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The effect of propranolol on human colonic myoelectric activity in the postoperative period
1382
ABSTRACTS OF PAPERS
October 1992
MDTILIN LEVELS DURING POSTOPERATIVE ILEUS. J. J. Cullen, J.C. Eaaon, and K.A. Kelly. Dept. of Surgery and Gastroenterology Unit, Mayo Clinic, Rochester, MN. Dctreotide shortens the duration of postoperative ileus in the small bowel and colon of dogs (Cullen et al, Am J Surg, in press). We hypothesized that octreotide would inhibit the release of motilin during postoperative ileus. Fifteen dogs had serosal electrodes placed on the stomach and small intestine. After recovery, electrical activity was recorded, and blood was drawn for radioinmrunoassayof motilin during the phases of the interdigestive migrating myoelectric complex (HMC) and after a liquid meal. Ileus was induced by celiotomy and intestinal abrasion, and studies were repeated on postoperative days O-3. Five dogs were randomized to receive saline, five octreotide, 0.19 rcg/kg/hr.and five octreotide, 0.83 pg/kg/hr. Cycling of serum motilin, which occurred preoperatively during fastin was abolished postoperatively in all groups (Table3' . Octreotide decreased serum motilin in all phases of the MMC during postoperative ileus. The decrease persisted after feeding when 0.83 M of octreotide was given. In conclusion, octreotide suppresses motilin release during postoperative ileus. Support: NIH Grants DK18;;8, DK07198. Mea&EM Serum Motilin (ho/ 1 Phase of Postoperative HMC Preop. Dav Dav &xQ Dav Control I 168&?6 227i17T 248*22 218t18 224*27
II III Meal
183*10$ 27Oi21 2Olk4
----221t23
:I III Meal
161i16$ 212tlO 179i25
----209t66
Octreotide (0.19 &kg/hr) 153i22$ 123*40*
217i27 288i23 204t22
218i22 238t26 190t15
96i17*
109i20* 105*19t*
93t28* 94*11** 132i20+* 129i25** 154k38 191*5
Octreotide (0.83 Irg/kg/hr) 88i22f* l&t;' 48t5t* --:I 121i47
III Meal
219t13 166ilO
--64*5t*
94i22t* 119*39
264i49 269*41 208t17 72*11t* 133t44 176t26
91*16* 84i13T*
107*23+* 90ilOt*
93t18+* 74*11t*
84*18t* 75*8t*
tpc0.05 vs preop. *p
DOES MINIMWY INVASIVE SURGERY RESULT IN A SHORTER PERIOD OF POSTOPERATIVEILEUS? MA. Mark A. Carlson, and Costas T. Frantzides, Medical College of Wisconsin, Milwaukee, WI One of the attractive features of laparoscopic surgery is the apparent lack of postoperative ileus. The physiology of this clinical observation has not been examined scientifically. The aim of this study was to determine if there are any differences in postoperative small and large bowel motility patterns in dogs undergoing open versus laparoscopic cholecystectomy. 8 mongrel dogs were instrumented with bipolar electrodes. 6 on the small bowel and 4 on the left colon. Does were allowed to recover for lo- 14 days. Baseline myoelectric m&dings were then made for 6-8 hours per day for 3 days. Four dogs then underwent open cholecystectomy and four dogs underwent laparoscopic cholecystectomy. None of the dogs received analgesics. Immediately following operation myoelectric recording resumed and was continued for 3 days. A striking feature, in both groups of dogs, was the disappearance of phase II activity in the fmt 24 hours after operation. The appearance of the migrating myoelectric complex (MMC) in the small intestine and the migrating colonic complex (MCC) were used as criteria for recovery from postoperative ileus. The MMC and MCC appeared 381*175 minutes and @2&t minutes after operation in the open cholecystectomy group and 328+105 minutes and -187 minutes after operation in the laparoscopic group. Furthermore, postoperative MMC cycle length (CL), MMC migration velocity (MV), and number of colonic spike bursts (CSB) per hour were determined in both groups of animals. Results, expressed as mean *EM, are shown below. Open
Laparoscopic 112.ti17.2
3.lti.l
27.w.8
There were no statistically significant differences by Students’t-test. We conclude the postoperative motility patterns in dogs undergoing open versus laparoscopic cholecystectomy are not different. Reduced pain and use of less narcotic analgesia may be responsible for the more rapid return to oral intake in those patients undergoing laparoscopic cholecystectomy.
