Application of Remote Ischemic Preconditioning in Patients Undergoing Chemotherapy with Anthracyclines

Author(s): Simone Meneghetti Zatta, Neif Murad, Beatriz da Costa Aguiar Alves, Ligia Ajaime Azzalis, Virginia Berlanga Campos Junqueira, Roberto Odebrecht Rocha, Marcelo Rodrigues Bacci, David Feder, Antonio Carlos Palandri Chagas, Fernando Adami, Fernando Luiz Affonso Fonseca*

Journal Name: Current Enzyme Inhibition

Volume 15 , Issue 2 , 2019

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Graphical Abstract:


Background: The most active agents for the treatment of breast cancer are the anthracyclines whose clinical usefulness is limited by cumulative dose-dependent cardiotoxicity, which results in congestive heart failure among other limiting factors. With all the attempts to minimize chemotherapeutic cardiotoxicity, remote ischemic preconditioning (RIPC) has been considered as a potent endogenous mechanism capable of inhibiting inflammatory responses.

Objective: This study aimed to verify if RIPC may be effective as prophylaxis to prevent anthracycline- induced cardiotoxicity in oncological patients.

Methods: The preconditioning method was based on four to five-minute cycles of a blood pressure cuff insufflation around the upper arm (either left or right) from 200 mmHg to 250 mmHg, inducing ischemic intervals interspersed with 5 minutes of reperfusion.

Results: In this work, echocardiogram results showed a ventricular mass variation that can get worse during chemotherapeutic treatment; however, in patients who had been undergoing RIPC sessions over a period of 6 months, it was observed that this change did not occur. The parameters for troponin T levels were considered; they were higher in patients who were not undergoing RIPC in relation to those who were. When both cases were compared, it was possible to infer that there was a clinically significant improvement for those who went through the procedure.

Conclusion: Thus, through the analysis of this study, it is possible to conclude that RIPC is a lowcost, non-invasive procedure which brings cardiac protection for patients undergoing chemotherapy with anthracyclines, providing support in the treatment of cancer.

Keywords: Anthracyclines, cardiotoxicity, chemotherapy, neoplasia, remote ischemic preconditioning, troponin T.

