Factors affecting the relative viability of centrifascicular and subperineurial axons in acute peripheral nerve ischemia

Abstract

An acute reduction in nerve blood flow commonly results in centrifascicular fiber degeneration with subperineurial fiber sparing (CD-SS pattern) in experimental and human peripheral nerve. The mechanism of CD-SS pattern is uncertain. Three hypotheses for the better resistance to ischemic degeneration of subperineurial fibers have been suggested. The subperineurial region has been proposed to have (i) better anastomotic flow (ii) an increased capillary density, or (iii) an extra source of oxygen (from surrounding tissue). We developed methodology that permitted testing of these hypotheses. Nerve blood flow and oxygen tension were measured simultaneously in the central and subperineurial regions using microelectrodes and polarographic techniques. The longitudinal distribution of nerve blood flow was also determined. To test the first hypothesis, nerve blood flow was measured before and after arterial ligation. Well defined watershed areas of reduced flow were found in the longitudinal axis. However, even within these zones, there was a uniform rather than a differential radial reduction in nerve blood flow resulting from ligation. To test the second hypothesis, nerve blood flow was measured during induced arterial hypotension. Nerve blood flow was reduced in proportion to the severity of the ischemic insult but there was no physiologically significant difference between the central and subperineurial areas. To test the oxygen diffusion hypothesis, nerve oxygen tension was monitored simultaneously in the two sites at rest and during ischemia produced by arterial hypotension. Arterial hypotension resulted in severe centrifascicular hypoxia whereas subperineurial oxygen tension was much better maintained as a result of diffusion of oxygen into nerve from the surrounding pool of oil. These findings strongly suggest that the sparing of subperineurial axons in ischemic nerve trunks is due to the diffusion of oxygen from surrounding viable tissues rather than greater capillary density or anastomotic flow.