Remote Ischemic Preconditioning is a Safe Adjuvant Technique to Myocardial Protection But Adds No Clinical Benefit After On-Pump Coronary Artery Bypass Grafting
Background: To evaluate the impact of remote ischemic preconditioning (RIPC) on clinical outcome, biological markers of myocardial injury, and its safety in patients undergoing on-pump coronary artery bypass grafting (CABG).
Material and Methods: This study was conducted at Ch. Pervaiz Elahi Institute of Cardiology (CPEIC) in Multan. The study took place from March 2012 to June 2013. Patients were randomly placed into two groups. Group A (N = 32) did not undergo RIPC; Group B (N = 35) received RIPC after induction of anesthesia. Similar standard general anesthesia, cardiopulmonary technique, myocardial protection strategies, and surgical techniques were used in both groups except the protocol for RIPC. Following postoperative outcome, i.e. cardiac defibrillation after removal of aortic cross clamp during the period of rewarming, demand for intra-aortic balloon pump (IABP), demand for antiarrhythmic before leaving the operation room, postoperative creatine kinase-myocardial band (CK-MB) level (at 1h, 12h, 24h, and 48h after surgery), postoperative serum creatinine level on first postoperative day, postoperative ejection fraction (EF) on third postoperative day, in-hospital mortality, and one-year mortality were noted, prospectively. Safety of protocol of RIPC was estimated by limb ischemia monitored by pulse oximetry during and after procedure of RIPC and postoperative neurapraxia by nerve examination of right upper limb.
Results: Post aortic cross clamp release cardiac defibrillation, demand for IABP, demand for high inotropes, and use of antiarrhythmic in the operation room were statistically insignificant in the non-RIPC and RIPC group with P values of .54, .78, .16, and .16, respectively. Mean postoperative CK-MB level (IU/L) showed the following results: At 1h (Group A 20.94 + 1.66, Group B 20.57 + 1.54, P = .35), at 12h (Group A 27.13 + 1.85, Group B 28.05 + 3.04, P = .135), at 24h (Group A 27.63 + 1.7, Group B 27.85 + 2.2, P = .63), and at 48h (Group A 22.95 + 2.76, Group B 23.27 + 3.6, P = .69). First postoperative day serum creatinine (Group A 1.29 + 0.395, Group B 1.33 + 0.57, P = .77) and postoperative ejection fraction percentage on the third postoperative day (Group A 50.78 + 8.72, Group B 50.57 + 8.38, P = .92) showed no statistical difference between two groups. Postoperative low cardiac output state, in-hospital mortality, and one-year mortality also were statistically insignificant between the groups with P values of .93, .29, and .33, respectively. None of the patients in either group showed evidence of limb ischemia and neurapraxia of the right upper limb.
Conclusion: RIPC is a safe technique, but it does not have additional clinical benefit after on-pump CABG surgery in the presence of a standard myocardial protective strategy.