Ministério da Saúde (BR), Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) Estimativa 2014: Incidência de Câncer no Brasil. Rio de Janeiro: Inca, 2014. 2014. (Accessed on: April 20, 2016)
Ewer, M.S.; Ewer, S.M. Cardiotoxicity of anticancer treatments: what the cardiologist needs to know. Nat. Rev. Cardiol., 2010, 7(10), 564-575.
[] [PMID: 20842180]
Monsuez, J.J.; Charniot, J.C.; Vignat, N.; Artigou, J.Y. Cardiac side-effects of cancer chemotherapy. Int. J. Cardiol., 2010, 144(1), 3-15.
[] [PMID: 20399520]
Sereno, M.; Brunello, A.; Chiappori, A.; Barriuso, J.; Casado, E.; Belda, C.; de Castro, J.; Feliu, J.; González-Barón, M. Cardiac toxicity: old and new issues in anti-cancer drugs. Clin. Transl. Oncol., 2008, 10(1), 35-46.
[] [PMID: 18208791]
Yeh, E.T.; Bickford, C.L. Cardiovascular complications of cancer therapy: incidence, pathogenesis, diagnosis, and management. J. Am. Coll. Cardiol., 2009, 53(24), 2231-2247.
[] [PMID: 19520246]
Yeh, E.T.; Tong, A.T.; Lenihan, D.J.; Yusuf, S.W.; Swafford, J.; Champion, C.; Durand, J.B.; Gibbs, H.; Zafarmand, A.A.; Ewer, M.S. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation, 2004, 109(25), 3122-3131.
[] [PMID: 15226229]
Kirova, Y.M. Recent advances in breast cancer radiotherapy: Evolution or revolution, or how to decrease cardiac toxicity? World J. Radiol., 2010, 2(3), 103-108.
[] [PMID: 21160943]
Kalil Filho, R.; Hajjar, L.A.; Bacal, F.; Hoff, P.M.G. Diz, Mdel.P.; Galas, F.R.B.G.; Fukushima, J.T.; Almeida, J.P.; Nakamura, R.E.; Trielli, T.R.; Bittar, C.S.; Santos, M.H.; Galdeano, F.G.; Auler Júnior, J.O.; Silvestrini, A.A.; Alencar, A.; Mota, A.C.; Gusmão, C.A.; Almeida, D.R.; Simões, C.M.; Bocchi, E.A.; Lima, E.M.; Fernandes, F.; Silveira, F.S.; Vilas-Boas, F.; Beck da Silva Neto, L.; Rohde, L.E.; Montera, M.W.; Barbosa, M.; Mano, M.S.; Riechelmann, R.S.; Arai, R.J.; Martins, S.M.; Ferreira, S.M.; Santos, V. I Diretriz Brasileira de Cardio-Oncologia da Sociedade Brasileira de Cardiologia. Arq. Bras. Cardiol., 2011, 96(2)(Suppl. 1), 1-52.
[] [PMID: 21468528]
Li, G.; Labruto, F.; Sirsjö, A.; Chen, F.; Vaage, J.; Valen, G. Myocardial protection by remote preconditioning: the role of nuclear factor kappa-B p105 and inducible nitric oxide synthase. Eur. J. Cardiothorac. Surg., 2004, 26(5), 968-973.
[] [PMID: 15519191]
Konstantinov, I.E.; Arab, S.; Li, J.; Coles, J.G.; Boscarino, C.; Mori, A.; Cukerman, E.; Dawood, F.; Cheung, M.M.; Shimizu, M.; Liu, P.P.; Redington, A.N. The remote ischemic preconditioning stimulus modifies gene expression in mouse myocardium. J. Thorac. Cardiovasc. Surg., 2005, 130(5), 1326-1332.
[] [PMID: 16256785]
Konstantinov, I.E.; Arab, S.; Kharbanda, R.K.; Li, J.; Cheung, M.M.; Cherepanov, V.; Downey, G.P.; Liu, P.P.; Cukerman, E.; Coles, J.G.; Redington, A.N. The remote ischemic preconditioning stimulus modifies inflammatory gene expression in humans. Physiol. Genomics, 2004, 19(1), 143-150.
[] [PMID: 15304621]
Oxman, T.; Arad, M.; Klein, R.; Avazov, N.; Rabinowitz, B. Limb ischemia preconditions the heart against reperfusion tachyarrhythmia. Am. J. Physiol., 1997, 273(4), H1707-H1712.
[PMID: 9362234]
Costa, J.F.; Fontes-Carvalho, R.; Leite-Moreira, A.F. Pré-condicionamento isquémico remoto do miocárdio: dos mecanismos fisiopatológicos à aplicação na prática clínica. Rev. Port. Cardiol., 2013, 32, 893-904.
[] [PMID: 24120469]
Antman, E.M. Decision making with cardiac troponin tests. N. Engl. J. Med., 2002, 346(26), 2079-2082.
[] [PMID: 12087146]
Everett, B.M.; Brooks, M.M.; Vlachos, H.E.; Chaitman, B.R.; Frye, R.L.; Bhatt, D.L. BARI 2D Study Group. Troponin and cardiac events in stable ischemic heart disease and diabetes. N. Engl. J. Med., 2015, 373(7), 610-620.
[] [PMID: 26267622]
Omland, T.; de Lemos, J.A.; Sabatine, M.S.; Christophi, C.A.; Rice, M.M.; Jablonski, K.A.; Tjora, S.; Domanski, M.J.; Gersh, B.J.; Rouleau, J.L.; Pfeffer, M.A.; Braunwald, E. Prevention of Events with Angiotensin Converting Enzyme Inhibition (PEACE) Trial Investigators. A sensitive cardiac troponin T assay in stable coronary artery disease. N. Engl. J. Med., 2009, 361(26), 2538-2547.
[] [PMID: 19940289]
Saunders, J.T.; Nambi, V.; de Lemos, J.A.; Chambless, L.E.; Virani, S.S.; Boerwinkle, E.; Hoogeveen, R.C.; Liu, X.; Astor, B.C.; Mosley, T.H.; Folsom, A.R.; Heiss, G.; Coresh, J.; Ballantyne, C.M. Cardiac troponin T measured by a highly sensitive assay predicts coronary heart disease, heart failure, and mortality in the Atherosclerosis Risk in Communities Study. Circulation, 2011, 123(13), 1367-1376.
[] [PMID: 21422391]
Murry, C.E.; Jennings, R.B.; Reimer, K.A. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation, 1986, 74(5), 1124-1136.
[] [PMID: 3769170]
Chung, R.; Maulik, A.; Hamarneh, A.; Hochhauser, D.; Hausenloy, D.J.; Walker, J.M.; Yellon, D.M. Effect of remote ischaemic conditioning in oncology patients undergoing chemotherapy: rationale and design of the ERIC-ONC study--a single-center, blinded, randomized controlled trial. Clin. Cardiol., 2016, 39(2), 72-82.
[] [PMID: 26807534]
Candilio, L.; Malik, A.; Ariti, C.; Barnard, M.; Di Salvo, C.; Lawrence, D.; Hayward, M.; Yap, J.; Roberts, N.; Sheikh, A.; Kolvekar, S.; Hausenloy, D.J.; Yellon, D.M. Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial. Heart, 2015, 101(3), 185-192.
[] [PMID: 25252696]
Hausenloy, D.J.; Mwamure, P.K.; Venugopal, V.; Harris, J.; Barnard, M.; Grundy, E.; Ashley, E.; Vichare, S.; Di Salvo, C.; Kolvekar, S.; Hayward, M.; Keogh, B.; MacAllister, R.J.; Yellon, D.M. 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.
[] [PMID: 17707752]
Davies, W.R.; Brown, A.J.; Watson, W.; McCormick, L.M.; West, N.E.; Dutka, D.P.; Hoole, S.P. 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(3), 246-251.
[] [PMID: 23696599]
Rentoukas, I.; Giannopoulos, G.; Kaoukis, A.; Kossyvakis, C.; Raisakis, K.; Driva, M.; Panagopoulou, V.; Tsarouchas, K.; Vavetsi, S.; Pyrgakis, V.; Deftereos, S. Cardioprotective role of remote ischemic periconditioning in primary percutaneous coronary intervention: enhancement by opioid action. JACC Cardiovasc. Interv., 2010, 3(1), 49-55.
[] [PMID: 20129568]
White, S.K.; Frohlich, G.M.; Sado, D.M.; Maestrini, V.; Fontana, M.; Treibel, T.A.; Tehrani, S.; Flett, A.S.; Meier, P.; Ariti, C.; Davies, J.R.; Moon, J.C.; Yellon, D.M.; Hausenloy, D.J. Remote ischemic conditioning reduces myocardial infarct size and edema in patients with ST-segment elevation myocardial infarction. JACC Cardiovasc. Interv., 2015, 8(1 Pt B), 178-188.
[] [PMID: 25240548]

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Article Details

Year: 2019
Published on: 06 September, 2019
Page: [114 - 119]
Pages: 6
DOI: 10.2174/1573408015666190906120640

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