Unilateral cooling in the region of locus coeruleus blocks the fall in respiratory output during hypoxia in anaesthetized neonatal sheep.

Abstract

In nineteen alpha-chloralose-anaesthetized 3- to 8-day-old lambs, the effect of cooling focally in the region of the locus coeruleus on respiratory output, as measured from phrenic nerve activity, was examined during normoxia and isocapnic hypoxia, and during infusion of adenosine or saline. Eleven lambs showed a 'biphasic' respiratory response to hypoxia, with an initial increase in phrenic nerve activity (phase 1) being followed by a decline to prehypoxic levels (phase 2). Cooling to 26-34 degrees C unilaterally in the locus coeruleus reversed the fall in respiratory output. When the probe temperature was returned to body temperature (39 degrees C) respiratory output fell again to phase 2 levels. Cooling had no effect during normoxia. In these lambs, adenosine infusion (0.3 mg kg-1 min-1 intra-arterially) during normoxia also decreased respiratory output. During adenosine infusion, cooling again increased respiratory output. Saline infusion did not affect respiratory output during normoxia with or without cooling. The other lambs did not show a biphasic respiratory response, i.e. increased respiratory output was maintained during isocapnic hypoxia. In these lambs adenosine had no effect on respiratory output. Cooling/rewarming the probe did not affect respiratory output during normoxia or hypoxia, or during adenosine or saline infusion. These results show that focal cooling in the dorsal pons at the locus coeruleus removes the inhibition of respiratory output seen in the neonatal biphasic respiratory response to hypoxia, but does not affect breathing in normoxia. This suggests that an important component of the biphasic respiratory response is mediated by the activation of neurones inhibitory to respiratory output, and involves either axons of passage or cell bodies lying in the locus coeruleus. Furthermore, the inhibitory effects of adenosine on breathing in the neonate appear to be mediated via this site.