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Effects of nicorandil on regional perfusion and left ventricular function

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Summary

Left ventricular function and regional perfusion were evaluated by two study designs in patient groups with stable ischemic coronary artery disease (CAD): (1) using conventional left ventricular angiographies and (2) applying myocardial contrast echocardiography. The aim of the studies was to establish the effects of sublingually or orally applied nicorandil (N) on pacing-induced myocardial ischemia (MIS). In the first angiographic study, in nine patients with ischemic CAD and with pacing-inducible MIS, the effect of N, 20 mg sublingually, on hemodynamics and regional wall motion (RWM) were studied. There were no parameter changes without MIS being induced when comparing measurements at the 7th and 14th minute after N application to control values (p>0.05). In the 15th and 16th minutes after N, pacing-induced MIS could no longer be elicited but left ventricular pump function improved; comparing MIS with N versus MIS without N: ejection fraction improved by 21%, cardiac index by 37%, and RWM by 21%, while filling pressure fell by 41% and systemic vascular resistance fell by 29%. Thus, N-mediated “protection from ischemia” with rather improved hemodynamics and RWM corresponds with alterations that theoretically could have been expected after nitroglycerin given under the above conditions. In the second echocardiographic study, regional perfusion was assessed in 10 patients by intracoronary injection of a newly developed echo contrast medium (ECM) and measurement of ECM washout halftime (t1/2) over opacified myocardial regions of interest, which displayed wall motion abnormalities already at rest. Echocardiographic evaluations were performed at rest and during MIS with and without the effects of 20 mg of oral N. The t1/2 shortened significantly by 60% and was accompanied by a decrease in filling pressure from 18±9 to 7±3 mmHg. The perfused myocardial area increased by 75%, displaying a partially regained wall motion in previously hypokinetic areas, which resulted in an augmentation of regional ejection fraction. Concomitantly, the degree of coronary stenoses was reduced by 21% (p<0.05). The antiischemic effects of the drug demonstrated were not accompanied by side effects.

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References

  1. Abrams J. Current status of long-acting nitrates in clinical medicine.Prac Cardiol 1977;3:17–22.

    Google Scholar 

  2. Brunton TL. On the use of nitrate of amyl in angina pectoris.Lancet 1867;2:97–100.

    Google Scholar 

  3. Thormann J, Schlepper M, Kramer W, Gottwilk M, Kindler M. Effectiveness of nicorandil (SG-75), a long-acting drug with nitroglycerin effects, in patients with coronary artery disease: Improved left ventricular function and regional wall motion and abolition of pacing-induced angina.J Cardiovasc Pharmacol 1983;5:371–377.

    PubMed  Google Scholar 

  4. Thormann J, Kramer W, Schlepper M, Gottwick M. ARL-L115BS in the treatment of heart failure.Eur Heart J 1982;3(Suppl D):87–95.

    PubMed  Google Scholar 

  5. Thormann J, Kremer P, Mitrovic V, Neuzner J, Bahawar H, Schlepper M. Effects of enoximone in coronary artery disease: Increased pump function, improved ventricular wall motion, and abolition of pacing-induced myocardial ischemia.J Appl Cardiol 1998;4:31–45.

    Google Scholar 

  6. Kambara OH, Tamaki S, Nakamura Y, Kawai C. Effects of intravenous administration of nicorandil on cardiovascular hemodynamics and left ventricular function.Am J Cardiol 1989;63:56J-60J.

    PubMed  Google Scholar 

  7. Uchida Y, Yoshimoto N, Murao S. Effects of 2-nicotin-amidethyl nitrate (SG-75) on coronary circulation.Jpn Heart J 1997;19:112–124.

    Google Scholar 

  8. Lamping KA, Warltier DC, Hardman HF, Gross GJ. Effects of nicorandil, a new antianginal agent, and nifedipine on collateral blood flow in a chronic coronary occlusion model.J Pharmacol Exp Ther 1984;229(2):359–363.

