中等度低体温循環停止における心房性ナトリウム利尿ペプチドの腎保護作用

胸部大血管手術において,腹部臓器虚血による合併症,特に周術期の急性腎不全は手術成績に影響を与える独立した危険因子である.今回われわれは中等度低体温循環停止における心房性ナトリウム利尿ペプチド(atrial natriuretic peptide: ANP)の腎臓への作用を,ブタ実験モデルを用いて検討した.体外循環を用いて直腸温30℃に冷却後,60分間循環停止した.体外循環再開し,37℃に復温後,体外循環より離脱した.体外循環離脱後1時間で実験を終了した.ANP投与群(n = 6)とコントロール群(n = 6)の2群間で比較検討した.ANP投与群では体外循環開始時より0.05μg/kg/minで...

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Published in昭和医学会雑誌 Vol. 69; no. 3; pp. 236 - 244
Main Authors 手取屋, 岳夫, 福隅, 正臣, 尾本, 正, 大野, 正裕, 石川, 昇, 大井, 正也
Format Journal Article
LanguageJapanese
Published 昭和大学学士会 28.06.2009
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ISSN0037-4342
2185-0976
DOI10.14930/jsma.69.236

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Abstract 胸部大血管手術において,腹部臓器虚血による合併症,特に周術期の急性腎不全は手術成績に影響を与える独立した危険因子である.今回われわれは中等度低体温循環停止における心房性ナトリウム利尿ペプチド(atrial natriuretic peptide: ANP)の腎臓への作用を,ブタ実験モデルを用いて検討した.体外循環を用いて直腸温30℃に冷却後,60分間循環停止した.体外循環再開し,37℃に復温後,体外循環より離脱した.体外循環離脱後1時間で実験を終了した.ANP投与群(n = 6)とコントロール群(n = 6)の2群間で比較検討した.ANP投与群では体外循環開始時より0.05μg/kg/minで実験終了時までcarperitide (recombinant ANP)を持続的に投与した.2群間で,(1)体血圧,(2)腎動脈血流量,(3)腎皮質および髄質組織血流量を,(1)実験開始時,(2)体外循環開始後,(3)循環停止開始前,(4)循環停止30分後,(5)体外循環再開後,(6)復温完了時,(7)体外循環離脱時,(8)離脱後30分後および(9)60分後で比較検討した.また(4)尿量,血中・尿中ナトリウム(Na)およびクレアチニン(Cre)を(1),(3),(5),(6)および(9)で測定した.実験終了後腎臓を摘出し,虚血再還流障害の指標である腎組織Myeloperoxidase活性を測定し比較検討した.本研究では,ANPは体血圧および腎動脈血流量に影響を与えることなく,循環停止後の腎髄質組織血流量を有意に増加させた(109.3 ± 35.7% vs. 207.5 ± 113.2%; p = 0.03).また,循環停止後の尿量およびFENaを有意に増加させた(1.6 ± 1.4 vs. 3.4 ± 1.1ml/min; p = 0.03 and 1.7 ± 1.5 vs. 4.9 ± 4.9; p = 0.02).さらに,Myeloperoxidase活性を腎髄質組織で有意に低下させた(0.057 ± 0.035 vs. 0.026 ± 0.019U/mg; p = 0.03).以上により,ANPは中等度低体温循環停止後の腎髄質組織虚血を改善し,さらに虚血再還流後の腎髄質組織障害を抑制した.
