Inhibitory mechanisms in hypoxic respiratory depression studied in an in vitro preparation

A medullary-spinal cord preparation without the pons isolated from the neonatal rat was used to investigate the role of inhibitory neurotransmitters in the respiratory depression induced by hypoxia (hypoxic respiratory depression; HRD). The burst frequency (C(4)-f) and peak amplitudes of the integrated activity of the C(4) roots (integral C(4)) and of the hypoglossal nerve (integral XII) were recorded. A marked decrease in C(4)-f (to 36+/-6% of control, P<0. 05) with no change in the peak amplitudes of integral C(4) or integral XII was observed 17-21 min after superfusion with hypoxic CSF bubbled with 5% CO(2) in N(2). Antagonists of GABA(A) (bicuculline; 10 microM), GABA(B) (phaclofen; 0.2-0.5 mM), glycine (strychnine; 10 mM), adenosine (aminophylline; 100 mM) or opioid (naloxone; 1 mM) receptors were added to the bathing solution to block inhibitory synaptic transmission. Among these antagonists, only strychnine and naloxone alleviated HRD reducing the decline in C(4)-f to 57+/-11 and 53+/-6%, respectively (P<0.05). Posthypoxic neural arrest (PHNA) following resumption of oxygenation was shortened by the application of aminophylline, strychnine or naloxone (by 91+/-17, 96+/-25 and 40+/-6 s, respectively, P<0.05). These findings indicate that the reduction in the frequency component of HRD depends on glycinergic and opioid-mediated neuronal inhibition in an in vitro medullary spinal cord preparation. It was also observed that the duration of PHNA was positively correlated with the severity of the fall in C(4)-f (r=0.60, P<0.01).