Advertisement

Möglichkeiten und Grenzen pharmakologischer Untersuchungsverfahren

  • G. Raberger

Zusammenfassung

Amylnitrit und Nitroglycerin sind schon seit über 100 Jahren in der Medizin bekannt [1]. Es dauerte jedoch sehr lange, bis auch die entsprechenden pharmakologischen Untersuchungsmethoden ausgearbeitet wurden, mit denen man die klinisch bekannte Wirksamkeit belegen konnte. Im folgenden soll vor allem auf Untersuchungsmethoden eingegangen werden, die am narkotisierten und wachen Ganztier zur Analyse der Nitratwirkung verwendet werden.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. [1]
    Parratt, J.R., Nitroglycerin-the first one hundred years: new facts about an old drug. J. Pharm. Pharmacol. 31, 801–809, 1979.PubMedGoogle Scholar
  2. [2]
    Mackenzie, J.E., Parratt, J.R., Comparative effects of glyceryl trinitrate on venous and arterial smooth muscle in vitro; relevance to antianginal activity. Br. J. Pharmacol. 60, 155–160, 1977.PubMedGoogle Scholar
  3. [3]
    Harder, D. R., Belardinelle, L., Sperelakis, N., Berne, R. M., Differential effects of adenosine and nitroglycerine on the action potentials of large and small coronary arteries. Circ. Res. 44, 176–182, 1979.PubMedGoogle Scholar
  4. [4]
    Bogaert, M. G., Herman, A. G., De Schaepdryver, A. F., Effects of nitroglycerin on vascular smooth muscle. Eur. J. Pharmacol. 12, 215–223, 1970.PubMedCrossRefGoogle Scholar
  5. [5]
    Wendt, R. L., Systemic and coronary vascular effects of the 2-and 5-mononitrate esters of isosorbide. J. Pharmacol. Exp. Ther. 180, 732–742, 1972.PubMedGoogle Scholar
  6. [6]
    Cohen, M. V., Kirk, E. S., Differential response of large and small coronary arteries to nitroglycerin and angiotensin. Circ. Res. 33, 445–453, 1973.PubMedGoogle Scholar
  7. [7]
    Honig, C. R., Tenney, S. M., Gabel, P. V., The mechanism of cardiovascular action of nitroglycerin. Am. J. Med. 29, 910–923, 1960.PubMedCrossRefGoogle Scholar
  8. [8]
    Weiss, H.R., Winbury, M.M., Intracoronary nitroglycerin, pentaerythriol trinitrate and dipyridamole on intramyocardial oxygen tension. Microvasc. Res. 4, 273–284, 1972.PubMedCrossRefGoogle Scholar
  9. [9]
    Ogilvie, R. I., Effect of nitroglycerin on peripheral blood flow and distribution and venous return. J. Pharmacol. Exp.-Ther. 207, 372–380, 1978.PubMedGoogle Scholar
  10. [10]
    Lochner, W., Grund, E, Müller-Ruchholtz, E. R., Lapp, E. R., Vergleichende Untersuchung über die Wirkung von Molsidomin auf das kapazitivvenöse System des großen Kreislaufs. In: Molsidomin. Ed.: Lochner, W., Bender, F., Urban und Schwarzenberg, 1978.Google Scholar
  11. [11]
    Ruthlen, D. L., Wackers, F. J. T., Zaret, B. L., Radionuclide assessment of peripheral intravascular volume changes in the capacitance circulation in man. Circulation 64, 146–152, 1983.CrossRefGoogle Scholar
  12. [12]
    Smith, E.R., Simseth, O.H., Kingma, I., Manyari, D., Belenkie, I., Tyberg, J.V., Mechanism of action of nitrates. Am. J. Med. 76, 14–21, 1984.PubMedCrossRefGoogle Scholar
  13. [13]
