European Heart Journal

European Heart Journal 1999 20(6):439-446; doi:10.1053/euhj.1998.1242
Copyright © 1999 by the European Society of Cardiology.

This Article Abstract FREE Full Text (PDF) E-letters: Submit a response Alert me when this article is cited Alert me when E-letters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (80) Request Permissions Disclaimer Google Scholar Articles by Klepzig, H. Articles by Burger, W. Search for Related Content PubMed PubMed Citation Articles by Klepzig, H. Articles by Burger, W. Social Bookmarking          What's this?

Sulfonylureas and ischaemic preconditioning; a double-blind, placebo-controlled evaluation of glimepiride and glibenclamide

H. Klepzig^a,f1, G. Kober^b, C. Matter^c, H. Luus^d, H. Schneider^a, K.H. Boedeker^b, W. Kiowski^c, F.W. Amann^c, D. Gruber^a, S. Harris^d and W. Burger^a

^a Department of Medicine, Division of Cardiology, J. W. Goethe University, Frankfurt/Main, Germany
^b Department of Cardiology, Klinik Nordrhein, Bad Nauheim, Germany
^c Division of Cardiology, University Hospital, University of Zurich, Zurich, Switzerland
^d Division of Biometry, Farmovs Research Centre for Clinical Pharmacology and Drug Development, University of the Orange Free State, Bloemfontein, South Africa

revised July 3, 1998; accepted July 12, 1998

Abstract

Aims

Glimepiride is a new sulfonylurea for diabetes treatment which is supposed to impact less on extra-pancreatic ATP-dependent K⁺channels than the conventional drug glibenclamide. This study was performed to evaluate whether this results in a better maintenance of ATP-dependent K⁺channel mediated ischaemic myocardial preconditioning.

Methods and Results

In a double-blind placebo-controlled study the period of total coronary occlusion during balloon angioplasty of high grade coronary artery stenoses was used as a model to compare the effects of both drugs. Quantification of myocardial ischaemia was achieved by recording the intracoronary ECG and the time to the occurrence of angina during vessel occlusion. All patients underwent three dilatations. The first dilatation (dilatation 1) served to determine the severity of ischaemia during vessel occlusion. During dilatation 2, baseline values were recorded. Thereafter, glimepiride (15 patients: 1·162mg), glibenclamide (15 patients: 2·54mg) or placebo (15 patients) were intravenously administered over 12min. Dilatation 3 started 10min after the beginning of the drug administration.

Mean ST segment shifts in the placebo group decreased by 35% (dilatation 2: 0·23; dilatation 3: 0·15mV; CI –0·55 to 0·00mV;P=0·049). A similar reduction also occurred in the glimepiride group, in which repetitive balloon occlusion led to a 34% reduction (dilatation 2: 0·35; dilatation 3: 0·23mV; CI –0·21 to –0·02mV;P=0·01). There was little influence however, on mean ST segment shifts in the glibenclamide group (dilatation 2 and dilatation 3: 0·24mV; CI –0·10 to 0·25mV;P=0·34). Accordingly, time to angina during balloon occlusion slightly increased (by 30%) in the placebo group (dilatation 2: 37s; dilatation 3: 48s; CI 0·0 to 15·0s;P=0·16); increased by 13% in the glimepiride group (dilatation 2: 40s; dilatation 3: 45s; CI 0·0 to 14·0s;P=0·023); and remained unchanged in the glibenclamide group (dilatation 2 and dilatation 3: 30s; CI –7·5 to 7·5s;P=0·67).

Conclusion

These results show that glimepiride maintains myocardial preconditioning, while glibenclamide might be able to prevent it.

Key Words: Glimepiride, glibenclamide, ischaemic preconditioning, percutaneous transluminal coronary angioplasty

^f1 Correspondence: Prof. Dr Harald Klepzig, J. W. Goethe University, Department of Medicine, Division of Cardiology, Theodor Stern Kai 7, D-60590 Frankfurt/Main, Germany.