AbstractList 胸部大血管手術において,腹部臓器虚血による合併症,特に周術期の急性腎不全は手術成績に影響を与える独立した危険因子である.今回われわれは中等度低体温循環停止における心房性ナトリウム利尿ペプチド(atrial natriuretic peptide: ANP)の腎臓への作用を,ブタ実験モデルを用いて検討した.体外循環を用いて直腸温30℃に冷却後,60分間循環停止した.体外循環再開し,37℃に復温後,体外循環より離脱した.体外循環離脱後1時間で実験を終了した.ANP投与群(n = 6)とコントロール群(n = 6)の2群間で比較検討した.ANP投与群では体外循環開始時より0.05μg/kg/minで実験終了時までcarperitide (recombinant ANP)を持続的に投与した.2群間で,(1)体血圧,(2)腎動脈血流量,(3)腎皮質および髄質組織血流量を,(1)実験開始時,(2)体外循環開始後,(3)循環停止開始前,(4)循環停止30分後,(5)体外循環再開後,(6)復温完了時,(7)体外循環離脱時,(8)離脱後30分後および(9)60分後で比較検討した.また(4)尿量,血中・尿中ナトリウム(Na)およびクレアチニン(Cre)を(1),(3),(5),(6)および(9)で測定した.実験終了後腎臓を摘出し,虚血再還流障害の指標である腎組織Myeloperoxidase活性を測定し比較検討した.本研究では,ANPは体血圧および腎動脈血流量に影響を与えることなく,循環停止後の腎髄質組織血流量を有意に増加させた(109.3 ± 35.7% vs. 207.5 ± 113.2%; p = 0.03).また,循環停止後の尿量およびFENaを有意に増加させた(1.6 ± 1.4 vs. 3.4 ± 1.1ml/min; p = 0.03 and 1.7 ± 1.5 vs. 4.9 ± 4.9; p = 0.02).さらに,Myeloperoxidase活性を腎髄質組織で有意に低下させた(0.057 ± 0.035 vs. 0.026 ± 0.019U/mg; p = 0.03).以上により,ANPは中等度低体温循環停止後の腎髄質組織虚血を改善し,さらに虚血再還流後の腎髄質組織障害を抑制した.
Author 石川, 昇
大野, 正裕
尾本, 正
手取屋, 岳夫
福隅, 正臣
大井, 正也
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References 4) Pacine D, Leone A, Di Marco L, et al: Antegrade selective cerebral perfusion in thoracic aorta surgery: safety of moderate hypothermia. Eur J Cardiothorac Surg 31: 618-622, 2007.
6) Chertow GM, Levy EM, Hammermeister KE, et al: Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 104: 343-348, 1998.
8) Brezis M and Rosen S: Hypoxia of the renal medulla-its implication for disease. N Engl J Med 332: 647-655, 1995.
1) Kazui T, Kimura N and Komatsu S: Surgical treatment of aortic arch aneurysms using selective cerebral perfusion. Experience with 100 patients. Eur J Cardiothorac Surg 9: 491-495, 1995.
10) Smith SM and Grocott HP: Renal medullary hypoxia during experimental cardiopulmonary bypass: a pilot study. Perfusion 20: 53-58, 2005.
7) Chertow GM, Lazarus JM, Christiansen CL, et al: Preoperative renal risk stratification. Circulation 95: 878-884, 1997.
24) Lloberas N, Torras J, Herrero-Fresneda I, et al: Postischemic renal oxidative stress induces inflammatory response through PAF and oxidized phospholipids. Prevention by antioxidant treatment. FASEB J 16: 908-910, 2002.
25) Okawa H, Horimoto H, Mieno S, et al: Preischemic infusion of aloha-human atrial natriuretic peptide elicits myoprotective effects against ischemic reperfusion in isolated rat heart. Mol Cell Biochem 248: 171-177, 2003.
3) Bartolomeo RD, Eusanio MD, Pacine D, et al: Antegrade selective cerebral perfusion during surgery of the thoracic aorta: risk analysis. Eur J Cardiothorac Surg 19: 765-770, 2001.
23) Malle E, Buch T and Grone HJ: Myeloperoxidase in kidney disease. Kidney Int 64: 1956-1967, 2003.
17) Costa MA, Elegaray R, Loria A, et al: Atrial natriuretic peptide influence on nitric oxide system in kidney and heart. Regul Pept 118: 151-157, 2004.
14) Stern MD, Bowen PD, Parma R, et al: Measurement of renal cortical and medullary blood flow by laser-Doppler spectroscopy in the rat. Am J Physiol 236: F80-F87, 1979.