    Szekeres, L., Csik, V., Udvary, E., Nitroglycerin and dipyridamole on cardiac metabolism and dynamics in a new experimental model of angina pectoris. J. Pharmacol. Exp.-Ther. 196, 15–28, 1976.PubMedGoogle Scholar
  14. [14]
    Seitelberger, R., Raberger, G., A canine model of transient myocardial dysfunction: regional shortening in the presence of critical stenosis and cardiac stimulation. J. Pharmacol. Meth. 12, 233–246, 1984.CrossRefGoogle Scholar
  15. [15]
    Lekven, J., Ilebekk, A., Fonstelien, E., Kiil, F., Relationship between ST-segment elevation and local tissue flow during myocardial ischaemia in dogs. Cardiovasc. Res. 9, 627–633, 1975.PubMedCrossRefGoogle Scholar
  16. [16]
    Waters, D.D., DaLuz, P., Wyatt, H.L., Swan, H.J.C., Forrester, J.S., Early changes in regional and global left ventricular function induced by graded reductions in regional coronary perfusion. Am. J. Cardiol. 39, 537–543, 1977.PubMedCrossRefGoogle Scholar
  17. [17]
    Battler, A., Froelicher, V. F., Gallagher, K. P., Kemper, S., Ross, J., Dissotiation beetween regional myocardial dysfunction and ECG changes during ischemia in the conscious dog. Circulation 62, 735–744, 1980.PubMedGoogle Scholar
  18. [18]
    Heyndrickx, G. R., Millard, R. W., McRitchie, R. J., Maroko, R. R., Vatner, S. F., Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs. J. Clin. Invest. 56, 978–985, 1975.PubMedCrossRefGoogle Scholar
  19. [19]
    Cohen, M. V., Sonnenblick, E. H., Kirk, E. S., Comparative effects of nitroglycerin and isosorbide dinitrate on coronary collateral vessels and ischemic myocardium in dogs. Am. J. Cardiol. 37, 244–249, 1976.PubMedCrossRefGoogle Scholar
  20. [20]
    Weintraub, W.S., Cluley, S., Naccarella, F., Akizuki, S., Argawal, J. B., Bodenheimer, M. M., Banka, V. S., Helfant, R. H., Influence of nitroglycerin on collateral blood flow during acute ischemia in the dog. Cardivasc. Res. 19, 169–176, 1985.CrossRefGoogle Scholar
  21. [21]
    Sakai, K., Akima, M., Shiraki, Y., Hoshino, E., Effects of a new antianginal agent, nicorandil, on the cardiovascular system of the miniature pig: with special reference to coronary vasospasm. J. Pharmacol. Exp. Ther. 227, 220–228, 1983.PubMedGoogle Scholar
  22. [22]
    Satoh, K., Yamashita, S., Maruyama, M., Taira, N., Comparison of the responses of simian and canine coronary circulations to autonomic drugs. J. Cardiovasc. Res. 4, 820–828, 1982.Google Scholar
  23. [23]
    Bagshaw, R.J., Cox, R.H., Baroreceptor reflexes and pulmonary hemodynamics during halothane and halothane-nitrous oxide anesthesia in the dog. Anesth. Analg. 60, 701–709, 1981.PubMedCrossRefGoogle Scholar
  24. [24]
    Zimpfer, M., Sit, S. P., Vatner, S. F., Effects of anesthesia on the canine carotid chemoreceptor reflex. Circ. Res. 48, 400–406, 1981.PubMedGoogle Scholar
  25. [25]
    Beck A., Zimpfer, M., Raberger, G., Inhibition of the carotid chemoreceptor reflex by enflurane in chronically instrumented dogs. N.-Sch.-Arch. Pharmacol. 321, 145–148, 1982.CrossRefGoogle Scholar
  26. [26]
