Circulatory Arrest as a Model for Studies of Global Ischemic Injury and Neuroprotection

Authors

  • LARS WIKLUND,

    Corresponding author
    1. Department of Surgical Sciences/Anesthesiology and Intensive Care Medicine, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
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  • HARI SHANKER SHARMA,

    1. Department of Surgical Sciences/Anesthesiology and Intensive Care Medicine, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
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  • SAMAR BASU

    1. Department of Public Health and Caring Sciences/Geriatrics/Clinical Nutrition, Uppsala University Hospital, SE-751 85 Uppsala, Sweden
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Address for correspondence: Lars Wiklund, M.D., Ph.D., Professor of Anesthesiology and Intensive Care Medicine, Department of Surgical Sciences/Anesthesiology and Intensive Care Medicine, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Voice: +46-18-6114851; fax: +46-18-559357. lars.wiklund@surgsci.uu.se

Abstract

Abstract: Despite many programs aimed at better immediate care of cardiac arrest victims, the subsequent mortality rate is high, with myocardial and central nervous system (CNS) injuries as the most common causes of death. Preclinical research is badly needed to produce a sound base for future clinical trials and possible improvements in clinical outcome. In our laboratory, we use piglets weighing approximately 25 kg. Ventricular fibrillation is produced by an AC current and left without treatment for 8-12 min, after which cardiopulmonary resuscitation according to current human guidelines is undertaken. The heart is then defibrillated and restoration of spontaneous circulation induced. During the procedure, blood pressure and flow measurements are obtained in the systemic, pulmonary, and cerebral circulation. Peroxidation and inflammation are monitored by systemic and cerebral venous plasma concentrations of isoprostane (8-iso-PGF), an indicator of oxidative damage, and prostaglandin F metabolite (15-keto-dihydro-PGF), an indicator of cyclooxygenase-2 activity, respectively. Neurocellular damage is monitored by the jugular plasma concentration of protein S-100β. Neurological outcome is assessed at >24 h after the incident. Our results show that plasma concentrations of 8-iso-PGF are greater after more extended periods of ischemia. PBN (α-phenyl-N-tert-butyl nitrone), a so-called spin-trap scavenger, has a neuroprotective effect since neurological outcome is enhanced, and the 8-iso-PGF concentration is decreased during reperfusion. Use of water-soluble sulfonated PBN (S-PBN) results in better autoregulation of cerebral cortical blood flow and less peroxidation of CNS lipids during reperfusion. These observations suggest that our model can be used to explore neuroprotective effects of potential therapeutic agents.

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