title: Effect of hyperglycemia on reperfusion-associated recovery of intracellular pH and high energy phosphates after transient cerebral ischemia in gerbils.
abstract: Hyperglycemia increases cerebral damage after transient cerebral ischemia. This study used in vivo 31P nuclear magnetic resonance spectroscopy to determine the relationship of intracellular tissue acidosis and delayed recovery of brain high-energy phosphates to increased damage during the reperfusion period. Mongolian gerbils were subjected to transient bilateral carotid ischemia for 20 min with 2 h reperfusion. All gerbils were pretreated intraperitoneally with equivalent volumes in saline of 0.003 units per kilogram of insulin or vehicle, or with 4 grams of glucose per kilogram. The gerbils were then scanned in a 4.7 Tesla Magnetic Resonance Imager-Spectrometer to determine levels of intracellular pH, inorganic phosphate, adenosine triphosphate, and phosphocreatine. In each group, intracellular pH decreased with ischemia, but most significantly in hyperglycemic animals (6.45 +/- 0.15), in which it had not recovered to preischemic levels by the end of the reperfusion period (6.8 +/- 0.1 vs 7.04 +/- 0.1, p < 0.05). High-energy phosphates phosphocreatine-inorganic phosphate and phosphocreatine-adenosine triphosphate showed partial recovery in all groups throughout the reperfusion period; the recovery was not significantly altered by glucose status. Hyperglycemia worsened pH but not the recovery of high-energy phosphates in animals reperfused after 20 min of transient cerebral ischemia. This sustained acidosis may be a primary event in transient damage in hyperglycemic animals.
authors.affiliation: Department of Neurological Surgery, University of Wisconsin, Madison 53792, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Dempsey
authors.forename: M K
authors.initials: MK
authors.lastname: Başkaya
authors.forename: D J
authors.initials: DJ
authors.lastname: Combs
authors.forename: D
authors.initials: D
authors.lastname: Donaldson
authors.forename: A M
authors.initials: AM
authors.lastname: Rao
authors.forename: M R
authors.initials: MR
authors.lastname: Prasad
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000378:metabolism; D001786:Blood Glucose; D001835:Body Weight; D002545:Brain Ischemia / Q000378:metabolism*; D002339:Carotid Arteries / Q000601:surgery; D004734:Energy Metabolism / Q000502:physiology*; D005849:Gerbillinae; D005947:Glucose / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D006943:Hyperglycemia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010710:Phosphates; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D005947:Glucose