Abstract
Objectives: Remote ischemic conditioning (RIC) by repetitive blood pressure cuff inflation/deflation around a limb provides cardioprotection in patients undergoing coronary artery bypass grafting (CABG). Cardioprotection is confounded by risk factors, comorbidities and comedications. We aimed to identify confounders that possibly attenuate the protection provided by RIC. Methods: In a retrospective analysis of our single-center, randomized, double-blind trial of patients undergoing elective CABG with/without RIC prior to ischemic cardioplegic arrest, we analyzed demographics, medications and intraoperative variables. The primary end point was myocardial injury, as reflected by the area under the curve for serum troponin I (TnI) from baseline to 72 h after surgery. Results: In models with 2 independent variables and in the multivariate analysis, age and aortic cross-clamp time impacted on TnI release. Subgroup analyses confirmed RIC-induced protection in all age tertiles. There was no protection with an aortic cross-clamp time ≤56 min (RIC/control = 1.026 not significant), but there was protection with 57-75 min (RIC/control = 0.757; p = 0.0348) and ≥76 min (RIC/control = 0.735; p = 0.0277). Gender, β-blockers, statins, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and intraoperative nitroglycerine did not impact on TnI release. Conclusion: Age, gender, β-blockers, statins, ACE inhibitors, ARBs and intraoperative nitroglycerine have no significant impact on RIC-induced cardioprotection during CABG. However, greater myocardial ischemia/reperfusion injury at longer cross-clamp time facilitates the detection of protection by RIC.
References
1.
Heusch G, Botker HE, Przyklenk K, Redington A, Yellon DM: Remote ischemic conditioning. J Am Coll Cardiol 2015;65:177-195.
2.
Davies WR, Brown AJ, Watson W, McCormick LM, West NE, Dutka DP, Hoole SP: Remote ischemic preconditioning improves outcome at 6 years after elective percutaneous coronary intervention: the CRISP stent trial long-term follow-up. Circ Cardiovasc Interv 2013;6:246-251.
3.
Thielmann M, Kottenberg E, Kleinbongard P, Wendt D, Gedik N, Pasa S, Price V, Tsagakis K, Neuhäuser M, Peters J, Jakob H, Heusch G: Cardioprotection and prognosis by remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet 2013;382:597-604.
4.
Sloth AD, Schmidt MR, Munk K, Kharbanda RK, Redington AN, Schmidt M, Pedersen L, Sorensen HT, Botker HE: Improved long-term clinical outcomes in patients with ST-elevation myocardial infarction undergoing remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention. Eur Heart J 2014;35:168-175.
5.
Le Page S, Bejan-Angoulvant T, Angoulvant D, Prunier F: Remote ischemic conditioning and cardioprotection: a systematic review and meta-analysis of randomized clinical trials. Basic Res Cardiol 2015;110:11.
6.
Günaydin B, Cakici I, Soncul H, Kalaycioglu S, Cevik C, Sancak B, Kanzik I, Karadenizli Y: Does remote organ ischaemia trigger cardiac preconditioning during coronary artery surgery? Pharmacol Res 2000;41:493-496.
7.
Iliodromitis EK, Kyrzopoulos S, Paraskevaidis IA, Kolocassides KG, Adamopoulos S, Karavolias G, Kremastinos DT: Increased C reactive protein and cardiac enzyme levels after coronary stent implantation. Is there protection by remote ischaemic preconditioning? Heart 2006;92:1821-1826.
8.
Rahman IA, Mascaro JG, Steeds RP, Frenneaux MP, Nightingale P, Gosling P, Townsend P, Townend JN, Green D, Bonser RS: Remote ischemic preconditioning in human coronary artery bypass surgery: from promise to disappointment? Circulation 2010;122:S53-S59.
9.
Karuppasamy P, Chaubey S, Dew T, Musto R, Sherwood R, Desai J, John L, Shah AM, Marber MS, Kunst G: Remote intermittent ischemia before coronary artery bypass graft surgery: a strategy to reduce injury and inflammation? Basic Res Cardiol 2011;106:511-519.
10.
Lomivorotov VV, Shmyrev VA, Nepomnyaschih VA, Ponomarev DN, Knyazkova LG, Lomivorotov VN, Karaskov AM: Remote ischaemic preconditioning does not protect the heart in patients undergoing coronary artery bypass grafting. Interact Cardiovasc Thorac Surg 2012;15:18-22.
