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Volume 3 Supplement 1

ESICM LIVES 2015

Hemodynamics effects of adrecizumab in sepsis rat

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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.

Figure 1
figure1

[Mean arterial pressure]

Grant Acknowledgment

Adrenomed

References

  1. 1.

    Nishio K, et al: Critical Care Medicine. 1997, 25 (6): 953-7. 10.1097/00003246-199706000-00010.

  2. 2.

    Struck , et al: Intensive Care Med Expe. 2013, 1: 3-10.1186/2197-425X-1-3.

  3. 3.

    Rittirsch , et al: Nature Protocols. 2009, 4: 31-36. n°1

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Author information

Correspondence to A Blet.

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Keywords

  • Septic Shock
  • Severe Sepsis
  • Mean Arterial Pressure
  • Hemodynamic Effect
  • Vascular Dysfunction