Impact of anesthesia on pathophysiology and mortality following subarachnoid hemorrhage in rats

Sprague-Dawley rats (n = 38) were randomly assigned to (1) chloral hydrate, (2) isoflurane or (3) midazolam/medetomidine/fentanyl (MMF) anesthesia. Arterial blood gases, intracranial pressure (ICP), mean arterial blood pressure (MAP), cerebral perfusion pressure (CPP), and regional cerebral blood flow (rCBF) were monitored before and for 3 hours after SAH. Brain water content, mortality and rate of secondary bleeding were also evaluated.Under baseline conditions isoflurane anesthesia resulted in deterioration of respiratory parameters (arterial pCO2 and pO2) and increased brain water content. After SAH, isoflurane and chloral hydrate were associated with reduced MAP, incomplete recovery of post-hemorrhagic rCBF (23 ± 13% and 87 ± 18% of baseline, respectively) and a high anesthesia-related mortality (17 and 50%, respectively). Anesthesia with MMF provided stable hemodynamics (MAP between 100-110 mmHg), high post-hemorrhagic rCBF values, and a high rate of re-bleedings (> 50%), a phenomenon often observed after SAH in humans.Based on these findings we recommend anesthesia with MMF for the endovascular perforation model of SAH.Experimental animal models are widely used to study the pathophysiology of subarachnoid hemorrhage (SAH) [1-4]. The induction of experimental SAH is performed by invasive surgical techniques which require continuous multimodal monitoring and adequate sedation and analgesia. Ventilation and, hence, blood gases can be controlled by intubation and mechanical ventilation [5], however, other parameters which are known to critically determine the outcome following experimental SAH such as intracranial pressure (ICP), mean arterial blood pressure (MAP) and regional cerebral blood flow (rCBF) [1,2,6-9] may well be influenced by the applied anesthetic protocol as already demonstrated for experimental models of cerebral ischemia [5] and traumatic brain injury [10,11].Various inhaled or injectable anesthetics have been used in experimental SAH, e.g. haloth