(1394) Early Low-Dose Norepinephrine Protects Against Post-CPR Neurogenic Injury After Experimental SAH

Introduction: Subarachnoid hemorrhage (SAH) can cause acute devastating systemic complications such as neurogenic pulmonary edema and Takotsubo cardiomyopathy. Early administration of low dose norepinephrine (NE), which has shown to be beneficial to organ dysfunction during hypotensive resuscitation in sepsis, may also be effective to critical situation at early stage after severe SAH. The aim of this study was to determine the role of early low dose NE for the prevention of brain and systemic injuries after experimental SAH-induced cardiopulmonary arrest.

Methods: Male C57BL/6 mice (n=24/group) were subjected to severe SAH by endovascular filament perforation, followed by induction of immediate cardiopulmonary arrest. After successful CPR (～5 min until spontaneous breathing recovered), NE infusion at a dose of 0.1 µg/kg/min to a maximal of 0.3 µg/kg/min or its vehicle (control) was started to achieve and maintain MAP at ≥60 mmHg for 1h. Serial analyses of stroke volume, cardiac output and cerebral blood volume (as assessed by 3D-reconstructed % vascularity of the brain), and pulmonary edema were performed by 3D high frequency Power Doppler and micro-CT imaging instruments. Acute cerebral infarction (CI) were assessed by a MRI scanner at 24h. Survival rate until 72h and microstructure of lung endothelial glycocalyx and its systemic biomarker syndecan-1 were measured.

Results: Early NE treated mice showed a better recovery from cerebral and cardiac depression than control after 3h of SAH onset. In both groups, lung edema was similarly observed in half of the animals at 12h; however, it disappeared significantly (P < 0.05) in mice treated with NE than control after 72h. The number of CT-evidenced lung edema was smaller in NE, which was confirmed by disrupted endothelial glycocalyx layer and increased plasma syndecan-1. The number of CI and survival rate were smaller in the NE treated group (P < 0.05).

Conclusions: Early administration of low dose NE during hypotensive resuscitation is suitable for critical treatment of SAH-induced cardiopulmonary arrest. Early initiation of NE, as a new approach, should be assessed detailed regarding the pathophysiology of the neurogenic dysfunctions in SAH.