Abstract:
BACKGROUND:Cerebral edema is a major cause of mortality following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Arginine vasopressin (AVP) and water channel aquaporin-4 (AQP4) have been implicated in the pathogenesis of CA-evoked cerebral edema. In this study, we examined if conivaptan, a V1a and V2 antagonist, attenuates cerebral edema following CA/CPR in wild type (WT) mice as well as mice with targeted disruption of the gene encoding α-syntrophin (α-syn(-/-)) that demonstrate diminished perivascular AQP4 pool. METHODS:Isoflurane-anesthetized adult male WT C57Bl/6 and α-syn(-/-) mice were subjected to 8 min CA/CPR and treated with either bolus IV injection (0.15 or 0.3 mg/kg) followed by continuous infusion of conivaptan (0.15 mg/kg/day or 0.3 mg/kg/day), or vehicle infusion for 48 h. Serum osmolality, regional brain water content, and blood-brain barrier (BBB) disruption were determined at the end of the experiment. Sham-operated mice in both strains served as controls. RESULTS:Treatment with conivaptan elevated serum osmolality in a dose-dependent manner. In WT mice, conivaptan at 0.3 mg dose significantly attenuated regional water content in the caudoputamen (81.0 ± 0.5 vs. 82.5 ± 0.4% in controls; mean ± SEM) and cortex (78.8 ± 0.2 vs. 79.4 ± 0.2% in controls), while conivaptan at 0.15 mg was not effective. In α-syn(-/-) mice, conivaptan at 0.3 mg dose did not attenuate water content compared with controls. Conivaptan (0.3 mg/kg/day) attenuated post-CA BBB disruption at 48 h in WT mice but not in α-syn(-/-) mice. CONCLUSIONS:Continuous IV infusion of conivaptan attenuates cerebral edema and BBB disruption following CA. These effects of conivaptan that are dependent on the presence of perivascular pool of AQP4 appear be mediated via its dual effect on V1 and V2 receptors.
journal_name
Neurocrit Carejournal_title
Neurocritical careauthors
Nakayama S,Amiry-Moghaddam M,Ottersen OP,Bhardwaj Adoi
10.1007/s12028-015-0236-4subject
Has Abstractpub_date
2016-04-01 00:00:00pages
273-82issue
2eissn
1541-6933issn
1556-0961pii
10.1007/s12028-015-0236-4journal_volume
24pub_type
杂志文章abstract:BACKGROUND:The management of symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH) can be often complicated by the presence of stunned myocardium and left ventricular failure. Vasopressors and inotropes are commonly used to optimize mean arterial pressure (MAP) and cerebral perfusion pressure (...
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pub_type: 杂志文章,评审
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abstract::Prophylactic use of hypervolemia and hypertension is believed to present an option to decrease the incidence of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage and improve neurologic outcome. A Medline literature search was conducted to review available evidence regarding volume management after subarac...
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更新日期:2018-10-01 00:00:00
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pub_type: 杂志文章,评审
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doi:10.1385/NCC:1:4:461
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abstract:: ...
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更新日期:2020-11-24 00:00:00
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pub_type: 杂志文章
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journal_title:Neurocritical care
pub_type: 杂志文章
doi:10.1007/s12028-012-9765-2
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更新日期:2007-01-01 00:00:00
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pub_type: 杂志文章,随机对照试验
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pub_type: 杂志文章
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