Application of Hemoglobin-based Oxygen Carriers in Cardiac Surgery_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

CHANG Xin , LONG Cun

Department of Extracorporeal Circulation, Fu Wai Hospital , Chinese Academy of Medical Science &;
Peking Union Medical College, Beijing 100037, P. R. China. E-mail: changxin718@yahoo.com.cn;

Corresponding author：

Keywords：

Blood substitutes; Hemoglobin-based oxygen carriers; Cardiac Surgery; Myocardial protection

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Hemoglobin-based oxygen carriers (HBOCs) is a kind of blood substitutes. It is a separated, ultra-purified, modified human or bovine hemoglobin in a balanced saline solution. After modification, it has longer half-time, less renal toxicity, and better delivery of O2 even at low temperature and pH. Its shelf life is long and it dose not require cross-matching. In the field of cardiac surgery, the use of HBOCs can reduce the amount of transfusion postoperatively, and can be used in cardiopulmonary bypass priming and myocardial protection.

Citation： CHANG Xin,LONG Cun. Application of Hemoglobin-based Oxygen Carriers in Cardiac Surgery. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2007, 14(6): 457-. doi: Copy

1.	Stanworth SJ, Cockburn HA, Boralessa H, et al. Which groups of patients are transfused A study of red cell usage in London and southeast England. Vox Sang, 2002, 83(4):352-357.
2.	Spahn DR, Kocian R. Artificial O2 carriers: status in 2005. Curr Pharm Des, 2005, 11(31):4099-4114.
3.	龙村. 主编. 体外循环学. 北京: 人民军医出版社, 2004. 576-577.
4.	Kleinman S, Chan P, Robillard P. Risks associated with transfusion of cellular blood components in Canda. Transfus Med Rev, 2003, 17(2):120-162.
5.	Caswell JE, Strange MB, Rimmer DM, et al. A novel hemoglobin-based blood substitute protects against myocardial reperfusion injury. Am J Physiol Heart Circ Physiol, 2005,288(4):H1796-1801.
6.	Schreiber GB, Busch MP, Kleinman SH, et al. The risk of transfusion-transmitted viral infections. The Retrovirus Epidemiology Donor Study. N Engl J Med, 1996, 334(26):1685-1690.
7.	Anbari KK, Garino JP, Mackenzie CF. Hemoglobin substitutes. Eur Spine J, 2004, 13( Suppl 1):S76-82.
8.	Stowell CP, Levin J, Speiss BD, et al. Progress in the development of RBC substitutes, Transfusion, 2001, 41(2):287-299.
9.	Greenburg AG, Kim HW. Hemoglobin-based oxygen carriers. Crit Care, 2004, 8(Suppl 2):S61-64.
10.	Cohn SM. Blood substitutes in surgery. Surgery,2000,127(6): 599-602.
11.	Winslow RM. Blood substitutes. Adv Drug Del Rev,2000,40(3):131-142.
12.	Spahn DR, Pasch T. Physiological properties of blood substitutes. News Physiol Sci,2001,16(1):38-41.
13.	Kim HW, Shen TJ, Sun DP, et al. A novel low oxygen affinity recombinant hemoglobin (alpha96val→Trp): switching quaternary structure without changing the ligation state. J Mol Biol, 1995, 248(4):867-882.
14.	Conover CD, Malatesta P, Lejeune L, et al. The effects of hemodilution with polyethylene glycol bovine hemoglobin(PEG-Hb) in a conscious porine model. J Investig Med, 1996, 44 (5):238-246.
15.	Hughes GS, Antal EJ, Locker PK , et al. Physiology and pharmacokinetics of a novel hemoglobin-based oxygen carrier in humans. Crit Care Med, 1996, 24(5):756-764.
