The benefit of hypothermia in experimental ischemic stroke is not affected by pethidine

Emily S. Sena; Amy L. Jeffreys; Susan F. Cox; Stephen A. Sastra; Leonid Churilov; Sarah Rewell; Peter E. Batchelor; H. Bart van der Worp; Malcolm R. Macleod; David W. Howells

doi:10.1111/j.1747-4949.2012.00834.x

The benefit of hypothermia in experimental ischemic stroke is not affected by pethidine

Emily S. Sena, Amy L. Jeffreys, Susan F. Cox, Stephen A. Sastra, Leonid Churilov, Sarah Rewell, Peter E. Batchelor, H. Bart van der Worp, Malcolm R. Macleod, David W. Howells^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Background
Hypothermia is a promising experimental treatment for acute ischemic stroke. Human trials are still at an early stage, with the focus now on using hypothermia in awake patients. Pethidine (meperidine) is the principle agent used to control shivering in humans; however, whether it has any modulating effects on the neuroprotective efficacy of hypothermia is unknown.

Aim
The aim of this study was to determine if pethidine influences the neuroprotective effect of hypothermia in experimental stroke.

Methods
Seventy-two male spontaneously hypertensive rats were anesthetized with isoflurane and randomly assigned to either normothermia (37 center dot 4 degrees C rectal temperature); hypothermia (33 degrees C maintained for 130mins); normothermia plus pethidine (2 center dot 5mg/kg); or hypothermia plus pethidine. Temporary (90mins) endovascular occlusion of the middle cerebral artery was induced blinded to treatment allocation and was confirmed with laser Doppler flowmetry. Pethidine and cooling were started immediately after vessel occlusion. Animals in the normothermia group had active temperature management using a heat lamp and fan. Assessments of outcome were carried out 24 after the induction of injury.

Results
Thirteen animals met our prespecified criteria for exclusion, and data for 59 rats were presented here. Hypothermia was associated with a 63% reduction in infarct size, and pethidine had no significant impact on the efficacy of hypothermia. No effects were observed in neurobehavioral outcome or edema volume across experimental groups.

Conclusions
The effects of hypothermia in a model of focal ischemia are not affected by administration of pethidine.

Original language	English
Pages (from-to)	180-185
Number of pages	6
Journal	International Journal of Stroke
Volume	8
Issue number	3
DOIs	https://doi.org/10.1111/j.1747-4949.2012.00834.x
Publication status	Published - Apr 2013

Keywords / Materials (for Non-textual outputs)

ischemic stroke
OCCLUSION
BRAIN
MIDDLE CEREBRAL-ARTERY
intervention
hypertension
THERAPEUTIC HYPOTHERMIA
hypothermia
RATS
neuroprotection
METAANALYSIS
acute stroke therapy

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10.1111/j.1747-4949.2012.00834.x

http://onlinelibrary.wiley.com/doi/10.1111/j.1747-4949.2012.00834.x/abstract;jsessionid=90A03C88B60D6816D03FB30DA1D8BC7A.f03t03

Cite this

@article{97ad5d3288784875952bd85cb6876dcc,

title = "The benefit of hypothermia in experimental ischemic stroke is not affected by pethidine",

abstract = "Background Hypothermia is a promising experimental treatment for acute ischemic stroke. Human trials are still at an early stage, with the focus now on using hypothermia in awake patients. Pethidine (meperidine) is the principle agent used to control shivering in humans; however, whether it has any modulating effects on the neuroprotective efficacy of hypothermia is unknown. Aim The aim of this study was to determine if pethidine influences the neuroprotective effect of hypothermia in experimental stroke. Methods Seventy-two male spontaneously hypertensive rats were anesthetized with isoflurane and randomly assigned to either normothermia (37 center dot 4 degrees C rectal temperature); hypothermia (33 degrees C maintained for 130mins); normothermia plus pethidine (2 center dot 5mg/kg); or hypothermia plus pethidine. Temporary (90mins) endovascular occlusion of the middle cerebral artery was induced blinded to treatment allocation and was confirmed with laser Doppler flowmetry. Pethidine and cooling were started immediately after vessel occlusion. Animals in the normothermia group had active temperature management using a heat lamp and fan. Assessments of outcome were carried out 24 after the induction of injury. Results Thirteen animals met our prespecified criteria for exclusion, and data for 59 rats were presented here. Hypothermia was associated with a 63% reduction in infarct size, and pethidine had no significant impact on the efficacy of hypothermia. No effects were observed in neurobehavioral outcome or edema volume across experimental groups. Conclusions The effects of hypothermia in a model of focal ischemia are not affected by administration of pethidine.",

keywords = "ischemic stroke, OCCLUSION, BRAIN, MIDDLE CEREBRAL-ARTERY, intervention, hypertension, THERAPEUTIC HYPOTHERMIA, hypothermia, RATS, neuroprotection, METAANALYSIS, acute stroke therapy",

