Dependence of cerebral energy phosphate and evoked potential recovery on end-ischemic pH.
We determined whether the rate of metabolic recovery and electrophysiological deficit after incomplete cerebral ischemia is related to intracellular pH (pHi) achieved at the end of ischemia in a dose-dependent manner. End-ischemic pHi was varied by employing two ischemic durations, 12 and 30 min, and by setting preischemic plasma glucose to approximately 80 or 400 mg/dl. Incomplete global ischemia was produced in anesthetized dogs by transient intracranial hypertension followed by 4 h of reperfusion, and pHi, ATP, and phosphocreatine (PCr) were measured with 31P magnetic resonance spectroscopy. Cerebral blood flow was reduced to approximately 6 ml.min-1.100 g-1 during ischemia. End-ischemic pHi was greater than 5.7 in all animals from various treatment groups except for four of seven dogs treated with 30-min hyperglycemic ischemia. When end-ischemic pHi remained greater than 5.7, there was nearly complete recovery of ATP, PCr, pHi, intracellular bicarbonate concentration [( HCO3-]i), and O2 consumption. Partial recovery of somatosensory-evoked potentials (SEP) occurred in most of these animals. In the 30-min hyperglycemic animals in which pHi fell below 5.5, ATP, PCr, and O2 consumption recovered by only one-half over 60 min of reperfusion and then declined to near-zero levels without SEP recovery. In addition, pHi remained less than 6.0, and [HCO3-]i remained less than 2 mM throughout reperfusion. We conclude that there is an apparent in vivo pHi threshold of approximately 5.5-5.7 during incomplete cerebral ischemia that is associated with an inability to significantly restore pHi and [HCO3-]i and with secondary deterioration of high-energy phosphate levels.
Hurn
P D
PD
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Koehler
R C
RC
Norris
S E
SE
Blizzard
K K
KK
Traystman
R J
RJ
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D004056:Differential Threshold; D004285:Dogs; D004734:Energy Metabolism; D005073:Evoked Potentials, Somatosensory; D006439:Hemodynamics; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging; D010710:Phosphates / Q000378:metabolism*
D010710:Phosphates; D006859:Hydrogen