Therapy and Prevention Pharmacology

In a placebo-controlled, randomized, cross-over, double-blind study of 12 patients with stable exertional angina, we measured at rest and during bicycle exercise the effects of 20 mg of nifedipine administered sublingually on hemodynamics and systemic and regional oxygen extraction and metabolism. Nifedipine decreased systemic vascular resistance by 38% at rest (p < .001) and by 28% during exercise (p < .001). Cardiac output increased from 4.6 ± 0.6 to 6.0 0.9 liters/min (p < .001) at rest after nifedipine and from 10.6 3.7 to 11.8 + 3.4 liters/min (p < .005) during exercise. After nifedipine, the arterial-mixed venous 02 content difference decreased from 4.7 ± 0.6 to 3.5 + 0.5 ml/100 ml (p < .001) at rest and from 10.5 ± 1.7 to 8.8 ± 1.6 ml/100 ml (p < .001) during exercise. After nifedipine the arterial-iliac venous 02 content difference also decreased at rest, from 5.9 + 1.5 to 4.8 ± 1.7 ml/100 ml (p = .06) but increased during exercise from 13.1 1.5 to 14.0 1.8 ml/100 ml (p < .05). Oxygen consumption was not significantly altered at rest or during exercise. Nifedipine decreased mixed venous carbon dioxide tension (PCo2) during exercise from 53 ± 3.5 to 50 + 4.0 mm Hg (p < .05) but increased iliac venous Pco2 slightly from 61 ± 4.6 to 63 ± 5.2 mm Hg (p < .01). Exercise pH was not significantly altered, but arterial lactate increased more after nifedipine (2.65 ± 1.95 mmol/liter placebo, 3.54 + 2.74 mmol/liter nifedipine; p < .05). Thus nifedipine produces similar changes in 02 extraction in mixed venous and iliac venous blood at rest but directionally opposite changes during exercise. The data support the hypothesis that nifedipine does not alter the distribution of cardiac output to the legs at rest, but during dynamic leg exercise reduces the redistribution of cardiac output to the legs. This probably results from the shunting of blood flow away from exercising muscles by the generalized vasodilatation of nifedipine. Circulation 71, No. 4, 787-796, 1985. NIFEDIPINE, a calcium blocker, is a potent arteriolar vasodilator that is effective in the treatment of exertionall' and vasospastic5 angina. Investigations of its potential use as an afterload-reducing agent in patients with cardiac failure have recently been reported.68 At rest it decreases systemic vascular resistance and arterial pressure and reflexly increases heart rate and cardiac output.9-12 Regional blood flow to the legs and splanchnic organs increases."3-15 However, the important effect of nifedipine on regional blood flow to working muscles during dynamic exercise has not been described. From the Hallstrom Institute of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia. * Supported by grants from the National Heart Foundation and the Postgraduate Committee of the University of Sydney. Address for correspondence: David T. Kelly, M.B., Hallstrom Institute of Cardiology, Royal Prince Alfred Hospital, Camperdown, N.S.W. 2050, Australia. Received Sept. 17, 1984; revision accepted Dec. 27, 1984. During dynamic exercise the increase in cardiac output is accompanied by local vasodilatation in the exercising muscles and reflex vasoconstriction in nonexercising muscles and other vascular beds. This important adaptation diverts a much larger proportion of the cardiac output to the active muscles.'6 Nifedipine produces systemic vasodilatation during exercise beyond that occurring physiologically, so that systemic vascular resistance falls further and arterial pressure increases less."' Heart rate and cardiac output increase more.""'2 It is possible that nifedipine, by dilating the vascular beds that normally vasoconstrict during exercise, may reduce the normal redistribution of cardiac output to exercising muscles. Although the concept of such a steal phenomenon is not new,'7 objective data during exercise in man are few, and these effects of nifedipine have not been previously reported. In a previous study of 15 patients with stable exerVol. 71, No. 4, April 1985 787 by gest on A uust 4, 2017 http://ciajournals.org/ D ow nladed from