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Hemodynamics effects of adrecizumab in sepsis rat
Intensive Care Medicine Experimental volume 3, Article number: A618 (2015)
Sepsis and septic shock still represent major health issues, with persisting high morbidity and mortality rates in critically ill patients. Cardiac dysfunction occurs frequently during severe sepsis.
Adrenomedullin (ADM) has been identified as a key mediator in vascular tone regulation. A newly developed anti-ADM antibody Adrecizumab (ADZ) may improve hemodynamic dysfunction during resuscitated murine, cecal ligation and puncture (CLP)-induced septic shock.
To determine the beneficial role of ADZ on hemodynamic impairment in a rat model of acute sepsis.
For induction of polymicrobial sepsis, cecal ligation and puncture (CLP) 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.
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).
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.
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