13) Hayashida N, Chihara S, Kashikie H, et al: Effects of intraoperative administration of atrial natriuretic peptide. Ann Thorac Surg 70: 1319-1326, 2000.
22) Cooper WA, Duarte IG, Thourani VH, et al: Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis. Ann Thorac Surg 69: 696-703, 2000.
9) Brezis M and Epstein FH: Cellular mechanisms of acute ischemic injury in the kidney. Annu Rev Med 44: 27-37, 1993.
15) Hillegass LM, Griswold DE, Brickson B, et al: Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods 24: 285-295, 1990.
5) Kamiya H, Hagl C, Kropivnitskaya I, et al: The safety of moderate hypothermic lower body circulatory arrest with selective cerebral perfusion: a propensity score analysis. J Thorac Cardiovasc Surg 133: 501-509, 2007.
19) Banks RO: Effects of a physiological dose of ANP on renal function in dog. Am J Physiol 255: F907-F910, 1988.
20) Salazar FJ, Fiksen-Olsen MJ, Opgenorth TJ, et al: Renal effects of ANP without changes in glomerular filtration rate and blood pressure. Am J Physiol 251: F532-F536, 1986.
16) Zeidel ML, Silva P, Brenner BM, et al: cGMP mediates effects of atrial peptides on medullary collecting duct cells. Am J Physiol 252: F551-F559, 1987.
11) Nakao K, Ogawa Y, Suga S, et al: Molecular biology and biochemistry of the natriuretic peptide system. I: Natriuretic peptide. J Hypertens 10: 907-912, 1992.
21) Evans RG, Eppel GA, Anderson WP, et al: Mechanisms underlying the differential control of blood flow in the renal medulla and cortex. J Hypertens 22: 1439-1451, 2004.
2) Di Eusanio M, Schepens MA, Morshuis WJ, et al: Antegrade selective cerebral perfusion during operations on the thoracic aorta: factors influencing survival and neurologic outcome in 413 patients. J Thorac Cardiovasc Surg 124: 1080-1086, 2002
18) Maack T, Marion DN, Camargo MJ, et al: Effects of auriculin (atrial natriuretic peptide) on blood pressure, renal function, and the renin-aldosterone system in dog. Am J Med 77: 1069-1075, 1987.
12) Sezai A, Shiono M, Orime Y, et al: Low-dose continuous infusion of human atrial natriuretic peptide during and after cardiac surgery. Ann Thorac Surg 69: 732-738, 2000.
References_xml – reference: 8) Brezis M and Rosen S: Hypoxia of the renal medulla-its implication for disease. N Engl J Med 332: 647-655, 1995.
– reference: 24) Lloberas N, Torras J, Herrero-Fresneda I, et al: Postischemic renal oxidative stress induces inflammatory response through PAF and oxidized phospholipids. Prevention by antioxidant treatment. FASEB J 16: 908-910, 2002.
– reference: 11) Nakao K, Ogawa Y, Suga S, et al: Molecular biology and biochemistry of the natriuretic peptide system. I: Natriuretic peptide. J Hypertens 10: 907-912, 1992.
– reference: 23) Malle E, Buch T and Grone HJ: Myeloperoxidase in kidney disease. Kidney Int 64: 1956-1967, 2003.
– reference: 6) Chertow GM, Levy EM, Hammermeister KE, et al: Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 104: 343-348, 1998.
– reference: 12) Sezai A, Shiono M, Orime Y, et al: Low-dose continuous infusion of human atrial natriuretic peptide during and after cardiac surgery. Ann Thorac Surg 69: 732-738, 2000.
– reference: 20) Salazar FJ, Fiksen-Olsen MJ, Opgenorth TJ, et al: Renal effects of ANP without changes in glomerular filtration rate and blood pressure. Am J Physiol 251: F532-F536, 1986.
– reference: 19) Banks RO: Effects of a physiological dose of ANP on renal function in dog. Am J Physiol 255: F907-F910, 1988.
