Adrenomedullin (ADM) is a vasoactive peptide hormone, mainly secreted by the endothelial cells and smooth muscles cells, surrounding the blood vessel. Adrenomedullin is a protective factor of vascular integrity that stabilizes the endothelial barrier and prevents vascular leakage. Adrenomedullin is also known as a relaxant factor that acts of vascular smooth muscles and regulates blood pressure by regulating blood vessel width.
Blood vessels integrity is impaired in a variety of severe medical condition such as sepsis and acute heart failure. Increased Adrenomedullin activity reflects the body’s attempt to restore integrity.
1. Vascular integrity is compromised in various acute pathologies e.g. in Acute Heart Failure or Sepsis
2. Increase in plasma ADM level is the acute response of the body to improve vascular integrity
3. However, excess interstitial ADM may lead to systemic vasodilation & acute circulatory failure (shock)
The only assay to measure the bioactive Adrenomedullin
Like most peptide hormones, Adrenomedullin is excised from a larger precursor molecule (prohormone). The resulting prohormone fragments are secreted into the bloodstream, but do not possess any biological activity. MR-proADM e.g. that is produced in a 1:1 ratio to immature Adrenomedullin (ADM) is used as a prognostic biomarker. However, only a certain amount (5-20%) of ADM is converted into biologically active Adrenomedullin (bio-ADM). Furthermore, in contrast to prohormone fragments, bio-ADM plasma levels change dynamically, in correspondence to the changing clinical status of the patient – making it possible to get timely information about the demand for decongestion in acute heart failure and for vasopressors in patients with risk of shock, e.g. in sepsis.
Only measurement of bio-ADM reflects the dynamically changing Adrenomedullin activity
bio-ADM – Marker for Acute Circulatory Failure (e.g. Septic Shock)
Blood vessel integrity is compromised in a variety of medical conditions, e.g. sepsis. The systemic inflammation-induced damage of the endothelial barrier leads to increased blood vessel permeability, reduced blood flow and finally to acute circulatory failure (Septic shock). Acute circulatory failure constitutes a medical emergency that is associated with high mortality. The earlier the patient receives adequate medical treatment (e.g. vasopressors) the higher the survival rate [Bai et al.]. Due to its dynamic nature, bio-ADM enables close monitoring of vasopressor therapy.
bio-ADM plasma levels are elevated above normal 1-2 days before the onset of shock, reflecting the body’s early response to the beginning loss of integrity.
bio-ADM – Marker for Congestion in Acute Heart Failure
Shortness of breath is one of the most common symptoms of Acute Heart Failure. Due to the low pump efficacy, the blood backs up into the blood vessels. This increases the pressure on blood vessel walls and leads to leakage of fluid into lungs and tissues (Congestion).
“bio-ADM reflects the severity of congestion by reflecting the body’s actual demand to improve vascular integrity.”