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Mild hypothermia alone or in combination with anesthetic post-conditioning reduces expression of inflammatory cytokines in the cerebral cortex of pigs after cardiopulmonary resuscitation.

Meybohm P, Gruenewald M, Zacharowski KD, Albrecht M, Lucius R, Fösel N, Hensler J, Zitta K, Bein B - Crit Care (2010)

Bottom Line: Hypothermia was associated with a significant (P < 0.05 versus normothermia) reduction in cerebral inflammatory cytokine mRNA expression (IL-1beta 1.7 +/- 1.0, IL-6 2.2 +/- 1.1, IL-10 0.8 +/- 0.4, TNFalpha 1.1 +/- 0.6, ICAM-1 1.9 +/- 0.7-fold compared with sham control).These results were also confirmed for IL-1beta on protein level.Experimental settings employing hypothermia in combination with sevoflurane showed that the volatile anesthetic did not confer additional anti-inflammatory effects compared with hypothermia alone.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 21, Kiel, 24105, Germany. meybohm@anaesthesie.uni-kiel.de

ABSTRACT

Introduction: Hypothermia improves survival and neurological recovery after cardiac arrest. Pro-inflammatory cytokines have been implicated in focal cerebral ischemia/reperfusion injury. It is unknown whether cardiac arrest also triggers the release of cerebral inflammatory molecules, and whether therapeutic hypothermia alters this inflammatory response. This study sought to examine whether hypothermia or the combination of hypothermia with anesthetic post-conditioning with sevoflurane affect cerebral inflammatory response after cardiopulmonary resuscitation.

Methods: Thirty pigs (28 to 34 kg) were subjected to cardiac arrest following temporary coronary artery occlusion. After seven minutes of ventricular fibrillation and two minutes of basic life support, advanced cardiac life support was started according to the current American Heart Association guidelines. Return of spontaneous circulation was achieved in 21 animals who were randomized to either normothermia at 38 degrees C, hypothermia at 33 degrees C or hypothermia at 33 degrees C combined with sevoflurane (each group: n = 7) for 24 hours. The effects of hypothermia and the combination of hypothermia with sevoflurane on cerebral inflammatory response after cardiopulmonary resuscitation were studied using tissue samples from the cerebral cortex of pigs euthanized after 24 hours and employing quantitative RT-PCR and ELISA techniques.

Results: Global cerebral ischemia following resuscitation resulted in significant upregulation of cerebral tissue inflammatory cytokine mRNA expression (mean +/- SD; interleukin (IL)-1beta 8.7 +/- 4.0, IL-6 4.3 +/- 2.6, IL-10 2.5 +/- 1.6, tumor necrosis factor (TNF)alpha 2.8 +/- 1.8, intercellular adhesion molecule-1 (ICAM-1) 4.0 +/- 1.9-fold compared with sham control) and IL-1beta protein concentration (1.9 +/- 0.6-fold compared with sham control). Hypothermia was associated with a significant (P < 0.05 versus normothermia) reduction in cerebral inflammatory cytokine mRNA expression (IL-1beta 1.7 +/- 1.0, IL-6 2.2 +/- 1.1, IL-10 0.8 +/- 0.4, TNFalpha 1.1 +/- 0.6, ICAM-1 1.9 +/- 0.7-fold compared with sham control). These results were also confirmed for IL-1beta on protein level. Experimental settings employing hypothermia in combination with sevoflurane showed that the volatile anesthetic did not confer additional anti-inflammatory effects compared with hypothermia alone.

Conclusions: Mild therapeutic hypothermia resulted in decreased expression of typical cerebral inflammatory mediators after cardiopulmonary resuscitation. This may confer, at least in part, neuroprotection following global cerebral ischemia and resuscitation.

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Cerebral Bcl-2 and Bax mRNA expression. Transcript levels of the cerebral apoptosis-associated proteins Bcl-2 and Bax were determined by quantitative RT-PCR. NT, normothermia; HT, hypothermia; HT+SEV, hypothermia combined with sevoflurane. Data are expressed as mean ± SD (x-fold upregulation compared with Sham control). *P < 0.05 vs. Sham. §P < 0.05 vs. NT. RT-PCR data analysis was performed using two-sided Pair-wise fixed Reallocation Randomisation Test.
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Figure 4: Cerebral Bcl-2 and Bax mRNA expression. Transcript levels of the cerebral apoptosis-associated proteins Bcl-2 and Bax were determined by quantitative RT-PCR. NT, normothermia; HT, hypothermia; HT+SEV, hypothermia combined with sevoflurane. Data are expressed as mean ± SD (x-fold upregulation compared with Sham control). *P < 0.05 vs. Sham. §P < 0.05 vs. NT. RT-PCR data analysis was performed using two-sided Pair-wise fixed Reallocation Randomisation Test.

Mentions: We found a significant (P < 0.01) upregulation of both Bcl-2 mRNA and Bax expression after global cerebral ischemia (NT: Bcl-2 3.2 ± 1.8-fold, Bax 2.3 ± 1.3-fold compared with sham control). Hypothermia was associated with significantly (P < 0.05) less upregulation of mRNA expression (Bcl-2 1.2 ± 0.5-fold, Bax 1.2 ± 0.6-fold compared with sham control). Sevoflurane did not confer additional effects (Bcl-2 1.1 ± 0.4-fold, Bax 1.1 ± 0.4-fold compared with sham control; Figure 4).