References

1. Dräger E. Clinical profile of glimepiride. Diabetes Res Clin Pract. 1995;28:139–146[CrossRef]
2. Diabetes. 1970;19:787–830
3. Lomuscio A, Vergani D, Marano L, Castagnone M, Fiorentini C. Effects of glibenclamide on ventricular fibrillation in non-insulin-dependent diabetics with acute myocardial infarction. Cor Art Dis. 1994;5:767–771
4. Kantor PF, Coetzee WA, Carmeliet EE, Dennis SC, Opie LH. Reduction of ischemic K⁺. Circ Res. 1990;66:478–485[Abstract/Free Full Text]
5. Billman GE, Avendano CE, Halliwill JR, Burroughs JM. The effects of the ATP-dependent potassium channel antagonist, glyburide, on coronary blood flow and susceptibility to ventricular fibrillation in unanesthetized dogs. J Cardiovasc Pharmacol. 1993;21:197–204[Web of Science][Medline]
6. Daut J, Maier-Rudolph W, von Beckerath, Mehrke G, Günther K, Goedel-Meinen L. Hypoxic dilatation of coronary arteries is mediated by ATP-sensitive potassium channels. Science. 1990;247:1341–1344[Abstract/Free Full Text]
7. Auchampach JA, Maruyama M, Cavero I, Gross GJ. Pharmacological evidence for a role of ATP-dependent potassium channels in myocardial stunning. Circulation. 1992;86:311–319[Abstract/Free Full Text]
8. Cole WC, McPherson CD, Sontag D. ATP-regulated K⁺. Circ Res. 1991;69:571–581[Abstract/Free Full Text]
9. Tomai F, Crea F, Gaspardone A. Ischemic preconditioning during coronary angioplasty is prevented by gliben-clamide, a selective ATP-sensitive K⁺. Circulation. 1994;90:700–705[Abstract/Free Full Text]
10. Friedman PL, Shook TL, Kirshenbaum JM, Selwyn AP, Ganz P. Value of the intracoronary electrocardiogram to monitor myocardial ischemia during percutaneous trans-luminal coronary angioplasty. Circulation. 1986;74:330–339[Abstract/Free Full Text]
11. Kober G, Kästner R, Hopf R, Kaltenbach M. Die direkte myokardiale antiischämische Wirkung von Diltiazem beim Menschen. Z Kardiol. 1986;75:386–393[Web of Science][Medline]
12. Kober G, Buck T, Sievert H, Vallbracht C. Myocardial protection during percutaneous transluminal coronary angioplasty: effects of trimetazidine. Eur Heart J. 1992;13:1109–1115[Abstract/Free Full Text]
13. Sievert H, Friedmann A, Schräder R, Kaltenbach M, Kober G. Untersuchungen zum Einfluß des Kalzium-antagonisten Nisoldipin auf den koronaren Blutfluß und die Myokardischämie bei temporärer Koronarokklusion. Z Kardiol. 1990;79:683–688[Web of Science][Medline]
14. Murry CE, Jennings RB, Reimer KA. Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation. 1986;74:1124–1136[Abstract/Free Full Text]
15. Kloner RA, Yellon D. Does ischemic preconditioning occur in patients? J Am Coll Cardiol. 1994;24:1133–1142[Abstract]
16. Deutsch E, Berger M, Kussmaul WG, Hirshfeld JW Jr, Hermann HC, Laskey K. Adaptation to ischemia during percutaneous transluminal coronary angioplasty. Clinical, hemodynamic, and metabolic features. Circulation. 1990;82:2044–2051[Abstract/Free Full Text]
17. Cribier A, Korsatz L, Koning R. Improved myocardial ischemic response and enhanced collateral circulation with long repetitive coronary occlusion during angioplasty: a prospective study. J Am Coll Cardiol. 1992;20:578–586[Abstract]
18. Ottani F, Galvani M, Ferrini D, Sorbello F, Limonetti P, Pantoli D, Rusticali F. Prodromal angina limits infarct size. A role for ischemic preconditioning. Circulation. 1995;91:291–297[Abstract/Free Full Text]
19. Marber MS, Baxter GF, Yellon DM. Prodromal angina limits infarct size. Letter to the editor. Circulation. 1995;92:1061–1062[Medline]
20. Grover GJ, Sleph PG, Dzwonczyk S. Role of myocardial ATP-sensitive potassium channels in mediating preconditioning in the dog heart and their possible interaction with adenosine A₁. Circulation. 1992;86:1310–1316[Abstract/Free Full Text]
21. Noma A. ATP-regulated K⁺. Nature. 1983;305:147–148[CrossRef][Medline]
22. Nakaya H, Takeda Y, Tohse N, Kanno M. Effects of ATP-sensitive K⁺. Br J Pharmacol. 1991;103:1019–1026[Web of Science][Medline]
23. Murry CE, Richard VJ, Reimer KA, Jennings RB. Ischemic preconditioning slows energy metabolism and delays ultra-structural damage during a sustained ischemic episode. Circ Res. 1990;66:913–931[Abstract/Free Full Text]
24. Toombs CF, Moore TL, Shebuski RJ. Limitation of infarct size in the rabbit by ischaemic preconditioning is reversible with glibenclamide. Cardiovasc Res. 1993;27:617–622[Abstract/Free Full Text]
25. Gross GJ, Auchampach JA. Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs. Circ Res. 1992;70:223–233[Abstract/Free Full Text]
26. Müller G, Satoh Y, Geissen K. Extrapancreatic effects of sulfonylureas-a comparison between glimepiride and conventional sulfonylureas. Diabetes Res Clin Pract. 1995;28:S115–S137[Medline]
27. Müller G, Hartz D, Pünter J, Ökonomopulos R, Kramer W. Differential interaction of glimepiride and glibenclamide with the ß-cell sulfonylurea receptor. I. Binding characteristics. Biochim Biophys Acta. 1994;1191:267–277[Medline]
28. Imamura Y, Tomoike H, Narishige T, Takahashi T, Kasuya H, Takeshita A. Glibenclamide decreases basal coronary blood flow in anesthetized dogs. Am J Physiol. 1992;263:H399–H404[Web of Science][Medline]
29. Schulz R, Rose J, Martin C, Heusch G. Activation of ATP-dependent potassium channels is involved in ischemic pre-conditioning in swine (Abstr). Circulation. 1993;88:I–102
30. Kubota I, Yamaki M, Shibata T, Ikeno E, Hosoya Y, Tomoike H. Role of ATP-sensitive K⁺. Circulation. 1993;88:1845–1851[Abstract/Free Full Text]
31. Kondo T, Kubota I, Tachibana H, Yamaki M, Tomoike H. Glibenclamide attenuates peaked T wave in early phase of myocardial ischemia. Cardiovasc Res. 1996;31:683–687[CrossRef][Web of Science][Medline]
32. Kahn AM, Lichtenberg RA, Allen JC, Seidel CL, Song T. Insulin-stimulated glucose transport inhibits Ca²⁺. Circulation. 1995;92:1597–1603[Abstract/Free Full Text]
33. Cacciapuoti F, Spiezia R, Bianchi U, Lama D, D’Avino M, Varricchio M. Effectiveness of glibenclamide on myocardial ischemic ventricular arrhythmias in non-insulin-dependent diabetes mellitus. Am J Cardiol. 1991;67:843–847[CrossRef][Web of Science][Medline]
34. Okishige K, Yamashita K, Yoshinaga H. Electrophysiologic effects of ischemic preconditioning on QT dispersion during coronary angioplasty. J Am Coll Cardiol. 1996;28:70–73[Abstract]

