The effect of perhexiline on myocardial protection during coronary artery surgery: A two-centre, randomized, double-blind, placebo-controlled trial

European Journal of Cardio-thoracic Surgery

Volumn 47, Issue 3, 2015, Pages 464-472

  Drury, Nigel E ^a,b   Howell, Neil J ^a,b   Calvert, Melanie J ^b   Weber, Ralf J M ^b   Senanayake, Eshan L ^a,b   Lewis, Michael E ^c   Hyde, Jonathan A J ^c   Green, David H ^a   Mascaro, Jorge G ^a   Wilson, Ian C ^a   Graham, Timothy R ^a   Rooney, Stephen J ^a   Viant, Mark R ^b   Freemantle, Nick ^d   Frenneaux, Michael P ^e   Pagano, Domenico ^a,b  

^a QUEEN ELIZABETH HOSPITAL   (United Kingdom)

^b UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^c ROYAL SUSSEX COUNTY HOSPITAL   (United Kingdom)

^d UNIVERSITY COLLEGE LONDON   (United Kingdom)

^e UNIVERSITY OF ABERDEEN   (United Kingdom)

Author keywords

Cardiac output; Metabolism; Metabolomics; Myocardial reperfusion injury; Myocardial stunning

Indexed keywords

FATTY ACID; INOTROPIC AGENT; INSULIN; NORADRENALIN; PERHEXILINE; PHENYLEPHRINE; PLACEBO; TROPONIN T; VASOCONSTRICTOR AGENT; CARDIOTONIC AGENT;

ADULT; AGED; ARTICLE; CARDIAC PATIENT; CEREBROVASCULAR ACCIDENT; CONTROLLED STUDY; CORONARY ARTERY BYPASS SURGERY; DIZZINESS; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; ELECTROCARDIOGRAM; EUROSCORE; FATTY ACID BLOOD LEVEL; FEMALE; FORWARD HEART FAILURE; HEART INDEX; HEART MUSCLE; HEART MUSCLE BIOPSY; HEART MUSCLE INJURY; HEART MUSCLE REPERFUSION; HEART PROTECTION; HUMAN; KIDNEY DYSFUNCTION; LENGTH OF STAY; MAJOR CLINICAL STUDY; MALE; MASS SPECTROMETRY; METABOLOME; METABOLOMICS; MITRAL VALVE SURGERY; MULTICENTER STUDY; NAUSEA; OUTCOME ASSESSMENT; PATIENT SAFETY; PRIORITY JOURNAL; PROSPECTIVE STUDY; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; RENAL REPLACEMENT THERAPY; REOPERATION; TREATMENT DURATION; ADVERSE EFFECTS; CHEMISTRY; CLINICAL TRIAL; CORONARY ARTERY BYPASS GRAFT; CORONARY BLOOD VESSEL; DRUG EFFECTS; HEART OUTPUT; HEART VENTRICLE; METABOLISM; MIDDLE AGED; MYOCARDIAL REPERFUSION INJURY; POSTOPERATIVE COMPLICATION; PROCEDURES; SURGERY;

AGED; CARDIAC OUTPUT; CARDIOTONIC AGENTS; CORONARY ARTERY BYPASS; CORONARY VESSELS; DOUBLE-BLIND METHOD; FEMALE; HEART VENTRICLES; HUMANS; MALE; METABOLOME; MIDDLE AGED; MYOCARDIAL REPERFUSION INJURY; PERHEXILINE; PLACEBOS; POSTOPERATIVE COMPLICATIONS; PROSPECTIVE STUDIES;

EID: 84928184320     PISSN: 10107940     EISSN: 1873734X     Source Type: Journal    
DOI: 10.1093/ejcts/ezu238     Document Type: Article

References (25)

