Skip Navigation

European Heart Journal 1999 20(3):196-202; doi:10.1053/euhj.1998.1311
Copyright © 1999 by the European Society of Cardiology.
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (28)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Tomai, F.
Right arrow Articles by Gioffrè, P.A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tomai, F.
Right arrow Articles by Gioffrè, P.A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Effects of KATPchannel blockade by glibenclamide on the warm-up phenomenon

F. Tomaia,f1, A. Danesib, A.S. Ghinia, F. Creac, M. Perinoa, A. Gaspardonea, G. Ruggerib, L. Chiarielloa and P.A. Gioffrèa

a Divisione di Cardiochirurgia, Università di Roma Tor Vergata, European Hospital, Rome, Italy
b Divisione di Cardiologia, Ospedale S. Giuseppe Albano, Rome, Italy
c Istituto di Cardiologia, Università Cattolica del Sacro Cuore, Rome, Italy

accepted September 2, 1998

Abstract

Aims

The increased tolerance to myocardial ischaemia observed during the second of two sequential exercise tests, i.e. the warm-up phenomenon, has been proposed as a clinical model of ischaemic preconditioning. As ATP-sensitive K+channels appear to be a mediator of ischaemic preconditioning in both experimental and clinical studies, the aim of this study was to investigate the role of KATPchannels in the warm-up phenomenon.

Methods and Results

Twenty-six patients with coronary artery disease were randomized to receive 10mg oral glibenclamide, a selective ATP-sensitive K+channel blocker, or placebo. Sixty minutes after glibenclamide or placebo administration, patients were given an infusion of 10% dextrose (8ml.min–1) to correct glucose plasma levels or, respectively, an infusion of saline at the same infusion rate. Thirty minutes after the beginning of the infusions, both patient groups underwent two consecutive treadmill exercise tests, with a recovery period of 15min to re-establish baseline conditions. Before exercise tests, blood glucose levels were similar in placebo and glibenclamide groups (96±10 vs 105±22mg.100ml–1,P=ns). After placebo administration, rate-pressure product at 1·5mm ST-segment depression significantly increased during the second exercise test compared to the first (220±41 vs 186±29 beats.min–1.mmHg.102,P<0·01), but it did not change after glibenclamide (191±34 vs 187±42 beats.min–1.mmHg.102,P=ns), with a significant drug-test interaction (P=0·0091, at two-way ANOVA).

Conclusions

Glibenclamide, at a dose previously shown to abolish ischaemic preconditioning during coronary angioplasty, prevents the increase of ischaemic threshold observed during the second of two sequential exercise tests. These findings confirm that ischaemic preconditioning plays a key role in the warm-up phenomenon and that in this setting is, at least partially, mediated by activation of ATP-sensitive K+channels.

Key Words: Glibenclamide • ischaemic preconditioning • KATPchannel • warm-up phenomenon

f1 Correspondence:Dr Fabrizio Tomai, Divisione di Cardiochirurgia, Università di Roma Tor Vergata, European Hospital, via Portuense 700, 00149 Rome, Italy.

