Abstract
To obtain multiple dose-response haemodynamic and radionuclide data on i.v. diltiazem, 12 ischaemic patients were studied during routine catheterization. At rest, following a 20 min stable control period, the effects of four doses (0.0625, 0.0625, 0.125 and 0.25 mg kg-1 diltiazem at 5 min intervals) were measured in the 3-5 min following i.v. injection. The exercise effects of the cumulative 0.5 mg kg-1 dosage were assessed by comparing a control and post drug period of supine bicycle exercise. The increase in plasma diltiazem levels correlated linearly with the administered dose and achieved therapeutic levels. There were significant dose-related reductions in systemic arterial blood pressure and vascular resistance index; the heart rate fell and cardiac stroke index increased. The calculated double-product (heart rate X systolic blood pressure) was significantly reduced. The left ventricular filling pressures, ejection fraction and cardiac volumes were unaltered. During supine bicycle exercise, the systemic diastolic blood pressure, heart rate and calculated double-product were reduced without change in other parameters. Over the dose range 0.0625-0.5 mg kg-1, diltiazem acutely increased cardiac stroke index and reduced resting heart rate. These haemodynamic data, taken together with its described coronary vasodilator activity suggest that its role in acute vasospastic angina and during angiographic procedures ought to be explored further.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arnman K., Rydén L. Comparison of metoprolol and verapamil in the treatment of angina pectoris. Am J Cardiol. 1982 Mar;49(4):821–827. doi: 10.1016/0002-9149(82)91964-6. [DOI] [PubMed] [Google Scholar]
- Atterhög J. H., Ekelund L. G., Melin A. L. Effect of nifedipine on exercise tolerance in patients with angina pectoris. Eur J Clin Pharmacol. 1975 Feb 28;8(2):125–130. doi: 10.1007/BF00561561. [DOI] [PubMed] [Google Scholar]
- Bacharach S. L., Green M. V., Borer J. S., Ostrow H. G., Redwood D. R., Johnston G. S. ECG-gated scintillation probe measurement of left ventricular function. J Nucl Med. 1977 Dec;18(12):1176–1183. [PubMed] [Google Scholar]
- Berger H. J., Davies R. A., Batsford W. P., Hoffer P. B., Gottschalk A., Zaret B. L. Beat-to-beat left ventricular performance assessed from the equilibrium cardiac blood pool using a computerized nuclear probe. Circulation. 1981 Jan;63(1):133–142. doi: 10.1161/01.cir.63.1.133. [DOI] [PubMed] [Google Scholar]
- Bertrand M. E., Dupuis B. A., Lablanche J. M., Tilmant P. Y., Thieuleux F. A. Coronary hemodynamics following intravenous or intracoronary injection of diltiazem in man. J Cardiovasc Pharmacol. 1982 Sep-Oct;4(5):695–699. doi: 10.1097/00005344-198209000-00001. [DOI] [PubMed] [Google Scholar]
- Bourassa M. G., Cote P., Theroux P., Tubau J. F., Genain C., Waters D. D. Hemodynamics and coronary flow following diltiazem administration in anesthetized dogs and in humans. Chest. 1980 Jul;78(1 Suppl):224–230. doi: 10.1378/chest.78.1_supplement.224. [DOI] [PubMed] [Google Scholar]
- Dargie H., Rowland E., Krikler D. Role of calcium antagonists in cardiovascular therapy. Br Heart J. 1981 Jul;46(1):8–16. doi: 10.1136/hrt.46.1.8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Feild B. J., Russell R. O., Jr, Dowling J. T., Rackley C. E. Regional left ventricular performance in the year following myocardial infarction. Circulation. 1972 Oct;46(4):679–689. doi: 10.1161/01.cir.46.4.679. [DOI] [PubMed] [Google Scholar]
- Forrester J. S., Ganz W., Diamond G., McHugh T., Chonette D. W., Swan H. J. Thermodilution cardiac output determination with a single flow-directed catheter. Am Heart J. 1972 Mar;83(3):306–311. doi: 10.1016/0002-8703(72)90429-2. [DOI] [PubMed] [Google Scholar]
