Kardioprotektive Eigenschaften von Xenon und Isofluran auf den myokardialen Ischämie-Reperfusions-Schaden der Ratte

摘要

Due to the increasing incidence of cardiovascular diseases anesthesiologists are increasingly confronted with the risk of patients’ intraoperative myocardial ischemia. Hence, preventive measures reducing the likelihood of occurrence of ischemia-reperfusion conditions as well as therapeutical solutions are desired. Thus, researchers in the field of cardioprotective anesthetics have examined these issues for many years and tried to find an optimal solution. Xenon possesses many characteristics of an ideal anesthetic gas and induces a good circulatory stability. Furthermore, several studies with different species proved a pre- as well as a post-conditioning effect with reduction of infarct size after transient myocardial ischemia. These studies varied immensely with respect to species, ischemia and reperfusion time as well as anesthetic regimes. Since the transfer of cardioprotective therapies into clinical daily routine has not been very successful so far, the goal of this study has been to transfer an already established protocol, comparing cardioprotective effects of isoflurane and xenon in large animals, to a small-animal model. To the best of our knowledge, previous literature lacks a description of the hemodynamic and structural effects of cardioprotection of xenon and isoflurane after prolonged ischemia in the rat, and hence this study addresses this issue. After induction of barbiturate-narcosis in 35 Sprague-Dawley rats a left-side thoracotomy with subsequent ligation of the left anterior descending artery was conducted over 60 minutes. During the 60 minutes before ischemia 0.43 MAC isoflurane or xenon were already administered in the treatment groups, while the barbiturate-dose was accordingly reduced in the control group. These conditions were preserved for the following period of ischemia and the 120 minutes of reperfusion. The resulting myocardial damage was illustrated by a planimetric infarct size determination and serum levels of troponin. The inflammatory reaction was observed by measuring the parameters IL-6 and TNFα in the serum. The hemodynamic effects have additionally been examined with the aid of a pressure catheter and the expression of BNP in the myocardium. Side effects on liver, kidney and lungs were scrutinized by serological markers (NGAL, L-FABP) and the quantification of pulmonary edema. The infarct size reduction caused by xenon and isoflurane was exactly the same as previously described despite a prolonged period of ischemia and a wide area at risk. There are no remarkable differences between the two substances. These findings were also confirmed by lower troponin levels. While no significant differences regarding the hemodynamics occurred, the inflammatory response was more suppressed by xenon than by isoflurane. Both volatile anesthetics in reperfusion merely caused an improvement of the diastolic pump function. Although both substances reduced the renal damage, an inspection of the control group revealed a more severe liver damage after isoflurane-narcosis. This research contributes to existing literature since the evidence indicates that isoflurane as well as xenon exhibit a constant cardio protection after longer ischemia time (60 minutes) in rats and hence they show a superior effectiveness compared to pigs (large animals). Although the anticipated advantage of xenon over isoflurane could not be proven, a direct comparison between two species under identical test conditions became possible for the first time with this study. Since the influence of the two substances on the process of cardiac remodeling after myocardial ischemia remains unclear, this issue can be examined in future research. The results displayed here prove that the rat functions as an appropriate experimental setting and thus one can use our findings for comparative analysis in the future.