Cation dysfunction associated with cerebral ischemia followed by reperfusion: a comparison of microdialysis and ion-selective electrode methods

Object. Disruption of ionic homeostasis during ischemia is a well-characterized event and is identified by a rise in the concentration of extracellular potassium [K+](e), with a concomitant reduction in the concentration of extracellular sodium [Na+](e). Results of clinical studies in which microdialysis has been used, however, have shown only modest changes in the levels of extracellular ions. The object of this study was to measure [K+](e) and [Na+](e) by using ion-selective electrodes (ISEs) and to compare these measurements with those obtained using the well-established method of microdialysis. Methods. Fifteen Sprague-Dawley rats were separated into three groups. Five animals were subjected to a 15-minute period of ischemia, and another five animals to a 60-minute period of ischemia; animals in both of these groups received K+-free microdialysis perfusate. The third group of five rats underwent a 60-minute period of ischemia and received a reduced-Na+ microdialysis perfusate. Transient forebrain ischemia was produced by bilateral carotid artery occlusion combined with hypotension. A custom-fabricated glass Na+ electrode and a flexible plastic K+ and reference electrodes were used to monitor extracellular ion transients. Microdialysis samples were obtained with the aid of a 2-mm microdialysis probe that was perfused with K+-free mock cerebrospinal fluid at a rate of 2 mul/minute. Baseline measurements of [K+](e) and [Na+](e), obtained using ISEs, were 3.41 +/- 0.09 mM and 145 +/- 7.75 mM, respectively. Ischemia resulted in a rapid accumulation of [K+](e) (in animals subjected to 15 minutes of ischemia, the concentration was 41.9 +/- 13.7 mM; and in animals subjected to 60 minutes of ischemia, the concentration was 66.9 +/- 11.5 mM), with a concomitant decrease in [Na+](e) (in animals subjected to 15 minutes of ischemia, the concentration was 71.7 +/- 2.9 mM; and in animals subjected to 60 minutes of ischemia, the concentration was 74.7 +/- 1.9 mM). A comparison of microdialysis and ISE methods revealed that microdialysis underestimated the [K+](e) changes and was insensitive to concomitant [Na+](e) alterations that occur during ischemia. Conclusions. Our results indicate that the flexible ISE is a reliable and accurate tool for monitoring ionic dysfunction that accompanies brain injury.