JOURNAL ARTICLE

Effects of the Non-Neutralizing Humanized Monoclonal Anti-Adrenomedullin Antibody Adrecizumab on Hemodynamic and Renal Injury in a Porcine Two-Hit Model

Christoph Thiele, Tim-Philipp Simon, Jeanine Szymanski, Christoph Daniel, Christos Golias, Oliver Hartmann, Joachim Struck, Lukas Martin, Gernot Marx, Tobias Schuerholz
Shock 2020 June 9
32554994
Adrenomedullin is a vasoactive peptide that improves endothelial barrier function in sepsis, but may also cause hypotension and organ failure. Treatment with a non-neutralizing monoclonal anti-adrenomedullin antibody showed improvement in murine sepsis models. We tested the effects of the humanized monoclonal anti-adrenomedullin antibody Adrecizumab in a porcine two hit model of hemorrhagic and septic shock.In this randomized, blinded study 12 German Landrace pigs were bled to half of baseline mean arterial pressure for 45 minutes. Sepsis was induced using an E.coli clot placed into the abdominal cavity 6 hours after hemorrhagic shock. Animals received either 2 mg/kg BW anti-adrenomedullin antibody or vehicle solution immediately after sepsis induction. After 4 hours, resuscitation was initiated using balanced crystalloids and noradrenalin to maintain a CVP of 8-12 mmHg, a MAP ≥ 65mmHg and a ScvO2 ≥70% for another 8 hours. Hemodynamic parameters, laboratory parameters and kidney histology were assessed.The amount of volume resuscitation was significantly lower and significantly less animals developed a septic shock in the antibody-treated group, compared to the vehicle group. Kidney histology showed significantly lower granulocytes in both cortex and medulla in antibody-treated animals, while the remaining four kidney measures (serum creatinine and urine output and cortical and medullary injury in histopathology) did not reach the significance levels. After induction of sepsis, plasma adrenomedullin increased immediately in both groups, but increased quicker and more pronounced in the antibody group.In this two hit shock model, treatment with an anti-adrenomedullin antibody significantly increased plasma adrenomedullin levels, while significantly less animals developed septic shock and renal granulocyte extravasation was significantly reduced. Thus, therapy with Adrecizumab may provide benefit in sepsis, and clinical investigation of this drug candidate is warranted.

Full Text Links

We have located links that may give you full text access.

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
32554994
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"