TRANSLATIONAL PHYSIOLOGY Effects of midodrine on exercise-induced hypotension and blood pressure recovery in autonomic failure

Schrage, William G., John H. Eisenach, Frank A. Dinenno, Shelly K. Roberts, Christopher P. Johnson, Paola Sandroni, Philip A. Low, and Michael J. Joyner. Effects of midodrine on exercise-induced hypotension and blood pressure recovery in autonomic failure. J Appl Physiol 97: 1978–1984, 2004. First published July 23, 2004; doi:10.1152/japplphysiol.00547.2004.—We tested the hypothesis that the oral 1-adrenergic agonist, midodrine, would limit the fall in arterial pressure observed during exercise in patients with pure autonomic failure (PAF). Fourteen subjects with PAF underwent a stand test, incremental supine cycling exercise (25, 50, and 75 W), and ischemic calf exercise, before (control) and 1 h after ingesting 10 mg midodrine. Heart rate (ECG), beat-to-beat blood pressure (MAP, arterial catheter), cardiac output (Q̇, open-circuit acetylene breathing), forearm blood flow (FBF, Doppler ultrasound), and calf blood flow (CBF, venous occlusion plethysmography) were measured. The fall in MAP after standing for 2 min was similar ( 60 mmHg; P 0.62). Supine MAP immediately before cycling was greater after midodrine (124 6 vs 117 6 mmHg; P 0.03), but cycling caused a workload-dependent hypotension (P 0.001), whereas increases in Q̇ were modest but similar. Midodrine increased MAP and total peripheral resistance (TPR) during exercise (P 0.04), but the exerciseinduced fall in MAP and TPR were similar during control and midodrine (P 0.27 and 0.14). FBF during cycling was not significantly reduced by midodrine (P 0.2). By contrast, recovery of MAP after cycling was faster (P 0.04) after midodrine ( 25 mmHg higher after 5 min). Ischemic calf exercise evoked similar peak CBF in both trials, but midodrine reduced the hyperemic response over 5 min of recovery (P 0.02). We conclude midodrine improves blood pressure and TPR during exercise and dramatically improves the recovery of MAP after exercise.