- Franklin D., Millard R. W., Nagao T. Responses of coronary collateral flow and dependent myocardial mechanical function to the calcium antagonist, diltiazem. Chest. 1980 Jul;78(1 Suppl):200–204. doi: 10.1378/chest.78.1.200. [DOI] [PubMed] [Google Scholar]
- Hermann P., Morselli P. L. Pharmacokinetics of diltiazem and other calcium entry blockers. Acta Pharmacol Toxicol (Copenh) 1985;57 (Suppl 2):10–20. doi: 10.1111/j.1600-0773.1985.tb03570.x. [DOI] [PubMed] [Google Scholar]
- Hoel B. L. Some aspects of the clinical use of thermodilution in measuring cardiac output. With particular reference to the Swan-Ganz thermodilution catheters. Scand J Clin Lab Invest. 1978 Jun;38(4):383–388. doi: 10.3109/00365517809108438. [DOI] [PubMed] [Google Scholar]
- Hossack K. F., Bruce R. A. Improved exercise performance in persons with stable angina pectoris receiving diltiazem. Am J Cardiol. 1981 Jan;47(1):95–101. doi: 10.1016/0002-9149(81)90296-4. [DOI] [PubMed] [Google Scholar]
- Hossack K. F., Bruce R. A., Ritterman J. B., Kusumi F., Trimble S. Divergent effects of diltiazem in patients with exertional angina. Am J Cardiol. 1982 Feb 18;49(3):538–546. doi: 10.1016/s0002-9149(82)80009-x. [DOI] [PubMed] [Google Scholar]
- Joyal M., Pieper J., Cremer K., Feldman R. L., Pepine C. J. Pharmacodynamic aspects of intravenous diltiazem administration. Am Heart J. 1986 Jan;111(1):54–61. doi: 10.1016/0002-8703(86)90553-3. [DOI] [PubMed] [Google Scholar]
- Kawai C., Konishi T., Matsuyama E., Okazaki H. Comparative effects of three calcium antagonists, diltiazem, verapamil and nifedipine, on the sinoatrial and atrioventricular nodes. Experimental and clinical studies. Circulation. 1981 May;63(5):1035–1042. doi: 10.1161/01.cir.63.5.1035. [DOI] [PubMed] [Google Scholar]
- Kieval J., Myerburg R. J. The hemodynamic effects of calcium channel blocking agents: a brief review. Angiology. 1982 Aug;33(8):516–521. doi: 10.1177/000331978203300803. [DOI] [PubMed] [Google Scholar]
- Kimura E., Kishida H. Treatment of variant angina with drugs: a survey of 11 cardiology institutes in Japan. Circulation. 1981 Apr;63(4):844–848. doi: 10.1161/01.cir.63.4.844. [DOI] [PubMed] [Google Scholar]
- Lahiri A., Bowles M. J., Jones R. I., Crawley J. C., Raftery E. B. Assessment of left ventricular function in coronary artery disease with the nuclear probe during intervention studies. Br Heart J. 1984 Oct;52(4):422–430. doi: 10.1136/hrt.52.4.422. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Legrand V., Hastir F., Vandormael M., Collignon P., Kulbertus H. E. Haemodynamic effects of intravenous diltiazem at rest and exercise in patients with coronary artery disease. Eur Heart J. 1984 Jun;5(6):456–463. doi: 10.1093/oxfordjournals.eurheartj.a061691. [DOI] [PubMed] [Google Scholar]
- Links J. M., Becker L. C., Shindledecker J. G., Guzman P., Burow R. D., Nickoloff E. L., Alderson P. O., Wagner H. N. Measurement of absolute left ventricular volume from gated blood pool studies. Circulation. 1982 Jan;65(1):82–91. doi: 10.1161/01.cir.65.1.82. [DOI] [PubMed] [Google Scholar]
- McKay R. G., Aroesty J. M., Heller G. V., Royal H., Parker J. A., Silverman K. J., Kolodny G. M., Grossman W. Left ventricular pressure-volume diagrams and end-systolic pressure-volume relations in human beings. J Am Coll Cardiol. 1984 Feb;3(2 Pt 1):301–312. doi: 10.1016/s0735-1097(84)80013-3. [DOI] [PubMed] [Google Scholar]
