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Vascul Pharmacol. 2016 May;80:59-66. doi: 10.1016/j.vph.2015.12.005. Epub 2016 Jan 15.

Lipid-lowering drugs prevent neurovascular and cognitive consequences of cardiopulmonary bypass.

Author information

1
Inserm, CHU Lille, U1171, Degenerative & Vascular Cognitive Disorders, Univ. Lille, F-59000 Lille, France.
2
Inserm, CHU Lille, U1171, Degenerative & Vascular Cognitive Disorders, Univ. Lille, F-59000 Lille, France; Service de Chirurgie Cardiovasculaire, Hôpital cardiologique; Centre Hospitalier Universitaire de Lille, F-59000 Lille, France.
3
Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Univ. Lille, F-59000 Lille, France.
4
Inserm, CHU Lille, U1171, Degenerative & Vascular Cognitive Disorders, Univ. Lille, F-59000 Lille, France; Service de Chirurgie Cardiovasculaire, Hôpital cardiologique; Centre Hospitalier Universitaire de Lille, F-59000 Lille, France. Electronic address: thomas.modine@chru-lille.fr.

Abstract

Inflammatory injury and hypoperfusion following cardiopulmonary bypass (CPB) are associated with potential brain injury in relationship between CPB, memory impairment, changes in cerebral vascular reactivity and both systemic and cerebral inflammatory reaction. The objective of this study was to assess the preventive effect of a pretreatment with simvastatin or fenofibrate on neurovascular and cognitive consequences of CPB. Male Sprague-Dawley rats were treated by control diet, simvastatin 10 mg/kg/day or fenofibrate 200 mg/kg/day for 14 days before CPB surgery and were sacrificed immediately after surgery or 24h later. Cognitive function, vascular reactivity, neuronal counts in CA1 and CA3 hippocampal regions, and inflammatory markers were assessed. CPB induced memory impairment and endothelial dysfunction 24h after surgery associated with neuronal loss. Neuronal loss was reduced by simvastatin or fenofibrate treatment in parallel to memory alteration prevention. Pretreatment by simvastatin and fenofibrate prevented CPB-induced endothelial dysfunction. CPB led to early and marked release of TNFα and overexpression of ICAM-1. Both inflammatory marker expression was decreased in the pretreated groups by lipid-lowering drugs. In a rat model of CPB, we demonstrated that simvastatin and fenofibrate protected against CPB-induced endothelial dysfunction, cerebral and systemic inflammation in parallel to memory impairment prevention.

KEYWORDS:

Cardiopulmonary bypass; Cerebrovascular diseases; Endothelium; Inflammation; Lipid-lowering drugs

PMID:
26779598
DOI:
10.1016/j.vph.2015.12.005
[Indexed for MEDLINE]

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