11.
Lucchinetti E, Bestmann L, Feng J, Freidank H, Clanachan AS, Finegan BA, Zaugg M: Remote ischemic preconditioning applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass graft surgery: lack of synergy or evidence of antagonism in cardioprotection? Anesthesiology 2012;116:296-310.
12.
Young PJ, Dalley P, Garden A, Horrocks C, La FA, Mahon B, Miller J, Pilcher J, Weatherall M, Williams J, Young W, Beasley R: A pilot study investigating the effects of remote ischemic preconditioning in high-risk cardiac surgery using a randomised controlled double-blind protocol. Basic Res Cardiol 2012;107:256.
13.
Prasad A, Gossl M, Hoyt J, Lennon RJ, Polk L, Simari R, Holmes DR Jr, Rihal CS, Lerman A: Remote ischemic preconditioning immediately before percutaneous coronary intervention does not impact myocardial necrosis, inflammatory response, and circulating endothelial progenitor cell counts: a single center randomized sham controlled trial. Catheter Cardiovasc Interv 2013;81:930-936.
14.
Iliodromitis EK, Andreadou I, Iliodromitis K, Dagres N: Ischemic and postischemic conditioning of the myocardium in clinical practice: challenges, expectations and obstacles. Cardiology 2014;129:117-125.
15.
Hausenloy DJ, Candilio L, Laing C, Kunst G, Pepper J, Kolvekar S, Evans R, Robertson S, Knight R, Ariti C, Clayton T, Yellon DM: Effect of remote ischemic preconditioning on clinical outcomes in patients undergoing coronary artery bypass graft surgery (ERICCA): rationale and study design of a multi-centre randomized double-blinded controlled clinical trial. Clin Res Cardiol 2011;101:339-348.
16.
Meybohm P, Zacharowski K, Cremer J, Roesner J, Kletzin F, Schaelte G, Felzen M, Strouhal U, Reyher C, Heringlake M, Schon J, Brandes I, Bauer M, Knuefermann P, Wittmann M, Hachenberg T, Schilling T, Smul T, Maisch S, Sander M, Moormann T, Boening A, Weigand MA, Laufenberg R, Werner C, Winterhalter M, Treschan T, Stehr SN, Reinhart K, Hasenclever D, Brosteanu O, Bein B: Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial: the RIP Heart Study. Eur Heart J 2012;33:1423-1426.
17.
Heusch G: Cardioprotection: chances and challenges of its translation to the clinic. Lancet 2013;381:166-175.
18.
Ferdinandy P, Hausenloy DJ, Heusch G, Baxter GF, Schulz R: Interaction of risk factors, comorbidities and comedications with ischemia/reperfusion injury and cardioprotection by preconditioning, postconditioning, and remote conditioning. Pharmacol Rev 2014;66:1142-1174.
19.
Pickard JM, Botker HE, Crimi G, Davidson B, Dutka D, Ferdinandy P, Ganske R, Garcia-Dorado D, Giricz Z, Gourine AV, Heusch G, Kharbanda R, Kleinbongard P, MacAllister R, McIntyre C, Meybohm P, Prunier F, Redington A, Robertson NJ, Suleiman MS, Vanezis A, Walsh S, Yellon DM, Hausenloy DJ: Remote ischemic conditioning: from experimental observation to clinical application: report from the 8th Biennial Hatter Cardiovascular Institute Workshop. Basic Res Cardiol 2015;110:453.
20.
Kottenberg E, Thielmann M, Bergmann L, Heine T, Jakob H, Heusch G, Peters J: Protection by remote ischaemic preconditioning during coronary artery bypass grafting with isoflurane but not with propofol anesthesia - a clinical trial. Acta Anaesthesiol Scand 2012;56:30-38.
21.
Kottenberg E, Musiolik J, Thielmann M, Jakob H, Peters J, Heusch G: Interference of propofol with signal transducer and activator of transcription 5 activation and cardioprotection by remote ischemic preconditioning during coronary artery bypass grafting. J Thorac Cardiovasc Surg 2013;147:376-382.
22.
Bautin AE, Mazurok VA, Osovskikh VV, Afanas'eva K: Hemodynamic effects of the alveolar recruitment maneuver in cardiosurgical patients with left ventricular systolic dysfunction. Anesteziol Reanimatol 2014;59:43-48.
23.
Peters J: Remote ischaemic preconditioning of the heart: remote questions, remote importance, or remote preconditions? Basic Res Cardiol 2011;106:507-509.
24.
Sloth AD, Schmidt MR, Munk K, Schmidt M, Pedersen L, Sorensen HT, Botker HE; CONDI Investigators: Impact of cardiovascular risk factors and medication use on the efficacy of remote ischaemic conditioning: post hoc subgroup analysis of a randomised controlled trial. BMJ Open 2015;5:e006923.
25.
Kottenberg E, Thielmann M, Kleinbongard P, Frey UH, Heine T, Jakob H, Heusch G, Peters J: Myocardial protection by remote ischaemic pre-conditioning is abolished in sulphonylurea-treated diabetics undergoing coronary revascularisation. Acta Anaesthesiol Scand 2014;58:453-462.
26.
Boengler K, Schulz R, Heusch G: Loss of cardioprotection with ageing. Cardiovasc Res 2009;83:247-261.
27.
Zhou C, Liu Y, Yao Y, Zhou S, Fang N, Wang W, Li L: Beta-blockers and volatile anesthetics may attenuate cardioprotection by remote preconditioning in adult cardiac surgery: a meta-analysis of 15 randomized trials. J Cardiothorac Vasc Anesth 2013;27:305-311.
28.
Kleinbongard P, Heusch G: Extracellular signalling molecules in the ischaemic/reperfused heart - druggable and translatable for cardioprotection? Br J Pharmacol 2015;172:2010-2025.
29.
Kleinbongard P, Thielmann M, Jakob H, Peters J, Heusch G, Kottenberg E: Nitroglycerin does not interfere with protection by remote Ischemic preconditioning in patients with surgical coronary revascularization under isoflurane anesthesia. Cardiovasc Drugs Ther 2013;27:359-361.
30.
Candilio L, Malik A, Ariti C, Barnard M, Di SC, Lawrence D, Hayward M, Yap J, Roberts N, Sheikh A, Kolvekar S, Hausenloy DJ, Yellon DM: Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial. Heart 2015;10:185-192.
31.
Windecker S, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Juni P, Kappetein AP, Kastrati A, Knuuti J, Landmesser U, Laufer G, Neumann FJ, Richter DJ, Schauerte P, Uva MS, Stefanini GG, Taggart DP, Torracca L, Valgimigli M, Wijns W, Witkowski A: 2014 ESC/EACTS guidelines on myocardial revascularization: the Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014;35:2541-2619.
32.
Assmann SF, Pocock SJ, Enos LE, Kasten LE: Subgroup analysis and other (mis)uses of baseline data in clinical trials. Lancet 2000;355:1064-1069.
33.
D'Ascenzo F, Moretti C, Omede P, Cerrato E, Cavallero E, Er F, Presutti DG, Colombo F, Crimi G, Conrotto F, Dinicolantonio JJ, Chen S, Prasad A, Biondi ZG, Gaita F: Cardiac remote ischaemic preconditioning reduces periprocedural myocardial infarction for patients undergoing percutaneous coronary interventions: a meta-analysis of randomised clinical trials. EuroIntervention 2014;9:1463-1471.
34.
Heusch G: Molecular basis of cardioprotection: signal transduction in ischemic pre-, post- and remote conditioning. Circ Res 2015;116:674-699.
35.
Birdi I, Angelini GD, Bryan AJ: Biochemical markers of myocardial injury during cardiac operations. Ann Thorac Surg 1997;63:879-884.
36.
Hausenloy D, Kunst G, Boston-Griffiths E, Kolvekar S, Chaubey S, John L, Desai J, Yellon D: The effect of cyclosporin-A on peri-operative myocardial injury in adult patients undergoing coronary artery bypass graft surgery: a randomised controlled clinical trial. Heart 2014;100:544-549.
37.
Pinaud F, Corbeau JJ, Baufreton C, Binuani JP, De Brux JL, Fouquet O, Angoulvant D, Furber A, Prunier F: Remote ischemic preconditioning in aortic valve surgery: results of a randomized controlled study. J Cardiol 2015, .
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2015
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