Effects of a single-dose hypertonic saline hydroxyethyl starch on cerebral blood flow, long-term outcome, neurogenesis, and neuronal survival after cardiac arrest and cardiopulmonary resuscitation in rats*

Abstract

Objective: The beneficial effects of hypertonic saline on neuronal survival and on cerebral blood flow have been shown in several animal models of global and focal brain ischemia. Because of the potential benefits of hypertonic solutions, it is hypothesized that hydroxyethyl starch enhances cerebral blood flow and improves long-term outcome after cardiac arrest and cardiopulmonary resuscitation in an animal model.

Design: Laboratory animal study.

Setting: University animal research laboratory.

Subjects: Fifty-nine male Sprague-Dawley rats.

Interventions: Rats were randomized to receive either 7.2% saline/6% hypertonic saline hydroxyethyl starch (4 mL/kg) or vehicle (NaCl 0.9 %) after 9 mins of asphyxic cardiac arrest and cardiopulmonary resuscitation. Local cerebral blood flow and physiologic parameters were evaluated during arrest and early restoration of spontaneous circulation. Survival and neurologic assessment were evaluated over a 7-day observation period. Animals received 5-bromo-2-deoxyuridine for 6 days. Neuronal injury and neurogeneration (5-bromo-2-deoxyuridine positive neurons) were quantified on day 7 after cardiac arrest and cardiopulmonary resuscitation.

Measurements and main results: Hypertonic saline hydroxyethyl starch treatment resulted in an accentuated local cerebral blood flow during early reperfusion, compared to the vehicle group. Animal survival and neurologic outcome were not altered between groups. Neurohistopathological injury was present in hippocampal CA1 and neocortex with no effects of hypertonic saline hydroxyethyl starch on neuronal survival. Increased neurogeneration was found in the dentate gyrus after cardiac arrest/cardiopulmonary resuscitation, which was not influenced by hypertonic saline hydroxyethyl starch administration.

Conclusions: Despite promising results in other models of brain injury, hypertonic saline hydroxyethyl starch failed to improve the outcome when administered after asphyxic cardiac arrest/cardiopulmonary resuscitation in rats. One major difference between the cardiac arrest/cardiopulmonary resuscitation model and other models of brain ischemia is that the effects of asphyxic cardiac arrest involve the whole organism (post-cardiac arrest syndrome) and not exclusively the brain leading to a more severe injury. This might explain why hypertonic saline hydroxyethyl starch has failed to improve outcome in the present model.