16.	Winslow RM. alpha-crosslinked hemoglobin: was failure predicted by preclinical testing Vox Sang, 2000, 79(1):1-20.
17.	Winslow RM. Blood substitutes. Adv Drug Deliv Rev, 2000, 40(3):131-142.
18.	赵明霞，龙村，贺学英，等. 兔体外循环中聚乙二醇牛血红蛋白偶联物对平均动脉压、胶体渗透压及p50的影响. 中华实验外科杂志, 2006, 23(9): 1044-1046.
19.	LaMuraglia GM, O’Hara PJ, Baker WH, et al. The reduction of the allogenic transfusion requirement in aortic surgery with a hemoglobin-based solution. J Vasc Surg, 2000, 31(2):299-308.
20.	Lamy ML, Daily EK, Brichant JF, et al. Randomized trial of diaspirin cross-linked hemoglobin solution as an alternative to blood transfusion after cardiac surgery. The DCLHb Cardiac Surgery Trial Collaborative Group. Anesthesiology, 2000, 92(3):646-656.
21.	Levy JH, Goodnough LT, Greilich PE, et al. Polymerized bovine hemoglobin solution as a replacement for allogeneic red blood cell transfusion after cardiac surgery: results of a randomized, double-blind trial. J Thorac Cardiovasc Surg, 2002, 124(1):35-42.
22.	Hill SE, Gottschalk LI, Grichnik K. Safety and preliminary efficacy of hemoglobin raffimer for patients undergoing coronary artery bypass surgery. J Cardiothorac Vasc Anesth, 2002, 16(6):695-702.
23.	Young MA, Riddez L, Kjellstrm BT, et al . MalPEG-hemoglobin (MP4) improves hemodynamics, acid-base status, and survival after uncontrolled hemorrhage in anesthetized swine. Crit Care Med , 2005, 33(8): 1794-1804.
24.	Schechter AN, Gladwin MT. Hemoglobin and the paracrine and endocrine functions of nitric oxide. N Engl J Med, 2003, 348(15):1483-1485.
25.	Gulati A, Sharma AC, Singh G. Role of endothelin in the cardiovascular effects of diaspirin crosslinked and stroma reduced hemoglobin. Crit Care Med, 1996, 24(1):137-147.
26.	Cheng DC, Mazer CD, Martineau R, et al. A phase II dose-response study of hemoglobin raffimer (Hemolink) in elective coronary artery bypass surgery. J Thorac Cardiovasc Surg, 2004, 127(1):79-86.
27.	Helm RE, Klemperer JD, Rosengart TK , et al. Intraoperative autologous blood donation preserves red cell mass but dose not decrease postoperative bleeding. Ann Thorac Surg, 1996, 62(5):1431-1441.
28.	刘晋萍, 贺学英 , 龙村, 等. 聚乙二醇-牛血红蛋白在体外循环中对机体血流动力学变化的研究. 中国体外循环杂志, 2005, 3(3):157-160.
29.	Mueller XM, Tevaearai HT, Jegger D, et al. Hemoglobin substitute and cardiopulmonary bypass. ASAIO J, 2000, 46(4):403-408.
30.	Rajesh KG, Sasaguri S, Tian ZZ, et al. Potential role of mitochondrial permeability transition pore following long-time hypothermic heart preservation. Transplant Proc, 2002, 34(7):2645-2646.
31.	Marinello E, Tabucchi A, Miraldi F, et al. Role of bovine hemoglobin enriched cardioplegia in myocardial preservation. Adv Exp Med Biol, 2000, 486:171-174.
32.	Carlucci F, Miraldi F, Barretta A , et al. Preservation of myocardial energy status by bovine hemoglobin solutions during ischemia. Biomed Pharmacother, 2002, 56(5):247-253.
33.	Serna DL, Powell LL, Kahwaji C, et al. Cardiac function after eight hour storage by using polyethylene glycol hemoglobin versus crystalloid perfusion. ASAIO J, 2000, 46(5):547-552.
34.	Jones BU, Serna DL, Smulowitz P, et al. Extended ex vivo myocardial preservation in the beating state using a novel polyethylene glycolated bovine hemoglobin perfusate based solution. ASAIO J, 2003, 49(4):388-394.

