hematoxylin-Eosin staining ῌ 40. 20 ml kg min 30 ml kg min 40 ml kg min Fig. 4. There was no significant di#erence among the three groups in pathological findings of Kluver-Barrera staining ῌ 40. 45 327

ῐῑ 328 ΐῒ ῌ 20 ml kg min 30 ml kg min 40 ml kg min Fig. 5. The appearance of the astroglia in the brain mantles increased with B group, further C groups, and cerebral tissue pressure elevation compared with A group by glial fibrillary acidic protein ῌGFAP staining ῌ 4. 20 ml kg min 30 ml kg min 40 ml kg min Fig. 6. Expansion of astroglia was more notably accepted with B group, further C groups, and cerebral tissue pressure elevation compared with A group by glial fibrillary acidic protein ῌGFAP staining ῌ 40. 46

329 20 ml kg min 30 ml kg min 40 ml kg min 11 RCP HCA 12 13 SCP Hagl SEP ph HCA SCP 14 Crittenden HCA HCA HCA RCP HCA SCP 4 HCA SCP 15 Ye MRI SCP RCP 16 SCP SCP 10 ml kg min Tanaka 50 Fig. 7. The appearance of microglia was increasing with B group, further C groups, and cerebral tissue pressure elevation compared with A group by Ionized Calcium Binding Adapter Molecule 1 Iba 1 staining 40. 30 mmhg 17 Ito 18 24 C 28 C 90 SCP SEP 5ml kg min 6 2 20 C 120 SCP 7.5ml kg min 9 20 C 120 SCP 47

330 SEP 10 30 ml kg min SCP HE KB 3 GFAP Iba 1 19 20 21 SEP KB SEP HE KB MRI 22 15 30 6 TNF a SCP KB 9 20 C 2 20 ml kg min CE 1 Teruhisa Kazui, Katsushi Yamashita, Naoki 48

331 Washiyama, Hitoshi Terada, Abul Hasan Muhammado Bashar, Kazuchika Suzuki and Takayasu Suzuki. Aortic Arch Replacement Using Selective Cerebral Perfusion. Ann Thorac Surg 2007; 83: S796 S798. 2 Di Eusanio M, Schepens M, Morshuis W, Dossche K, Pacini D, Di Marco L, Pierageli A and Di Bartolomeo R. Operations on the thoracic aorta and antegrade selective cerebral perfusion: our experience with 462 patients. Ital Heart J 2004; 5: 217 222. 3 Marco Di Eusanio MD, Marco A.A.M. Schepens MD, PhD, Wim J. Morshuis MD, PhD, Karl M. Dossche MD, PhD, Roberto Di Bartolomeo MD, PhD, Davide Pacini MD, Angelo Pierangeli MD, Teruhisa Kazui MD, Kazuhiro Ohkura MD and Naoki Washiyama MD. Brain Protection Using Antegrade Seloective Cerebral Perfusion: A Multicenter Study. Ann Thorac Surg 2003; 76: 1181 1189. 4 Ueda Y. Nagoya J Med Sci 2001 Nov; 64 3 4 : 93 102. 5 2003; 32; 190 196. 6 Murakami H, Kawada T, Okada Y, Hosonn M and Ikeshita M. Minimum cerebral blood flow in selective cerebral perfusion for brain protection within a limited period of time. J Artficial Organs 2000; 3: 29 33. 7 G. Wozniak, F. Dapper, E. Schindler, H. Akinturk, B. Zickmann, J. Gehron and F. Hehrlein. An Assessment of Selective Cerebral Perfusion Via the Innominate Artery in Aortic Arch Replacement. Thorac Cardiovasc Surg 1998; 46: 7 11. 8 Hiroaki Sasaki MD, Hitoshi Ogino MD, Hitoshi Matsuda MD, Kenji Minatoya MD, Motomi Ando MD and Soichiro Kitamura MD. Integrated Total Arch Replacement Using Selective Cerebral Perfusion: A 6-Year Experience. Ann Thorac Surg 2007; 83: S805 S810. 9 2004; 32: 301 307. 10 Kawada T, Nakamura S and Nishimura K. Continuous Monitoring of Short-Latency Somatosensory Evoked Potentials During Cardiac and Aortic Surgery. Surg Today 1996; 26: 328 332. 11 Griepp RB, Stinson EB, Hollingsworth JF, and Buehler D. Prosthetic replacement of the aortic arch. J Thorac Cardiovasc Surg 1975; 70: 1051 1063. 12 Griepp RB. Strategies for cerebral protection during aortic aneurysm surgery. Brain Protection in Aortic Surgery, Elsevier Science, Amsterdam, 1997; 127 137. 13 Stauch JT, Spielvogel D, Lauten A, Gall JD, Lansman SL, McMurtry K and Griepp RB. Technical advances in total aortic arch replacement. Ann Thorac Surg 2004; 77: 581 590. 14 Hagl C, Khaladj N, Peterss S, Hoe%er K, Winterhalter M, Karck M and Haverrich A. Hypothermic circulatory arrest with and without cold selective antegrade cerebral perfusion: impact on neurological recovery and tissue metabolism in an acute porcine model. Eur J Cardio-thoracic Surg 2004; 26: 73 80. 15 Crittenden MD, Roberts CS, Rosa L, Vatsia SK, Katz D, Clark RE, and. Swain JA Brain Protection During Circulatory Arrest. Ann Thorac Surg 1991; 51: 942 947. 16 Ye J, Ryner LN, Yang L and Marc R. Bigio D, Retrograde Cerebral Perfusion Result in Flow Distribution Abnormalities and Neuronal Damage -A Magnetic Resonance Imaging and Histopathological Study in Pig. Circulation 1998; 98: 313 318. 17 Tanaka H, Kazui T, sato H, Inoue N, Yamada O, and Komatu S. Experimental Study on the Optimum Flow Rate and Pressure for Selective Cerebral Perfusion. Ann Thorac Surg 1995; 59: 651 657. 18 Ito T. E#ect of Deep Hypothermia on Cerebral Hemodynamics during Selective Cerebral Perfusion With Systemic Circulatory Arrest. Jpn J Thorac Cardivasc Surg 2002; 50: 109 115. 49

