The Effects of Urapidil Therapy on Hemodynamics and Gas Exchange in Exercising Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension

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Abstract
To examine the hemodynamic changes induced by vasodilator therapy with urapidil during exercise in patients with chronic obstructive pulmonary disease (COPD) and their potential impact on symptom-limited maximal oxygen consumption, we studied 12 clinically stable patients using a randomized, crossover design. Placebo or urapidil (60 mg orally thrice a day) was given during 48 h preceding each incremental maximal exercise testing. Urapidil compared to placebo consistently lowered the pulmonary artery pressure either at rest from 29 .+-. 2.5 to 24 .+-. 1.5 mm Hg (p < 0.001) or during exercise from 55 .+-. 3 to 46 .+-. 2 mm Hg (p < 0.01). At rest, the systemic arterial pressure was reduced from 97.5 .+-. 4 to 88.5 .+-. 3 mm Hg (p < 0.001) with no significant difference in heart rate or cardiac index. During exercise, systemic arterial pressure decreased from 135 .+-. 4 to 119 .+-. 3 mm Hg (p < 0.001). As compared to placebo, urapidil tended to increase the cardiac index from 6.1 .+-. 0.4 to 6.6 .+-. 0.4 L/min .cntdot. m2 (NS) and to decrease heart rate, from 122 to 116 beats/min (NS); the resulting stroke volume index increased with urapidil from 49 .+-. 3 to 57 .+-. 4 ml/m2 (p < 0.01); at rest, urapidil did not induce alteration in gas exchange, while during exercise, C(a -v)O2 decreased from 8.6 .+-. 0.5 to 7.7 .+-. 0.4 vol% (p < 0.01), SVO2 increased from 39.5 .+-. 2 to 44.5 .+-. 1.5% (p < 0.01), and SaO2 from 82 .+-. 2 to 85 .+-. 2% (p < 0.03). Arterial lactates were lower during exercise with urapidil (2.2 .+-. 0.2 versus 3 .+-. 0.2 mmol/L, p < 0.01), and the ph were less acidotic (7.36 .+-. 0.01 versus 7.34 .+-. 0.01, p < 0.01). Decreased lactate concentration under urapidil appeared unrelated to the changes in cardiac output. Only 4 of the 12 patients slightly increased their workload capacity. There was no change in symptom-limited maximal oxygen consumption(506 .+-. 36 with urapidil versus 500 .+-. 37 ml/min 7. m2 with placebo, NS). We conclude that short-term therapy with urapidil consistently pulmonary hemodynamics and gas exchange in exercising patients with COPD but did not increase their exercise performance.