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Correspondence  |   January 2006
Is Xenon Really Neuroprotective after Cardiac Arrest?
Author Affiliations & Notes
  • Michael Schmidt, M.D., P.D.
    *
  • *University of Ulm, Ulm, Germany.
Article Information
Correspondence
Correspondence   |   January 2006
Is Xenon Really Neuroprotective after Cardiac Arrest?
Anesthesiology 1 2006, Vol.104, 211-212. doi:
Anesthesiology 1 2006, Vol.104, 211-212. doi:
In Reply:—
The study presented in “Xenon Attenuates Cerebral Damage after Ischemia in Pigs”1 was designed and performed in our Department of Cardiac Anesthesia (Ulm, Germany). After cardiac bypass surgery, neurologic complications are well known to be a major problem leading to prolonged intensive care unit stay and additional costs.2 With this investigation, we aimed to simulate a situation of expected  transient cessation of cerebral perfusion with a definitive offset and onset. In this clinically relevant situation, the depletion of central nervous system’s energy stores occurs within 2–4 min of anoxia, leading to cellular damage and possible consecutive irreversible cell death. As described, this expected  situation might be relevant, e.g.  , in temporary clipping in cerebral aneurysm, aortic arch surgery, or carotid surgery.
In preliminary studies, we observed that the percentage of animals with return of spontaneous circulation after cardiac fibrillation times exceeding the period as applied in our study significantly decreased. Therefore, the given times were found to be the maximum periods of ventricular fibrillation in pigs with a realistic option of successful cardiac  resuscitation.
The effect of ischemia/hypoxia was investigated using cerebral microdialysis in identical setups during anesthesia with inhalation of xenon versus  total intravenous anesthesia. Regarding the results of intracerebral microdialysis, we have discussed that the lack of peak increase of glutamate concentrations could also be due to harvesting time of microdialysis fluid volume. Regarding the question of glycerol concentrations and possible extracerebral sources, we measured identical changes of concentrations until 90 min after cardiac arrest for both groups. This finding is not surprising at all, because the primary lesion due to anoxia, the described resuscitation regimens, and the measured cardiopulmonary resuscitation times did not differ significantly between the groups. In case of relevant extracerebral production of glycerol, differences in glycerol concentrations should be seen directly after return of spontaneous circulation, which was not the case. Therefore, it is not likely that changes in glycerol kinetics or extracerebral sources would explain the differences in glycerol concentrations between the groups after 90 min of reperfusion. Even if there would be a relevant exogenous concentration of glycerol, the effect, if at all, would be same in both groups. In our opinion, the difference in glycerol concentrations after 90 min during the time of reperfusion is more likely to be interpreted as a neuroprotective effect of xenon.
Like Fries et al.  , we considered the influence of comedication to contribute to a possible neuroprotective effect, which in that case would not have been the effect of xenon. However, the contribution of a different depth of anesthesia leading to a different level of metabolism in the central nervous system during hypoxia/ischemia was considered to have an important influence on our findings, too. Therefore, we adjusted the level of background anesthesia according to comparable electroencephalographic levels, and, as described in our article, reduced  amounts of comedication were administered in the xenon group. The difference in glycerol kinetics after establishment of return of spontaneous circulation with lower  postcardiopulmonary resuscitation concentrations in the xenon group is therefore not likely to be explained by lower  amounts of comedication.
We agree with Fries et al.  and regard it to be an advantage if additional diagnostic tools are used to contribute to the explanation of central nervous system damage assessment. Being a noninvasive tool and therefore possibly an option for human studies as well, magnetic resonance imaging scans were added to this experimental setting. We performed magnetic resonance imaging scans 4 h after return of spontaneous circulation and calculated the apparent diffusion coefficients, being used as a method to assess the water content of the central nervous system as a parameter for tissue damage.3 Interpretation of technical and anatomical aspects regarding the achieved data was difficult because, to our knowledge, there have been no comparable data published about German Landrace pigs until the present. Preliminary technical data from this study were published recently.4 
Regarding neuroprotective effects of xenon after global ischemia, we found a significant benefit for the xenon-treated group versus  the total intravenous anesthesia group in apparent diffusion coefficients results. The combination of magnetic resonance imaging findings and cerebral microdialysis results are regarded to be valuable to demonstrate the neuroprotective effect of xenon more clearly.
*University of Ulm, Ulm, Germany.
References
Schmidt M, Marx T, Glöggl E, Reinelt H, Schirmer U: Xenon attenuates cerebral damage after ischemia in pigs. Anesthesiology 2005; 102:929–36Schmidt, M Marx, T Glöggl, E Reinelt, H Schirmer, U
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Marx T, Schmidt M, Schirmer U, Reinelt H: Cerebral damage assessment using apparent diffusion coefficients and intracerebral microdialysis. Biomed Eng 2005; 50:239–40Marx, T Schmidt, M Schirmer, U Reinelt, H