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Basic Research in Cardiology

, Volume 83, Issue 5, pp 560–566 | Cite as

Influence of spontaneous hypertension and cardiac hypertrophy on the severity of ischemic arrhythmias in the rat

  • P. Bélichard
  • D. Pruneau
  • L. Rochette
Original Contributions

Summary

Cardiac hypertrophy (CH) and hypertension (HT) are major determinants of sudden cardiac death in patients with coronary artery disease. To investigate the hypothesis that CH and HT increase the incidence of severe ventricular arrhythmias in an animal model, we performed a 30-min period of coronary artery ligation in anesthetized spontaneously hypertensive rats (SHR), normotensive Wistar Kyoto (WKY) and Wistar (W) rats. The incidence and duration of ventricular fibrillation resulting from coronary artery occlusion were significantly (p<0.01) increased in hypertensive rats compared to normotensive animals. The calcium entry blocker nicardipine was administered orally to SHR either chronically for 8 weeks (20 mg·kg−1 twice daily) or acutely as a single dose of 20 mg·kg−1. After long-term treatment with nicardipine, left ventricular hypertrophy index and systolic blood pressure were significantly (p<0.001) reduced when compared to vehicle-treated SHR, whereas a single administration of nicardipine only decreased blood pressure without affecting cardiac mass. In the long-term nicardipine-treated SHR group, acute coronary artery ligation induced significantly less ventricular fibrillation (p<0.05) and mortality (p<0.001) than in acutely nicardipine-treated or untreated SHR groups. In conclusion, the data suggest that the severity and incidence of lethal ventricular arrhythmias are more elevated in hypertensive than in normotensive rats and this may be related to the myocardial hypertrophic state.

