Abstract | INTRODUCTION: METHODS: Using isoflurane anesthesia, rats were subjected to a lethal hemorrhagic shock. After 5 min of no flow, hypothermia was induced with an aortic flush. Three groups were studied: ice-cold (IC) flush, room-temperature (RT) flush, and RT flush followed by minocycline treatment (RT-M). After 20 min of CA, resuscitation was achieved via cardiopulmonary bypass. Survival, Overall Performance Category (1 = normal, 5 = death), Neurologic Deficit Score (0%-10% = normal, 100% = max deficit), neuronal death ( Fluoro-Jade C), and microglial proliferation (Iba1 immunostaining) in hippocampus were assessed at 72 h. RESULTS: Rats in the IC group had lower tympanic temperature during CA versus other groups (IC, 20.9 degrees C +/- 1.3 degrees C; RT, 28.4 degrees C +/- 0.6 degrees C; RT-M, 28.3 degrees C +/- 0.7 degrees C; P < 0.001). Although survival was similar in all groups (RT, 6/9; IC, 6/7; RT-M, 6/11), neurological outcome was better in the IC group versus other groups (Overall Performance Category: IC, 1 +/- 1; RT, 3 +/- 1; RT-M, 2 +/- 1; P < 0.05; Neurologic Deficit Score: IC, 8% +/- 9%; RT, 55% +/- 19%; RT-M, 27% +/- 16%; P < 0.05). Histological damage assessed in survivors showed selective neuronal death in CA1 and dentate gyrus, similar in all groups (P = 0.15). In contrast, microglial proliferation was attenuated in the IC group versus all other groups (P < 0.01). CONCLUSIONS: Deeper levels of hypothermia induced by the IC versus RT flush resulted in better neurological outcome in survivors. Surprisingly, deep hypothermia attenuated microglial activation but not hippocampal neuronal death. Minocycline had modest benefit on neurologic outcome in survivors but did not attenuate microglial activation in brain. Our findings suggest a novel effect of deep hypothermia on microglial proliferation during exsanguination CA.
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Authors | Tomas Drabek, Samuel A Tisherman, Lauren Beuke, Jason Stezoski, Keri Janesko-Feldman, Manuella Lahoud-Rahme, Patrick M Kochanek |
Journal | Anesthesia and analgesia
(Anesth Analg)
Vol. 109
Issue 3
Pg. 914-23
(Sep 2009)
ISSN: 1526-7598 [Electronic] United States |
PMID | 19690267
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Neuroprotective Agents
- Minocycline
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Topics |
- Animals
- Aorta
(pathology)
- Body Weight
- Cardiopulmonary Resuscitation
(methods)
- Cell Proliferation
- Heart Arrest
(physiopathology)
- Heart Rate
- Hypothermia, Induced
(methods)
- Male
- Microglia
(drug effects, pathology)
- Minocycline
(pharmacology)
- Neurons
(drug effects, pathology)
- Neuroprotective Agents
(pharmacology)
- Rats
- Rats, Sprague-Dawley
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