ACIDOSIS INDUCED BY HYPERCAPNIA EXAGGERATES ISCHEMIC BRAIN-DAMAGE

Although preischemic hyperglycemia is known to aggravate damage due to transient ischemia, it is a matter of controversy whether or not this is a result of the exaggerated acidosis. It has recently been reporte d that although tissue acidosis of a comparable severity could be indu ced in normoglycemic dogs by an excessive rise in arterial CO2 tension , short-term functional recovery was improved, rather than compromised . In the present experiments we induced excessive hypercapnia (P(a)co( 2) similar to 300 mm Hg) in normoglycemic rats before inducing forebra in ischemia of 10-min duration. This reduced the brain extracellular p H to values normally encountered in hyperglycemic rats subjected to is chemia. The events induced by hypercapnia dearly enhanced ischemic bra in damage, as assessed histologically after 7 days of recovery. We hyp othesize that the decisive event was an exaggerated decrease in extra- and intracellular pH and that the results thus demonstrate an adverse effect of acidosis. However, since postischemic seizures did not occu r in the hypercapnic ischemic rats, the results also demonstrate that changes in intra-extracellular pH and bicarbonate concentrations modul ated ischemic damage in an unexpected way.