| Background:Gastrointestinal dysmotility refers to various primary or secondary factors that cause damage to gastrointestinal nerves,humoral regulation,and muscle cells,resulting in dysfunction of gastrointestinal smooth muscle cells.More than a quarter of the world’s population has gastrointestinal motility abnormalities,and common gastrointestinal motility disorders include functional dyspepsia,gastroparesis,and postoperative ileus.At present,the clinical treatment of gastrointestinal motility disorders is very limited.Prokinetic drugs can increase gastrointestinal motility,but at the same time may reduce gastric accommodation,coupled with side effects,which greatly limits the clinical application.In recent years,a large number of studies have shown that nerve electrical stimulation can relieve pain and improve gastrointestinal motility.However,most of these methods are in the research stage,and further studies are needed to improve its methodology and to evaluate its effectiveness and safety.Aims:1.To screen the best locaton and parameters of spinal cord electrical stimulation(SCS)to enhance gastrointestinal motility in healthy dogs;2.To verify the efficacy of optimized SCS in the treatment of gastrointestinal hypomotility model dogs and explore its mechanisms;3.To verify the efficacy of optimized transcutaneous electrical acustimulation(TEA)in accelerating the postoperative recovery in patients with gastrointestinal cancer and explore its mechanisms;4.To verify the efficacy of optimized TEA in accelerating the recovery in patients after laparoscopic cholecystectomy and explore its mechanisms.Methods:1.Locations and parameters screening of SCS1)Establishment of a SCS model dog.Seven healthy female dogs were implanted with a pair of gastrointestinal slow-wave recording lead,two gastrointestinal cannula,and two multi-electrode pedal spinal leads under general anesthesia.2)Experimental protocol:(1)Find the optimal location of SCS to promote gastrointestinal motility by using our previous rodent parameters(2)Systematically screen the optimal parameters of SCS to promote gastric motility at the optimal position.(3)The effect of SCS on norepinephrine(NE)and pancreatic polypeptide(PP)was tested.2.Verification of the optimized SCS efficacy in the treatment of gastrointestinalhypomotility and delayed emptying1)Verification of the optimized SCS efficacy in the treatment of gastrointestinal hypomotility.The gastrointestinal contraction,gastrointestinal slow wave and autonomic function of the experimental animals were recorded in three sessions(glucagon + sham-SCS,glucagon + SCS at T10,glucagon + SCS at T10-T11).2)Verification of the optimized SCS efficacy in the treatment of delayed gastric emptying.The solid gastric emptying was recorded in the three sessions(control,glucagon + sham-SCS,glucagon + SCS at T10).3.Verification of the efficacy of transcutaneous electrical acustimulation(TEA)with optimized parameters in accelerating the postoperative recovery in patients with gastrointestinal cancerForty-two patients(33 Male,age: 69.5±1.5 yrs)after abdominal surgical removal of gastrointestinal cancers were randomized to TEA(n=21)and sham-TEA(n=21).TEA was performed via acupoints ST36 and PC6 1 h twice daily from the postoperative day(POD)1 to day 3.Sham-TEA was performed at non-acupoints.Measurements included the first postoperative flatus,defecation,restoring a solid diet,walking for the first time independently,postoperative hospital stay,autonomic function,and inflammatory factors.4.Verification of the efficacy of TEA with optimized parameters in accelerating postoperative recovery in patients with laparoscopic cholecystectomy.Sixty patients scheduled for laparoscopic cholecystectomy(LC)were randomized to TN(n=30)and sham-TN(n=30).TN was performed via acupoints ST36 and PC6 for 30 min twice daily from 24 hours before surgery to 72 hours after surgery.Sham-TN was performed using the same parameters at non-acupoints.The measurements in this study were the same as the previous TEA study.Results:1.Effects of SCS with different parameters on gastrointestinal motility and NE\PP in healthy dogs1)Our data indicated that SCS at location of T10 could significantly increase gastric motility(34.4% increase in MI