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				J. N. Peart and J. P. Headrick Clinical cardioprotection and the value of conditioning responses Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1705 - H1720. [Abstract] [Full Text] [PDF]

				F. A. McAlister, D. T. Eurich, S. R. Majumdar, and J. A. Johnson The risk of heart failure in patients with type 2 diabetes treated with oral agent monotherapy Eur J Heart Fail, July 1, 2008; 10(7): 703 - 708. [Abstract] [Full Text] [PDF]

				J. W. Elrod, M. Harrell, T. P. Flagg, S. Gundewar, M. A. Magnuson, C. G. Nichols, W. A. Coetzee, and D. J. Lefer Role of Sulfonylurea Receptor Type 1 Subunits of ATP-Sensitive Potassium Channels in Myocardial Ischemia/Reperfusion Injury Circulation, March 18, 2008; 117(11): 1405 - 1413. [Abstract] [Full Text] [PDF]

				A. S. Gangji, T. Cukierman, H. C. Gerstein, C. H. Goldsmith, and C. M. Clase A Systematic Review and Meta-Analysis of Hypoglycemia and Cardiovascular Events: A comparison of glyburide with other secretagogues and with insulin Diabetes Care, February 1, 2007; 30(2): 389 - 394. [Abstract] [Full Text] [PDF]

				P. Valensi and G. Slama Review: Sulphonylureas and cardiovascular risk: facts and controversies The British Journal of Diabetes & Vascular Disease, July 1, 2006; 6(4): 159 - 165. [Abstract] [PDF]

				Z. T. Bloomgarden Cardiovascular Disease Diabetes Care, May 1, 2006; 29(5): 1160 - 1166. [Full Text] [PDF]

				R. J. Edwards, S. R. Redwood, P. D. Lambiase, and M. S. Marber The effect of an angiotensin-converting enzyme inhibitor and a K+ATP channel opener on warm up angina Eur. Heart J., March 2, 2005; 26(6): 598 - 606. [Abstract] [Full Text] [PDF]

				U. Quast, D. Stephan, S. Bieger, and U. Russ The Impact of ATP-Sensitive K+ Channel Subtype Selectivity of Insulin Secretagogues for the Coronary Vasculature and the Myocardium Diabetes, December 1, 2004; 53(suppl_3): S156 - S164. [Abstract] [Full Text] [PDF]

				S. Clement, S. S. Braithwaite, M. F. Magee, A. Ahmann, E. P. Smith, R. G. Schafer, and I. B. Hirsch Management of Diabetes and Hyperglycemia in Hospitals Diabetes Care, February 1, 2004; 27(2): 553 - 591. [Full Text] [PDF]