author = "Sena, {Emily S.} and Jeffreys, {Amy L.} and Cox, {Susan F.} and Sastra, {Stephen A.} and Leonid Churilov and Sarah Rewell and Batchelor, {Peter E.} and {van der Worp}, {H. Bart} and Macleod, {Malcolm R.} and Howells, {David W.}",

note = "{\textcopyright} 2012 The Authors. International Journal of Stroke {\textcopyright} 2012 World Stroke Organization.",

year = "2013",

month = apr,

doi = "10.1111/j.1747-4949.2012.00834.x",

language = "English",

volume = "8",

pages = "180--185",

journal = "International Journal of Stroke",

issn = "1747-4930",

publisher = "SAGE Publications",

number = "3",

}

TY - JOUR

T1 - The benefit of hypothermia in experimental ischemic stroke is not affected by pethidine

AU - Sena, Emily S.

AU - Jeffreys, Amy L.

AU - Cox, Susan F.

AU - Sastra, Stephen A.

AU - Churilov, Leonid

AU - Rewell, Sarah

AU - Batchelor, Peter E.

AU - van der Worp, H. Bart

AU - Macleod, Malcolm R.

AU - Howells, David W.

PY - 2013/4

Y1 - 2013/4

N2 - Background Hypothermia is a promising experimental treatment for acute ischemic stroke. Human trials are still at an early stage, with the focus now on using hypothermia in awake patients. Pethidine (meperidine) is the principle agent used to control shivering in humans; however, whether it has any modulating effects on the neuroprotective efficacy of hypothermia is unknown. Aim The aim of this study was to determine if pethidine influences the neuroprotective effect of hypothermia in experimental stroke. Methods Seventy-two male spontaneously hypertensive rats were anesthetized with isoflurane and randomly assigned to either normothermia (37 center dot 4 degrees C rectal temperature); hypothermia (33 degrees C maintained for 130mins); normothermia plus pethidine (2 center dot 5mg/kg); or hypothermia plus pethidine. Temporary (90mins) endovascular occlusion of the middle cerebral artery was induced blinded to treatment allocation and was confirmed with laser Doppler flowmetry. Pethidine and cooling were started immediately after vessel occlusion. Animals in the normothermia group had active temperature management using a heat lamp and fan. Assessments of outcome were carried out 24 after the induction of injury. Results Thirteen animals met our prespecified criteria for exclusion, and data for 59 rats were presented here. Hypothermia was associated with a 63% reduction in infarct size, and pethidine had no significant impact on the efficacy of hypothermia. No effects were observed in neurobehavioral outcome or edema volume across experimental groups. Conclusions The effects of hypothermia in a model of focal ischemia are not affected by administration of pethidine.

AB - Background Hypothermia is a promising experimental treatment for acute ischemic stroke. Human trials are still at an early stage, with the focus now on using hypothermia in awake patients. Pethidine (meperidine) is the principle agent used to control shivering in humans; however, whether it has any modulating effects on the neuroprotective efficacy of hypothermia is unknown. Aim The aim of this study was to determine if pethidine influences the neuroprotective effect of hypothermia in experimental stroke. Methods Seventy-two male spontaneously hypertensive rats were anesthetized with isoflurane and randomly assigned to either normothermia (37 center dot 4 degrees C rectal temperature); hypothermia (33 degrees C maintained for 130mins); normothermia plus pethidine (2 center dot 5mg/kg); or hypothermia plus pethidine. Temporary (90mins) endovascular occlusion of the middle cerebral artery was induced blinded to treatment allocation and was confirmed with laser Doppler flowmetry. Pethidine and cooling were started immediately after vessel occlusion. Animals in the normothermia group had active temperature management using a heat lamp and fan. Assessments of outcome were carried out 24 after the induction of injury. Results Thirteen animals met our prespecified criteria for exclusion, and data for 59 rats were presented here. Hypothermia was associated with a 63% reduction in infarct size, and pethidine had no significant impact on the efficacy of hypothermia. No effects were observed in neurobehavioral outcome or edema volume across experimental groups. Conclusions The effects of hypothermia in a model of focal ischemia are not affected by administration of pethidine.

KW - ischemic stroke

KW - OCCLUSION

KW - BRAIN

KW - MIDDLE CEREBRAL-ARTERY

KW - intervention

KW - hypertension

KW - THERAPEUTIC HYPOTHERMIA

KW - hypothermia

KW - RATS

KW - neuroprotection

KW - METAANALYSIS

KW - acute stroke therapy

U2 - 10.1111/j.1747-4949.2012.00834.x

DO - 10.1111/j.1747-4949.2012.00834.x

M3 - Article

C2 - 22759525

SN - 1747-4930

VL - 8

SP - 180

EP - 185

JO - International Journal of Stroke

JF - International Journal of Stroke

IS - 3

ER -

The benefit of hypothermia in experimental ischemic stroke is not affected by pethidine

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Keywords / Materials (for Non-textual outputs)

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