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.

Influence of bed rest on plasma galanin and adrenomedullin at presyncope

“…This is in contrast to our previous findings [4,21] in which significant rises in adrenomedullin levels were demonstrated using only HUT to simulate orthostatic challenge. This is in contrast to our previous findings [4,21] in which significant rises in adrenomedullin levels were demonstrated using only HUT to simulate orthostatic challenge.…”

The Relationships Between Plasma Adrenomedullin and Endothelin-1 Concentrations and Doppler Echocardiographic Indices of Left Ventricular Function During Static Exercise in Healthy Men

“…Rat studies showed that NA increases ADM production and secretion from endothelial cells by stimulation of protein kinase C through the alpha-1 receptors and cAMP through beta receptors (Isumi et al, 1998). In a study conducted by Roessler et al (2011) a marked increase in plasma ADM concentration was observed after A infusion during head up tilt in humans. However, we found no significant correlation between plasma A and ADM levels.…”

1H NMR-metabolomics: Can they be a useful tool in our understanding of cardiac arrest?

“…6 In addition, the activated platelets release 5-hydroxytryptamine and the expression of cyclooxygenase-2 is induced, enhancing the contractile response and the development of intracellular acidosis which increases the concentration of inorganic phosphate, pyruvate, hydrogen ions, and lactate. 4 Furthermore, the ROS-mediated damage of the fatty acids of membrane phospholipids increases cell membrane permeability, diminishing the concentration of intracellular K + and Mg 2+ and increases that of Na + and Ca 2+ which together with the depletion of adenosine triphosphate (ATP) and the increased oxidative stress form the mitochondrial permeability transition pore (MTP). 4,7 Of note, the mitochondrial metabolism is impaired and free fatty acids, long-chain acyl CoA, and acylcarnitine accumulate and are incorporated into membranes impairing their function.…”

“…Interestingly, the adrenal blood flow further worsens due to microvessel contraction, a phenomenon which is partly mediated by adrenomedullin. 4 At the same time, various cytokines, complement components, and other molecules are synthesized and released in response to global hypoxia, such as tumor necrosis factor-a (TNF-a), interleukin 1b (IL-1b), C3, C4, C5, C5b-9, P-selectin, and intercellular adhesion molecule-1, and reactive oxygen species (ROS) are released from activated polymorphonuclear leukocytes (PMN). 3 The cellular response to hypoxia is coordinated by the hypoxia-inducible factor (HIF) and its regulator, the Von Hippel-Lindau tumor suppressor protein.…”