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Effects of ranolazine on left ventricular regional diastolic function in patients with ischemic heart disease

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Hayashida, Wataru van Eyll, Christian [UCL] Rousseau, Michel [UCL] Pouleur, Hubert [UCL]

To assess the effects of ranolazine, a new antiischemic drug, on regional myocardium of the left ventricle, left ventricular (LV) hemodynamic and angiographic data were obtained in 15 patients with previous transmural myocardial infarction before and after intravenous infusion of ranolazine (200 or 500 micrograms/kg body weight). LV angiogram was analyzed by the area method and was divided into six segments. Regional LV segments were classified as normal (perfused by intact coronary vessels, n = 20), ischemic (perfused by stenotic vessels but without ECG evidence suggesting myocardial necrosis, n = 25), or infarcted (total coronary occlusion and with the ECG evidence for necrosis, n = 45). Regional area fractional shortening, peak filling rate, and segmental wall motion during isovolumic relaxation period were analyzed. After ranolazine, regional area fractional shortening was unchanged in all segments. However, regional peak filling rate was decreased in the normal segments (1499 +/- 315 to 1368 +/- 303 mm2/sec, p < 0.05). In the ischemic segments, by contrast, the administration of ranolazine significantly increased the regional peak filling rate (1050 +/- 410 to 1133 +/- 439 mm/sec, p < 0.05) and regional wall lengthening during the isovolumic relaxation period (0.9 +/- 4.1% to 2.8 +/- 5.7% of end-diastolic segmental area, p < 0.05), which indicates an improvement of regional diastolic function. Infarct segments were little affected by ranolazine. Thus, ranolazine improves diastolic function of the noninfarcted myocardium under chronic ischemic conditions and also may exert a mild negative lusitropic effect on the normal myocardium, although the former beneficial effect appears to be more clinically important.(ABSTRACT TRUNCATED AT 250 WORDS)

