Carbonic acid buffer changes during complete brain ischemia

Abstract

Simultaneous measurements of tissue PCO2 (PtCO2), interstitial H+ concentration ([H+]o), and tissue lactate content were used to examine changes in interstitial HCO3- concentration ([HCO3-]o) during complete ischemia. In normoglycemic rats (blood glucose of 6-8 mM; neocortical ischemic-induced lactate content 8-12 mmol/kg) [H+]o increased from 7.22 +/- 0.02 to 6.79 +/- 0.02 pH (n = 3). By contrast, in hyperglycemic rats (blood glucose 18-75 mM; ischemic-induced lactate content 19-31 mmol/kg) [H+]o rose by a significantly larger amount to 6.19 +/- 0.02 pH (n = 7). Given that HCO3- is the predominant interstitial H+ buffer, changes in peak PtCO2 show why peak [H+]o were bimodally distributed compared with lactate content. Between 8 and 12 mmol/kg lactate, when peak PtCO2 rose from 99 to 186 Torr but [H+]o was constant at 6.79 pH, calculated [HCO3-]o increased from 11.9 to 21.9 mM. Then after transitional changes, peak PtCO2 and [H+]o remained constant at 389 +/- 9 Torr (n = 7) and 6.19 pH despite the fact that tissue lactate ranged from 19 to 31 mmol/kg lactate, respectively; [HCO3-]o must have remained constant at 12.3 +/- 0.7 mM (n = 7). Since ischemic brain continued to produce another 12 more mmol/kg of lactic acid above 19 mmol/kg lactate without further changes in PtCO2 or [H+]o, H+ and HCO3- must have been heterogeneously compartmented. The continued lactic acid production occurred in a compartment that occupied 36% of neocortical space. This compartment is likely to represent glial cells.

Tissue Pco2in Brain Ischemia Related to Lactate Content in Normo- and Hypercapnic Rats

“…This is a higher LlPtC02 than expected from previous measurements in cats (Ponten and Siesj6, 1966); however, the LlPC02 is similar to that reported by Kraig et al (1986). We interpret the difference to mean that, in the rat, a craniotomy with surface electrode measurements artificially raises Ptco2, probably by some impediment of venous return.…”

“…This is the predicted result since hypercapnic animals have a higher tissue HC03 -content and hence a larger "source" of CO2 (Siesj6 et aI., 1990). The results make it clear that a discontinuous Pco2/lactate relationship of the type described by Kraig et al (1986) could not be verified.…”

“…, 1974a). This contention was sub stantiated by Kraig et al (1986), who induced vary ing degrees of hyperglycemia prior to inducing com plete ischemia, with subsequent measurements of Ptco2 with a surface CO2 electrode. Unexpectedly, the results revealed a discontinuous Pco2/lactate re lationship, with a gradual increase in Ptco2 in the tissue lactate range of 7-15 mm Hg, and a precipi tous rise to 390 mm Hg at lactate contents of 17-20 mmol kg -1.…”

“…Since Kraig et al (1986) studied animals that had relatively high arterial Peo2 values, their tissue CO2 tensions rose to maximal values of 400 mm Hg. The question arose of whether a similar discontinuous relationship could be obtained in normocapnic ani mals.…”

Acidosis Causes Endoplasmic Reticulum Stress and Caspase-12-Mediated Astrocyte Death

“…The ER stress response can promote either cell survival or cell death, depending on the degree of injury and other factors (Harding and Ron, 2002;Paschen, 2003;Rao et al, 2004). Acidosis is a major factor contributing to cell death after cerebral ischemia (Rehncrona et al, 1981;Kraig et al, 1986Kraig et al, , 1987Siesjo, 1988;Nedergaard et al, 1991;Katsura et al, 1994). Cerebral artery occlusion produces acidosis in regions of incomplete ischemia where residual blood flow carries glucose but not oxygen, leading to anaerobic glycolysis and the production of lactic acid (Nedergaard et al, 1986;Peek et al, 1989;Obrenovitch, 1995;Swanson et al, 1997).…”