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Effect of urapidil on the performance of ischemic myocardium in anesthetized dogs

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Summary

Urapidil (URA) is used to treat acute hypertension in patients with coronary artery disease, but the effect of URA on the performance of ischemic myocardium has not yet been investigated. The present study was intended to assess the function of ischemic myocardium following URA administration. In eight anesthetized (piritramide) open-chest dogs systolic contraction (dL) and end-diastolic length (edL) of myocardium supplied by the left descending (LAD) and circumflex (LCA) coronary arteries were measured by sonomicrometry simultaneously with aortic pressure (AoP), left ventricular end-diastolic pressure (LVedP), heart rate (HR), stroke volume (SV), and LAD-flow (QLAD). QLAD was reduced by LAD stenosis to about 50% of control, decreasing dLLAD by 55%. Concomitantly, edLLAD increased by about 9% and LVedP by 22%, whereas AoP decreased by 5%. Then, URA was given i.v. (0.25+0.25+0.50+1.0 mg/kg) in 15-min intervals. Following URA, the performance of the non-ischemic area was not systematically affected, but dLLAD increased by about 50%. This could neither be related to the significant reduction in afterload (AoP: −8%), nor to an increase in preload (LVedP and edLLAD did not change significantly), nor to an improved oxygen supply via the LAD (QLAD even decreased), although an increased collateral flow from the LCA could not be excluded. The increase in systolic shortening correlated very closely to a decrease in heart rate (r=−0.92). It is concluded that the improved function of ischemic myocardium following urapidil resulted from a reduced oxygen demand in consequence to the decrease in heart rate.

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References

  1. Barankay A, Göb E, Richter JA (1981) Treatment of hypertension in coronary bypass surgery, clinical experience with urapidil. Arzneim Forsch Drug Res 31:849–852

    Google Scholar 

  2. Fozard JR, Mir AK (1987) Are 5-HT receptors involved in the antihypertensive effects of urapidil? Brit J Pharmacol 90:24P

  3. Frank O (1895) Zur Dynamik des Herzmuskels. Z Biol 32:370–437

    Google Scholar 

  4. Franke N, Schmucker P, Vogel H, Lühr H (1982) Veränderungen der Hämodynamik und des myokardialen Sauerstoffverbrauchs bei intraoperativer Drucksenkung mit Urapidil. In: Kaufmann W, Bruckschen EG (eds) Urapidil. Darstellung einer neuen antihypertensiven Substanz. Excerpta Medica Amsterdam, pp 113–118

    Google Scholar 

  5. Freissmuth M, Tuisl E, Steurer G, Schütz W (1984) Interaction of the antihypertensive drug urapidil with cardiac beta0adrenoceptors in vitro. European J Pharmacol 104:169–172

    Google Scholar 

  6. Floer KL, Hagl S, Heimisch W, Hall D, Rudolph W (1980) Verbesserung der Funktion akut ischämischer Myokardbezirke unter dem Einfluß von Isosorbiddinitrat in der Kombination mit der intraaortalen Ballongegenpulsation. In: Rudolph W, Schrey A (eds) Nitrate II. Wirkung auf Herz und Kreislauf. Urban & Schwarzenberg Verlag, München, pp 333–336

    Google Scholar 

  7. Gillis A, Kellar KJ, Quest JA, Namath IJ, Martino-Barrows A, Hill K, Gatti PJ, Dretchen K (1988) Experimental studies on the neurocardiovascular effects of urapidil. Drugs 35, Suppl 6:20–33

    Google Scholar 

  8. Heimisch W, Hagl S, Gebhardt K, Meisner H, Mendler N, Sebening F (1981) Direct measurement of cyclic changes in regional wall geometry in the left ventricle of the dog. Innov Tech Biol Med 2:487–501

    Google Scholar 

  9. Heimisch W, Hagl S, Mendler N, Schad H, Sebening F (1988) Experimental studies on acute coronary stenosis: pathophysiology of hemodynamics and mechanics of the ischemic and nonischemic myocardium. Thorac Cardiovasc Surgeon 36, Suppl 1:93

    Google Scholar 

  10. Helfant RH, Bamanathan KB, Bodenheimer MM, Banka VS (1980) Comparative effects of nitroglycerin and nitroprusside on regional coronary flow and contraction after partial coronary occlusion. In: Rudolph W, Schrey A (eds) Nitrate II. Urban & Schwarzenberg, München Wien Baltimore, pp 110–118

    Google Scholar 

  11. Hess W, Schulte-Sasse U, Tarnow J, Veit S (1985) Comparison of phentolamine and urapidil in controlling acute intra-operative hypertension in patients subjected to coronary artery bypass surgery. Europ J Anesth 2:21–27

    Google Scholar 

  12. Isoyama S, Maruyama Y, Ashikawa K, Sato S, Suzuki H, Watanabe J, Shimizu Y, Ino-Oka E, Takishima T (1983) Effects of afterload reduction on global left ventricular and regional myocardial functions in the isolated canine heart with stenosis of a coronary arterial branch. Circulation 67:139–147

    PubMed  Google Scholar 

  13. Junger H, van Deyk K, Kopp M (1982) Hämodynamik unter antihypertensiver Therapie mit Urapidil und Nitroprussid-Natrium. In: Kaufmann W, Bruckschen EG (eds) Urapidil. Darstellung einer neuen antihypertensiven Substanz. Excerpta Medica. Amsterdam, pp 139–146

    Google Scholar 

  14. Kellar KJ, Quest JA, Spera AC, Buller A, Conforti A, Dias-Souza J, Gillis RA (1984) Comparative effects of urapidil, prazosin, and clonidine on ligand binding to central nervous system receptors, arterial blood pressure, and heart rate in experimental animals. Am J Med 77(4A):87–95

