Abstract

„Investigations on effects of Xenon application time on cerebral outcome following cardiopulmonary bypass with cerebral air embolism in the rat” Cerebral air embolism (CAE) is thought to be one of the risk factors for adverse cerebral outcome following cardiac surgery with cardiopulmonary bypass (CPB). Neurologic and neurocognitive deficits after cardiac surgery remain a common and severe complication, alleviating patients´ quality of life for years. Providing neuroprotective properties and cardiovascular stability Xenon may also improve cerebral outcome after cardiac surgery with CPB. However, Xenon`s disposition to expand air bubbles could possibly be a disadvantage for its use in combination with CPB, as such air bubbles can be detected during CPB. In this study Xenon was administered before (group XEv), during (group XEw) or after CPB (group XEn) to investigate differential effects of application time on cerebral outcome after CPB with cerebral air embolism in a rat model. 50 male Sprague-Dawley rats (BW: 330-390 g) were assigned to five groups of ten animals each. Control group (Ko) animals were neither exposed to CPB nor received Xenon. The CPB-groups such as Xenon before CPB, Xenon during CPB, Xenon after CPB and no Xenon (kXE) were anesthetized with isofluran, intubated and ventilated with 2.0-2.5 Vol % isoflurane in 50 % oxygen. The right superficial epigastric artery and vein, the right external jugular vein and the sacral artery were cannulated for blood sampling, application of drugs, invasive blood pressure monitoring as well as inflow and return connection to the CPB circuit. A catheter was inserted into the right internal carotid artery and ten repetitively administered air emboli of 0.3 µl each were applicated. After completion of surgery all animals received an additional basic intravenous anesthesia (continuous infusion of midazolam, fentanyl and atracurium) which was maintained until the end of operation (60 min after CPB). Rats subjected to Xenon before CPB were ventilated with Xenon (56 % Xenon, 5 % N2, 34 % O2 and 5 % CO2) applied for 60 minutes before connection to CPB. The Xenon during CPB group received the above mentioned Xenon gas mixture through the oxygenator for 90 minutes during CPB. Xenon after CPB animals were treated in the same fashion but inhaled Xenon for 60 minutes after CPB and no Xenon animals continously received an oxygen-air-mixture (61 % N2, 34 % O2 und 5 % CO2). Emerging from anesthesia the rats recovered by being placed in an oxygen-enriched environment. Animals underwent standardized functional neurologic testing on the 1st-4th, 8th, 12th, 16th and 21st postoperative days. Beginning with the 4th postoperative day cognitive performance as well as behaviour was ascertained up to the 21st postoperative day using the modified hole-board test. All neurologic, cognitive and behavioural testing was performed by a investigator blinded to treatment. After testing on the 21st postoperative day the rats were killed by exsanguination in deep isofluran anesthesia and subjected to in situ brain fixation with formaline. Brains were removed in total, were serially cut and stained with hematoxylin and eosin for further histological evaluation determining maximal infarction size and infarction volume. This is the first investigative study on the effects of different Xenon application times, that is before, during and after CPB in combination with CAE. The occurrence of CAE is more likely during CPB in contrast to before and after CPB where CAE are rarer. In this setting rats showed short-time sensomotoric and long-term cognitive and behavioural changes which was confirmed by histopathological results. The significant worse outcome of animals treated with Xenon after CPB is of profound relevance discussing the safety of Xenon`s use associated with CPB. Interestingly rats subjected to CPB without Xenon achieved no better results neither at cognitive and behavioural testing nor at histopathological evaluation. Knowledge about the pathophysiology of CAE remains sparse and further investigation in this direction would be of high importance in trying to explain the results of this study.