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Hemodynamics effects of adrecizumab in sepsis rat
Intensive Care Medicine Experimental volume 3, Article number: A618 (2015)
Introduction
Sepsis and septic shock still represent major health issues, with persisting high morbidity and mortality rates in critically ill patients. Cardiac dysfunction[1] occurs frequently during severe sepsis.
Adrenomedullin (ADM) has been identified as a key mediator in vascular tone regulation[1]. A newly developed anti-ADM antibody Adrecizumab (ADZ) may improve hemodynamic dysfunction during resuscitated murine, cecal ligation and puncture (CLP)-induced septic shock[2].
Objectives
To determine the beneficial role of ADZ on hemodynamic impairment in a rat model of acute sepsis.
Methods
For induction of polymicrobial sepsis, cecal ligation and puncture (CLP)[3] was performed in Wistar male rats. ADZ (2 mg/kg) was injected IV 24 h after the surgery. There were 7 animals per group. Invasive blood pressure and cardiac function (by echocardiography) were assessed until 2 hours after ADZ injection. Statistical analysis was performed with 2 ways ANOVA.
Results
Septic rats had lower mean arterial pressure (MAP) (p < 0.0001) 24 h after surgery (at baseline) compared to sham. Septic animas with ADZ had a trend to have a greater MAP. A transient decrease of SF was observed 15 min and 1 h after injection of ADZ (p = 0.05). On the other hand cardiac output seems to be increased by ADZ (p = 0.61).
Conclusions
During sepsis in rats, treatment by ADZ seems to have a beneficial effect on cardiac and vascular dysfunction. These preliminary results need to be confirmed in preclinical and clinical studies.
Grant Acknowledgment
Adrenomed
References
Nishio K, et al: Critical Care Medicine. 1997, 25 (6): 953-7. 10.1097/00003246-199706000-00010.
Struck , et al: Intensive Care Med Expe. 2013, 1: 3-10.1186/2197-425X-1-3.
Rittirsch , et al: Nature Protocols. 2009, 4: 31-36. n°1
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Blet, A., Sadoune, M., Polidano, E. et al. Hemodynamics effects of adrecizumab in sepsis rat. ICMx 3 (Suppl 1), A618 (2015). https://doi.org/10.1186/2197-425X-3-S1-A618
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DOI: https://doi.org/10.1186/2197-425X-3-S1-A618