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  3. Tierärztliche Fakultät - Digitale Hochschulschriften der LMU - Teil 03/07 Podcast
  4. Untersuchungen zum Einfluss des Applikationszeitpunkts von Xenon auf die zentralnervoese Leistung von Ratten nach extrakorporaler Zirkulation und zerebralen Luftemboli
„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.

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„Untersuchungen zum Einfluss des Applikationszeitpunkts von Xenon auf die zentralnervoese Leistung von Ratten nach extrakorporaler Zirkulation und zerebralen Luftemboli“

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