Pyruvate enhances neurological recovery following cardiopulmonary arrest and resuscitation

• Published in: Resuscitation Vol. 76; no. 1; pp. 108 - 119
• Main Authors: Sharma, Arti B, Barlow, Matthew A, Yang, Shao-Hua, Simpkins, James W, Mallet, Robert T
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.01.2008; Elsevier
• Subjects: Analysis of Variance; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antioxidants - pharmacology; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Brain - enzymology; Brain - metabolism; Brain ischemia; Cardiac arrest; Cardiopulmonary Resuscitation; Cardiopulmonary resuscitation (CPR); Caspase 3 - metabolism; Cerebral blood flow; Cerebrovascular Circulation - drug effects; Dinoprost - analogs & derivatives; Dinoprost - metabolism; Dogs; Emergency; Emergency and intensive cardiocirculatory care. Cardiogenic shock. Coronary intensive care; Energy Metabolism; Heart Arrest - therapy; In Situ Nick-End Labeling; Inflammatory response; Intensive care medicine; Matrix Metalloproteinases - metabolism; Medical sciences; Metabolism; Neurological dysfunction; Oxidative Stress; Peroxidase - metabolism; Post-resuscitation period; Pyruvic Acid - pharmacology; Regional Blood Flow; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Inflammatory response; BL; terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling; cardiac arrest; MPO; relative fluorescence units; OCCC; Q; CA1; TUNEL; analysis of variance; Post-resuscitation period; ANOVA; Cerebral blood flow; pre-arrest baseline; cornus ammonis region 1 of hippocampus; reactive oxygen species; NDS; matrix metalloproteinases; Neurological dysfunction; CA; RFU; monocarboxylate transporter; return of spontaneous circulation; DAPI; 4′,6-diamidino-2-phenylindole; myeloperoxidase; ROSC; Cardiopulmonary resuscitation (CPR); Metabolism; open-chest cardiac compressions; MMP; regional blood flow; ROS; Brain ischemia; neurological deficit score; MCT; Cardiac arrest; Intensive cardiocirculatory care; Nervous system diseases; Cardiocirculatory arrest; Intensive care; Central nervous system; Pyruvate; Cardiovascular disease; Cerebral disorder; Blood flow; Encephalon; Vascular disease; Central nervous system disease; Hemodynamics; Cerebrovascular disease; Resuscitation
• ISSN: 0300-9572; 1873-1570
• DOI: 10.1016/j.resuscitation.2007.04.028

Summary Purpose Cerebral oxidative stress and metabolic dysfunction impede neurological recovery from cardiac arrest-resuscitation. Pyruvate, a potent antioxidant and energy-yielding fuel, has been shown to protect against oxidant- and ischemia-induced neuronal damage. This study tested whether acute pyruvate treatment during cardiopulmonary resuscitation can prevent neurological dysfunction and cerebral injury following cardiac arrest. Methods Anesthetized, open-chest mongrel dogs underwent 5 min cardiac arrest, 5 min open-chest cardiac compression (OCCC), defibrillation and 3-day recovery. Pyruvate ( n = 9) or NaCl volume control ( n = 8) were given (0.125 mmol kg−1 min−1 i.v.) throughout OCCC and the first 55 min recovery. Sham dogs ( n = 6) underwent surgery and recovery without cardiac arrest-resuscitation. Results Neurological deficit score (NDS), evaluated at 2-day recovery, was sharply increased in NaCl-treated dogs (10.3 ± 3.5) versus shams (1.2 ± 0.4), but pyruvate treatment mitigated neurological deficit (NDS = 3.3 ± 1.2; P < 0.05 versus NaCl). Brain samples were taken for histological examination and evaluation of inflammation and cell death at 3-day recovery. Loss of pyramidal neurons in the hippocampal CA1 subregion was greater in the NaCl controls than in pyruvate-treated dogs (11.7 ± 2.3% versus 4.3 ± 1.2%; P < 0.05). Cardiac arrest increased caspase-3 activity, matrix metalloproteinase activity, and DNA fragmentation in the CA1 subregion; pyruvate prevented caspase-3 activation and DNA fragmentation, and suppressed matrix metalloproteinase activity. Conclusion Intravenous pyruvate therapy during cardiopulmonary resuscitation prevents initial oxidative stress and neuronal injury and enhances neurological recovery from cardiac arrest.