    PubMed  Google Scholar 

  9. Nakano H, Nagano H, Uchida Y. In: Scriabine A, ed.New Drug Annual: Cardiovascular Drugs. New York: Raven Press, 1983:227–242.

    Google Scholar 

  10. Sakai K. Nicorandil: Animal pharmacology.Am J Cardiol 1989;63:2J-10J.

    PubMed  Google Scholar 

  11. Aizawa T, Ogasawara K, Kato K. Effects of nicorandil on coronary circulation in patients with ischemic heart disease: Comparison with nitroglycerin.J Cardiovasc Pharmacol 1987;10(Suppl 8):123–129.

    PubMed  Google Scholar 

  12. Gross GJ, Pieeper G, Farber N, Warltier DC, Hardman H. Effects of nicorandil on coronary circulation and myocardial ischemia.Am J Cardiol 1989;63:11J-17J.

    PubMed  Google Scholar 

  13. Lamping K, Christensen CW, Pelc L, Warltier DC, Gross GJ. Effects of nicorandil and nifedipine on protection of ischemic myocardium.J Cardiovasc Pharmacol 1984;6:536–542.

    PubMed  Google Scholar 

  14. Lamping KA, Gross GJ. Improved recovery of myocardial segment function following a short coronary occlusion in dogs by nicorandil, a potential new antianginal agent, and nifedipine.J Cardiovasc Pharmacol 1985;7:158–166.

    Google Scholar 

  15. Berdeau A, LaRochelle CD, Richard V, Gindicelli JF. Differential effects of nitrovasodilators, K+-channel openers, and nicorandil on large and small coronary arteries in conscious dogs.J Cardiovasc Pharmacol 1992;20:17–21.

    Google Scholar 

  16. Bernstein L, Friesinger GC, Lichtlen PR, Ross RS. The effect of nitroglycerin on the systemic and coronary circulation in man and dogs.Circulation 1965;33:107–112.

    Google Scholar 

  17. Engel HJ, Lichtlen RR. Beneficial enhancement of coronary blood flow by nifedipine. Comparison with nitroglycerin and beta blocking agents.Am J Med 1981:658–666.

  18. Fujibayashi Y, Yamazaki S, Chang B, Rajagopalan RE, Meerbaum S, Corday E. Comparative echocardiographic study of recovery of diastolic versus systolic function after brief periods of coronary occlusion: Differential effects of intravenous nifedipine administered before and during occlusion.J Am Coll Cardiol 1985;6:1289–1298.

    PubMed  Google Scholar 

  19. Lambertz H, Kreis A, Trümper H. Simultaneous transesophageal atrial pacing and transesophageal two-dimensional echocardiography: A new method of stress echocardiography.J Am Coll Cardiol 1990;16:1143–1153.

    PubMed  Google Scholar 

  20. Brown R, Rahimtoola SHG, Davis GD, Swan HJC. The effect of angiographic contrast medium on circulatory dynamics in man: Cardiac output during angiography.Circulation 1965;31:234–241.

    PubMed  Google Scholar 

  21. Gottwik M, Kirkeeide R, Stämmler G, Schlepper M. Interrelation of regional wall motion, severity of coronary lesions and collateral vessels: A quantitative analysis of computer-assisted readings.Clin Res 1981;29:198a.

    Google Scholar 

  22. Dodge HT, Sandler H, Bellew DW, Lord JD. The use of biplane angiocardiography for the measurement of left ventricular volume in man.Am Heart J 1960;60:762–776.

    PubMed  Google Scholar 

  23. Armstrong WF, O'Donnell J, Ryan T, Feigenbaum H. Effect of prior myocardial infarction and extent and location of coronary artery disease on accuracy of exercise echocardiography.J Am Coll Cardiol 1987;10:531–538.

    PubMed  Google Scholar 

  24. Robertson WS, Feigenbaum H, Armstrong WF, Dillon JC, O'Donnell J, McHenry PW. Exercise echocardiography: A clinical practical addition in the evaluation of coronary artery disease.J Am Coll Cardiol 1983;2:1085–1091.