- Nelson G. I., Silke B., Ahuja R. C., Hussain M., Forsyth D., Taylor S. H. The effect on left ventricular performance of nifedipine and metoprolol singly and together in exercise-induced angina pectoris. Eur Heart J. 1984 Jan;5(1):67–79. doi: 10.1093/oxfordjournals.eurheartj.a061554. [DOI] [PubMed] [Google Scholar]
- Petru M. A., Crawford M. H., Sorensen S. G., Chaudhuri T. K., Levine S., O'Rourke R. A. Short- and long-term efficacy of high-dose oral diltiazem for angina due to coronary artery disease: a placebo-controlled, randomized, double-blind crossover study. Circulation. 1983 Jul;68(1):139–147. doi: 10.1161/01.cir.68.1.139. [DOI] [PubMed] [Google Scholar]
- Rackley C. E., Dear H. D., Baxley W. A., Jones W. B., Dodge H. T. Left ventricular chamber volume, mass, and function in severe coronary artery disease. Circulation. 1970 Apr;41(4):605–613. doi: 10.1161/01.cir.41.4.605. [DOI] [PubMed] [Google Scholar]
- Rovel V., Mitchard M., Morselli P. L. Simple sensitive and specific gas chromatographic method for the quantification of diltiazem human body fluids. J Chromatogr. 1977 Aug 11;138(2):391–398. doi: 10.1016/s0021-9673(00)94974-4. [DOI] [PubMed] [Google Scholar]
- Schroeder J. S., Lamb I. H., Ginsburg R., Bristow M. R., Hung J. Diltiazem for long-term therapy of coronary arterial spasm. Am J Cardiol. 1982 Feb 18;49(3):533–537. doi: 10.1016/s0002-9149(82)80008-8. [DOI] [PubMed] [Google Scholar]
- Silke B., Frais M. A., Muller P., Verma S. P., Reynolds G., Taylor S. H. Haemodynamic dose-response effects of intravenous nisoldipine in coronary artery disease. Br J Clin Pharmacol. 1985 Dec;20(6):675–680. doi: 10.1111/j.1365-2125.1985.tb05127.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Silke B., Verma S. P., Ahuja R. C., Nelson G. I., Hussain M., Taylor S. H. Haemodynamic dose-response effects of i.v. verapamil in coronary artery disease. Herz. 1984 Dec;9(6):353–361. [PubMed] [Google Scholar]
- Silke B., Verma S. P., Nelson G. I., Hussain M., Taylor S. H. Haemodynamic dose-response effects of i.v. nicardipine in coronary artery disease. Br J Clin Pharmacol. 1984 Nov;18(5):717–724. doi: 10.1111/j.1365-2125.1984.tb02534.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Singh B. N. Pharmacological basis for the therapeutic applications of slow-channel blocking drugs. Angiology. 1982 Aug;33(8):492–515. doi: 10.1177/000331978203300802. [DOI] [PubMed] [Google Scholar]
- Sorensen M. B., Bille-Brahe N. E., Engell H. C. Cardiac output measurement by thermal dilution: reproducibility and comparison with the dye-dilution technique. Ann Surg. 1976 Jan;183(1):67–72. doi: 10.1097/00000658-197601000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stone P. H., Antman E. M., Muller J. E., Braunwald E. Calcium channel blocking agents in the treatment of cardiovascular disorders. Part II: Hemodynamic effects and clinical applications. Ann Intern Med. 1980 Dec;93(6):886–904. doi: 10.7326/0003-4819-93-6-886. [DOI] [PubMed] [Google Scholar]
- Strashun A., Horowitz S. F., Goldsmith S. J., Teichholz L. E., Dicker A., Miceli K., Gorlin R. Noninvasive detection of left ventricular dysfunction with a portable electrocardiographic gated scintillation probe device. Am J Cardiol. 1981 Mar;47(3):610–617. doi: 10.1016/0002-9149(81)90545-2. [DOI] [PubMed] [Google Scholar]
- Wagner H. N., Jr The nuclear cardiac probe. Hosp Pract (Hosp Ed) 1982 Apr;17(4):163-5, 169-77. doi: 10.1080/21548331.1982.11698063. [DOI] [PubMed] [Google Scholar]
- Weiner D. A., McCabe C. H., Cutler S. S., Creager M. A., Ryan T. J., Klein M. D. Efficacy and safety of verapamil in patients with angina pectoris after 1 year of continuous, high-dose therapy. Am J Cardiol. 1983 May 1;51(8):1251–1255. doi: 10.1016/0002-9149(83)90294-1. [DOI] [PubMed] [Google Scholar]