Skip to main content
British Heart Journal logoLink to British Heart Journal
. 1984 Jul;52(1):106–111. doi: 10.1136/hrt.52.1.106

Detrimental effects of verapamil in patients with primary pulmonary hypertension.

M Packer, N Medina, M Yushak, I Wiener
PMCID: PMC481593  PMID: 6743418

Abstract

Calcium channel blockade provides a logical approach to the treatment of pulmonary hypertension because these drugs exert direct vasodilator effects in the highly constricted pulmonary circulation. To determine the effectiveness of verapamil in the treatment of primary pulmonary hypertension the haemodynamic effects of the drug were evaluated in seven patients with this disorder; 10 mg was given intravenously to six patients and 120 mg orally to one patient. Verapamil produced a 20% decline in pulmonary vascular resistance and a 27% decrease in mean pulmonary arterial pressure without significant changes in systemic vascular resistance. One patient who received verapamil 480 mg orally daily for three months showed sustained haemodynamic and clinical improvement. Concomitant with its beneficial effects on the pulmonary circulation, however, verapamil produced a pronounced decrease in right ventricular stroke work index (42%) and increase in right ventricular filling pressure (50%), indicating a direct depressant effect of the drug on right ventricular function. In one patient these cardiodepressant effects were sufficiently pronounced to produce severe hypotension and cardiac arrest. In conclusion, although verapamil appears to exert preferential vasodilator effects on the pulmonary circulation, its negative inotropic effects may be particularly detrimental to patients with primary pulmonary hypertension who have pre-existing right ventricular dysfunction; hence, treatment with verapamil is not recommended in such cases.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allen G. S., Ahn H. S., Preziosi T. J., Battye R., Boone S. C., Boone S. C., Chou S. N., Kelly D. L., Weir B. K., Crabbe R. A. Cerebral arterial spasm--a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med. 1983 Mar 17;308(11):619–624. doi: 10.1056/NEJM198303173081103. [DOI] [PubMed] [Google Scholar]
  2. Antman E., Muller J., Goldberg S., MacAlpin R., Rubenfire M., Tabatznik B., Liang C. S., Heupler F., Achuff S., Reichek N. Nifedipine therapy for coronary-artery spasm. Experience in 127 patients. N Engl J Med. 1980 Jun 5;302(23):1269–1273. doi: 10.1056/NEJM198006053022301. [DOI] [PubMed] [Google Scholar]
  3. Camerini F., Alberti E., Klugmann S., Salvi A. Primary pulmonary hypertension: effects of nifedipine. Br Heart J. 1980 Sep;44(3):352–356. doi: 10.1136/hrt.44.3.352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chew C. Y., Hecht H. S., Collett J. T., McAllister R. G., Singh B. N. Influence of severity of ventricular dysfunction on hemodynamic responses to intravenously administered verapamil in ischemic heart disease. Am J Cardiol. 1981 Apr;47(4):917–922. doi: 10.1016/0002-9149(81)90194-6. [DOI] [PubMed] [Google Scholar]
  5. DRESDALE D. T., MICHTOM R. J., SCHULTZ M. Recent studies in primary pulmonary hypertension, including pharmacodynamic observations on pulmonary vascular resistance. Bull N Y Acad Med. 1954 Mar;30(3):195–207. [PMC free article] [PubMed] [Google Scholar]
  6. Davidson A., McMurtry I., Reeves J. T. Pulmonary vascular effects of verapamil. Am Heart J. 1978 Jun;95(6):810–811. doi: 10.1016/0002-8703(78)90515-x. [DOI] [PubMed] [Google Scholar]
  7. De Feyter P. J., Kerkkamp H. J., de Jong J. P. Sustained beneficial effect of nifedipine in primary pulmonary hypertension. Am Heart J. 1983 Feb;105(2):333–334. doi: 10.1016/0002-8703(83)90539-2. [DOI] [PubMed] [Google Scholar]
  8. Ellrodt G., Chew C. Y., Singh B. N. Therapeutic implications of slow-channel blockade in cardiocirculatory disorders. Circulation. 1980 Oct;62(4):669–679. doi: 10.1161/01.cir.62.4.669. [DOI] [PubMed] [Google Scholar]
  9. Fleckenstein A., Döring H. J., Kammermeier H. Einfluss von Beta-Receptorenblockern und verwandten Substanzen auf Erregung, Kontraktion und Energiestoffwechsel der Myokardfaser. Klin Wochenschr. 1968 Apr 1;46(7):343–351. doi: 10.1007/BF01734125. [DOI] [PubMed] [Google Scholar]
  10. Fleckenstein A. Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Annu Rev Pharmacol Toxicol. 1977;17:149–166. doi: 10.1146/annurev.pa.17.040177.001053. [DOI] [PubMed] [Google Scholar]
  11. Henry P. D. Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem. Am J Cardiol. 1980 Dec 1;46(6):1047–1058. doi: 10.1016/0002-9149(80)90366-5. [DOI] [PubMed] [Google Scholar]
