Pathophysiology of Myocardial Ischemia and Myocardial Protection during Cardiac Surgery_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

XIAOQian-hui , XIONGJi-yue , QINZhen ,  DULei

Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding author：

DULei, Email: 43615774@qq.com

Keywords：

Myocardial protection; Cardiopulmonary bypass; Cardiac surgery

DOI：

10.7507/1007-4848.20140195

Video：

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Cardiac injury is a major complication of cardiac surgery. Surgical manipulation, systemic inflammatory response and cardiac ischemia/reperfusion injury (IRI)are main reasons of cardiac injury. Gentle and swift surgical manipulation can reduce mechanical myocardial injury, shorten myocardial ischemic time, and reduce myocardial IRI. Satisfactory myocardial protection plays a key role to improve postoperative recovery. In recent years, more and more myocardial protection strategies are employed to reduce myocardial IRI and improve myocardial protection, including modifications of temperature, composition and instillation approach of cardioplegia in order to increase myocardial oxygen supply, decrease myocardial oxygen consumption, inhibit inflammatory response and eliminate oxygen free radicals. Endogenous myocardial protection is also achieved by supplement of certain medications in cardioplegia.

Citation： XIAOQian-hui, XIONGJi-yue, QINZhen, DULei. Pathophysiology of Myocardial Ischemia and Myocardial Protection during Cardiac Surgery. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2014, 21(5): 681-685. doi: 10.7507/1007-4848.20140195 Copy

