Effect of Drugs on Myocardial Microcirculation

  • H. Tillmanns
  • M. Steinhausen
  • H. Leinberger
  • H. Thederan
  • W. Kübler
  • J. R. Parratt

Abstract

Regarding the clinical and pharmacologic effects of two coronary vasodilator drugs, nitroglycerin and dipyridamole, an interesting paradox can be noted. On the one hand, nitroglycerin is widely used nowadays in the treatment of patients with coronary artery disease. However, the extent to which it relieves anginal pain by its effects on the coronary as opposed to the systemic circulation is unclear. Following sublingual or intravenous administration of nitroglycerin, an increase in myocardial blood flow was occasionally observed (Brachfeld et al., 1959, Luebs et al., 1966). In most studies, however, only minor and irregular changes (Eckstein et al., 1951, Sarnoff et al., 1958) or a decrease in total coronary flow occurred (Bernstein et al., 1966, Lichtlen, 1975, Rudolph et al., 1975). In the majority of clinical and experimental studies, intracoronary injection of nitroglycerin caused a slight increase in myocardial blood flow (Bernstein et al., 1966, Eckstein et al., 1951, Rudolph et al., 1975). On the other hand, dipyridamole as a potent coronary vasodilator is known to enhance total coronary flow by 360%–400% (Bretschneider et al., 1959, Elliott, 1961, Bretschneider, 1963, De Graff and Lyon, 1963, Fam and McGregor, 1968), but this drug does not relieve angina pectoris. The increase in total coronary flow could be due to a rise in blood flow velocity in individual capillaries, or due to a recruitment of myocardial capillaries previously not perfused.

