Cardiovascular Drugs and Therapy

, Volume 1, Issue 6, pp 687–694 | Cite as

Influence of minoxidil on myocardial hemodynamics, regional blood flow, and morphology in beagle dogs

  • G. Kimble Jett
  • Eugene H. Herman
  • Michael Jones
  • Victor J. Ferrans
  • Richard E. Clark
Experimental Pharmacology


Studies were made of the effects of two doses of minoxidil (3 mg/kg), given 24 hours apart, on cardiovascular hemodynamics, regional myocardial blood flow, and cardiac morphology in beagle dogs. Minoxidil caused increases in mean right atrial and left ventricular end-diastolic pressure. Systemic and pulmonary vascular resistance were reduced; cardiac output was increased. Left ventricular stroke work and the systolic pressure time index were unchanged by monoxidil administration. The diastolic pressure time index and ratio of diastolic/systolic pressure time index were decreased by minoxidil. Regional myocardial blood flow, measured with radioactive microspheres, increased in all regions of the heart except to the left ventricular papillary muscles. Minoxidil increased blood flow to left ventricular subendocardial tissue; however, this increase was significantly less than that observed in corresponding areas of subepicardial tissue, thus reducing the subendocardial/subepicardial tissue blood flow ratio. These results suggest that minoxidil is an effective peripheral vasodilator but may result in inadequate subendocardial perfusion. Morphologic studies disclosed two types of minoxidil-induced cardiac lesions: left ventricular papillary muscle necroses, and hemorrhagic lesions which were most prominent in right atrium and were associated with inflammation, intramural hemorrhage, and fibrinoid necrosis of small arteries. The papillary muscle necroses were attributed to hypoxia. The atrial lesions were not of ischemic or hypoxic origin, because minoxidil did not decrease blood flow to atrial tissue. It is suggested that the atrial lesions are related to excessive vasodilatation.

Key words

minoxidil hemodynamics regional myocardial blood flow myocardial necrosis arteritis atrial lesions 