THE EFFECT OF PROPRANOLOL ON HUMAN COLONIC MYOELECIRIC ACI’MTY IN THE POSTOPERATIVEPERIOD M. A. CarlsM. K. A. Ludwig, V. E. Cowles, C. T. Frantzides, and R. E. Condon , Medical College of Wisconsin, Milwaukee, WI Adrenergic overactivity is a postulated mechanism involved in the genesis of postoperative ileus. The colon is the intestinal segment in which ileus (defined as the resumption of contractions) is most prolonged. Adrenergic stimulation and blockade in awake instrumented animals have been shown to decrease and increase, respectively, colonic myoelectric activity. In contrast, human studies of adrenergic effects usually are based on clinical observations rather than myoelectric parameters. The objective of this study was to evaluate the effect in humans of a beta-adrenergic blocker, propranolol (prop), on the resumption of organized colonic myoelectric activity after abdominal operations, and on myoelectric activity in the colon after resolution of ileus. With informed consent, 6 bipolar serosal electrodes were placed at laparotomy in the anterior taeniae of the colon, 3 on the ascending and 3 on the sigmoid. None of the patients underwent vagotomy. Group A (n = 5) received prop chronically preoperatively or were given 20 mg po q8O for 3 or 4 doses preoperatively, and then were continuedon prop 20 mg po or via ng tube postoperatively. Myoelectric activity was recorded on paper (Grass 79E polygraph) and simultaneously on magnetic tape (Hewlett Packard) for 3 h qD until the patient was tolerating a diet and having BM’s. In group B (ileus resolved), myc-electric activity was recorded for 1.5 h, prop (20 mcg/kg IM) was administered, and activity was recorded for an additional 1.5 h. In group A, organized myoelectric activity did not return earlier compared to historical controls. In group B spike bursts, which have a 1:l correlation with contractions, were counted before and after administration of prop.
Statebaseline
13.4 f 16.0
popran
14.8 * 25.3
41.6 + 51.4
) p>o.o5
) p>o.o5
42.5 + 53.6
We conclude that p&operative administration of propranolol in group A did not shorten the time required for resumption of organized myoelectric activity, and that in group B there is no difference (paired ttest) in spike burst activity in either the right or left colon in response to an acute injection of propranolol.
CHOLECYSTOKININAND GASTRIN RESPONSES DURING POSTOPERATIVElLEUS v Costas T. Frantzides, Verne E. Cowles, Mark A. Carlson, Robert E. Condon, Medical College of Wisconsin, Milwaukee, Wisconsin Administration of cholecystokinin octapeptide (OP-CCK) or pentagastrin stimulates the physiologic gastrocolic response to a meal by promoting an increase in the number of spike bursts in the colon. Administration of these drugs might facilitate recovery from postoperative ileus. Bipolar electrodes were placed on the amending and descending colon of 8 patients undergoing elective laparotomy. Myoelectric recordings were made for 2-4 hrs on each postoperative day until ileus spontaneously cleared. Following a 60-98 minute baseline recording period, OP-CCK (80 mcgkg IV over 30 minutes) was infused in 17 experiments in 5 patients, or pentagastrin (0.5 mcg/kg IVP over 1 minute) was infused in 11 experiments in 4 patients. Recording was continued following infusion for 90-120 minutes. Recordings were analyzed for slow wave and spike burst activity. Power spectrum analysis of slow wave activity showed dominant frequencies in both lower (2-9) and higher (9-14) ranges. Infusion of OP-CCK or pentagasuin dii not affect the slow wave power spectrum. Spike activity was quantified as the number of spike bursts730 min f SEM before and after drug infusion. Myoelecmc Response
(Burstsl30minJQg)
OP-CCK Pentagastrin
fi!%FtF 38*10 4MlO
kif2EYi lo=12 9&18
15428
14323
148+29
161*38
There are no differences in these responses (paired t-test). Drug infusion failed to induce flatus or a bowel movement. We conclude that OP-CCK and pentagastrin have no effect on colonic myoelectric activity in the early postoperative period.
ABSTRACTS OF PAPERS
October 1992
MDTILIN LEVELS DURING POSTOPERATIVE ILEUS. J. J. Cullen, J.C. Eaaon, and K.A. Kelly. Dept. of Surgery and Gastroenterology Unit, Mayo Clinic, Rochester, MN. Dctreotide shortens the duration of postoperative ileus in the small bowel and colon of dogs (Cullen et al, Am J Surg, in press). We hypothesized that octreotide would inhibit the release of motilin during postoperative ileus. Fifteen dogs had serosal electrodes placed on the stomach and small intestine. After recovery, electrical activity was recorded, and blood was drawn for radioinmrunoassayof motilin during the phases of the interdigestive migrating myoelectric complex (HMC) and after a liquid meal. Ileus was induced by celiotomy and intestinal abrasion, and studies were repeated on postoperative days O-3. Five dogs were randomized to receive saline, five octreotide, 0.19 rcg/kg/hr.and five octreotide, 0.83 pg/kg/hr. Cycling of serum motilin, which occurred preoperatively during fastin was abolished postoperatively in all groups (Table3' . Octreotide decreased serum motilin in all phases of the MMC during postoperative ileus. The decrease persisted after feeding when 0.83 M of octreotide was given. In conclusion, octreotide suppresses motilin release during postoperative ileus. Support: NIH Grants DK18;;8, DK07198. Mea&EM Serum Motilin (ho/ 1 Phase of Postoperative HMC Preop. Dav Dav &xQ Dav Control I 168&?6 227i17T 248*22 218t18 224*27
