Abstract 19371: Potential Neuroprotective Effect of Serelaxin During Hypoxia in a Sheep Model
Introduction: It is well established that the intravenous administration of a recombinant human relaxin-2 (Serelaxin®, Novartis Pharma, Basel, Switzerland) modulates the endothelial vasodilator function and increase the cortical blood flow.
Hypothesis: Serelaxin may be neuroprotective during an severe haemorrhage.
Methods: Vasal catheters were inserted in 17 female sheep under general isoflurane anesthesia. 6 animals received an intravenous injection of 30 μg/kg Serelaxin (SH), 6 animals served as a control group (CH), 5 animals are control non haemorrhage group (NH). Controlled haemorrhage was induced by withdrawing 50% of the estimated total blood volume (7% of total body weight) over 20 minutes, follow to 20 minutes in a state interval and recovered the anticoagulated and normothermic blood over 20 minutes. Over the time monitored vital parameters. Cerebral liquor was collected at the beginning and the end of the experiment for standard clinical laboratory measurements of S100B and NSE (neuron-specific enolase) levels. Formalin fixed samples were collected from the frontal cortex. Furthermore, paraffin-embedded tissue sections were stained with antibodies against markers for neurons (NeuN) and astrocytes (S100B) using antigen retrieval and indirect immunofluorescence, the intensities (grey values) were estimated using the ImageJ2.0 software.
Results: In the CH concentration of S100 increased from 58±35 (all data in mean ± standard deviation) to 156±127 μg/l (p<0.05) and NSE increased from 7±5 to 13±23 ng/ml (p>0.07). In the SH S100 decreased from 59±4 to 23±16 μg/l (p<0.06) while the NSE decreased from 5±5 to 1±0.5 ng/ml, p=0.07). We found significant reductions of the neuroprotein levels of S100 after the hypovolemia in the SH compared to the CH (p<0.02) and no significant differences for NSE (p>0.07). Preliminary analyses of neuronal (NeuN) and glial (S100B) marker levels in the histological sections did not reveal differences between the SH, CH and NH.
Conclusions: Our findings support that Serelaxin can have a neuroprotective effect during hypovolemia in a sheep model. Further experiments, in particular long-term follow-up studies, are required to validate this notion at the molecular and structural level.
Author Disclosures: S.J. Bischoff: None. M. Schmidt: None. A. Irintchev: None. C. Kletta: None. T. Lehmann: None. M. Schwab: None. G. Matziolis: None. R. Schiffner: Other Research Support; Modest; Novartis Pharma GmbH.
- © 2016 by American Heart Association, Inc.