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Species and developmental differences in mammalian respiratory rhythm generation Gajda, Barbara Marie


Mammalian neonates can recover spontaneously from hypothermia-induced respiratory arrest when re-warmed (termed autoresuscitation). As a rat ages, autoresuscitation ability is lost during a transitional period ('developmental window') between 16 - 20 post-natal days (PND) so that hypothermic respiratory arrest results in death for a mature rat. Hamsters retain the ability to autoresuscitate past this developmental window. The retention of this ability in hamsters implies that there may be fundamental differences in the central rhythm generator (CRG) of rats and hamsters. This study tests the hypothesis that the contribution to respiratory rhythm generation of the putatively rhythmogenic persistent Na⁺ current (INaP) and Ca²⁺activated non-selective cation current (ICAN). two currents which may facilitate the initiation of breathing after arrest, is different between rats and hamsters. Because autoresuscitation ability is lost during development, we also test the hypothesis that the INaP and I CANcontribution to respiratory rhythm generation change as a rat ages. We applied riluzole (INaP blocker) and flufenamic acid (FFA; ICAN blocker) to the arterially perfused in situ working heart-brainstem preparation in hamsters and two age groups of rats (12 - 14 PND, >23 PND). Application of riluzole and FFA to rats and hamsters showed that elimination of INaP and ICAN resulted in profound decrease in phrenic burst frequency in hamsters with little change in rats. This result is consistent with the hypothesis that a phylogenetic difference exists in the mechanism of setting respiratory rhythm in the CRG of rats and hamsters. Comparisons between young and weaned rats showed that young rats tended to be more sensitive to the application of riluzole and FFA than weaned rats. The small differences observed between young and weaned rats in the reliance on INaP and ICAN for respiratory rhythm generation are consistent with the hypothesis that a developmental change occurs in the CRG of rats during maturation. Increasing the proportion of CO₂ that the preparations were exposed to increased neural ventilation in weaned rats suggesting that INaP and ICAN provide a source of excitatory drive to the CRG.

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