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès restreint
Publication date 1994
Journal information "Cardiovascular Drugs and Therapy" - Vol. 8, no. 5, p. 741-747 (1994)
Peer reviewed yes
Publisher Springer New York LLC (New York)
issn 0920-3206
e-issn 1573-7241
Publication status Publié
Affiliations UCL - MD/FSIO - Département de physiologie et pharmacologie
UCL - MD/MINT - Département de médecine interne
UCL - (SLuc) Service de cardiologie
MESH Subject Acetanilides ; Angina Pectoris - drug therapy ; Blood Pressure - drug effects ; Female ; Heart Rate - drug effects ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Myocardial Infarction - drug therapy ; Myocardial Ischemia - drug therapy - physiopathology ; Piperazines - administration & dosage - pharmacology - therapeutic use ; Ventricular Function, Left - drug effects
Keywords Ranolazine ; Ischemic heart disease ; Diastolic function ; Regional wall motion ; Hibernating myocardium
Links
  1. Allely MC, Alps BJ, Kilpatrick AT. The effects of the novel anti-anginal agent RS 43285 on [lactic acid], [K+] and pH in a canine model of transient myocardial ischaemia.Biochem Soc Trans 1987;15:1057?1058.
  2. Brown CM, Clarke B, Fraser S, et al. Pharmacological profile of ranolazine, a metabolic modulator active in ischaemia.Br J Pharmacol 1988;93(Suppl):248.
  3. Alley MC, Alps BJ. Prevention of myocardial enzyme release by ranolazine in a primate model of ischemia with reperfusion.Br J Pharmacol 1990;99:5?6.
  4. Opie LH. Metabolic regulation in ischemia and hypoxia. Effects of regional ischemia on metabolism of glucose and fatty acids. Relative rates of aerobic and anaerobic energy production during myocardial infarction and comparison with effects of anoxia.Circulation 1976;38:52?68.
  5. Pouleur H, Hue L, Harlow BJ, Rousseau MF. Metabolic pathway modulation: A new approach to treat myocardial ischemia?Circulation 1989;80(Suppl II):II52.
  6. Cocco G, Rousseau MF, Bouvy T, et al. Effects of a new metabolic modulator, ranolazine, on exercise tolerance in angina pectoris patients treated with ?-blocker or diltiazem.J Cardiovasc Pharmacol 1992;20:131?138.
  7. Rousseau MF, van Eyll C, Van Mechelen H, Harlow BJ, Pouleur H. Novel metabolic modulator ranolazine selectively improves diastolic function in heart failure.Circulation 1992;86(Suppl I):I375.
  8. Rousseau MF, Cocco G, Bouvy T, et al. Effects of a novel metabolic modulator, ranolazine, on exercise tolerance and left ventricular filling dynamics in patients with angina pectoris.Circulation 1992;86(Suppl I):I714.
  9. Pouleur H, van Eyll C, Gurne O, Rousseau MF. Analysis of the mechanisms underlying the changes in left ventricular filling dynamics during oral nisoldipine therapy in patients with anterior myocardial infarction.Eur Heart J 1992;13:952?959.
  10. Hayashida W, van Eyll C, Rousseau MF, Pouleur H. Regional remodeling and nonuniform changes in diastolic function in patients with left ventricular dysfunction: Modification by long-term enalapril treatment.J Am Coll Cardiol 1993;22:1403?1410.
  11. Hayashida W, Kumada T, Kohno F, et al. Left ventricular regional relaxation and its nonuniformity in hypertrophic nonobstructive cardiomyopathy.Circulation 1991;84:1496?1504.
  12. Pouleur H, Rousseau MF, van Eyll C, Charlier AA. Assessment of regional left ventricular relaxation in patients with coronary artery disease: Importance of geometric factors and changes in wall thickness.Circulation 1984;69:696?702.
  13. Packer M. Abnormalities of diastolic function as a potential cause of exercise intolerance in chronic heart failure.Circulation 1990;81(Suppl III):III78-III86.
  14. Braunwald E, Rutherford JD. Reversible ischemic left ventricular dysfunction: Evidence for the ?hibernating myocardium?.J Am Coll Cardiol 1986;8:1467?1470.
  15. Lorell BH, Grossman W. Cardiac hypertrophy: Consequences for diastole.J Am Coll Cardiol 1987;9:1189?1193.
  16. Brutsaert DL, Rademakers FE, Sys SU. Triple control of relaxation: Implications in cardiac disease.Circulation 1984;69:190?196.
  17. Gilbert JC, Glantz SA. Determinants of left ventricular filling and of the diastolic pressure-volume relation.Circ Res 1989;64:827?852.
  18. Ishida Y, Meisner JS, Tsujioka J, et al. Left ventricular filling dynamics: Influence of left ventricular relaxation and left atrial pressure.Circulation 1986;74:187?196.
  19. Lodge JPA, Lam FT, Perry SL, Giles GR. Ranolazine?A new drug with beneficial effects on renal preservation.Transplantation 1990;50:755?759.
  20. Veitch K, Hombroeckx A, Caucheteux D, Pouleur H, Hue L. Global ischemia induces a biphasic response of the mitochondrial respiratory chain. Anoxic pre-prefusion protects against ischaemic damage.Biochem J 1992;281:709?715.
  21. Perrone-Filardi P, Bacharach SL, Dilsizian V, et al. Metabolic evidence of viable myocardium in regions with reduced wall thickness and absent wall thickening in patients with chronic ischemic left ventricular dysfunction.J Am Coll Cardiol 1992;20:161?168.
Bibliographic reference Hayashida, Wataru ; van Eyll, Christian ; Rousseau, Michel ; Pouleur, Hubert. Effects of ranolazine on left ventricular regional diastolic function in patients with ischemic heart disease. In: Cardiovascular Drugs and Therapy, Vol. 8, no. 5, p. 741-747 (1994)
Permanent URL http://hdl.handle.net/2078.1/13417