1.	Meybohm P, Zacharowski K, Cremer J, et al. Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial--the RIPHeart-Study. Eur Heart J, 2012, 33(12):1423-1426.
2.	Edmunds LH. Cardiopulmonary bypass after 50 years. N Engl J Med, 2004, 351(16):1603-1606.
3.	Durdu S, Sirlak M, Cetintas D, et al. The efficacies of modified mechanical post conditioning on myocardial protection for patients undergoing coronary artery bypass grafting. J Cardiothorac Surg, 2012, 7:73.
4.	Mangano DT, Tudor IC, Dietzel C. Multicenter study of periopera-tive ischemia research group; ischemia research and education foundation. The risk associated with aprotinin in cardiac surgery. N Engl J Med, 2006, 354(4):353-365.
5.	Kloner RA, Jennings RB. Consequences of brief ischemia:stunning, preconditioning, and their clinical implications:part 1. Circulation, 2001, 104(24):2981-2989.
6.	Schurr UP, Zünd G, Hoerstrup SP, et al. Preoperative administration of steroids:influence on adhesion molecules and cytokines after cardiopulmonary bypass. Ann Thorac Surg, 2001, 72(4):1316-320.
7.	Morita K. Surgical reoxygenation injury of the myocardium in cyanotic patients:clinical relevance and therapeutic strategies by normoxic management during cardiopulmonary bypass. Gen Thorac Cardiovasc Surg, 2012, 60(9):549-556.
8.	Wu QP, Purusram G, Wang HQ, et al. The efficacy of parecoxib on systemic inflammatory response associated with cardiopulmonary bypass during cardiac surgery. Br J Clin Pharmacol, 2013, 75(3):769-778.
9.	Rezkalla SH, Kloner RA. No-Reflow Phenomenon. Circulation, 2002, 105(5):656-662.
10.	Jackson KA, Majka SM, Wang H, et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest, 2001, 107(11):1395-1402.
11.	Eltzschig HK, Carmeliet P. Hypoxia and Inflammation. N Engl J Med, 2011, 364(7):656-665.
12.	Karhausen J, Haase VH, Colgan SP. Inflammatory hypoxia:role of hypoxia-inducible factor. Cell Cycle, 2005, 4(2):256-258.
13.	Colgan SP, Eltzschig HK. Adenosine and hypoxia-inducible factor signaling in intestinal injury and recovery. Annu Rev Physiol, 2012, 74:153-175.
14.	Verma S, Fedak PW, Weisel RD, et al. Fundamentals of reperfusion injury for the clinical cardiologist. Circulation, 2002, 105(20):2332-2336.
15.	Gupta-Malhotra M, Kern JH, Flynn PA, et al. Cardiac troponin Ⅰ after cardiopulmonary bypass in infants in comparison with older children. Cardiol Young, 2013, 23(3):431-435.
16.	Perrelli MG, Pagliaro P, Penna C. Ischemia/reperfusion injury and cardioprotective mechanisms:Role of mitochondria and reactive oxygen species. World J Cardiol, 2011, 3(6):186-200.
17.	Whitehouse JS, Riggle KM, Purpi DP, et al. The protective role of intestinal alkaline phosphatase in necrotizing enterocolitis. J Surg Res, 2010, 163(1):79-85.
18.	Boodram S, Evans E. Use of leukocyte-depleting filters during cardiac surgery with cardiopulmonary bypass:a review. J Extra Corpor Technol, 2008, 40(1):27-42.
19.	Bhakri K, Mulholland J, Punjabi P. Understanding innovations in the evolving practice of blood and crystalloid cardioplegia. Perfusion, 2014, [Epub ahead of print].
20.	Abah U, Garfjeld Roberts P, Ishaq M, et al. Is cold or warm blood cardioplegia superior for myocardial protection? Interact Cardiovasc Thorac Surg, 2012, 14(6):848-855.
21.	Mauney MC, Kron IL. The physiologic basis of warm cardioplegia. Ann Thorac Surg, 1995, 60(3):819-823.
22.	Albert AA, Arnrich B, Walter JA, et al. Hyperkalemic blood versus crystalloid cardioplegia in longer clamping times. Asian Cardiovasc Thorac Ann, 2004, 12(2):115-120.
23.	Franke UF, Korsch S, Wittwer T, et al. Intermittent antegrade warm myocardial protection compared to intermittent cold blood cardioplegia in elective coronary surgery--do we have to change? Eur J Cardiothorac Surg, 2003, 23(3):341-346.
24.	Sanada S, Komuro I, Kitakaze M. Pathophysiology of myocardial reperfusion injury:preconditioning, postconditioning, and translational aspects of protective measures. Am J Physiol Heart Circ Physiol, 2011, 301(5):H1723-H1741.
25.	Hausenloy DJ, Mwamure PK, Venugopal V, et al. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery:a randomised controlled trial. Lancet, 2007, 370(9587):575-579.
26.	Ascione R, Suleiman SM, Angelini GD. Retrograde hot-shot cardioplegia in patients with left ventricular hypertrophy undergoing aortic valve replacement. Ann Thorac Surg, 2008, 85(2):454-458.
27.	Kouerinis IA, Manopoulos CG, Zografos GC, et al. Retrograde cardioplegia in CABG:is it really useful? The microcirculation and a capillary unit model. Med Sci Monit, 2006, 12(11):265-268.
28.	Fazel S, Borger MA, Weisel RD, et al. Myocardial protection in reoperative coronary artery bypass grafting:J Card Surg, 2004, 19(4):291-295.
29.	Nader ND, Karamanoukian HL, Reedy RL, et al. Inclusion of sevof-lurane in cardioplegia reduces neutrophil activity during cardiopulmonary bypass. J Cardiothorac Vasc Anesth, 2006, 20(1):57-62.
30.	Chouraqui P, Rabinowitz B, Livschitz S, et al. Effects of antegrade versus combined antegrade/retrograde cardioplegia on postoperative septal wall motion in patients undergoing open heart surgery. Cardiology, 1998, 88(6):526-529.
31.	Walsh SR, Tang TY, Kullar P, et al. Ischaemic preconditioning during cardiac surgery:systematic review and meta-analysis of perioperative outcomes in randomised clinical trials. Eur J Cardiothorac Surg, 2008, 34(5):985.
32.	Kolwicz SC, Purohit S, Tian R. Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes. Circ Res, 2013, 113(5):603-616.
33.	Maslov LN, Lishmanovlu B, Headrick JP, et al. Perspective of crea-tion of drugs on basis of opioids increasing cardiac tolerance to pathogenic impact of ischemia reperfusion. Eksp Klin Farmakol, 2012, 75(10):22-28.
34.	Landoni G, Turi S, Bignami E, et al. Organ protection by volatile anesthetics in non-coronary artery bypass grafting surgery. Future Cardiol, 2009, 5(6):589-603.
35.	Zaugg M, Lucchinetti E. Sevoflurane-compared with propofol-based anesthesia reduces the need for inotropic support in patients undergoing abdominal aortic aneurysm repair:evidence of cardioprotection by volatile anesthetics in noncardiac surgery. Anesthesiology, 2014, 120(5):1289-1290.
36.	Venugopal V, Hausenloy DJ, Ludman A, et al. Remote ischaemic preconditioning reduces myocardial injury in patients undergoing cardiac surgery with cold-blood cardioplegia:a randomised controlled trial. Heart, 2009, 95(19):1567-1571.
37.	Esmon CT. The interactions between inflammation and coagulation. Br J Haematol, 2005, 131(4):417-430.
38.	Kawamura T, Nara N, Kadosaki M, et al. Prostaglandin E1 reduces myocardial reperfusion injury by inhibiting proinflammatory cytokines production during cardiac surgery. Crit Care Med, 2000, 28(7):2201-2208.
39.	Kanemitsu S, Nishikawa M, Onoda K, et al. Pharmacologic platelet anesthesia by glycoprotein Ⅱb/Ⅲa complex antagonist and argatroban during in vitro extracorporeal circulation. J Thorac Cardiovasc Surg, 2003, 126(2):428-435.
40.	Chung A, Wildhirt SM, Wang S, et al. Combined administration of nitric oxide gas and iloprost during cardiopulmonary bypass reduces platelet dysfunction:a pilot clinical study. J Thorac Cardiovasc Surg, 2005, 129(4):782-790.
41.	Troncy E, Hubert B, Pang D, et al. Pre-emptive and continuous inhaled NO counteracts the cardiopulmonary consequences of extr-acorporeal circulation in a pig model. Nitric Oxide, 2006, 14(3):261-271.
42.	Andreadou I, Iliodromitis EK, Rassaf T, et al. The role of gasotransmitters NO, H2 S, CO in myocardial ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Br J Pharmacol, 2014, doi:10.1111/bph.12811.[Epubaheadofprint].
43.	Hubble CL, Cheifetz IM, Craig DM, et al. Inhaled nitric oxide results in deteriorating hemodynamics when administered during cardiopulmonary bypass in neonatal swine. Pediatr Crit Care Med, 2004, 5(2):157-162.
44.	Asanuma H, Sanada S, Asakura M, et al. Carperitide induces coronary vasodilation and limits infarct size in canine ischemic hearts:role of NO. Hypertens Res, 2014, doi:10.1038/hr.2014.70.[Epubaheadofprint].
45.	Carrier M, Perrault LP, Fortier A, et al. L-arginine supplemented nondiluted blood cardioplegia:a clinical trial. J Cardiovasc Surg (Torino), 2010, 51(2):283-287.

1. Meybohm P, Zacharowski K, Cremer J, et al. Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial--the RIPHeart-Study. Eur Heart J, 2012, 33(12):1423-1426.
2. Edmunds LH. Cardiopulmonary bypass after 50 years. N Engl J Med, 2004, 351(16):1603-1606.
3. Durdu S, Sirlak M, Cetintas D, et al. The efficacies of modified mechanical post conditioning on myocardial protection for patients undergoing coronary artery bypass grafting. J Cardiothorac Surg, 2012, 7:73.
4. Mangano DT, Tudor IC, Dietzel C. Multicenter study of periopera-tive ischemia research group; ischemia research and education foundation. The risk associated with aprotinin in cardiac surgery. N Engl J Med, 2006, 354(4):353-365.
5. Kloner RA, Jennings RB. Consequences of brief ischemia:stunning, preconditioning, and their clinical implications:part 1. Circulation, 2001, 104(24):2981-2989.
6. Schurr UP, Zünd G, Hoerstrup SP, et al. Preoperative administration of steroids:influence on adhesion molecules and cytokines after cardiopulmonary bypass. Ann Thorac Surg, 2001, 72(4):1316-320.
7. Morita K. Surgical reoxygenation injury of the myocardium in cyanotic patients:clinical relevance and therapeutic strategies by normoxic management during cardiopulmonary bypass. Gen Thorac Cardiovasc Surg, 2012, 60(9):549-556.
8. Wu QP, Purusram G, Wang HQ, et al. The efficacy of parecoxib on systemic inflammatory response associated with cardiopulmonary bypass during cardiac surgery. Br J Clin Pharmacol, 2013, 75(3):769-778.
9. Rezkalla SH, Kloner RA. No-Reflow Phenomenon. Circulation, 2002, 105(5):656-662.
10. Jackson KA, Majka SM, Wang H, et al. Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest, 2001, 107(11):1395-1402.
11. Eltzschig HK, Carmeliet P. Hypoxia and Inflammation. N Engl J Med, 2011, 364(7):656-665.
12. Karhausen J, Haase VH, Colgan SP. Inflammatory hypoxia:role of hypoxia-inducible factor. Cell Cycle, 2005, 4(2):256-258.
13. Colgan SP, Eltzschig HK. Adenosine and hypoxia-inducible factor signaling in intestinal injury and recovery. Annu Rev Physiol, 2012, 74:153-175.
14. Verma S, Fedak PW, Weisel RD, et al. Fundamentals of reperfusion injury for the clinical cardiologist. Circulation, 2002, 105(20):2332-2336.
15. Gupta-Malhotra M, Kern JH, Flynn PA, et al. Cardiac troponin Ⅰ after cardiopulmonary bypass in infants in comparison with older children. Cardiol Young, 2013, 23(3):431-435.
16. Perrelli MG, Pagliaro P, Penna C. Ischemia/reperfusion injury and cardioprotective mechanisms:Role of mitochondria and reactive oxygen species. World J Cardiol, 2011, 3(6):186-200.
17. Whitehouse JS, Riggle KM, Purpi DP, et al. The protective role of intestinal alkaline phosphatase in necrotizing enterocolitis. J Surg Res, 2010, 163(1):79-85.
18. Boodram S, Evans E. Use of leukocyte-depleting filters during cardiac surgery with cardiopulmonary bypass:a review. J Extra Corpor Technol, 2008, 40(1):27-42.
19. Bhakri K, Mulholland J, Punjabi P. Understanding innovations in the evolving practice of blood and crystalloid cardioplegia. Perfusion, 2014, [Epub ahead of print].
20. Abah U, Garfjeld Roberts P, Ishaq M, et al. Is cold or warm blood cardioplegia superior for myocardial protection? Interact Cardiovasc Thorac Surg, 2012, 14(6):848-855.
21. Mauney MC, Kron IL. The physiologic basis of warm cardioplegia. Ann Thorac Surg, 1995, 60(3):819-823.
22. Albert AA, Arnrich B, Walter JA, et al. Hyperkalemic blood versus crystalloid cardioplegia in longer clamping times. Asian Cardiovasc Thorac Ann, 2004, 12(2):115-120.
23. Franke UF, Korsch S, Wittwer T, et al. Intermittent antegrade warm myocardial protection compared to intermittent cold blood cardioplegia in elective coronary surgery--do we have to change? Eur J Cardiothorac Surg, 2003, 23(3):341-346.
24. Sanada S, Komuro I, Kitakaze M. Pathophysiology of myocardial reperfusion injury:preconditioning, postconditioning, and translational aspects of protective measures. Am J Physiol Heart Circ Physiol, 2011, 301(5):H1723-H1741.
25. Hausenloy DJ, Mwamure PK, Venugopal V, et al. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery:a randomised controlled trial. Lancet, 2007, 370(9587):575-579.
26. Ascione R, Suleiman SM, Angelini GD. Retrograde hot-shot cardioplegia in patients with left ventricular hypertrophy undergoing aortic valve replacement. Ann Thorac Surg, 2008, 85(2):454-458.
27. Kouerinis IA, Manopoulos CG, Zografos GC, et al. Retrograde cardioplegia in CABG:is it really useful? The microcirculation and a capillary unit model. Med Sci Monit, 2006, 12(11):265-268.
28. Fazel S, Borger MA, Weisel RD, et al. Myocardial protection in reoperative coronary artery bypass grafting:J Card Surg, 2004, 19(4):291-295.
29. Nader ND, Karamanoukian HL, Reedy RL, et al. Inclusion of sevof-lurane in cardioplegia reduces neutrophil activity during cardiopulmonary bypass. J Cardiothorac Vasc Anesth, 2006, 20(1):57-62.
30. Chouraqui P, Rabinowitz B, Livschitz S, et al. Effects of antegrade versus combined antegrade/retrograde cardioplegia on postoperative septal wall motion in patients undergoing open heart surgery. Cardiology, 1998, 88(6):526-529.
31. Walsh SR, Tang TY, Kullar P, et al. Ischaemic preconditioning during cardiac surgery:systematic review and meta-analysis of perioperative outcomes in randomised clinical trials. Eur J Cardiothorac Surg, 2008, 34(5):985.
32. Kolwicz SC, Purohit S, Tian R. Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes. Circ Res, 2013, 113(5):603-616.
33. Maslov LN, Lishmanovlu B, Headrick JP, et al. Perspective of crea-tion of drugs on basis of opioids increasing cardiac tolerance to pathogenic impact of ischemia reperfusion. Eksp Klin Farmakol, 2012, 75(10):22-28.
34. Landoni G, Turi S, Bignami E, et al. Organ protection by volatile anesthetics in non-coronary artery bypass grafting surgery. Future Cardiol, 2009, 5(6):589-603.
35. Zaugg M, Lucchinetti E. Sevoflurane-compared with propofol-based anesthesia reduces the need for inotropic support in patients undergoing abdominal aortic aneurysm repair:evidence of cardioprotection by volatile anesthetics in noncardiac surgery. Anesthesiology, 2014, 120(5):1289-1290.
36. Venugopal V, Hausenloy DJ, Ludman A, et al. Remote ischaemic preconditioning reduces myocardial injury in patients undergoing cardiac surgery with cold-blood cardioplegia:a randomised controlled trial. Heart, 2009, 95(19):1567-1571.
37. Esmon CT. The interactions between inflammation and coagulation. Br J Haematol, 2005, 131(4):417-430.
38. Kawamura T, Nara N, Kadosaki M, et al. Prostaglandin E1 reduces myocardial reperfusion injury by inhibiting proinflammatory cytokines production during cardiac surgery. Crit Care Med, 2000, 28(7):2201-2208.
39. Kanemitsu S, Nishikawa M, Onoda K, et al. Pharmacologic platelet anesthesia by glycoprotein Ⅱb/Ⅲa complex antagonist and argatroban during in vitro extracorporeal circulation. J Thorac Cardiovasc Surg, 2003, 126(2):428-435.
40. Chung A, Wildhirt SM, Wang S, et al. Combined administration of nitric oxide gas and iloprost during cardiopulmonary bypass reduces platelet dysfunction:a pilot clinical study. J Thorac Cardiovasc Surg, 2005, 129(4):782-790.
41. Troncy E, Hubert B, Pang D, et al. Pre-emptive and continuous inhaled NO counteracts the cardiopulmonary consequences of extr-acorporeal circulation in a pig model. Nitric Oxide, 2006, 14(3):261-271.
42. Andreadou I, Iliodromitis EK, Rassaf T, et al. The role of gasotransmitters NO, H2 S, CO in myocardial ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Br J Pharmacol, 2014, doi:10.1111/bph.12811.[Epubaheadofprint].
43. Hubble CL, Cheifetz IM, Craig DM, et al. Inhaled nitric oxide results in deteriorating hemodynamics when administered during cardiopulmonary bypass in neonatal swine. Pediatr Crit Care Med, 2004, 5(2):157-162.
44. Asanuma H, Sanada S, Asakura M, et al. Carperitide induces coronary vasodilation and limits infarct size in canine ischemic hearts:role of NO. Hypertens Res, 2014, doi:10.1038/hr.2014.70.[Epubaheadofprint].
45. Carrier M, Perrault LP, Fortier A, et al. L-arginine supplemented nondiluted blood cardioplegia:a clinical trial. J Cardiovasc Surg (Torino), 2010, 51(2):283-287.

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Pathophysiology of Myocardial Ischemia and Myocardial Protection during Cardiac Surgery

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