vs.baseline,P<0.05)and vagal activity(HF)(21.3% increase vs.baseline,P<0.01).2)SCS at location of T10-T11 increased duodenal motility(19.5% increase in MI vs.baseline,P<0.05).3)Our findings revealed that 0.5ms,20 Hz and amplitude of 90% motor threshold at T10 were the best parameters in increasing MI and HF.4)Optimized SCS elevated PP release in the fasting state(0.47±0.03 vs.0.77±0.05,P<0.01)and reduced the NE release both in fasting(0.49±0.05 vs.0.39±0.03,P<0.05)and in fed state(0.48±0.05 vs.0.40±0.04,P<0.05).2.The effects of SCS on gastrointestinal hypomotility and delayed gastric emptying1)SCS at T10 improved glucagon-induced gastric dysmotility.(1)Compared with baseline,glucagon decreased antral motility index(MI)(6315 ± 565 vs.3243 ± 775,P<0.001),reduced the percentage of normal gastric slow waves(GSW)(89 ± 3% vs.58 ± 3%,P<0.01),and increased sympathetic activity(0.25 ±0.06 vs.0.60 ± 0.07,P<0.01).(2)The sympathetic activity was negatively correlated with the percentage of gastric slow waves(r=-0.492,P<0.01)and antral MI(r=-0.419,P<0.05)(3)SCS prevented the glucagon-induced impairment in antral hypomotility(MI: 5770 ± 927 vs 5521 ± 1238,P>0.05)and GSW(% of normal waves: 84 ± 4 % vs 79 ± 6%,P>0.05)and sympathetic activity(0.27 ± 0.03 vs 0.33 ± 0.07,P>0.05).2)SCS at T10-T11 improved glucagon-induced duodenal hypomotility.(1)Compared with baseline,glucagon decreased duodenal motility index(MI)(164656 ± 10667 vs.97339 ± 10830,P<0.01),reduced the percentage of normal duodenal slow waves(DSW)(88.4 ± 3.7 % vs.66.8 ± 4.5 %,P<0.05),and increased sympathetic activity(0.25 ±0.06 vs.0.5 ± 0.03,P<0.01).(2)The sympathetic activity was negatively correlated with the frequency(r=-0.499,P<0.05)and MI of the duodenal contractions(r=-0.518,P<0.05)(3)SCS prevented the glucagon-induced impairment in duodenal hypomotility(MI: 171263 ± 13687 vs 156916 ± 21009,P>0.05)and DSW abnormalities(% of normal waves: 90 ± 11 % vs 87 ± 8%,P>0.05)and sympathetic activity(0.31 ± 0.04 vs 0.28 ± 0.03,P>0.05).3)SCS at T10 improved glucagon-induced delayed gastric emptying.Glucagon significantly delayed gastric emptying(vs.,P<0.05),and this inhibitory effect was partially blocked by SCS.Gastric emptying at 120 min was 25.49 ± 2.59 gram in the control session and 15.69 ± 3.43 gram in glucagon session(P< 0.05 vs.control),while it was 25.1 ± 2.09 gram with SCS session(P< 0.05 vs.glucagon).3.The effect of TEA on postoperative recovery and autonomic functions in patients after open surgery.1)TEA shortened the recovery time of clinic symptoms.TEA shortened time to defecation by 31.7%(P<0.01)and time to first flatus by 35.9%(P<0.001).2)TEA significantly increased vagal activity(P<0.001)and decreased sympathetic activity on POD 4(P<0.001)compared with POD1 as well as the serum level of NE(P<0.05).3)The vagal activity was negatively correlated with time to resuming diet,whereas,the sympathetic measurement,serum norepinephrine was positively correlated with time to resuming diet and time to flatus.4)TEA but not sham-TEA decreased TNF-α by 17.4% from POD 1 to POD 4.5)TEA was an independent predictor of a shorter hospital stay.4.The effect of TEA on postoperative recovery and autonomic functions in patinets after laparoscopic surgery.1)Compared to sham-TEA,TEA shortened time to first flatulence(38.9±4.0 vs.24.9±2.4 h,P<0.01)and time to defecation(63.1 ± 4.5 vs.42.5 ± 3.1 h,P<0.001).2)Compared to sham-TEA,TEA increased the percentage of normal pace-making activity(66.2 ± 2.2 vs.73.8 ± 2.3 %,P<0.05).3)TEA enhanced vagal activity.Compared to that 24 hours before surgery,surgery decreased vagal activity(HF)(0.41 ± 0.02 vs.0.34 ± 0.02,P<0.05)3 hours after the operation.Compared to sham-TEA,TEA increased HF(0.45 ± 0.02 vs.0.52 ± 0.02,P<0.05)72 hours after the operation.Further,HF was negatively correlated with time to defecation and serum norepinephrine.4)Surgery increased serum IL-6(1.1 ± 0.1 before surgery vs.2.9 ± 0.7 pg/ml,P<0.05)72 hours after the operation,which was reduced to baseline by TEA(0.9 ± 0.1).Conclusion: The optimazed neuroelectric stimulation accelerates postoperative recovery in patients undergoing gastrointestinal surgery probably by inhibiting sympathetic activity and increasing vagal activity. |
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