				J J Meier, B Gallwitz, W E Schmidt, A Mugge, and M A Nauck Is impairment of ischaemic preconditioning by sulfonylurea drugs clinically important? Heart, January 1, 2004; 90(1): 9 - 12. [Abstract] [Full Text] [PDF]

				M. Zaugg, E. Lucchinetti, C. Garcia, T. Pasch, D. R. Spahn, and M. C. Schaub Anaesthetics and cardiac preconditioning. Part II. Clinical implications Br. J. Anaesth., October 1, 2003; 91(4): 566 - 576. [Abstract] [Full Text] [PDF]

				J. F. Huizar, L. A. Gonzalez, J. Alderman, and H. S. Smith Sulfonylureas attenuate electrocardiographic ST-segment elevation during an acute myocardial infarction in diabetics J. Am. Coll. Cardiol., September 17, 2003; 42(6): 1017 - 1021. [Abstract] [Full Text] [PDF]

				O. Torffvit Hyperglycaemia in diabetes: impact on nephropathy and cardiac risk Nephrol. Dial. Transplant., September 1, 2003; 18(9): 1711 - 1715. [Full Text] [PDF]

				N. Lavanchy, G. Christe, F. Cand, N. Wiernsperger, and J. Verdetti Effects of chronic treatment with glibenclamide and/or metformin on the resistance to ischaemia of isolated hearts from Zucker Diabetic Fatty rats (ZDF/GMI-fa/fa) The British Journal of Diabetes & Vascular Disease, September 1, 2003; 3(5): 375 - 380. [Abstract] [PDF]

				M. C. Riddle Sulfonylureas Differ in Effects on Ischemic Preconditioning--Is it Time to Retire Glyburide? J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 528 - 530. [Full Text] [PDF]

				T.-M. Lee and T.-F. Chou Impairment of Myocardial Protection in Type 2 Diabetic Patients J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 531 - 537. [Abstract] [Full Text] [PDF]

				M. T. Caulfield and K. D. O'Brien Cardiovascular Safety of Oral Antidiabetic Agents: The Insulin Secretagogues Clin. Diabetes, April 1, 2002; 20(2): 81 - 84. [Abstract] [Full Text] [PDF]

				T Reffelmann, H G Klues, P Hanrath, and E R Schwarz Post-stenotic coronary blood flow at rest is not altered by therapeutic doses of the oral antidiabetic drug glibenclamide in patients with coronary artery disease Heart, January 1, 2002; 87(1): 54 - 60. [Abstract] [Full Text] [PDF]

				Z S Kyriakides, S Psychari, N Chrysomallis, M Georgiadis, E Sbarouni, and D T Kremastinos Type II diabetes does not prevent the recruitment of collateral vessels and the normal reduction of myocardial ischaemia on repeated balloon inflations during angioplasty Heart, January 1, 2002; 87(1): 61 - 66. [Abstract] [Full Text] [PDF]

				M. M. Mocanu, H. L. Maddock, G. F. Baxter, C. L. Lawrence, N. B. Standen, and D. M. Yellon Glimepiride, a Novel Sulfonylurea, Does Not Abolish Myocardial Protection Afforded by Either Ischemic Preconditioning or Diazoxide Circulation, June 26, 2001; 103(25): 3111 - 3116. [Abstract] [Full Text] [PDF]

				P. Spallarossa, M. Schiavo, P. Rossettin, S. Cordone, L. Olivotti, R. Cordera, and C. Brunelli Sulfonylurea Treatment of Type 2 Diabetic Patients Does Not Reduce the Vasodilator Response to Ischemia Diabetes Care, April 1, 2001; 24(4): 738 - 742. [Abstract] [Full Text]

				G. R. McAnulty, H. J. Robertshaw, and G. M. Hall Anaesthetic management of patients with diabetes mellitus Br. J. Anaesth., July 1, 2000; 85(1): 80 - 90. [Full Text] [PDF]

				D.J. Betteridge and L. Close Diabetes, coronary heart disease and sulphonylureas--not the final word Eur. Heart J., May 2, 2000; 21(10): 790 - 792. [PDF]

				S. Ghosh, N. B Standen, and M. Galinanes Evidence for mitochondrial KATP channels as effectors of human myocardial preconditioning Cardiovasc Res, March 1, 2000; 45(4): 934 - 940. [Abstract] [Full Text] [PDF]

This Article Abstract FREE Full Text (PDF) E-letters: Submit a response Alert me when this article is cited Alert me when E-letters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Search for citing articles in: ISI Web of Science (80) Request Permissions Disclaimer Google Scholar Articles by Klepzig, H. Articles by Burger, W. Search for Related Content PubMed PubMed Citation Articles by Klepzig, H. Articles by Burger, W. Social Bookmarking          What's this?

Online ISSN 1522-9645 - Print ISSN 0195-668x

Copyright © 2009 European Society of Cardiology

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics