Effect Of Pentoxifyllinel On Antagonizing Inhibition Of Respiration Induced By Poisoning With Pentobarbital Sodium In Rabbits

AIM: To observe the effect of pentoxifyllinel on inhibition of respiration induced by acute poisoning with pentobarbital sodium , and to study the mechanisms for action of pentoxifyllinel on antagonizing the central inhibition of respiration resulted from the barbitalism. METHODS: (1) The rabbits anesthetized with pentobarbital sodium in routine dose were divided into groups A, B (which was further divided into B1, B2 and B3) and C. There were six rabbits in each group. In these rabbits, an additional dose (15mg/kg) of pentobarbital sodium was injected intravenously to form the model of respiratory depression. (2) Group A was used as a negative control. In groups B1, B2 and B3 , after 10 minutes of injecting the additional dose of pentobarbital sodium, pentoxifyllinel in doses of 60mg/kg, 30mg/kg and 15mg/kg were injected respectively. In group C, 125mg/kg of nikethamide was injected after 10 minutes of injecting the additional dose of pentobarbital sodium. (3) The average peak amplitude and frequency of the phrenic nerve discharges, the inspiratory and expiratory flow rates and the frequency of respiration, before and after treating with the drugs, were recorded and analyzed with a biological signal processor. RESULTS: (1) In the rabbits of control group which were treated without any antidote, the peak amplitude and frequency of phrenic nerve discharges and the inspiratory and expiratory flow rates showed no significant difference as comparing with the data before injecting the additional dose of pentobarbital sodium (P>0.05). While the frequency of respiration decreased significantly (P<0.05). (2) For all three groups treated with pentoxifyllinel, the peak amplitude of phrenic nerve discharges showed trending upward during the course after 10 minutes of additional injection of pentobarbital sodium as comparing with the first 5 minutes after injection. However, there was no evident change of the frequency of discharge. The respiratory flow rates also showed trending upward. In the groups treated with pentoxifyllinel in doses of 15mg/kg and of 30mg/kg, both the inspiratory and expiratory flow rates increased significantly (P<0.05). In the group treated with pentoxifyllinel in dose of 60mg/kg, the expiratory flow rate increased significantly (P<0.05). In all three groups treated with pentoxifyllinel, the rates of respiration showed no remarkable changes (P>0.05). In the group treated with nikethamide, the changes of phrenic nerve discharges were not evident. The inspiratory flow rate increased transiently after 1 minute of injection and recovered to the original level soon. The expiratory flow rate and the rate of respiration showed no evident changes. In the course of observation, the trends for the peak amplitude and frequency of discharges of phrenic nerve and the respiratory flow rates and frequency in the three groups treated with pentoxifyllinel were not parallel to those in the control group and nikethamide-treated group. Trends for changes of the respiratory functional indexes in the groups treated with pentoxifyllinel revealed that pentoxifyllinel possessed an excitatory effect for respiration. CONCLUSION: (1) Pentoxifyllinel possesses an excitatory effect for respiration. It can antagonize the respiratory depression resulted from poisoning of pentobarbital sodium. This effect of pentoxifyllinel is better than nikethamide. (2) This effect of pentoxifyllinel is dose-dependent.