Marber, MSYellon, DM

References

  1. Williams DO, Bass TA, Gewirtz H, Most A. Adaptation to the stress of tachycardia in patients with coronary artery disease: insight into the mechanisms of the warm-up phenomenon. Circulation. 1985;71:687–692[Abstract/Free Full Text]
  2. Okazaki Y, Kodama K, Sato H. Attenuation of increased regional myocardial oxygen consumption during exercise as a major cause of warm-up phenomenon. J Am Coll Cardiol. 1993;21:1597–1604[Abstract]
  3. Stewart RAH, Simmonds MB, Williams MJA. Time course of ‘‘warm-up’’ in stable angina. Am J Cardiol. 1995;76:70–73[CrossRef][Web of Science][Medline]
  4. Tomai F, Crea F, Danesi A. Mechanisms of the warm-up phenomenon. Eur Heart J. 1996;17:1022–1027[Abstract/Free Full Text]
  5. Maybaum S, Ilan M, Mogilevsky J, Tzivoni D. Improvement in ischemic parameters during repeated exercise testing: a possible model for myocardial preconditioning. Am J Cardiol. 1997;78:1087–1091
  6. Wayne EJ, Laplace LB. Observations on angina of effort. Clin Sci. 1933;1:103–129
  7. Marber MS, Joy MD, Yellon DM. Is warm-up in angina ischaemic preconditioning? Br Heart J. 1994;72:213–215[Free Full Text]
  8. 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]
  9. Parrat JR, Kane KA. KATP. Cardiovasc Res. 1994;28:783–787[Free Full Text]
  10. Speechly-Dick ME, Grover GJ, Yellon DM. Does ischemic preconditioning in the human involve protein kinase C and the ATP-dependent K+. Circ Res. 1995;77:1030–1035[Abstract/Free Full Text]
  11. Cleveland JC, Meldrum DR, Cain BS, Banerjee A, Harken AH. Oral sulfonylurea hypoglicemic agents prevent ischemic preconditioning in human myocardium. Two paradoxes re-visited. Circulation. 1997;96:29–32[Abstract/Free Full Text]
  12. Tomai F, Crea F, Gaspardone A. Ischemic preconditioning during coronary angioplasty is prevented by glibenclamide, a selective ATP-sensitive K+. Circulation. 1994;90:700–705[Abstract/Free Full Text]
  13. Saito S, Mizumura T, Takayama T. Anti-ischemic effects of nicorandil during coronary angioplasty in humans. Cardiovasc Drugs Ther. 1995;9:257–263
  14. Karttunen P, Uusitupa M, Nykanen S, Robinson JD, Sipila J. The pharmacokinetics of glibenclamide: a single dose comparison of four preparations in human volunteers. Int J Clin Pharmacol. 1985;23:642–646
  15. Gobel FL, Nordstrom LA, Nelson RR, Jorgensen CR, Wang Y. The rate-pressure product as an index of myocardial oxygen consumption during exercise in patients with angina pectoris. Circulation. 1978;57:549–556[Abstract/Free Full Text]
  16. Waters DD, McCans JL, Crean PA. Serial exercise testing in patients with effort angina: variable tolerance, fixed threshold. J Am Coll Cardiol. 1985;6:1011–1015[Abstract]
  17. Romano M, Carella G, Cotecchia MR. Exercise time: a possible source of misleading results during long-term pharmacological studies by multiple stress testings in coronary artery disease. Clin Cardiol. 1989;12:39–41[Web of Science][Medline]
  18. Correa SD, Schaefer S. Blockade of KATP. Am J Cardiol. 1997;79:75–78[CrossRef][Web of Science][Medline]
  19. Downey JM, Cohen MV. Mechanisms of preconditioning: correlates and epiphenomena. Ischemia: preconditioning and adaptation. Oxford: UCL Molecular Pathology Series, BIOS Scientific Publishers Limited; 1996. p. 21–34
  20. Tomai F, Crea F, Danesi A. Effects of A1. Cardiologia. 1997;42:385–392[Medline]
  21. Daut J, Maier-Rudolph W, von Beckerath N, Mehrke G, Gunther K, Goedel-Meinen L. Hypoxic dilation of coronary arteries is mediated by ATP-sensitive potassium channels. Science. 1990;247:1341–1344[Abstract/Free Full Text]
  22. 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:H399–404
  23. Klimt CR, Knatterud GL, Meinert CL, Prout TE, (University Group Diabetes Program). A study of the effects of hypo-glicemic agents on vascular complications in patients with adult-onset diabetes. Diabetes. 1970;19:747–830
  24. The BARI (Bypass Angioplasty Revascularization Investigation) Investigators. Influence of diabetes on 5-year mortality and morbidity in a randomized trial comparing CABG and PTCA in patients with multivessel disease. The bypass angi-oplasty revascularization investigation (BARI). Circulation. 1997;96:1761–1769[Abstract/Free Full Text]
  25. Rytter L, Troelsen S, Beck-Nielsen H. Prevalence and mortality of acute myocardial infarction in patients with diabetes. Diabetes Care. 1985;8:230–234[Abstract]
  26. Engler RL, Yellon DM. Sulfonylurea KATP. Circulation. 1996;94:2297–2301[Free Full Text]

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


This article has been cited by other articles:


Home page
 Eur. J. Cardiothorac. Surg.Home page
V. Venugopal, A. Ludman, D. M. Yellon, and D. J. Hausenloy
'Conditioning' the heart during surgery
Eur. J. Cardiothorac. Surg., June 1, 2009; 35(6): 977 - 987.
[Abstract] [Full Text] [PDF]

Home page
 British Journal of Diabetes & Vascular DiseaseHome page
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]

Home page
 Eur Heart JHome page
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]

Home page
 Physiol. Rev.Home page
D. M. YELLON and J. M. DOWNEY
Preconditioning the Myocardium: From Cellular Physiology to Clinical Cardiology
Physiol Rev, October 1, 2003; 83(4): 1113 - 1151.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
R. A Kloner, M. T Speakman, and K. Przyklenk
Ischemic preconditioning: a plea for rationally targeted clinical trials
Cardiovasc Res, August 15, 2002; 55(3): 526 - 533.
[Full Text] [PDF]

Home page
 HeartHome page
F Tomai
Warm up phenomenon and preconditioning in clinical practice
Heart, February 1, 2002; 87(2): 99 - 100.
[Full Text] [PDF]

Home page
 HeartHome page
A D Kelion, T P Webb, M A Gardner, O J M Ormerod, G L Shepherd, and A P Banning
Does a selective adenosine A1 receptor agonist protect against exercise induced ischaemia in patients with coronary artery disease?
Heart, February 1, 2002; 87(2): 115 - 120.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
H. F. del Valle, E. C. Lascano, J. A. Negroni, and A. J. Crottogini
Glibenclamide effects on reperfusion-induced malignant arrhythmias and left ventricular mechanical recovery from stunning in conscious sheep
Cardiovasc Res, June 1, 2001; 50(3): 474 - 485.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
D. M. Yellon and A. Dana
The Preconditioning Phenomenon : A Tool for the Scientist or a Clinical Reality?
Circ. Res., September 29, 2000; 87(7): 543 - 550.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (28)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Tomai, F.
Right arrow Articles by Gioffrè, P.A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tomai, F.
Right arrow Articles by Gioffrè, P.A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?