1. Bridgewater B, Keogh BE, Kinsman R, Walton P. Sixth National Adult Cardiac Surgery Database Report 2008. Demonstrating Quality. Henley-on-Thames: Dendrite Clinical Systems, Ltd, 2009.
2. Doenst T, Borger MA, Weisel RD, Yau TM, Maganti M, Rao V. Relation between aortic cross-clamp time and mortality-not as straightforward as expected. Eur J Cardiothorac Surg 2008;33:660-5.
3. Fremes SE, Tamariz MG, Abramov D, Christakis GT, Sever JY, Sykora K et al. Late results of the Warm Heart Trial: the influence of nonfatal cardiac events on late survival. Circulation 2000;102:III339-345.
4. Doenst T, Bugger H, Schwarzer M, Faerber G, Borger MA, Mohr FW. Three good reasons for heart surgeons to understand cardiac metabolism. Eur J Cardiothorac Surg 2008;33:862-71.
5. Lopaschuk GD, Ussher JR, Folmes CD, Jaswal JS, Stanley WC. Myocardial fatty acid metabolism in health and disease. Physiol Rev 2010;90:207-58.
6. Quinn DW, Pagano D, Bonser RS, Rooney SJ, Graham TR, Wilson IC et al. Improved myocardial protection during coronary artery surgery with glucose-insulin-potassium: a randomized controlled trial. J Thorac Cardiovasc Surg 2006;131:34-42.
7. Howell NJ, Ashrafian H, Drury NE, Ranasinghe AM, Contractor H, Isackson H et al. Glucose-insulin-potassium reduces the incidence of low cardiac output episodes after aortic valve replacement for aortic stenosis in patients with left ventricular hypertrophy: results from the Hypertrophy, Insulin, Glucose, and Electrolytes (HINGE) Trial. Circulation 2011;123:170-7.
8. Cole PL, Beamer AD, McGowan N, Cantillon CO, Benfell K, Kelly RA et al. Efficacy and safety of perhexiline maleate in refractory angina. A doubleblind placebo-controlled clinical trial of a novel antianginal agent. Circulation 1990;81:1260-70.
9. Lee L, Campbell R, Scheuermann-Freestone M, Taylor R, Gunaruwan P, Williams L et al. Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment. Circulation 2005;112:3280-8.
10. Abozguia K, Elliott P, McKenna W, Phan TT, Nallur-Shivu G, Ahmed I et al. Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy. Circulation 2010;122:1562-9.
11. Horowitz JD, Sia ST, Macdonald PS, Goble AJ, Louis WJ. Perhexiline maleate treatment for severe angina pectoris--correlations with pharmacokinetics. Int J Cardiol 1986;13:219-29.
12. Kennedy JA, Unger SA, Horowitz JD. Inhibition of carnitine palmitoyltransferase-1 in rat heart and liver by perhexiline and amiodarone. Biochem Pharmacol 1996;52:273-80.
13. Griffin JL, Atherton H, Shockcor J, Atzori L. Metabolomics as a tool for cardiac research. Nat Rev Cardiol 2011;8:630-43.
14. Wu H, Southam AD, Hines A, Viant MR. High-throughput tissue extraction protocol for NMR- and MS-based metabolomics. Anal Biochem 2008;372:204-12.
15. Weber RJM, Southam AD, Sommer U, Viant MR. Characterization of isotopic abundance measurements in high resolution FT-ICR and Orbitrap mass spectra for improved confidence of metabolite identification. Anal Chem 2011;83:3737-43.
16. Southam AD, Payne TG, Cooper HJ, Arvanitis TN, Viant MR. Dynamic range and mass accuracy of wide-scan direct infusion nanoelectrospray Fourier transform ion cyclotron resonance mass spectrometry-based metabolomics increased by the spectral stitching method. Anal Chem 2007;79:4595-602.
17. Payne TG, Southam AD, Arvanitis TN, Viant MR. A signal filtering method for improved quantification and noise discrimination in Fourier transform ion cyclotron resonance mass spectrometry-based metabolomics data. J Am Soc Mass Spectrom 2009;20:1087-95.
18. Hrydziuszko O, Viant MR. Missing values in mass spectrometry based metabolomics: an undervalued step in the data processing pipeline. Metabolomics 2012;(Suppl 8):161-74.
19. Weber RJM, Viant MR. MI-Pack: increased confidence of metabolite identification in mass spectra by integrating accurate masses and metabolic pathways. Chemom Intell Lab Syst 2010;104:75-82.
20. Benjamini Y, Hochberg Y. Controlling the false discovery rate-a practical and powerful approach to multiple testing. J R Stat Soc Ser B Methodol 1995;57:289-300.
21. Parsons HM, Ekman DR, Collette TW, ViantMR. Spectral relative standard deviation:a practical benchmark in metabolomics. Analyst 2009;134:478-85.
22. Fan Y, Zhang AM, Xiao YB, Weng YG, Hetzer R. Glucose-insulin-potassium therapy in adult patients undergoing cardiac surgery: a meta-analysis. Eur J Cardiothorac Surg 2011;40:192-9.
23. Yin X, Dwyer J, Langley SR, Mayr U, Xing Q, Drozdov I et al. Effects of perhexiline-induced fuel switch on the cardiac proteome and metabolome. J Mol Cell Cardiol 2013;55:27-30.
24. Unger SA, Kennedy JA, McFadden-Lewis K, Minerds K, Murphy GA, Horowitz JD. Dissociation between metabolic and efficiency effects of perhexiline in normoxic rat myocardium. J Cardiovasc Pharmacol 2005;46:849-55.
25. Ngo DT, Drury NE, Frenneaux M, Pagano D, Horowitz JD. How does perhexiline modulate myocardial energetics and ameliorate redox stress? Circulation 2011;124:Abstract 14461.