Ali N, Rizwi F, Iqbal A, Rashid A. 2010. Induced Remote Ischemic Pre-Conditioning on Ischemia-Reperfusion Injury in Patients Undergoing Coronary Artery Bypass. JCPSP Vol. 20 (7): 427-431.nBirnbaum Y, Hale SL, Kloner RA. 1997. Ischemic preconditioning at a distance: reduction of myocardial infarct size by partial reduction of blood supply combined with rapid stimulation of the gastrocnemius muscle in the rabbit. Circulation 96:1641-1646.nBrevoord D, Kranke P, Kuijpers M, Weber N, Hollmann M, Preckel B. 2012. Remote Ischemic Conditioning to Protect against Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis. PLoS One 7(7): e42179.nChen XG, Wu BY, Wang JK, Bai T. 2005. Mechanism of the protective effects of noninvasive limbs preconditioning on myocardial ischemia-reperfusion injury. Chin Med J 118:1723-1727.nDiwan V, Kant R, Jaggi AS, Singh N, Singh D. 2008. Signal mechanism activated by erythropoietin preconditioning and remote renal preconditioning-induced cardioprotection. Mol Cell Biochem 315:195-201.nGeorge I, Oz MC. 2008. Myocardial revascularization after acute myocardial infarction. In: Lawrence HC. Cardiac Surgery in the Adults. 3rd ed. Massachusetts: Mc Graw-Hill 669-698.nGho BC, Schoemaker RG, van den Doel MA, Duncker DJ, Verdouw PD. 1996. Myocardial protection by brief ischemia in noncardiac tissue. Circulation 94:2193-2200.nHong DM, Jeon Y, Lee CS, et al. 2012. Effects of remote ischemic preconditioning with postconditioning in patients undergoing off-pump coronary artery bypass surgery-randomized controlled trial. Circ J 76(4):884-90.nKlatte K, Chaitman BR, Theroux P, et al. 2001. Increased mortality after coronary artery bypass graft surgery is associated with increased levels of postoperative creatine kinase-myocardial band isoenzyme release. J Am Coll Cardiol 38:1070.nKristiansen SB, Henning O, Kharbanda RK, et al. 2005. Remote preconditioning reduces ischemic injury in the explanted heart by a KATP channel-dependent mechanism. Am J Physiol Heart Circ Physiol 288:H1252-H1256.nLiem DA, Verdouw PD, Ploeg H, Kazim S, Duncker DJ. 2002. Sites of action of adenosine in interorgan preconditioning of the heart. Am J Physiol Heart Circ Physiol 283:H29-H37.nLomivorotov VV, Shmyrev VA, Nepomnyaschih VA, et al. 2012. Remote ischaemic preconditioning does not protect the heart in patients undergoing coronary artery bypass grafting. Interactive CardioVascular and Thoracic Surgery 15 18-22.nMarczak J, Nowicki R, Kulbacka J, Saczko J. 2012. Is remote ischaemic preconditioning of benefit to patients undergoing cardiac surgery? Interact Cardiovasc Thorac Surg May; 14(5):634-9.nMentzer Jr. RM, Jahania MS, Lasley RD. 2008. Myocardial Protection. In: Lawrence HC. Cardiac Surgery in the Adults. 3rd ed. Massachusetts: McGraw-Hill p.443-463.nPatel HH, Moore J, Hsu AK, Gross GJ. 2002. Cardioprotection at a distance: mesenteric artery occlusion protects the myocardium via an opioid sensitive mechanism. J Mol Cell Cardiol 34:1317-1323.nPrzyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. 1993. Regional ischemic ‘preconditioning’ protects remote virgin myocardium from subsequent sustained coronary occlusion. Circulation 87:893-899.nRahman IA, Mascaro JG, Steeds RP, et al. 2010. Remote ischemic preconditioning in human coronary artery bypass surgery: from promise to disappointment? Circulation Sep 14;122(11 Suppl):S53-91.nThielmann M, Kottenberg E, Kleinbongard P, et al. 2013. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet Aug 17;382(9892):597-604.nWeinbrenner C, Nelles M, Herzog N, Sarvary L, Strasser RH. 2002. Remote pre-conditioning by infrarenal occlusion of the aorta protects the heart from infarction: a newly identified non-neural but PKC-dependent pathway. Cardiovasc Res 55:590-601.nWeman SM, Karhunen PJ, Penttila A, Jarvinen AA, Salminen US. 2000. Reperfusion injury associated with one-fourth of deaths after coronary artery bypass grafting. Ann Thorac Surg 70:807-812.nXiao L, Lu R, Hu CP, Deng HW, Li YJ. 2001. Delayed cardioprotection by intestinal preconditioning is mediated by calcitonin gene-related peptide. Eur JPharmacol 427:131-135.nYoung PJ, Dalley P, Garden A, et al. 2012. A pilot study investigating the effects of remote ischemic preconditioning in high-risk cardiac surgery using a randomized controlled double-blind protocol. Basic Res Cardiol 107(3):256.nZhou W, Zeng D, Chen R, et al. 2010. Limb ischemic preconditioning reduces heart and lung injury after an open heart operation in infants. Pediatr Cardiol Jan;31(1):22-9.n
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