Association between Mild‐Hyponatremia with Sustained Increased Intracranial Pressure in a New Animal Model and Assessment of the Effect of dDVAP during Severe Water Intoxication
Authors: Bordoni Luca , Gutierrez Eugenio , Østergaard Leif , Frische Sebastian 
Published: June 2021

Introduction

Brain Edema (BE) has been studied in animals using water intoxication (WI). Classical models of WI involve the infusion of 10–20% body weight (BW) distilled water. This induces severe hyponatremia and dramatic pathology (brain stem herniation and death) due to very elevated intracranial pressure (ICP). Several studies coupled WI with the administration of antidiuretics as desmopressin (dDAVP).

Aims of the study

To establish a mouse model of mild‐WI which enable studies of sustained increased ICP and to evaluate the effect of dDAVP in a classical model of BE by severe WI

Methods

Six groups of mice (n=6) (C57Bl/6) were anesthetized with isoflurane. Severe WI‐groups received distilled water (20% BW), either with or without dDAVP (0.4 μg/kg) by IP injection. Sham‐groups received no water load with or without dDAVP. A last group (mild‐WI) received 10% BW of a 36.25 mM Na+ solution. During the WI protocols, we measured ICP, cerebral perfusion pressure (CPP), Mean arterial pressure (MAP), heart rate (HR), end‐tidal CO2 (EtCO2), pH, blood gasses, and urine production.

Results

A drastic increase in ICP was observed during severe WI (maximum value: 84.7 ± 12.3 mmHg at 23 ± 2.9 min). CPP significantly dropped 8 min. after severe WI and was 0.9 ± 2.0 mmHg 26 min after WI. MAP showed a reproducible pattern of hypertension / peak / drop / in all severe WI animals. dDAVP admnistration significantly anticipated time to peak of MAP (2.9 ± 1.1 min, p=0.036). Brain stem herniation occurred 30 min. from WI in all animals. Plasma ions (mmol/L) were significantly decreased in all severe groups early (5 min) after WI (Na+=128 ± 1.4) and metabolic acidosis developed (pH= 7.34 ± 0.03) (HCO3−:19 ± 0.5). Urine production dropped after WI without any significant effect of dDAVP (0.0035 ± 0.0012 μl*min−1*g−1 ‐dDAVP vs 0.00705 ± 0.006 μl*min−1*g−1 for +dDAVP, p=0.757).

In mild‐WI protocol, urine production, EtCO2 and MAP were not affected at any time point. Na+ chronically decreased to mild HN level (Na+=130). ICP was chronically high for the whole monitoring time (36.1 ± 4.8 mmHg at 40 min, 33.7 ± 6.3 mmHg, at 90 min.). CPP experienced a significant drop 26 minutes after mild‐WI, but remained stable afterwards (35.2 ± 8.9, 40% drop from baseline at 60 min.)

Conclusions

In the model of severe WI, only MAP, and not urine production, was significantly affected by dDVAP administration, and dDAVP was therefore not included in the new model. In mild‐WI animals, we observed mild‐hyponatremia and dramatic elevation in ICP high enough to decrease CPP for most of the experimental time, but cardiovascular, respiratory and renal effects were absent or reduced. The new mild‐WI model is thus suitable for experimental studies of sustained cranial hypertension.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.