    Google Scholar 

  15. Kolassa N, Beller KD, Sanders KH (1989) Evidence for the interaction of urapidil with 5-HT-1A receptors in the brain leading to a decrease in blood pressure. Am J Cardiol 63:36C-39C

    PubMed  Google Scholar 

  16. Lekven J, Kiil F (1975) Myocardial function in general and regional left ventricular ischemia in dogs at control and high aortic blood pressure. Cardiovasc Res 9:373–383

    PubMed  Google Scholar 

  17. Luft FC, Veelken R, Becker H, Ganten D, Lang RE, Unger T (1986) Effects of clondine, and prazosin on sympathetic tone in conscious rats. Hypertension 8:303–311

    PubMed  Google Scholar 

  18. Maier W, Hagl S, Heimisch W, Meisner H Mendler N, Sebening F (1984) β1-selektive/nichtselektive β-Rezeptorenblockade: Die Wirkung auf die Funktion des ischämischen Myokards. In: Lohmann FW (ed) β-Rezeptorenblockade: Die klinische Bedeutung der β1-Selektivität. Verlag für angewandte Wissenschaften. München, pp 79–97

    Google Scholar 

  19. Rassier ME, Shebuski RJ, Zimmermann BG (1986) beta-1-adrenoceptor antagonism by urapidil prior to and after the alpha-2-antagonist rauwolscine in anesthetized dogs. Europ J Pharmacol 122:37–43

    Google Scholar 

  20. Sanders KH, Jurna I (1985) Effects of urapidil, clonidine, prazosin and propranolol on autonomic nerve activity, blood pressure and heart rate in anesthetized rats and cats. Europ J Pharmacol 110:181–190

    Google Scholar 

  21. Sanders KH, Kilian U, Kolassa N, Schoetensack W (1985) Influence of urapidil on alpha- and beta-adrenoceptors in pithed rats. J Autonom Pharmacol 5:307–316

    Google Scholar 

  22. Schad H, Heimisch W, Kalke Y, Mendler N (1988) Effect of heart rate (HR) changes by vagal stimulation on normally perfused and ischemic myocardium in anaesthetized dogs. Pflügers Arch 411, Suppl 1:R34

    Google Scholar 

  23. Schad H, Heimisch W, Mendler N (1988) Effect of a critical coronary artery stenosis on the function of the depending myocardial area in anaesthetized dogs. Pflügers Arch 412, Suppl 1:R32

    Google Scholar 

  24. Schoetensack W (1982) Tierexperimentelle Untersuchungen über die Wirkung und Wirkungsweise sowie Toxikologie von Urapidil. In: Kaufmann W, Bruckschen EG (eds) Urapidil. Excerpta Medica, Amsterdam, pp 34–47

    Google Scholar 

  25. Schümann HJ, Bielefeld FW (1986) The effect of urapidil on cardiac alpha- and beta-adrenoceptors. Arzneim Forsch Drug Res 36:1471–1476

    Google Scholar 

  26. Vatner SF (1980) Correlation between acute reductions in myocardial blood flow and function in conscious dogs. Circ Res 47:201–207

    PubMed  Google Scholar 

  27. Vatner SF (1985) Regulation of coronary resistance vessels and large coronary arteries. Am J Cardiol 56:16E-22E

    PubMed  Google Scholar 

  28. Verberne AJM, Rand MJ (1984) Pharmacological activities of the antihypertensive drug urapidil in the rat. Clin Exp Pharmacol Physiol 11:407–412

    PubMed  Google Scholar 

  29. Verberne AJM, Rand MJ (1985) Effect of urapidil on beta-adrenoceptors of rat atria. European J Pharmacol 108:193–195

    Google Scholar 

  30. Wang RYC, Chow JSF, Chan KH, Pan HYM, Wong RPY (1984) Acute haemodynamic and myocardial metabolic effects of intravenous urapidil in severe heart failure. European Heart J 5:745–751

    Google Scholar 

  31. Zeigler DW, Shebuski RJ, Zimmerman BG (1984) Central and peripheral cardiovascular actions of urapidil in normotensive and Goldblatt hypertensive animals. Am J Med 77(4A):81–86

    PubMed  Google Scholar 

  32. Zeigler DW, Zimmerman BG (1985) Comparison of effects of urapidil and prazosin on vascular influence of circulating and neuronally released catecholamines in canine muscle vascular bed. J Cardiovasc Pharmacol 7:1020–1026

    PubMed  Google Scholar 

  33. van Zwieten PA, Mathy MJ, Thoolen MJM, Wilffert B, de Jonge A, Timmermans PBM (1984) Effect of urapidil on blood pressure and adrenoceptors in various animal models. J Hypertension 2, Suppl 3:539–541

    Google Scholar 

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  1. H. Schad

    Present address: Klinik für Herz- und Gefäßchirurgie, Deutsches Herzzentrum München, Lothstraße 11, 8000, München 2, FRG

Authors and Affiliations

  1. Klinik für Herz- und Gefäßchirurgie, Deutsches Herzzentrum München, Lothstraße 11, 8000, München 2, FRG

    W. Heimisch, S. hesse & N. Mendler

  2. Institut für Anästhesiologie, Deutsches Herzzentrum München, Lothstraße 11, 8000, München, FRG

    A. Barankay

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  5. N. Mendler
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Schad, H., Heimisch, W., Barankay, A. et al. Effect of urapidil on the performance of ischemic myocardium in anesthetized dogs. Basic Res Cardiol 85, 270–278 (1990). https://doi.org/10.1007/BF01907115

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  • DOI: https://doi.org/10.1007/BF01907115

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