    Zimpfer, M., Beck, A., Mayer, N., Raberger, G., Steinbereithner, K., Einfluß von Morphium auf die Kontrolle des kardiovaskulären Systems durch den Carotis-Sinus-Reflex und den Carotis-Chemoreflex. Anaesthesist 32, 60–66, 1983.PubMedGoogle Scholar
  27. [27]
    O’Rourke, R. A., Bishop, V. S., Kot, P. A., Fernandez, J. P., Hemodynamic effects of nitroglycerin and amyl nitrite in the conscious dog. J. Pharmacol. Exp. Ther. 177, 426–432, 1971.PubMedGoogle Scholar
  28. [28]
    Vatner, S.F., Pagani, M., Rutherford, J.D., Millard, R.W., Manders, W. T., Effects of nitroglycerin on cardiac function and regional blood flow distribution in conscious dogs. Am. J. Physiol. 234, H244–H252, 1978.PubMedGoogle Scholar
  29. [29]
    Macho, P., Vatner, S. F., Effects of nitroglycerin and nitroprusside on large and small coronary vessels in conscious dogs. Circulation 64, 1101–1107, 1981.PubMedCrossRefGoogle Scholar
  30. [30]
    Kolin, A., MacAlpin, R. N., Induction Angiometer, Blood Vessels 14, 141–146, 1977.PubMedGoogle Scholar
  31. [31]
    Bassenge, E., Holtz, A., Kolin, A., Wirkung von Molsidomin auf Koronararteriendurchmesser, Koronarwiderstand und venöses System in wachen Hunden. In: Molsidomin. Ed.: Bassenge, E., Schmutzler, H., Urban und Schwarzenberg 1982.Google Scholar
  32. [32]
    Müller-Schweinitzer, E., The recording of venous compliance in the conscious dog. J. Parmacol. Meth. 12, 53–58, 1984.CrossRefGoogle Scholar
  33. [33]
    Bacher, S., Kraupp, O., Beck, A., Skoda, H., Raberger, G., Characterization of vasodilators by comparison of their effects on blood pressure, counterregulation and myocardial oxygen demand in conscious dogs. Drug. Res. 35, Ia, 288–291, 1985.Google Scholar
  34. [34]
    Liard, J. F., The baroreceptor reflexes in experimental hypertension. Clin. Exp. Hypertension 2, 479–498, 1980.CrossRefGoogle Scholar
  35. [35]
    Billman, G. E., Schartz, P. J., Stone, H. L., Baroreceptor reflex control of heart rate: a predictor of sudden cardiac death. Circulation 66, 874–880, 1982.PubMedCrossRefGoogle Scholar
  36. [36]
    Bache, R. J., Ball, R.M., Cobb, F. R., Remberg, J.C., Greenfield, J. C., Effects of nitroglycerin on transmural myocardial blood flow in the unanesthetized dog. J. Clin. Invest. 55, 1219–1228, 1975.PubMedCrossRefGoogle Scholar
  37. [37]
    Tomoike, H., Animal models of coronary spasm and the pathophysiological events in regional vascular hypercontraction. Jap. Circ. J. 49, 101–107, 1985.PubMedCrossRefGoogle Scholar
  38. [38]
    Kumada, T., Gallagher, K.P., Miller, M., McKown, M., White, F., McKown, D., Kemper, W. S., Ross, J., Improvement by isosorbide dinitrate of exercise-induced regional myocardial dysfunction. Am. J. Physiol. 239, H399–H405, 1980.PubMedGoogle Scholar
  39. [39]
    Raberger, G., Krumpl, G., Mayer, N., Teopranitol verbessert die laufbandbelastungsinduzierte regionale Dysfunktion in minderdurchbluteten Myokardarealen. In: Teopranitol. Ed.: Bender, F., Gerlach, E., Steinkopff Verlag 1985.Google Scholar

Copyright information

© Friedr. Vieweg & Sohn Verlagsgesellschaft mbH, Braunschweig 1986

Authors and Affiliations

  • G. Raberger

There are no affiliations available

Personalised recommendations