  12. Johnson S. M., Mauritson D. R., Willerson J. T., Hillis L. D. A controlled trial of verapamil for Prinzmetal's variant angina. N Engl J Med. 1981 Apr 9;304(15):862–866. doi: 10.1056/NEJM198104093041502. [DOI] [PubMed] [Google Scholar]
  13. Kentera D., Susić D., Zdravković M. Effects of verapamil and aspirin on experimental chronic hypoxic pulmonary hypertension and right ventricular hypertrophy in rats. Respiration. 1979;37(4):192–196. doi: 10.1159/000194026. [DOI] [PubMed] [Google Scholar]
  14. Klinke W. P., Gilbert J. A. Diazoxide in primary pulmonary hypertension. N Engl J Med. 1980 Jan 10;302(2):91–92. doi: 10.1056/NEJM198001103020204. [DOI] [PubMed] [Google Scholar]
  15. LEE T. D., Jr, ROVETI G. C., ROSS R. S. The hemodynamic effects of isoproterenol on pulmonary hypertension in man. Am Heart J. 1963 Mar;65:361–367. doi: 10.1016/0002-8703(63)90011-5. [DOI] [PubMed] [Google Scholar]
  16. Landmark K., Refsum A. M., Simonsen S., Storstein O. Verapamil and pulmonary hypertension. Acta Med Scand. 1978;204(4):299–302. doi: 10.1111/j.0954-6820.1978.tb08443.x. [DOI] [PubMed] [Google Scholar]
  17. Malinow M. R. Regression of atherosclerosis in humans: fact or myth? Circulation. 1981 Jul;64(1):1–3. doi: 10.1161/01.cir.64.1.1. [DOI] [PubMed] [Google Scholar]
  18. McMurtry I. F., Davidson A. B., Reeves J. T., Grover R. F. Inhibition of hypoxic pulmonary vasoconstriction by calcium antagonists in isolated rat lungs. Circ Res. 1976 Feb;38(2):99–104. doi: 10.1161/01.res.38.2.99. [DOI] [PubMed] [Google Scholar]
  19. Packer M., Greenberg B., Massie B., Dash H. Deleterious effects of hydralazine in patients with pulmonary hypertension. N Engl J Med. 1982 Jun 3;306(22):1326–1331. doi: 10.1056/NEJM198206033062203. [DOI] [PubMed] [Google Scholar]
  20. Reeves J. T., Noonan J. A. Microarteriographic studies of primary pulmonary hypertension. A quantitative approach in two patients. Arch Pathol. 1973 Jan;95(1):50–55. [PubMed] [Google Scholar]
  21. Rich S., Martinez J., Lam W., Levy P. S., Rosen K. M. Reassessment of the effects of vasodilator drugs in primary pulmonary hypertension: guidelines for determining a pulmonary vasodilator response. Am Heart J. 1983 Jan;105(1):119–127. doi: 10.1016/0002-8703(83)90288-0. [DOI] [PubMed] [Google Scholar]
  22. Rodeheffer R. J., Rommer J. A., Wigley F., Smith C. R. Controlled double-blind trial of nifedipine in the treatment of Raynaud's phenomenon. N Engl J Med. 1983 Apr 14;308(15):880–883. doi: 10.1056/NEJM198304143081507. [DOI] [PubMed] [Google Scholar]
  23. Rubin L. J., Nicod P., Hillis L. D., Firth B. G. Treatment of primary pulmonary hypertension with nifedipine. A hemodynamic and scintigraphic evaluation. Ann Intern Med. 1983 Oct;99(4):433–438. doi: 10.7326/0003-4819-99-4-433. [DOI] [PubMed] [Google Scholar]
  24. Rubin L. J., Peter R. H. Oral hydralazine therapy for primary pulmonary hypertension. N Engl J Med. 1980 Jan 10;302(2):69–73. doi: 10.1056/NEJM198001103020201. [DOI] [PubMed] [Google Scholar]
  25. Rubino J. M., Schroeder J. S. Diazoxide in treatment of primary pulmonary hypertension. Br Heart J. 1979 Sep;42(3):362–363. doi: 10.1136/hrt.42.3.362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Saito D., Haraoka S., Yoshida H., Kusachi S., Yasuhara K., Nishihara M., Fukuhara J., Hagashima H. Primary pulmonary hypertension improved by long-term oral administration of nifedipine. Am Heart J. 1983 Jun;105(6):1041–1042. doi: 10.1016/0002-8703(83)90414-3. [DOI] [PubMed] [Google Scholar]
  27. Shettigar U. R., Hultgren H. N., Specter M., Martin R., Davies D. H. Primary pulmonary hypertension favorable effect of isoproterenol. N Engl J Med. 1976 Dec 16;295(25):1414–1415. doi: 10.1056/NEJM197612162952506. [DOI] [PubMed] [Google Scholar]
  28. Simonneau G., Escourrou P., Duroux P., Lockhart A. Inhibition of hypoxic pulmonary vasoconstriction by nifedipine. N Engl J Med. 1981 Jun 25;304(26):1582–1585. doi: 10.1056/NEJM198106253042606. [DOI] [PubMed] [Google Scholar]
  29. Terry R. W. Nifedipine therapy in angina pectoris: evaluation of safety and side effects. Am Heart J. 1982 Sep;104(3):681–689. doi: 10.1016/0002-8703(82)90256-3. [DOI] [PubMed] [Google Scholar]
  30. Wise J. R., Jr Nifedipine in the treatment of primary pulmonary hypertension. Am Heart J. 1983 Apr;105(4):693–694. doi: 10.1016/0002-8703(83)90500-8. [DOI] [PubMed] [Google Scholar]
  31. Young T. E., Lundquist L. J., Chesler E., Weir E. K. Comparative effects of nifedipine, verapamil, and diltiazem on experimental pulmonary hypertension. Am J Cardiol. 1983 Jan 1;51(1):195–200. doi: 10.1016/s0002-9149(83)80035-6. [DOI] [PubMed] [Google Scholar]

Articles from British Heart Journal are provided here courtesy of BMJ Publishing Group

RESOURCES