    PubMed  Google Scholar 

  25. Illiceto S, D'Ambrosio G, Sorino M. Comparison on post-exercise and transesophageal atrial pacing two-dimensional echocardiography for detection of coronary artery disease.Am J Cardiol 1986;57:547–553.

    PubMed  Google Scholar 

  26. Illiceto S, Amico A, Marangelli V, D'Ambrosio G, Rizzon P. Doppler echocardiographic evaluation of the effect of atrial pacing-induced ischemia on left ventricular filling in patients with coronary artery disease.J Am Coll Cardiol 1988;11:953–561.

    PubMed  Google Scholar 

  27. Dehmer GJ, Firth BG, Nicod P, Lewis SE, Hillis LD. Alterations in left ventricular volumes and ejection fraction during atrial pacing in patients with coronary artery disease: Assessment with radionuclide ventriculography.Am Heart J 1983;106:114–124.

    PubMed  Google Scholar 

  28. Crawford MH, White DH, Amon KW. Echocardiographic evaluation of left ventricular size and performance during handgrip and supine and upright bicycle exercise.Circulation 1979;59:1188–1196.

    PubMed  Google Scholar 

  29. Goldstein RF, Rosing DR, Redwood DR, Beiser GE, Epstein SE. Clinical and circulatory effects of isosorbide dinitrate: Comparison with nitroglycerin.Circulation 1971;43:629–640.

    PubMed  Google Scholar 

  30. Takeshita A, Nakamura M, Tajimi T. Long lasting effect of oral molsidomine on exercise performance. A new antianginal agent.Circulation 1977;55:401–407.

    PubMed  Google Scholar 

  31. Berwing K, Schlepper M, Bahavar H. Significance and selection of contrast solution for myocardial contrast echocardiography. In: Meerbaum S, Meltzer R, eds.Myocardial Contrast Two-Dimensional Echocardiography. Boston: Kluwer Academic, 1989:62–84.

    Google Scholar 

  32. Kaul S, Glasheen W, Ruddy TD, Pandian NG, Weyman AE, Okada RD. The importance of defining left ventricular area at risk in vivo during acute myocardial infarction: An experimental evaluation with myocardial contrast two-dimensional echocardiography.Circulation 1987;75:1249–1255.

    PubMed  Google Scholar 

  33. Berwing K, Buchwald A, Bahavar H, Schaper W, Schlepper M. Versuch einer myokardialen Blutflussbestimmung mittels zweidimensionaler Kontrastechokardiographie. In: Felix R, Wolf KJ, Zeitler E, eds.Neues im Kontrastbild, Herz und gross Gefässe. Berlin: Schering, 1987:53–61.

    Google Scholar 

  34. Berwing K, Schlepper M, Kremer P, Bahavar H. Different changes of myocardial perfusion after intravenous injection of dipyridamole in humans—documentation by contrast echocardiography.Circulation 1989;(Suppl II)80:341.

    PubMed  Google Scholar 

  35. Kirkeeide RL, Wüsten B, Gottwik M. Computer assisted evaluation of angiographic findings. In: Breddin K, ed.Thrombose und Atherogenese. Baden-Baden: Witzstock, 1980:414–417.

    Google Scholar 

  36. Kirkeeide RL, Gould KL. Cardiovascular imaging: Coronary artery stenosis.Hosp Pract 1984;19:160.

    Google Scholar 

  37. Holbach H, Gottwik M, Kirkeeide RL, Stämmler G, Schepper M. Computergestützte Koronarographie.Z. Kardiologie 1980;69:236–241.

    Google Scholar 

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Schlepper, M., Thormann, J., Berwing, K. et al. Effects of nicorandil on regional perfusion and left ventricular function. Cardiovasc Drug Ther 9 (Suppl 2), 203–211 (1995). https://doi.org/10.1007/BF00878467

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