– reference: 1) Kazui T, Kimura N and Komatsu S: Surgical treatment of aortic arch aneurysms using selective cerebral perfusion. Experience with 100 patients. Eur J Cardiothorac Surg 9: 491-495, 1995.
– reference: 9) Brezis M and Epstein FH: Cellular mechanisms of acute ischemic injury in the kidney. Annu Rev Med 44: 27-37, 1993.
– reference: 14) Stern MD, Bowen PD, Parma R, et al: Measurement of renal cortical and medullary blood flow by laser-Doppler spectroscopy in the rat. Am J Physiol 236: F80-F87, 1979.
– reference: 2) Di Eusanio M, Schepens MA, Morshuis WJ, et al: Antegrade selective cerebral perfusion during operations on the thoracic aorta: factors influencing survival and neurologic outcome in 413 patients. J Thorac Cardiovasc Surg 124: 1080-1086, 2002
– reference: 10) Smith SM and Grocott HP: Renal medullary hypoxia during experimental cardiopulmonary bypass: a pilot study. Perfusion 20: 53-58, 2005.
– reference: 3) Bartolomeo RD, Eusanio MD, Pacine D, et al: Antegrade selective cerebral perfusion during surgery of the thoracic aorta: risk analysis. Eur J Cardiothorac Surg 19: 765-770, 2001.
– reference: 4) Pacine D, Leone A, Di Marco L, et al: Antegrade selective cerebral perfusion in thoracic aorta surgery: safety of moderate hypothermia. Eur J Cardiothorac Surg 31: 618-622, 2007.
– reference: 21) Evans RG, Eppel GA, Anderson WP, et al: Mechanisms underlying the differential control of blood flow in the renal medulla and cortex. J Hypertens 22: 1439-1451, 2004.
– reference: 7) Chertow GM, Lazarus JM, Christiansen CL, et al: Preoperative renal risk stratification. Circulation 95: 878-884, 1997.
– reference: 5) Kamiya H, Hagl C, Kropivnitskaya I, et al: The safety of moderate hypothermic lower body circulatory arrest with selective cerebral perfusion: a propensity score analysis. J Thorac Cardiovasc Surg 133: 501-509, 2007.
– reference: 17) Costa MA, Elegaray R, Loria A, et al: Atrial natriuretic peptide influence on nitric oxide system in kidney and heart. Regul Pept 118: 151-157, 2004.
– reference: 13) Hayashida N, Chihara S, Kashikie H, et al: Effects of intraoperative administration of atrial natriuretic peptide. Ann Thorac Surg 70: 1319-1326, 2000.
– reference: 16) Zeidel ML, Silva P, Brenner BM, et al: cGMP mediates effects of atrial peptides on medullary collecting duct cells. Am J Physiol 252: F551-F559, 1987.
– reference: 18) Maack T, Marion DN, Camargo MJ, et al: Effects of auriculin (atrial natriuretic peptide) on blood pressure, renal function, and the renin-aldosterone system in dog. Am J Med 77: 1069-1075, 1987.
– reference: 22) Cooper WA, Duarte IG, Thourani VH, et al: Hypothermic circulatory arrest causes multisystem vascular endothelial dysfunction and apoptosis. Ann Thorac Surg 69: 696-703, 2000.
– reference: 25) Okawa H, Horimoto H, Mieno S, et al: Preischemic infusion of aloha-human atrial natriuretic peptide elicits myoprotective effects against ischemic reperfusion in isolated rat heart. Mol Cell Biochem 248: 171-177, 2003.
– reference: 15) Hillegass LM, Griswold DE, Brickson B, et al: Assessment of myeloperoxidase activity in whole rat kidney. J Pharmacol Methods 24: 285-295, 1990.
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Snippet 胸部大血管手術において,腹部臓器虚血による合併症,特に周術期の急性腎不全は手術成績に影響を与える独立した危険因子である.今回われわれは中等度低体温循環停...
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SubjectTerms 低体温循環停止
体外循環
心房性ナトリウム利尿ペプチド
腎機能
Title 中等度低体温循環停止における心房性ナトリウム利尿ペプチドの腎保護作用
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