1. 　Stanworth SJ, Cockburn HA, Boralessa H, et al. Which groups of patients are transfused A study of red cell usage in London and southeast England. Vox Sang, 2002, 83(4):352-357.
2. 　Spahn DR, Kocian R. Artificial O2 carriers: status in 2005. Curr Pharm Des, 2005, 11(31):4099-4114.
3. 　龙村. 主编. 体外循环学. 北京: 人民军医出版社, 2004. 576-577.
4. 　Kleinman S, Chan P, Robillard P. Risks associated with transfusion of cellular blood components in Canda. Transfus Med Rev, 2003, 17(2):120-162.
5. 　Caswell JE, Strange MB, Rimmer DM, et al. A novel hemoglobin-based blood substitute protects against myocardial reperfusion injury. Am J Physiol Heart Circ Physiol, 2005,288(4):H1796-1801.
6. 　Schreiber GB, Busch MP, Kleinman SH, et al. The risk of transfusion-transmitted viral infections. The Retrovirus Epidemiology Donor Study. N Engl J Med, 1996, 334(26):1685-1690.
7. 　Anbari KK, Garino JP, Mackenzie CF. Hemoglobin substitutes. Eur Spine J, 2004, 13( Suppl 1):S76-82.
8. 　Stowell CP, Levin J, Speiss BD, et al. Progress in the development of RBC substitutes, Transfusion, 2001, 41(2):287-299.
9. 　Greenburg AG, Kim HW. Hemoglobin-based oxygen carriers. Crit Care, 2004, 8(Suppl 2):S61-64.
10. 　Cohn SM. Blood substitutes in surgery. Surgery,2000,127(6): 599-602.
11. 　Winslow RM. Blood substitutes. Adv Drug Del Rev,2000,40(3):131-142.
12. 　Spahn DR, Pasch T. Physiological properties of blood substitutes. News Physiol Sci,2001,16(1):38-41.
13. 　Kim HW, Shen TJ, Sun DP, et al. A novel low oxygen affinity recombinant hemoglobin (alpha96val→Trp): switching quaternary structure without changing the ligation state. J Mol Biol, 1995, 248(4):867-882.
14. 　Conover CD, Malatesta P, Lejeune L, et al. The effects of hemodilution with polyethylene glycol bovine hemoglobin(PEG-Hb) in a conscious porine model. J Investig Med, 1996, 44 (5):238-246.
15. 　Hughes GS, Antal EJ, Locker PK , et al. Physiology and pharmacokinetics of a novel hemoglobin-based oxygen carrier in humans. Crit Care Med, 1996, 24(5):756-764.
16. 　Winslow RM. alpha-crosslinked hemoglobin: was failure predicted by preclinical testing Vox Sang, 2000, 79(1):1-20.
17. 　Winslow RM. Blood substitutes. Adv Drug Deliv Rev, 2000, 40(3):131-142.
18. 　赵明霞，龙村，贺学英，等. 兔体外循环中聚乙二醇牛血红蛋白偶联物对平均动脉压、胶体渗透压及p50的影响. 中华实验外科杂志, 2006, 23(9): 1044-1046.
19. 　LaMuraglia GM, O’Hara PJ, Baker WH, et al. The reduction of the allogenic transfusion requirement in aortic surgery with a hemoglobin-based solution. J Vasc Surg, 2000, 31(2):299-308.
20. 　Lamy ML, Daily EK, Brichant JF, et al. Randomized trial of diaspirin cross-linked hemoglobin solution as an alternative to blood transfusion after cardiac surgery. The DCLHb Cardiac Surgery Trial Collaborative Group. Anesthesiology, 2000, 92(3):646-656.
21. 　Levy JH, Goodnough LT, Greilich PE, et al. Polymerized bovine hemoglobin solution as a replacement for allogeneic red blood cell transfusion after cardiac surgery: results of a randomized, double-blind trial. J Thorac Cardiovasc Surg, 2002, 124(1):35-42.
22. 　Hill SE, Gottschalk LI, Grichnik K. Safety and preliminary efficacy of hemoglobin raffimer for patients undergoing coronary artery bypass surgery. J Cardiothorac Vasc Anesth, 2002, 16(6):695-702.
23. 　Young MA, Riddez L, Kjellstrm BT, et al . MalPEG-hemoglobin (MP4) improves hemodynamics, acid-base status, and survival after uncontrolled hemorrhage in anesthetized swine. Crit Care Med , 2005, 33(8): 1794-1804.
24. 　Schechter AN, Gladwin MT. Hemoglobin and the paracrine and endocrine functions of nitric oxide. N Engl J Med, 2003, 348(15):1483-1485.
25. 　Gulati A, Sharma AC, Singh G. Role of endothelin in the cardiovascular effects of diaspirin crosslinked and stroma reduced hemoglobin. Crit Care Med, 1996, 24(1):137-147.
26. 　Cheng DC, Mazer CD, Martineau R, et al. A phase II dose-response study of hemoglobin raffimer (Hemolink) in elective coronary artery bypass surgery. J Thorac Cardiovasc Surg, 2004, 127(1):79-86.
27. 　Helm RE, Klemperer JD, Rosengart TK , et al. Intraoperative autologous blood donation preserves red cell mass but dose not decrease postoperative bleeding. Ann Thorac Surg, 1996, 62(5):1431-1441.
28. 　刘晋萍, 贺学英 , 龙村, 等. 聚乙二醇-牛血红蛋白在体外循环中对机体血流动力学变化的研究. 中国体外循环杂志, 2005, 3(3):157-160.
29. 　Mueller XM, Tevaearai HT, Jegger D, et al. Hemoglobin substitute and cardiopulmonary bypass. ASAIO J, 2000, 46(4):403-408.
30. 　Rajesh KG, Sasaguri S, Tian ZZ, et al. Potential role of mitochondrial permeability transition pore following long-time hypothermic heart preservation. Transplant Proc, 2002, 34(7):2645-2646.
31. 　Marinello E, Tabucchi A, Miraldi F, et al. Role of bovine hemoglobin enriched cardioplegia in myocardial preservation. Adv Exp Med Biol, 2000, 486:171-174.
32. 　Carlucci F, Miraldi F, Barretta A , et al. Preservation of myocardial energy status by bovine hemoglobin solutions during ischemia. Biomed Pharmacother, 2002, 56(5):247-253.
33. 　Serna DL, Powell LL, Kahwaji C, et al. Cardiac function after eight hour storage by using polyethylene glycol hemoglobin versus crystalloid perfusion. ASAIO J, 2000, 46(5):547-552.
34. 　Jones BU, Serna DL, Smulowitz P, et al. Extended ex vivo myocardial preservation in the beating state using a novel polyethylene glycolated bovine hemoglobin perfusate based solution. ASAIO J, 2003, 49(4):388-394.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Application of Hemoglobin-based Oxygen Carriers in Cardiac Surgery

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