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Improved short-term neurological recovery with flunarizine in a canine model of cardiac arrest

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      Abstract

      A 10-minute cardiac arrest was produced in dogs by electrical fibrillation of the heart. Recovery of cerebral function was monitored by estimating the cerebral metabolic rate of oxygen consumption (CMRO2), cerebral blood flow (CBF), electroencephalograph (EEG) and extent of neurological deficit. The study group received flunarizine (0.1 mg/kg intravenously) at the beginning of resuscitation, while control animals were given the drug vehicle. By four hours after resuscitation, CMRO2 in flunarizine-treated dogs was 121 ± 43% of pre-arrest baseline, as compared with 37 ± 9% in control animals (P < 0.02). In the flunarizine group, CBF was 83 ± 21% of baseline, while it was only 31 ± 8% in controls (P < 0.01). As compared with the control group, no other significant changes were detected in electrocardiographic, hemodynamic, or biochemical parameters in the flunarizine-treated dogs. A significant improvement in the visual EEG score (P < 0.001) and neurological deficit (P < 0.05) was seen in flunarizine-treated dogs six hours after ischemic insult.

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      References

        • Safar P
        • Bleyaert A
        • Nemoto EM
        • et al.
        Resuscitation after global brain ischemia-anoxia.
        Crit Care Med. 1978; 6: 215-227
        • Bleyaert A
        • Nemoto E
        • Safar P
        • et al.
        Thiopental amelioration of brain damage after global ischemia in monkeys.
        Anesthesiology. 1978; 49: 390-398
        • Todd MM
        • Chadwick HS
        • Shapiro HM
        • et al.
        The neurologic effects of thiopental therapy following experimental cardiac arrest in cats.
        Anesthesiology. 1982; 57: 76-86
        • Abramson NS
        • Safar P
        • Detre K
        • et al.
        Results of a randomized clinical trial of brain resuscitation with thiopental.
        Anesthesiology. 1983; 59: A101
        • Steen PA
        • Newberg LA
        • Milde JH
        • et al.
        Cerebral blood flow and neurologic outcome when nimodipine is given after complete cerbral ischemia in the dog.
        J Cer Blood Flow Metab. 1984; 4: 82-87
        • Van Belle H
        The disappearance of adenosine in blood. Effects of lidoflazine and other drugs.
        Europ J Pharmacol. 1970; 11: 241-248
        • Winegar CP
        • Henderson O
        • White BC
        • et al.
        Early amelioration of neurological deficit by lidoflazine after fifteen minutes of cardiopulmonary arrest in dogs.
        Anr. Emerg Med. 1983; 12: 471-477
        • Wauquier A
        • Ashton D
        • Hermans C
        • et al.
        Pharmacological effects in protective and resuscitative models of brain hypoxia.
        in: Wiedemann K Hoyer S Brain Protection. Springer-Verlag, Berlin1983: 100-111
        • Wauquier A
        • Ashton D
        • Edmonds Jr, HL
        Protection against cerebral hypoxia by antimigraine drugs.
        in: Amery WK Van Nueten JM Wauquier A The Pharmacological Basis of Migraine Therapy. Pitman, London1984: 134-148
        • Wauquier A
        • Clincke G
        • Van den Broeck WAE
        • et al.
        Global incomplete ischemia in dogs assessed by quantitative EEG analysis: Effects of hypnotics and flunarizine.
        in: Pfurtscheller J Jonkman EJ Lopes da Silva FH Quantitative EEG and Imaging Techniques in Brain Ischemia. Elsevier Biomedical Press, Amsterdam1984: 217-233
        • White BC
        • Winegar CD
        • Jackson RE
        • et al.
        Cerebral cortical perfusion during and following resuscitation from cardiac arrest in dogs.
        Am J Emerg Med. 1983; 2: 128-138
        • Holmes B
        • Brogden RG
        • Heel RC
        • et al.
        Flunarazine.
        Drugs. 1984; 27: 6-44
        • Wauquier A
        • Edmonds Jr, HL
        Effect of flunarizine on recovery of cerebral function following cardiac arrest.
        Neuropsychobiology. 1984; (in press)
        • Haider I
        • Matthew H
        • Oswald I
        Electroencephalographic changes in acute drug poisoning.
        Electroencephalogr Clin Neurophysiol. 1971; 30: 23-31
        • Nystrom E
        • Schurr A
        • Reid KH
        • et al.
        Effect of a calcium antagonist on recovery of electrical responsiveness in rat hippocampal slices after anoxia.
        in: Fed Proc. 43. 1984: 552
        • Tseng MT
        • Schurr A
        • Reid KH
        • et al.
        An ultrastructural study on the influence of flunarizine on hippocampal CAI cells after in vitro anoxia.
        in: Fed Proc. 43. 1984: 552
        • Van Nueten JM
        • Van Beek J
        • Janssen PAJ
        Effect of flunarizine on calcium-induced responses of peripheral vascular smooth muscle.
        Arch Pharmacodyn Ther. 1978; 232: 42-52
        • Nakayama K
        • Kasuya Y
        Selective abolition of Ca-dependent responses of smooth and cardiac muscles by flunarizine.
        Jpn J Pharmacol. 1980; 30: 731-742
        • Borgers M
        • De Clerck F
        • Van Reempts J
        • Xhonneux R
        • Van Nueten JM
        Selective blockade of cellular Ca2+-overload by flunarizine.
        Int Angiol. 1984; 3: 25-31
        • Meldrum B
        • Griffiths T
        • Evans M
        Hypoxia and neuronal hyperexcitability: A clue to mechanisms of brain protection.
        in: Wauquier A Borgers M Amery WK Protection of Tissues against Hypoxia. Elsevier Biomedical Press, Amsterdam1982: 275-286
        • Van Reempts J
        • Borgers M
        Morphological assessment of pharmacological brain protection.
        in: Wauquier A Borgers M Amery WK Protection of Tissues against Hypoxia. Elsevier Biomedical Press, Amsterdam1982: 263-274
        • Stam H
        • Hülsmann WC
        Release of lipolytic products from rat heart, hormonal stimulation, intracardiac origin, and pharmacological modification.
        Biochem Int. 1981; 2: 477-484
        • Nemoto EM
        • Shiu GK
        • Nemmer JP
        • et al.
        Free fatty acid accumulation in the pathogenesis and therapy of ischemic-anoxic brain injury.
        Am J Emerg Med. 1983; 2: 175-179