title: Bicarbonate conservation during incomplete cerebral ischemia with superimposed hypercapnia.
abstract: We superimposed extreme hypercapnia (arterial Pco2 400-450 mmHg) immediately before and during incomplete cerebral ischemia to distinguish the role of intracellular pH (pHi) and bicarbonate [( HCO3-]i) in postischemic metabolic and electrophysiological recovery. Incomplete global ischemia was produced in seven anesthetized dogs by 30 min of intracranial hypertension followed by 4 h of reperfusion. ATP, phosphocreatine (PCr), and pHi were measured with 31P magnetic resonance spectroscopy, and [HCO3-]i was calculated from the Henderson-Hasselbalch equation using the measured pHi and sagittal sinus Pco2. Cerebral blood flow was reduced to 7 +/- 1 ml.min-1.100 g-1 (+/- SE) during ischemia with extreme hypercapnia, and pHi decreased to 5.72 +/- 0.09. During normocapnic reperfusion, pHi rapidly returned to near baseline values by 14 min. [HCO3-]i fell from 12.1 +/- 0.9 to 6.0 +/- 1.2 mM by the midpoint of ischemia and recovered by 30 min of reperfusion. ATP, PCr, and O2 consumption also recovered rapidly and completely. Somatosensory-evoked potentials (SEP) recovered to 43 +/- 10% of control amplitude. These results are in marked contrast to the poor metabolic and SEP recovery previously observed in hyperglycemic dogs in which pHi decreased to the same range as with hypercapnic ischemia, but in which [HCO3-]i was much lower (1.1 +/- 0.5 mM). Therefore, [HCO3-]i depletion during hyperglycemic ischemia may be a more important factor in recovery than end-ischemic pHi per se. We speculate that higher [HCO3-]i may improve glial cell buffering capacity or decrease iron availability for hydroxyl radical production.
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
authors.forename: P D
authors.initials: PD
authors.lastname: Hurn
authors.forename: R C
authors.initials: RC
authors.lastname: Koehler
authors.forename: S E
authors.initials: SE
authors.lastname: Norris
authors.forename: A E
authors.initials: AE
authors.lastname: Schwentker
authors.forename: R J
authors.initials: RJ
authors.lastname: Traystman
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation; D004285:Dogs; D005073:Evoked Potentials, Somatosensory; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000150:complications / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000150:complications / Q000503:physiopathology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010101:Oxygen Consumption; D010313:Partial Pressure; D010725:Phosphocreatine / Q000378:metabolism; D015424:Reperfusion
chemical_list: D001639:Bicarbonates; D001786:Blood Glucose; D010725:Phosphocreatine; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate