Extracellular volume fraction and diffusion characteristics during progressive ischemia and terminal anoxia in the spinal cord of the rat

Abstract

Extracellular space (ECS) volume fraction (alpha), ECS tortuosity (lambda), and nonspecific uptake (k'), three parameters affecting the diffusion of substances in nervous tissue, were studied during ischemia and anoxia in the rat spinal cord gray matter in vivo. Progressive ischemia evoked by exsanguination, as well as anoxia evoked by respiratory or cardiac arrest, produced prominent extracellular K+ and pH changes closely related to a decrease in blood pressure and amplitude of field potentials. With use of ion-selective microelectrodes, the changes in the diffusion parameters were measured by quantitative analysis of concentration-time profiles of tetramethylammonium (TMA+) applied by iontophoresis concomitantly with ionic shifts. Under normoxic conditions (in rats with blood pressure of 80-110 mm Hg) diffusion parameters in the dorsal horn gray matter at depth 500-900 microns were as follows: alpha = 0.20 +/- 0.019, lambda = 1.62 +/- 0.12, k' = 4.6 +/- 2.5 x 10(-3) s-1 (mean +/- SD, n = 39). Extracellular K+, pH, and diffusion properties gradually changed during progressive ischemia. As the blood pressure fell to 50-60 mm Hg and field potential amplitude to 20-60%, K+ rose to 6-12 mM, pHe fell by approximately 0.05-0.1 pH unit, and volume fraction of the ECS significantly decreased, to alpha = 0.16 +/- 0.019 (n = 22). Even though the tortuosity remained virtually constant, the nonspecific uptake significantly decreased to k' = 3.4 +/- 1.8 x 10(-3) s-1. As the blood pressure fell to 20-30 mm Hg and field potential amplitude to 0-6%, K+ rose to 60-70 mM, pHe fell by approximately 0.6-0.8 pH unit, and all three diffusion parameters significantly changed. The ECS volume fraction decreased to alpha = 0.05 +/- 0.021, tortuosity increased to lambda = 2.00 +/- 0.24, and TMA+ uptake decreased to k' = 1.5 +/- 1.6 x 10(-3) s-1 (n = 12). No further increase in extracellular K+ or changes in the alpha were found during and up to 120 min after the death of the animal. However, there was a further significant increase in lambda = 2.20 +/- 0.14 and decrease in k' = 0.4 +/- 0.3 x 10(-3) s-1 (n = 24). The acid shift reached its maximum level at approximately 5-10 min after respiratory arrest and then the pHe gradually increased by approximately 0.2 unit. Full recovery to "normoxic" diffusion parameters was achieved after reinjection of the blood or after an injection of noradrenaline during severe ischemia, if this resulted in a rise in blood pressure above 80 mm Hg and a decrease in extracellular K+ below 12 mM.(ABSTRACT TRUNCATED AT 400 WORDS)