| Objective:To investigate the potential protective effect of Levosimendan in post-resuscitation cardiac function and intestinal microcirculation in a SD rat model of asphyxia.And identify the individual role of different subtypes of ATP sensitive potassium channel in regulating cardiac function and intestinal microcirculation.Methods:Rat models of asphyxia induced cardiac arrest-resuscitation were established and experimental animals were divided into five groups:1)KATP channel opener Levosimendan group?n=10?,2)control group?n=10?,3)SarcKATP channel blocker HMR-1098 group?n=5?,4)mitoKATP channel blocker 5-HD?n=5?,5)and sham group?n=3?.Echocardiography was performed to evaluate the cardiac function including ejection fraction?EF?,stroke volume?SV?and cardiac output?CO?.Sidestream dark field?SDF?was used to record the perfused vessel density?PVD?,microcirculation flow index?MFI?to assess the intestinal microcirculation.At the same time,the parameters during the procedure including the inducing time of cardiac arrest?CA?,resuscitation time,electrocardio changes,mean atrial pressure?MAP?,end tidal carbon dioxide?ETCO2?,lactate at different time points were also monitored and compared among different groups.ResultsPart 1 No difference was observed in baseline data in each group?P>0.05?.There were32 rats back to restoration of spontaneous circulation?ROSC?successfully,except 1rat failed to back in HMR-1098 group.No difference was observed in the cardiac arrest inducing time in Control group,Levo group,Levo+5-HD group,and Levo+HMR-1098group?186±17s,194±22s,245±21s,179±18s,respectively,P=0.664?.No difference of average resuscitation time was observed between the four groups?206±32s,212±20s,231±17s,223±13s respectively,P=0.561?.MAP has declined from baseline obviously,particularly in Levo group.Take PR1h as an example,the MAP decreased from125±10mmHg to 97±15mmHg,125±11mmHg to 73±13 mmHg,121±13 mmHg to 84±12mmHg,125±18 mmHg to 73±16 mmHg in the four groups?P<0.01?.There was a restoring tendency over time in 3 drug-intervened groups.ETCO2 has declined as well compared to baseline.However this decline was more mitigatory in Levo group?P<0.01?.Ventricular arrhythmia was mostly found within first 30min after resuscitation.No difference was found in the parameters of 5 minutes counting of PVC and VT among the 4groups.Part 2 The CO,EF and SV have declined dramatically after resuscitation compared to baseline in the four groups.Take PR1h as an example,the CO has decreased from100.36±9.91 ml/min to 50.26±21.8 in control group,from 98.8±20.73ml/min to57.58±31.93ml/min in HMR-1098 group.Moreover,in the Levo and 5-HD group,the CO decreased from 97.19±28.67 ml/min to 62.24±23.45 ml/min and 98.84±4.86ml/min to59.17±22.99ml/min respectively.Repeated measurements analysis and post hoc multiple comparisons were performed to indicate significant differences among the five groups?P<0.05?.Bonferroni test was operated to find significant differences between Levo and control,Levo and Levo+HMR-1098,Levo+5-HD and Levo+HMR-1098?P<0.05?respectively.No difference was found between Levo and Levo+5-HD,Levo+HMR-1098or control?P>0.05?.The similar changes were also found in EF and SV.However,no obvious changes of heart rate were monitored after resuscitation in each group.Part 3 MFI has decreased obviously compared with baseline after resuscitation?P<0.05?.Significant differences in MFI were observed between Levo group and control group in PR3-5h?P<0.05?.The similar findings were also observed in Levo group and Levo+HMR-1098 group.There no significant difference between other groups?P>0.05?.The changes of PVD were similar to those of MPI.Significant differences were observed in comparisons between 4 groups,between Levo group and control group,or Levo group and Levo+HMR-1098 group in PR2-4h?P<0.05?.Conclusions:Levosimendan improved the post-resuscitation cardiac function and intestinal microcirculation.This protective effect may be functioned by SarcKATP channel. |
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