332 19 20 Brain Med 2003; 15: 361 366. 21 2005; 4: 362 366. 22 Toshiro Kita, Lan Liu, Noriyuki Tanaka and Yoshimasa Kinoshita. The expression of tumour necrosis factor-alpha in the rat brain after fluid percussive injury. Int J Legal Med 1997; 110: 305 311. 50

333 Abstract Safe Upper Limit of Perfusion Rate in Selective Cerebral Perfusion Tokuichiro Nagata, Makuuchi Haruo, and Hiroshi Murakami Background Cerebral complication in aortic arch replacement is a serious problem, and various brain protecting methods have been adopted. In the antegrade selective cerebral perfusion method SCP, the perfusion rate of 10 ml kg min is generally adopted clinically under deep hypothermia of 20 C. Recently however, higher perfusion rates have been adopted clinically to obtain better clinical results. Purpose This experimental study was aimed to define the safe upper limit of cerebral perfusion rate under deep hypothermia. Procedure Fifteen crossbred dogs were divided into three groups: brain perfusion rates of 20 ml kg min Group A: n 5, 30ml kg min Group B: n 5, and 40 ml kg min Group C: n 5. SCP was performed for 120 minutes with cerebral temperature of 20 C. Tissue pressure, PO 2, ph, blood flow volume of the brain as well as somato-sensory evoked potential SEP were monitored to assess the cerebral function. The whole brain was fixed with formalin after the experiments for patho-histological evaluation. Result Complete return of SEP was obtained in all dogs in Group A. However, only one of the five dogs in Group B returned completely. No complete return was obtained in Group C. While the cerebral tissue pressure was stable in Group A, it went up significantly in Group B after SCP p 0.00066. In Group C, it went up significantly during SCP p 0.0064, and even higher after SCP p 0.0318. Although there was no significant di#erence among the three groups in pathological findings of Hematoxylin-Eosin or Kluver-Barrera staining, significant activation of the glia cells in the brain mantles of groups B and C was noted in GFAP stain and Iba-1 staining. Conclusion It was concluded that the safe upper limit of cerebral perfusion rate might be 20 ml kg min because brain disorder occurred after 120 minutes of SCP under deep hypothermia with the perfusion rate of 30 ml kg min or over. Key words aortic arch replacement, cerebral protection, deep hypothermia selective cerebral perfusion, perfusion rate Department of Cardiovascular, surgery, St. Marianna University School of Medicine 51