Key Words

spontaneoushypertension cardiachypertrophy nicardipine ventriculararrhythmia 

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References

  1. 1.
    Anderson KP (1982) Hypertension and sudden cardiac death. N Z Med J 95:33–34PubMedGoogle Scholar
  2. 2.
    Anderson KP (1984) Sudden death, hypertension and hypertrophy. J Cardiovasc Pharmacol 6:S498-S503PubMedGoogle Scholar
  3. 3.
    Aronson RS (1981) Afterpotentials and triggered activity in hypertrophied myocardium from rats with renal hypertension. Circ Res 48:720–727.PubMedGoogle Scholar
  4. 4.
    Bache RJ, Arentzen CE, Simon AB, Wrobel TR (1984) Abnormalities in myocardial perfusion during tachycardia in dogs with left ventricular hypertrophy. Metabolic evidence for myocardial ischemia. Circulation 69:409–417PubMedGoogle Scholar
  5. 5.
    Bakth S, Arena J, Lee W, Torres T, Haider B, Patel BC, Lyons MM, Regan TJ (1986) Arrhythmia susceptibility and myocardial composition in diabetes. J Clin Invest 77:382–395PubMedGoogle Scholar
  6. 6.
    Byrom FB, Wilson C (1938) A plethysmographic method for measuring systolic blood pressure in the intact rat. J Physiol 93:301–304Google Scholar
  7. 7.
    Capasso JM, Tepper D, Reichman P, Sonnenblick EH (1986) Renal hypertensive hypertrophy in the rat: a substrate for arrhythmogenicity. Basic Res Cardiol 81:10–19PubMedGoogle Scholar
  8. 8.
    Clark C, Foreman MI, Kane KA, Mc Donald FM, Parratt JR (1980) Coronary artery ligation in anaesthetized rats as a method for the production of experimental dysrhythmias and the determination of infarct size. J Pharmacol Method 3:357–368Google Scholar
  9. 9.
    Cohen MV (1986) Coronary vascular reserve in the greyhound with left ventricular hypertrophy. Cardiovasc Res 20:182–194PubMedGoogle Scholar
  10. 10.
    Endo T, Nejima J, Fujita S, Kiuchi K, Ida N, Kikuchi K, Kayakawa H, Okumura H (1986) Comparative effects of nicardipine, a new calcium antagonist, on size of myocardial infarction after coronary artery occlusion in dogs. Circulation 74:420–430PubMedGoogle Scholar
  11. 11.
    Harron DWG, Brezina M, Lillie C, Kobinger W (1985) Antifibrillatory properties of alinidine after coronary artery occlusion in rats. Eur J Pharmacol 110:301–308PubMedGoogle Scholar
  12. 12.
    Johnston KM, Mc Leod BA, Walker MJA (1983) Responses to ligation of a coronary artery in conscious rats and the actions of antiarrhythmics. Can J Physiol Pharmacol 61:1340–1353PubMedGoogle Scholar
  13. 13.
    Julian DG (1976) Toward preventing coronary death from ventricular fibrillation. Circulation 54:360–364PubMedGoogle Scholar
  14. 14.
    Kannel WB, Doyle JT, Nc Mamara PM, Quickenton P, Gordon T (1975) Precursors of sudden coronary death. Factors related to the incidence of sudden death. Circulation 51:606–613PubMedGoogle Scholar
  15. 15.
    Konishi T (1965) Electrophysiological study on hypertrophied cardiac muscle experimentally produced in the rabbit. Jpn Circ J 29:491–503PubMedGoogle Scholar
  16. 16.
    Koyanagi S, Eastham C, Marcus ML (1982) Effects of chronic hypertension and left ventricular hypertrophy on the incidence of sudden cardiac death after coronary occlusion in conscious dog. Circulation 65:1192–1197PubMedGoogle Scholar
  17. 17.
    Lupi GA, Wurthaler F, James TN (1979) Effects of verapamil on automaticity and conduction with particular reference to tachyphylaxis. Eur J Cardiol 9:345–368PubMedGoogle Scholar
  18. 18.
    Medugorac I (1980) Collagen content in different areas of normal and hypertrophied rat myocardium. Cardiovasc Res 14:551–554PubMedGoogle Scholar
  19. 19.
    Mirsky I, Pfeffer JM, Pfeffer MA, Braunwald E (1983) The contractile state as the major determinant in the evolution of the left ventricular dysfunction in the spontaneously hypertensive rat. Circ Res 53:767–778PubMedGoogle Scholar
  20. 20.
    Peyton RB, Wechsler AS (1982) Depressed high-energy phosphate content in hypertrophied ventricles of animal and man. Ann Surg 196:278–284PubMedGoogle Scholar
  21. 21.
    Robertson WB, Strong JP (1968) Atherosclerosis in persons with hypertension and diabetes mellitus. Lab Invest 18:538–551PubMedGoogle Scholar
  22. 22.
    Satoh K, Yanagisawa T, Taira N (1980) Mechanisms underlying the cardiovascular action of a new dihydropyridine vasodilator YC 93. Clin Exp Pharmacol Physiol 7:249–262PubMedGoogle Scholar
  23. 23.
    Strauer BE, Klepzig M, Motz W (1986) Reversal of left ventricular and coronary hypertrophy following antihypertensive treatment. In: Kauffmann W, Bönner G, Lang R, Meurer KA (eds) Primary hypertension. Springer, Berlin Heidelberg New York Tokyo, pp 115–125Google Scholar
  24. 24.
    Takenaka T, Asano M, Shiono K, Shibasaki M, Inagaki O (1985) Cardiovascular pharmacology of nicardipine in animals. Br J Clin Pharmac 20:7S-22SGoogle Scholar
  25. 25.
    Tisné-Versailles J, Verscheure Y, Le Kim A, Pourrias B (1982) Comparison between the ventricular fibrillation thresholds of SHR and WKY: investigation of antidysrhythmic drugs. J Cardiovasc Pharmacol 65:1192–1197Google Scholar
  26. 26.
    Tracy CM, Epstein SE (1985) Sudden death and hypertrophic cardiomyopathy. Am Heart J 110:1326–1327Google Scholar

Copyright information

© Dr. Dietrich Steinkopff Verlag 1988

Authors and Affiliations

  • P. Bélichard
    • 1
  • D. Pruneau
    • 1
  • L. Rochette
    • 2
  1. 1.Centre de RechercheLaboratoires Fournier S.A.Fontaine-lès-DijonFrance
  2. 2.Faculté de PharmacieUniversité de DijonFrance

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