Extracellular pH, Potassium, and Calcium Activities in Progressive Ischaemia of Rat Cortex

pH and K+ from the extracellular space, PO2, and CBF have been measured in the same region during progressive ischaemia of primate cerebral cortex. As blood flow was reduced, the other changes had the following sequence. PO2 fell rapidly to 30% of control levels at regional CBF (rCBF) of 30 ml 100 g−1 min−1. As CBF was further reduced, PO2 continued to fall. pH remained stable until around 20 ml 100 g−1 min−1, below which pH fell rapidly, with an exponential increase in H+ concentration. K+ showed the well-known relationship to CBF, remaining normal until around 10 ml 100 g−1 min−1, below which K+ rose rapidly. pHe and log K+ were linearly related and confirmed that pH fell by 0.3 U before K+ rose significantly, and fell by 0.6 U before the massive rise in K+. The mechanisms involved in this sequence of events and the role of pH changes in the development of the so-called “ischaemic penumbra” are discussed.

Section: Discussioncontrasting

confidence: 95%

Section: Methodsmentioning

confidence: 99%

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pH, K⁺, and PO₂ of the Extracellular Space during Ischaemia of Primate Cerebral Cortex

Harris

Richards

Symon

et al. 1987

“…Both the EEG and the high energy phosphates re covered completely after 10 min of ischemia while the lack of the recovery for both parameters after 30-min ischemia indicates that the point of func tional reversibility had been surpassed. The disrup tion of ion homeostasis occurs after 3 to 5 min (Hansen and Zeuthen, 1981;Harris and Symon, 1984) and minimal values for high energy phos phates are reached after �5 min (Siesjo, 1978). Ex tracellular amino acids increase almost linearly from the first 10 min fraction until the discontin uation of ischemia and return to normal during re circulation.…”

Section: Discussionmentioning

confidence: 99%

Ischemia-Induced Shift of Inhibitory and Excitatory Amino Acids from Intra- to Extracellular Compartments

Hagberg

Lehmann

Sandberg³

et al. 1985

660

246

Brain ischemia was induced for 10 or 30 min by clamping the common carotid arteries in rabbits whose vertebral arteries had previously been electrocauterized. EEG and tissue content of high energy phosphates were used to verify the ischemic state and to evaluate the degree of postischemic recovery. Extracellular levels and total contents of amino acids were followed in the hippocampus during ischemia and 4 h of recirculation. At the end of a 30-min ischemic period, GABA had increased 250 times, glutamate 160 times, and aspartate and taurine 30 times in the extracellular phase. The levels returned to normal within 30 min of reflow. A delayed increase of extracellular phosphoethanolamine and ethanolamine peaked after 1–2 h of reflow. Ten minutes of ischemia elicited considerably smaller but similar effects. With respect to total amino acids in the hippocampus, glutamate and aspartate decreased to 30–50% of control while GABA appeared unaffected after 4 h of reflow. Alanine, valine, phenylalanine, leucine, and isoleucine increased severalfold. The importance of toxic extracellular levels of excitatory amino acids, as well as of high extracellular levels of inhibitory amino acids, are considered in relation to the pathophysiology of neuronal cell loss during cerebral ischemia.

“…, 1977;Harris and Symon, 1984). Harris and Symon have suggested that intracellular pH would be better protected from acidotic shift than extracellular pH by physicochemical buffering during partial ischemia (before any major ion change).…”

Section: Discussionmentioning

confidence: 99%

Brain Tissue Acidosis and Changes of Energy Metabolism in Mild Incomplete Ischemia—Topographical Study

Kim

Handa

Ishikawa

et al. 1985

Summary: Regional changes of brain tissue pH and its correlation to energy metabolism were studied in various degrees of incomplete ischemia for 5 and 60 min in the unilateral common carotid occlusion of normally fed mongolian gerbils. The degree of ischemia was evaluated by the severity of neurological deficits following 60 min of occlusion, and animals were divided into three groups: symptomatic, borderline, and asymptomatic. Changes of NADH and ATP distribution corresponded well to the degree of ischemia. On the other hand, acidosis devel oped more clearly and extended in wider areas than the The brain is highly dependent on a continuous supply of glucose and oxygen to maintain neuronal function. Thus, the brain tissue is vulnerable to ischemia for lack of energy substrate and oxygen. Although it is evident that permanent breakdown of energy metabolism following ischemia causes irre versible brain tissue damage, energy failure during ischemia does not always result in permanent damage. Experimental studies have demonstrated a better recovery of energy metabolism (Hossmann and Kleihues, 1973; Nordstrom and Siesjo, 1978; Rehncrona et aI., 1980) following complete than in complete ischemia in spite of a similar perturbation of brain energy state. Thus, it seems clear that en ergy failure during ischemia is not a limiting factor for the functional and the structural damage during the postischemic reperfusion period. Instead, other possible factors such as formation of free radicals (Flamm et aI. , 1978), accumulation of free fatty acids (Bazan, 1970), and postischemic hypoperfu sion (Paschen et aI. , 1983) lactic acidosis following severe incomplete ischemia as an important factor of irreversible brain tissue damage (Rehncrona et aI. , 1980(Rehncrona et aI. , , 1981 Kalimo et aI. , 1981; Plum et aI. , 1983). However, development of lactic acidosis and its correlation to the changes of energy state in mild incomplete ischemia, which is not detrimental enough to cause irreversible cell damage, have not been well discussed (Ginsberg et a\. , 1983). In the present study, we have investi gated regional changes of brain tissue pH in various degrees of incomplete ischemia correlating with re gional changes of energy metabolism in normally fed mongolian gerbils following acute unilateral oc clusion of the common carotid. Regional changes of brain tissue pH were measured semiquantita tively using the umbelliferone technique (Fink and Koehler, 1970;Sundt et a\. , 1978; Welsh et aI. , 1982;Csiba et a\. , 1983). Regional changes of the redox state of brain tissue were assessed using NADH fluorescence histochemistry (Welsh and Rieder, 1978), and regional changes of ATP using the luci ferine luciferase bioluminescent method (Kogure and Alonso, 1978). MATERIALS AND METHODSForty-six mongolian gerbils of either sex, weighing 50-80 g, were used in this study. The animals were allowed REGIONAL METABOLISM AND pH IN CEREBRAL ISCHEMIA 433 FIG. 1. Ultraviolet light reflectance (UV), regional NADH fluorescence (NADH), regional ATP...