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  1. 1.
    Minoxidil (Loniten).Med Lett 1980; 22(5):21–22.Google Scholar
  2. 2.
    Linas ST, Nies AS. Minoxidil.Ann Intern Med 1981; 94:61–65.PubMedGoogle Scholar
  3. 3.
    Mitchell HC, Pettinger WA. Long-term treatment of refractory hypertension in patients with minoxidil.JAMA 1978; 239:2131–2138.CrossRefPubMedGoogle Scholar
  4. 4.
    Pettinger WA, Mitchell HC. Minoxidil—an alternative to nephrectomy for refractory hypertension.N Engl J Med 1973; 289:167–173.PubMedGoogle Scholar
  5. 5.
    Limas CJ, Freis ED. Minoxidil in severe hypertension with renal failure.Am J Cardiol 1973; 31:355–361.CrossRefPubMedGoogle Scholar
  6. 6.
    Oka M, Mahkela M. Minoxidil in severe hypertension.Acta Med Scand 1978; 203:43–47.PubMedGoogle Scholar
  7. 7.
    Sobota JT, Martin WB, Carlson RG, et al. Minoxidil: Right atrial cardiac pathology in animal and in man.Circulation 1980; 62:376–387.PubMedGoogle Scholar
  8. 8.
    Balazs T, Payne BJ. Myocardial papillary muscle necrosis induced by hypotensive agents in dogs.Toxicol Appl Pharmacol 1971; 20:422–445.CrossRefGoogle Scholar
  9. 9.
    Herman E, Balazs T, Earl F, et al. Influence of chronic diuretic therapy on minoxidil-induced necrosis in dogs.Toxical Appl Pharmacol 1975; 33:198–199.Google Scholar
  10. 10.
    Weiss LR, Balazs T, Krop S. Cardiac lesions induced by hydralazine, minoxidil and isoproterenol in rodents.Fed Proc 1976; 35:534.Google Scholar
  11. 11.
    Carlson RG, Feenstra FS. Toxicologic studies with the hypotensive agent minoxidil.Toxicol Appl Pharmacol 1977; 39:1–11.CrossRefPubMedGoogle Scholar
  12. 12.
    Herman EH, Balazs R, Young FJ, et al. Acute cardiomyopathy induced by the antihypertensive agent minoxidil.Toxicol Appl Pharmacol 1979; 47:493–503.CrossRefPubMedGoogle Scholar
  13. 13.
    Herman E, Balazs T, Ferrans VJ, et al. Divergent effects of propranolol and furosemide pretreatment on acute cardiomyopathy induced by minoxidil in beagle dogs.Toxicology 1981; 20:155–164.CrossRefPubMedGoogle Scholar
  14. 14.
    Traub YM, Aygen MM, Rosenfeld JB. Hazards in treatment of systolic hypertension.Am Heart J 1979; 97:174–177.CrossRefPubMedGoogle Scholar
  15. 15.
    Dargie HJ, Dollery CT, Daniel J. Minoxidil in resident hypertension.Lancet 1977; 2:515–518.CrossRefPubMedGoogle Scholar
  16. 16.
    Hall D, Charocopos F, Froer KL, et al. ECG changes during long-term minoxidil therapy for severe hypertension.Arch Intern Med 1979; 139:790–794.CrossRefPubMedGoogle Scholar
  17. 17.
    Jacomb RC, Brunnberg FJ. The use of minoxidil in the treatment of severe essential hypertension: A report on 100 patients.Clin Sci Mol Med 1976; 51:5795–5815.Google Scholar
  18. 18.
    Herman EH, Ferrans VJ, Balazs T, et al. Acute cardiac toxicity induced by minoxidil in miniature swine.Fed Proc 1981; 40:713.Google Scholar
  19. 19.
    Herman EH, Ferrans VJ, Balazs T. Minoxidil and cardiac lesions.Circulation 1981; 64:1299–1300.PubMedGoogle Scholar
  20. 20.
    Van Vleet JF, Herman EH, Ferrans VJ. Cardiac morphologic alterations in acute minoxidil cardiotoxicity in miniature swine.Exp Mol Pathol 1984; 41:10–25.CrossRefPubMedGoogle Scholar
  21. 21.
    Watson JT, Fixler DF, Platt MR, et al. The influence of combined intra-aortic balloon counterpulsation and hypertonic mannitol on regional myocardial blood flow in ischemic myocardium in the dog.Circ Res 1976; 38:506–525.PubMedGoogle Scholar
  22. 22.
    Rudolph AM, Heymann MA. Circulation of the fetus in utero: Methods for studying the distribution of blood flow, cardiac output and organ blood flow.Circ Res 1967; 21:163–184.PubMedGoogle Scholar
  23. 23.
    Gilmore EG, Weil J, Chidsey C. Treatment of essential hypertension with a new vasodilator in combination with beta-adrenergic blockade.N Engl J Med 1970; 282:521–527.PubMedGoogle Scholar
  24. 24.
    Zins GR. Alterations in renal function during vasodilator therapy: In: Wesson LG, Fanelli GM, eds.Recent Advances in Renal Physiology. Baltimore: University Park Press, 1974; 165–186.Google Scholar
  25. 25.
    Humphrey SJ, Zins GR. Whole body and regional hemodynamic effects of minoxidil in the conscious dog.J Cardiovasc Pharmacol 1984; 6:979–988.PubMedGoogle Scholar
  26. 26.
    Wilburn RL, Blaufuss A, Bennett CM: Long-term treatment of severe hypertension with minoxidil, propranolol and furosemide.Circulation 1975; 52:706–713.PubMedGoogle Scholar
  27. 27.
    Dormois JC, Young JL, Nies AS. Minoxidil in severe hypertension: Value when conventional drugs have failed.Am Heart J 1975; 90:360–368.CrossRefPubMedGoogle Scholar
  28. 28.
    Atkins JM, Mitchell HC, Pettinger WA. Increased pulmonary vascular resistance with systemic hypertension.Am J Cardiol 1977; 39:802–807.PubMedGoogle Scholar
