Modulation of plasma adrenomedullin by epinephrine infusion during head up tilt

Abstract

We investigated whether head up tilt (HUT) with and without simultaneous epinephrine infusion modulate plasma adrenomedullin. We studied eight healthy male volunteers, using two 5 min 70° HUT trials: control (saline infusion) and intervention (epinephrine infusion, titrated to a dose which increased supine systolic pressure by 20% above resting values). Protocols were randomized and separated by 2 weeks. Cardiac function and systolic time intervals, recorded using a phonocardiograph microphone, included left ventricular ejection time (LVET), pre-ejection period (PEP), PEP/LVET and electromechanical systole (QS2). Compared to saline infusion, epinephrine increased supine adrenomedullin (3.2 ± 0.8 pmol/l, i.e., mean ± SEM, respectively), heart rate (HR) (+11.3 ± 2.6 bpm), systolic pressure (+18.4 ± 2.6 mmHg) but decreased supine LVET, LVET corrected for HR (LVETi) and QS2-time (all p = 0.004). Despite similar HUT induced thoracic fluid shifts, reflected by similar thoracic impedance changes, HUT-induced adrenomedullin increases were minimal in epinephrine-supplemented men in comparison to controls (+8% vs. 42%). During HUT, epinephrine infusion decreased only the LVET (p = 0.039). Our findings confirm that short-term HUT increases plasma adrenomedullin. They further suggest that with increased supine epinephrine levels (epinephrine infusion clamping systolic arterial pressure at 120% control level), supine cardiac performance rises to a level similar to that during HUT, while adrenomedullin is still elevated with HUT. This might be in accordance with a ‘dampening’ role of adrenomedullin during catecholaminergic cardiovascular stimulation. As epinephrine is used as a drug to treat cardiac arrest and ventricular arrhythmias, our results may have important clinical/emergency resuscitation applications.