Mild hypothermia alone or in combination with anesthetic post-conditioning reduces expression of inflammatory cytokines in the cerebral cortex of pigs after cardiopulmonary resuscitation.

Meybohm P, Gruenewald M, Zacharowski KD, Albrecht M, Lucius R, Fösel N, Hensler J, Zitta K, Bein B - Crit Care (2010)

Cerebral Bcl-2 and Bax mRNA expression. Transcript levels of the cerebral apoptosis-associated proteins Bcl-2 and Bax were determined by quantitative RT-PCR. NT, normothermia; HT, hypothermia; HT+SEV, hypothermia combined with sevoflurane. Data are expressed as mean ± SD (x-fold upregulation compared with Sham control). *P < 0.05 vs. Sham. §P < 0.05 vs. NT. RT-PCR data analysis was performed using two-sided Pair-wise fixed Reallocation Randomisation Test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875536&req=5

Figure 4: Cerebral Bcl-2 and Bax mRNA expression. Transcript levels of the cerebral apoptosis-associated proteins Bcl-2 and Bax were determined by quantitative RT-PCR. NT, normothermia; HT, hypothermia; HT+SEV, hypothermia combined with sevoflurane. Data are expressed as mean ± SD (x-fold upregulation compared with Sham control). *P < 0.05 vs. Sham. §P < 0.05 vs. NT. RT-PCR data analysis was performed using two-sided Pair-wise fixed Reallocation Randomisation Test.
Mentions: We found a significant (P < 0.01) upregulation of both Bcl-2 mRNA and Bax expression after global cerebral ischemia (NT: Bcl-2 3.2 ± 1.8-fold, Bax 2.3 ± 1.3-fold compared with sham control). Hypothermia was associated with significantly (P < 0.05) less upregulation of mRNA expression (Bcl-2 1.2 ± 0.5-fold, Bax 1.2 ± 0.6-fold compared with sham control). Sevoflurane did not confer additional effects (Bcl-2 1.1 ± 0.4-fold, Bax 1.1 ± 0.4-fold compared with sham control; Figure 4).

Bottom Line: Hypothermia was associated with a significant (P < 0.05 versus normothermia) reduction in cerebral inflammatory cytokine mRNA expression (IL-1beta 1.7 +/- 1.0, IL-6 2.2 +/- 1.1, IL-10 0.8 +/- 0.4, TNFalpha 1.1 +/- 0.6, ICAM-1 1.9 +/- 0.7-fold compared with sham control).These results were also confirmed for IL-1beta on protein level.Experimental settings employing hypothermia in combination with sevoflurane showed that the volatile anesthetic did not confer additional anti-inflammatory effects compared with hypothermia alone.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Campus Kiel, Schwanenweg 21, Kiel, 24105, Germany. meybohm@anaesthesie.uni-kiel.de

ABSTRACT

Introduction: Hypothermia improves survival and neurological recovery after cardiac arrest. Pro-inflammatory cytokines have been implicated in focal cerebral ischemia/reperfusion injury. It is unknown whether cardiac arrest also triggers the release of cerebral inflammatory molecules, and whether therapeutic hypothermia alters this inflammatory response. This study sought to examine whether hypothermia or the combination of hypothermia with anesthetic post-conditioning with sevoflurane affect cerebral inflammatory response after cardiopulmonary resuscitation.

Methods: Thirty pigs (28 to 34 kg) were subjected to cardiac arrest following temporary coronary artery occlusion. After seven minutes of ventricular fibrillation and two minutes of basic life support, advanced cardiac life support was started according to the current American Heart Association guidelines. Return of spontaneous circulation was achieved in 21 animals who were randomized to either normothermia at 38 degrees C, hypothermia at 33 degrees C or hypothermia at 33 degrees C combined with sevoflurane (each group: n = 7) for 24 hours. The effects of hypothermia and the combination of hypothermia with sevoflurane on cerebral inflammatory response after cardiopulmonary resuscitation were studied using tissue samples from the cerebral cortex of pigs euthanized after 24 hours and employing quantitative RT-PCR and ELISA techniques.

Results: Global cerebral ischemia following resuscitation resulted in significant upregulation of cerebral tissue inflammatory cytokine mRNA expression (mean +/- SD; interleukin (IL)-1beta 8.7 +/- 4.0, IL-6 4.3 +/- 2.6, IL-10 2.5 +/- 1.6, tumor necrosis factor (TNF)alpha 2.8 +/- 1.8, intercellular adhesion molecule-1 (ICAM-1) 4.0 +/- 1.9-fold compared with sham control) and IL-1beta protein concentration (1.9 +/- 0.6-fold compared with sham control). Hypothermia was associated with a significant (P < 0.05 versus normothermia) reduction in cerebral inflammatory cytokine mRNA expression (IL-1beta 1.7 +/- 1.0, IL-6 2.2 +/- 1.1, IL-10 0.8 +/- 0.4, TNFalpha 1.1 +/- 0.6, ICAM-1 1.9 +/- 0.7-fold compared with sham control). These results were also confirmed for IL-1beta on protein level. Experimental settings employing hypothermia in combination with sevoflurane showed that the volatile anesthetic did not confer additional anti-inflammatory effects compared with hypothermia alone.

Conclusions: Mild therapeutic hypothermia resulted in decreased expression of typical cerebral inflammatory mediators after cardiopulmonary resuscitation. This may confer, at least in part, neuroprotection following global cerebral ischemia and resuscitation.

Show MeSH
Related in: MedlinePlus