Acid-base changes during complete brain ischemia.
We examined the proposal that preischemic hyperglycemia causes exaggerated brain damage by decreasing intracellular or extracellular pH to below a specified threshold value. We also provide a critical appraisal of two related hypotheses. The first is that hyperglycemia enhances brain damage by causing excessive intraglial acidosis; the second, that the critical degree of acidosis is reached not during the ischemia but when recirculation is instituted. The following conclusions are drawn. First, the evidence is inconclusive in favor of marked compartmentation of H+ during ischemia, based on a discontinuous delta lactate/delta PCO2 relation and on direct intracellular pH measurements. In fact, results obtained with identical techniques in normoglycemic animals suggest that the acid compartment assumed to be glia is very small and may be of another origin. Second, although recirculation may give rise to a further increase in either extracellular or intracellular acidosis under certain conditions, this acidosis is not a prerequisite for increased tissue damage or infarction. Third, a critical appraisal of reports supports the contention that enhanced damage is triggered below a specified threshold pH value. In complete or near-complete ischemia, this value corresponds to a tissue lactate content of 17-20 mM.kg-1 wet wt. No correlation exists between subthreshold values for delta lactate and the severity of tissue damage. Furthermore, hyperglycemia cannot be expected to enhance damage if conditions prevent lactate from reaching threshold values or if they uncouple changes in lactate and pH.
Siesjö
B K
BK
Laboratory for Experimental Brain Research, University of Lund, Sweden.
Ekholm
A
A
Katsura
K
K
Theander
S
S
D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000378:metabolism*; D000140:Acidosis, Lactic / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D001639:Bicarbonates / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006943:Hyperglycemia / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism
D001639:Bicarbonates; D004573:Electrolytes; D002245:Carbon Dioxide; D000255:Adenosine Triphosphate; D005947:Glucose