The role of tissue acidosis in ischaemic tissue injury: the concept of the pH integral.
Cerebral cortical tissue pH was monitored with an extracellular glass electrode in 32 rats subjected to total global cerebral ischaemia produced by ligation of the basilar and carotid arteries with systemic hypotension for periods of 8 to 60 min. The totality of the ischaemia, and its duration were confirmed by monitoring with a brain tissue O2 electrode. Reperfusion was induced by hypertension and maintained thereafter to exclude delayed ischaemia during 3 h survival after which the rats were sacrificed by perfusion fixation. The severity of tissue pH change was varied by inducing hyperglycaemia in some of the rats. Quantitative counts were made of neurons demonstrating changes reflecting severe ischaemic injury within 500 microns of the electrode tip. For the criterion of an ischaemically injured neuron count greater than 20%, there appeared to be a threshold at about 30 min, and more than 0.8 units change in pH. For quantitative assessment of the ischaemic insult a more satisfactory index was found by combining both time and acidosis as the integral of the pH change during the period of ischaemia. This was found to have a strong correlation with the histologic changes. There was a less strong correlation between the acidosis during reperfusion and the histologic change. Comparing these results with those for 3 rats subjected to 215 min of ischaemia without reperfusion, it appears that most of the effect of acidosis in aggravating ischaemic injury takes place during the first hour of ischaemia with little further aggravation for longer periods.
D000138:Acidosis / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D006863:Hydrogen-Ion Concentration; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000145:classification / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D001786:Blood Glucose