  29. 29.
    Tarazi RC, Magrini F, Dustan HP, et al. Pulmonary hypertension with diazoxide and minoxidil.Am J Cardiol 1975; 35:172.CrossRefGoogle Scholar
  30. 30.
    Froer DH, Loracher C. Treatment of severe hypertension with minoxidil and its effects on systemic and pulmonary hemodynamics.Clin Sci 1976; 51:5785–5795.Google Scholar
  31. 31.
    Alpert MA, Bauer JH, Parker BM, et al. The long-term effect of minoxidil on systemic and pulmonary hemodynamics.Prev Med 1978; 7:35.Google Scholar
  32. 32.
    Franciosa JA, Jordon RA, Wilen MM, et al. Minoxidil in patients with chronic left heart failure: Contrasting hemodynamic and clinical effects in a controlled trial.Circulation 1984; 70:63–68.PubMedGoogle Scholar
  33. 33.
    Utley J, Carlson EL, Hoffman JIE, et al. Total and regional myocardial blood flow measurements with 25µ, 15µ, 9µ and filtered 1–10µ diameter microspheres and antipyrine in sheep.Circ Res 1974; 34:391–405.PubMedGoogle Scholar
  34. 34.
    Buckberg GD, Fixler DE, Archie JP, et al. Experimental subendocardial ischemia in dogs with normal coronary arteries.Circ Res 1972; 30:67–81.PubMedGoogle Scholar
  35. 35.
    Brazier J, Cooper N, Buckberg GD. The adequacy of subendocardial oxygen delivery: The interaction of flow, arterial oxygen content and myocardial oxygen need.Circulation 1974; 49:968–970.PubMedGoogle Scholar
  36. 36.
    Hoffman JIE. Determinants and prediction of transmural myocardial perfusion.Circulation 1978; 58:381–391.PubMedGoogle Scholar
  37. 37.
    Buckberg GD. Progress in myocardial protection during cardiac operation. In: McGoon DC, ed.Cardiac surgery. Cardiovasc Clin 1982; 12(3):9–30.Google Scholar
  38. 38.
    Radvany P, Davis MA, Muller JE, et al. Effects of minoxidil on coronary collateral flow and acute myocardial injury following experimental coronary artery occlusion.Cardiovasc Res 1978; 12:120–126.PubMedGoogle Scholar
  39. 39.
    Reimer KA, Ideker RE. Myocardial ischemia and infarction: Anatomic and biochemical substrates for ischemic cell death and ventricular arrhythmias.Hum Pathol 1987; 18:462–475.PubMedGoogle Scholar
  40. 40.
    Nayler WG, Daly MJ. Calcium and the injured cardiac myocyte. In: Sperelakis N, ed.Physiology and Pathophysiology of the Heart. Boston: Martinus Nijhoff, 1984;477–492.Google Scholar
  41. 41.
    Gans JH, Korson R, Cater MR, et al. Effect of short-term and long-term theobromine administration to male dogs.Toxicol Appl Pharmacol 1980; 53:481–496.CrossRefPubMedGoogle Scholar
  42. 42.
    Bourdois PS, Dancla J-L, Faccini JM, et al. The sub-acute toxicology of digoxin in dogs; Clinical chemistry and histopathology of heart and kidneys.Arch Toxicol 1982; 51:273–283.CrossRefGoogle Scholar
  43. 43.
    Hu HC, Lieu VT, Li RC. Anatomical changes in the hearts of dogs and frogs poisoned by glucosides of the digitalis group.China Med J 1936; Suppl 1:31–42.Google Scholar
  44. 44.
    Teske RH, Bishop SP, Righter HS, et al. Sub-acute digoxin toxicosis in the beagle dog.Toxicol Appl Pharmacol 1976; 35:283–301.CrossRefPubMedGoogle Scholar
  45. 45.
    Schenk EA, Moss AJ. Cardiovascular effects of sustained norepinephrine infusions. II. Morphology.Circ Res 1966; 18:605–615.PubMedGoogle Scholar
  46. 46.
    Szakacs JE, Mehlman B. Pathologic changes induced by 1-norepinephrine: Quantitative aspects.Am J Cardiol 1960; 5:619–627.CrossRefPubMedGoogle Scholar
  47. 47.
    Waters LL, de Suto-Nagy GI. Lesions of the coronary arteries and great vessels of the dog following injections of adrenalin. Their prevention by dibenamine.Science 1950; 111:634–635.PubMedGoogle Scholar
  48. 48.
    Nahas GG, Brunson JG, King WM, et al. Functional and morphologic changes in heart-lung preparations following administration of adrenal hormones.Am J Pathol 1958; 34:717–725.PubMedGoogle Scholar
  49. 49.
    Harleman JH, Joseph EC, Eden RJ, et al. Cardiotoxicity of a new inotrope/vasodilator drug (SKF 94120) in the dog.Arch Toxicol 1985; 59:51–55.CrossRefGoogle Scholar
  50. 50.
    DeWit RH, Peter GK, Fitzgerald JE, et al. Preliminary toxicologic evaluation of a novel cardiotonic agent.Toxicologist 1985; 5:94.Google Scholar
  51. 51.
    Rogers S, Barsoum N, Fonzo CD, et al. Intravenous toxicology of a new cardiotonic agent.Toxicologist 1985; 5:111.Google Scholar

Copyright information

© Kluwer Academic Publishers 1988

Authors and Affiliations

  • G. Kimble Jett
    • 1
    • 2
  • Eugene H. Herman
    • 1
    • 2
  • Michael Jones
    • 1
    • 2
  • Victor J. Ferrans
    • 1
    • 2
  • Richard E. Clark
    • 1
    • 2
  1. 1.National Heart, Lung and Blood Institute, National Institutes of HealthBethesda
  2. 2.Food and Drug AdministrationWashington, D.C.

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