Studies On Effect Of Pentoxifylline On Antagonizing The Inhibition Of Respiratory Rhythm Discharge Induced By Barbiturates In Medullary Slices From Neonatal Rat

Objective: To observe the effect of pentoxifylline on respiratory rhythm discharge inhibited by pentobarbital sodium with recording the discharge of hypoglossal in the in vitro brain stem-spinal cord preparation of the neonatal rat, and to study the mechanisms of pentoxifylline on antagonizing the inhibition of respiration resulted from the pentobarbital sodium.Methods: (1) Experiments were performed on the in vitro brainstem slices from neonatal SD rats(0-4days) of either sex under ether anaesthesia . The preparation was placed in a 0.5-2ml bath and perfused at a rate of 4-6ml/min with Kreb's solution (pH:7.35-7.45) equilibrated with 95%O2-5%CO2 gas. The temperature of the perfusion medium was kept at 27℃。Suction electrode was used to introduce the spontaneous periodic activity of theⅫth cranial nerve to the computer in which the discharge of hypoglossal was recorded with the medical biological signal processor. (RM6240BD). Pentobarbital sodium (4mmol/L) was perfused for 30 minutes to made a respiratory depression model. (2) The preparations of ,the model, with stable discharge of hypoglossal nerve, were divided into five groups:I—V.Each group included six preparations. GroupⅠ(pentobarbital group ) was only perfused with pentobarbital sodium. II—IV groups were perfused with pentobarbital sodium and different concentration of pentoxifylline(2.25,4.5,9mmol/L).GroupⅤwas perfused with pentobarbital sodium and nikethamide(5mmol/L).(3)Preparations in group I were washed with Kreb solution and preparations in groupⅡ-Ⅴwere washed with Kreb solution containing pentobarbital sodium after treatment.(4)The average peak amplitude, discharge time and frequency of hypoglossal nerve discharges, before and 1,5,10,15,30min after being treated with the drugs, were recorded and analyzed with medical biological signal processor(RM6240BD).Result: 1. The average peak amplitude, discharge time and frequency of hypoglossal nerve discharges showed obvious depression in the respiratory depressive model .The difference between the data before and after being perfused with pentobarbital sodium was significant (p<0.05)2. In groupsⅡ-Ⅳ, from 1min to 30min ,the average peak amplitude of hypoglossal nerve discharges showed increase during 1-15min,and then decrease during 15-30min.There was significant difference between groupsⅡ-Ⅳ(p<0.05) The frequency was effected in a similar way. The discharge time of hypoglossal nerve discharges showed prolonged gradually during 30min. And at 15min,the discharge time was the longest all of 30min.Meanwhile, the time of expiration was gradually decreased. Significant difference was showed between groupsⅡ-Ⅳand between at 15min and 30min.(p<0.05). There was no significant difference at1min (p>0.05).3. There was significant difference between groupⅤand pentobarbital group in comparison with the average peak amplitude , frequency and the discharge time of hypoglossal nerve discharges (p<0.05).4 There was no significant difference between groupⅢand groupⅤin comparison with the average peak amplitude and frequency of hypoglossal nerve discharges (p>0.05).The significant difference was showed in comparison to the discharge time of hypoglossal nerve discharge(p<0.05).Conclusion: 1. In the in vitro medullary brain slice of neonatal rat, pentoxifylline stimulates the respiratory rhythm discharge inhibited by pentobarbital sodium via direct action on the respiratory centre in medulla oblongata.2. This effect of pentoxifylline is concentration -dependent.