Keywords

Noradrenaline Cardiol Propranolol Isoptin Glucagon 

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References

  1. 1.
    Bernstein L, Friesinger GC, Lichtlen PR, Ross RS (1966) The effect of nitroglycerin on the systemic and coronary circulation in man and dogs. Circulation 33: 107PubMedGoogle Scholar
  2. 2.
    Brachfeld N, Bozer J, Gorlin R (1959) Action of nitroglycerin on the coronary circulation in normal and in mild cardiac subjects. Circulation 19: 697PubMedGoogle Scholar
  3. 3.
    Bretschneider HJ (1963) Pharmakotherapie coronarer Durchblutungsstörungen mit kreislaufwirksamen Substanzen. Verh Dt sch Ges Inn Med 69: 583Google Scholar
  4. 4.
    Bretschneider HJ, Frank A, Bernard U, Kochsiek K, Scheler E (1959) The effect of a pyrimido- pyrimidine derivative on the oxygen supply to the myocardium. Arzneimittel-Forschg 9: 49Google Scholar
  5. 5.
    De Graff AC, Lyon AF (1963) Evaluation of dipyridamole (Persantin). Amer Heart J 65: 423CrossRefGoogle Scholar
  6. 6.
    Eckstein RW, Newberry WB, McEachern JA, Smith G (1951) Studies of the antiadrenergic effects of nitroglycerin on the dog heart Circulation 4: 534Google Scholar
  7. 7.
    Elliott EC (1961) The effect of Persantin on coronary flow and cardiac dynamics. Can Med Ass J 85: 469Google Scholar
  8. 8.
    Fam WM, McGregor M (1968) Effect of nitroglycerin and dipyridamole on regional coronary resistance. Circ Res 22: 649PubMedGoogle Scholar
  9. 9.
    Intaglietta M, Pawula RF, Tompkins WR (1970) Pressure measurements in the mammalian micro- vasculature. Microvasc Res 2: 212PubMedCrossRefGoogle Scholar
  10. 10.
    Lichtlen P (1975) Die Wirkung von Nitriten und Nitraten auf die linksventrikuläre und koronare Dynamik in Ruhe und während dynamischer Belastung. In: Nitrate, Wirkung auf Herz und Kreislauf. Rudolph W, Siegenthaler W (eds). Urban u. Schwarzenberg, München, p 80Google Scholar
  11. 11.
    Luebs E-D, Cohen A, Zaleski EJ, Bing RJ (1966) Effect of nitroglycerin, Intensain, Isoptin and papaverine on coronary blood flow in man. Am J Cardiol 17: 535PubMedCrossRefGoogle Scholar
  12. 12.
    Rudolph W, Dacian S, Dirschinger J, Fleck E, Loracher C, Redl A (1975) Änderung der regionalen Myokarddurchblutung und der linksventrikulären Wandbewegung nach Nitraten. In: Nitrate, Wirkung auf Herz und Kreislauf. Rudolph W, Siegenthaler W (eds). Urban u. Schwarzenberg, München, p 94Google Scholar
  13. 13.
    Sarnoff SJ, Case RB, Macruz R (1958) Observations on the vasodilating properties of urine: Comparison of the effect of human urine and nitroglycerin on coronary resistance and myocardial oxygen consumption in the isolated supported heart preparation. Circ Res 6: 522PubMedGoogle Scholar
  14. 14.
    Steinhausen M, Tillmanns H, Thederan H (1978) Micro circulation of the epimyocardial layer of the heart. I. A method for in vivo observation of the microcirculation of superficial ventricular myocardium of the heart and capillary flow pattern under normal and hypoxic conditions. Pflügers Arch 378: 9PubMedCrossRefGoogle Scholar
  15. 15.
    Tillmanns H, Leinberger H, Steinhausen M, Thederan H (1978) The effect of nitroglycerin on the microcirculation of the beating cat and rat ventricular myocardium. J Mol Cell Cardiol 10: Suppl., p 123 (abstr.)Google Scholar
  16. 16.
    Tillmanns H, Steinhausen M, Leinberger H, Thederan H (1979) Different response of the ventricular micro circulation to coronary vasodilators. Circulation 59 and 60 (Suppl. II, 11–142)Google Scholar
  17. 17.
    Tillmanns H, Steinhausen M, Thederan H, Parekh N (1977) In vivo microscopic studies of the ventricular microcirculation of the rat heart. J Mol Cell Cardiol 9 (Suppl.): 57CrossRefGoogle Scholar
  18. 18.
    Wiederhielm CA, Woodbury JW, Kirk ES, Rushmer RF (1964) Pulsatile pressures in the microcirculation of the frog’s mesentery. Am J Physiol 207: 173PubMedGoogle Scholar
  19. 1.
    Grayson J, Parratt JR (1966) A species comparison of the effects of changing perfusion pressure on blood flow and metabolic heat production in the myocardium. J Physiol 187: 465–489PubMedGoogle Scholar
  20. 2.
    Grayson J, Irvine M, Parratt JR (1971) Effects of carbochromen and dipyridamole on blood flow and heat production in the normal and ischaemic canine myocardium. Cardiovasc Res 5: 41–47PubMedCrossRefGoogle Scholar
  21. 3.
    Ledingham IMcA, Parratt JR, Vance JP (1972) Myocardial blood flow and metabolism in shock. In: Ledingham IMcA, McAllister TA (eds) Shock. Kimpton, London, pp 13–19Google Scholar
  22. 4.
    Maroko PR, Kjekshus JK, Sobel BE, Watanabe T, Covell JW, Ross J, Braunwald E (1971) Factors influencing infarct size following experimental coronary occlusion. Circulation 43: 67–82PubMedGoogle Scholar
  23. 5.
    Marshall RJ, Parratt JR (1973) The effect of dipyridamole on blood flow and oxygen handling in the acutely ischaemic and normal canine myocardium. Br J Pharmacol 49: 391–399PubMedGoogle Scholar
  24. 6.
    Marshall RJ, Parratt JR (1973) The effect of noradrenaline on blood flow and oxygen con-sumption in normal and ischaemic areas of myocardium. Am Heart J 86: 653–662CrossRefGoogle Scholar
  25. 7.
    Marshall RJ, Parratt JR (1974) Drug-induced changes in blood flow in the acutely ischaemic canine myocardium; relationship to subendocardial driving pressure. Clin Exp Pharmacol Physiol 1: 99–112PubMedCrossRefGoogle Scholar
  26. 8.
    Marshall RJ, Parratt JR (1974) The effect of dilazep on blood flow and oxygen handling in the early stages of canine myocardial infarction: simultaneous comparison with changes in the normal myocardium. Naunyn Schmiedebergs Arch Pharmacol 281: 427–436PubMedCrossRefGoogle Scholar
  27. 9.
    Marshall RJ, Parratt JR (1976) Comparative effects of propanolol and practolol in the early stages of experimental canine myocardial infarction. Br J Pharmacol 57: 295–303PubMedGoogle Scholar
  28. 10.
    Marshall RJ, Parratt JR (1977) A comparative study of beta-adrenoceptor blocking agentson blood flow and metabolism in the acutely ischaemic myocardium. Proc R Soc Med (Suppl II) 70: 62–68Google Scholar
  29. 11.
    Marshall RJ, Parratt JR (to be published) The early consequences of myocardial ischaemia and their modification. J Physiol (Paris)Google Scholar
  30. 12.
    Marshall RJ, Parratt JR, Ledingham IMcA (1974) Changes in blood flow and oxygen consump-tion in normal and ischaemic regions of the myocardium following acute coronary artery ligation. Cardiovasc Res 8: 204–215PubMedCrossRefGoogle Scholar
  31. 13.
    Parratt JR, Ledingham IMcA (1972) Myocardial infarction in the dog: changes in blood flow and oxygen extraction induced by oxyfedrine in areas of developing myocardial ischaemia. In: Gerlach E, Moser K (eds) Action of oxyfedrine. Schattauer, Stuttgart, pp 201–208Google Scholar
  32. 14.
    Parratt JR, Ledingham IMcA, McArdle CS (1973) Effect of a coronary vasodilator drug (carbo-chromen) on blood flow and oxygen extra in acute myocardial infarction. Cardiovasc Res 7: 401–407PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1982

Authors and Affiliations

  • H. Tillmanns
    • 1
  • M. Steinhausen
    • 1
  • H. Leinberger
    • 1
  • H. Thederan
    • 1
  • W. Kübler
    • 1
  • J. R. Parratt
    • 2
  1. 1.Abt. Innere Medizin III, KardiologieMed. Universitätsklinik HeidelbergHeidelberg 1Germany
  2. 2.Department of Physiology and PharmacologyRoyal College, University of StrathclydeGlasgowScotland, UK

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