Early Administration of Hypertonic-Hyperoncotic Hydroxyethyl Starch (HyperHES) Improves Cerebral Blood Flow and Outcome After Experimental Subarachnoid Hemorrhage in Rats

Abstract

Early cytotoxic brain edema may be a decisive factor that maintains cerebral malperfusion after subarachnoid hemorrhage (SAH). In addition, endothelial cell swelling may be an independent factor restricting cerebral blood flow (CBF) in a very early stage after SAH. Immediate and aggressive treatment may be able to restore CBF in this critical period. Male Sprague-Dawley rats were subjected to SAH by the endovascular filament model and treated by a bolus of hyperoncotic-hypertonic hydroxyethyl starch (4mL/kg body weight) immediately after vessel perforation and 150 minutes later (n= 12) or by the same amount of normal saline (n= 9). Mean arterial blood pressure, intracranial pressure, and local CBF over both hemispheres were continuously measured by laser-Doppler flowmetry. Neurologic assessment was performed 24 hours later. Hippocampal damage was assessed by hematoxylin-eosin and Caspase-3 staining. Arterial blood gases and mean arterial blood pressure were not significantly different between the 2 groups. Intracranial pressure was significantly reduced in the treatment group (P < 0.05). Local CBF was significantly improved in the treatment group over both hemispheres (P< 0.05; 180 minutes after treatment, P < 0.01). There was a trend to better neurologic performance in the treatment group. The rate of injured neurons was significantly reduced in animals of the treatment group compared with controls (P < 0.01). The number of Caspase-3-positive neurons in the hippocampal CA1 field was not reduced. In this study, the effects of very early and repeated treatment with a high-dose hyperoncotic-hypertonic hydroxyethyl starch were investigated. The results of this series show that this therapy can be highly effective to improve CBF and attenuate hippocampal cell damage in the early stage of SAH. Whether delayed cell death could be treated by longer therapy cannot be answered by this study. Because no differential diagnosis of the clinical suspicion of SAH prohibits the administration of hypertonic-hyperoncotic solutions, it may be useful as a first-tier preclinical therapy in suspected SAH and could even be used by emergency rescue services before the patient is admitted to a hospital.