The influence of benzamil hydrochloride on the evolution of hyponatremic brain edema as assessed by in vivo MRI study in rats.

OBJECTIVE

The present study was undertaken to reveal the influence of intracerebroventricular (ICV) benzamil on the dynamics of brain water accumulation in hyponatremic rats. Parameters of brain water homeostasis were continuously monitored, using in vivo magnetic resonance imaging (MRI) methods. The results were compared with those obtained in a previous study by tissue desiccation.

METHODS

A 3-T MRI instrument was applied to perform serial diffusion-weighted imaging to measure the apparent diffusion coefficient (ADC) and MR spectroscopy to determine water signal. A decrease of ADC is thought to represent an increase of intracellular water, whereas water signal is used to quantify brain water content. Five groups of male Wistar rats were studied as follows: normonatremic, native animals (group NN, n = 7), hyponatremic animals (group HN, n = 8), hyponatremic animals treated with ICV benzamil (group HNB, n = 8), hyponatremic animals treated with ICV saline (group HNS, n = 5) and normonatremic animals treated with ICV benzamil (group NNB, n = 5). Hyponatremia was induced by intraperitoneal administration of 140 mmol/l dextrose solution in a dose of 20% of body weight. Benzamil hydrochloride (4 μg) was injected ICV to the treated animals.

RESULTS

During the course of hyponatemia, ADC declined steadily from the baseline (100%) to reach a minimum of 92.32 ± 3.20% at 90 min (p < 0.0005). This process was associated with an increase in water signal to a maximum of 5.95 ± 2.62% at 100 min (p < 0.0005). After pretreatment with benzamil, no consistent changes occurred either in ADC or in water signal.

CONCLUSIONS

These findings suggest that sodium channel blockade with ICV benzamil has an immediate protective effect against the development of hyponatremic brain edema. Sodium channels, therefore, appear to be intimately involved in the initiation and progression of brain water accumulation in severe hyponatremia.