title: Effects of hyperglycemia or hypoglycemia on brain cell membrane function and energy metabolism during the immediate reoxygenation-reperfusion period after acute transient global hypoxia-ischemia in the newborn piglet.
abstract: This study was done to determine the effects of hyperglycemia or hypoglycemia on brain cell membrane function and energy metabolism during the immediate reoxygenation-reperfusion period after hypoxia-ischemia (HI). Forty-five newborn piglets were divided randomly into four experimental groups: normoxia control (NC, n=9); HI/reoxygenation-reperfusion (RR) control (HC, n=11); HI/RR hyperglycemia (HE, n=12); and HI/RR hypoglycemia (HO, n=13) group. Animals were subjected to transient HI for 30 min followed by 2 h of RR. Cerebral HI was induced by temporary but complete occlusion of bilateral common carotid arteries with surgical clips and simultaneous breathing with 8% oxygen. Glucose was unregulated in HC group, and controlled by modified glucose clamp technique immediately after HI in HE (350 mg/dl) and HO (50 mg/dl) groups. During HI, heart rate, base deficit, glucose and lactate level in the blood and cerebrospinal fluid increased, and arterial pH, oxygen saturation and blood pressure decreased significantly in HC, HE and HO groups. During RR, these abnormalities returned to normal values, but lactic acidosis persisted especially in HO group. Cerebral Na(+),K(+)-ATPase activity decreased, and lipid peroxidation products increased significantly in HC group than in NC group, and these abnormalities were significantly aggravated in HE, but not in HO, group. Brain ATP and phosphocreatine levels in HE group were significantly reduced compared to the corresponding values in NC, HC and HO groups. In summary, hyperglycemia, but not hypoglycemia immediately after HI interfered with the recovery of brain cell membrane function and energy metabolism. These findings suggest that post-hypoxic-ischemic hyperglycemia is not beneficial and might even be harmful in neonatal hypoxic-ischemic encephalopathy.
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: W S
authors.initials: WS
authors.lastname: Park
authors.forename: Y S
authors.initials: YS
authors.lastname: Chang
authors.forename: M
authors.initials: M
authors.lastname: Lee
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000293:injuries / Q000378:metabolism; D001238:Asphyxia Neonatorum / Q000378:metabolism* / Q000503:physiopathology; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000254:growth & development / Q000378:metabolism / Q000503:physiopathology; D002320:Cardiovascular Physiological Phenomena; D002462:Cell Membrane / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology; D005947:Glucose / Q000134:cerebrospinal fluid; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006943:Hyperglycemia / Q000378:metabolism* / Q000503:physiopathology; D007003:Hypoglycemia / Q000378:metabolism* / Q000503:physiopathology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000503:physiopathology; D007231:Infant, Newborn; D019344:Lactic Acid / Q000097:blood / Q000134:cerebrospinal fluid; D015227:Lipid Peroxidation / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D012964:Sodium / Q000378:metabolism; D013552:Swine
chemical_list: D001786:Blood Glucose; D019344:Lactic Acid; D012964:Sodium; D000251:Adenosine Triphosphatases; D005947:Glucose; D011188:Potassium