Shin Nakayama1, Noriko Taguchi2, Yumi Isaka3, Takako Nakamura3, Makoto Tanaka4. 1. Department of Anesthesiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan. snakayama@md.tsukuba.ac.jp. 2. Department of Anesthesiology, Tsukuba University Hospital Mito Clinical Education and Training Center, Mito Kyodo General Hospital, 3-2-7 Miya-Mach, Mito, Ibaraki, Japan. 3. Technical Service Office for Medical Sciences, University of Tsukuba, 1-1-1 tennodai, Tsukuba, Ibaraki, Japan. 4. Department of Anesthesiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, Japan.
Abstract
BACKGROUND: Global ischemia due to cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR) causes significant neuronal damage in vulnerable areas in the brain. Currently, a majority of patients eventually die after successful CPR due to neurological injury. Statins have pleiotropic effects including anti-inflammatory and/or antioxidant responses. These pleiotropic effects can have a beneficial role in the post-CPR phase. We tested whether two different types of statins, hydrophilic pravastatin and lipophilic simvastatin, attenuated neurological injury following CA/CPR. The efficacy of pravastatin and simvastatin combination treatment was also assessed. METHODS: Isoflurane-anesthetized adult male wild-type C57Bl/6 mice subjected to 8-min CA/CPR were randomized into four groups: control, 2 mg/kg pravastatin, 20 mg/kg simvastatin, or a combination of 3 mg/kg pravastatin and 10 mg/kg simvastatin. Neurobehavioral assessment and histological analyses were performed to assess overall general health condition and neuronal injury, respectively. RESULTS: Combination treatment with pravastatin and simvastatin significantly reduced neuronal injury in the striatum and hippocampus, reduced cerebral edema, and improved general health at 4 days after CA/CPR. Combination statin treatment upregulated endothelial nitric oxide synthase mRNA in the brain. Pravastatin alone, but not simvastatin alone, improved general health after CA/CPR. Pravastatin was less potent than simvastatin at reducing neuronal injury in the brain. CONCLUSION: Combination treatment with two different types of statins at the correct dose may be a promising approach to neuroprotection following CA/CPR.
BACKGROUND: Global ischemia due to cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR) causes significant neuronal damage in vulnerable areas in the brain. Currently, a majority of patients eventually die after successful CPR due to neurological injury. Statins have pleiotropic effects including anti-inflammatory and/or antioxidant responses. These pleiotropic effects can have a beneficial role in the post-CPR phase. We tested whether two different types of statins, hydrophilic pravastatin and lipophilic simvastatin, attenuated neurological injury following CA/CPR. The efficacy of pravastatin and simvastatin combination treatment was also assessed. METHODS:Isoflurane-anesthetized adult male wild-type C57Bl/6 mice subjected to 8-min CA/CPR were randomized into four groups: control, 2 mg/kg pravastatin, 20 mg/kg simvastatin, or a combination of 3 mg/kg pravastatin and 10 mg/kg simvastatin. Neurobehavioral assessment and histological analyses were performed to assess overall general health condition and neuronal injury, respectively. RESULTS: Combination treatment with pravastatin and simvastatin significantly reduced neuronal injury in the striatum and hippocampus, reduced cerebral edema, and improved general health at 4 days after CA/CPR. Combination statin treatment upregulated endothelial nitric oxide synthase mRNA in the brain. Pravastatin alone, but not simvastatin alone, improved general health after CA/CPR. Pravastatin was less potent than simvastatin at reducing neuronal injury in the brain. CONCLUSION: Combination treatment with two different types of statins at the correct dose may be a promising approach to neuroprotection following CA/CPR.
Authors: Connie B Newman; David Preiss; Jonathan A Tobert; Terry A Jacobson; Robert L Page; Larry B Goldstein; Clifford Chin; Lisa R Tannock; Michael Miller; Geetha Raghuveer; P Barton Duell; Eliot A Brinton; Amy Pollak; Lynne T Braun; Francine K Welty Journal: Arterioscler Thromb Vasc Biol Date: 2019-02 Impact factor: 8.311
Authors: B C White; J M Sullivan; D J DeGracia; B J O'Neil; R W Neumar; L I Grossman; J A Rafols; G S Krause Journal: J Neurol Sci Date: 2000-10-01 Impact factor: 3.181