II III Meal
183*10$ 27Oi21 2Olk4
----221t23
:I III Meal
161i16$ 212tlO 179i25
----209t66
Octreotide (0.19 &kg/hr) 153i22$ 123*40*
217i27 288i23 204t22
218i22 238t26 190t15
96i17*
109i20* 105*19t*
93t28* 94*11** 132i20+* 129i25** 154k38 191*5
Octreotide (0.83 Irg/kg/hr) 88i22f* l&t;' 48t5t* --:I 121i47
III Meal
219t13 166ilO
--64*5t*
94i22t* 119*39
264i49 269*41 208t17 72*11t* 133t44 176t26
91*16* 84i13T*
107*23+* 90ilOt*
93t18+* 74*11t*
84*18t* 75*8t*
tpc0.05 vs preop. *p
DOES MINIMWY INVASIVE SURGERY RESULT IN A SHORTER PERIOD OF POSTOPERATIVEILEUS? MA. Mark A. Carlson, and Costas T. Frantzides, Medical College of Wisconsin, Milwaukee, WI One of the attractive features of laparoscopic surgery is the apparent lack of postoperative ileus. The physiology of this clinical observation has not been examined scientifically. The aim of this study was to determine if there are any differences in postoperative small and large bowel motility patterns in dogs undergoing open versus laparoscopic cholecystectomy. 8 mongrel dogs were instrumented with bipolar electrodes. 6 on the small bowel and 4 on the left colon. Does were allowed to recover for lo- 14 days. Baseline myoelectric m&dings were then made for 6-8 hours per day for 3 days. Four dogs then underwent open cholecystectomy and four dogs underwent laparoscopic cholecystectomy. None of the dogs received analgesics. Immediately following operation myoelectric recording resumed and was continued for 3 days. A striking feature, in both groups of dogs, was the disappearance of phase II activity in the fmt 24 hours after operation. The appearance of the migrating myoelectric complex (MMC) in the small intestine and the migrating colonic complex (MCC) were used as criteria for recovery from postoperative ileus. The MMC and MCC appeared 381*175 minutes and @2&t minutes after operation in the open cholecystectomy group and 328+105 minutes and -187 minutes after operation in the laparoscopic group. Furthermore, postoperative MMC cycle length (CL), MMC migration velocity (MV), and number of colonic spike bursts (CSB) per hour were determined in both groups of animals. Results, expressed as mean *EM, are shown below. Open
Laparoscopic 112.ti17.2
3.lti.l
27.w.8
There were no statistically significant differences by Students’t-test. We conclude the postoperative motility patterns in dogs undergoing open versus laparoscopic cholecystectomy are not different. Reduced pain and use of less narcotic analgesia may be responsible for the more rapid return to oral intake in those patients undergoing laparoscopic cholecystectomy.
THE EFFECT OF PROPRANOLOL ON HUMAN COLONIC MYOELECIRIC ACI’MTY IN THE POSTOPERATIVEPERIOD M. A. CarlsM. K. A. Ludwig, V. E. Cowles, C. T. Frantzides, and R. E. Condon , Medical College of Wisconsin, Milwaukee, WI Adrenergic overactivity is a postulated mechanism involved in the genesis of postoperative ileus. The colon is the intestinal segment in which ileus (defined as the resumption of contractions) is most prolonged. Adrenergic stimulation and blockade in awake instrumented animals have been shown to decrease and increase, respectively, colonic myoelectric activity. In contrast, human studies of adrenergic effects usually are based on clinical observations rather than myoelectric parameters. The objective of this study was to evaluate the effect in humans of a beta-adrenergic blocker, propranolol (prop), on the resumption of organized colonic myoelectric activity after abdominal operations, and on myoelectric activity in the colon after resolution of ileus. With informed consent, 6 bipolar serosal electrodes were placed at laparotomy in the anterior taeniae of the colon, 3 on the ascending and 3 on the sigmoid. None of the patients underwent vagotomy. Group A (n = 5) received prop chronically preoperatively or were given 20 mg po q8O for 3 or 4 doses preoperatively, and then were continuedon prop 20 mg po or via ng tube postoperatively. Myoelectric activity was recorded on paper (Grass 79E polygraph) and simultaneously on magnetic tape (Hewlett Packard) for 3 h qD until the patient was tolerating a diet and having BM’s. In group B (ileus resolved), myc-electric activity was recorded for 1.5 h, prop (20 mcg/kg IM) was administered, and activity was recorded for an additional 1.5 h. In group A, organized myoelectric activity did not return earlier compared to historical controls. In group B spike bursts, which have a 1:l correlation with contractions, were counted before and after administration of prop.
Statebaseline
13.4 f 16.0
popran
14.8 * 25.3
41.6 + 51.4
) p>o.o5
) p>o.o5
42.5 + 53.6
We conclude that p&operative administration of propranolol in group A did not shorten the time required for resumption of organized myoelectric activity, and that in group B there is no difference (paired ttest) in spike burst activity in either the right or left colon in response to an acute injection of propranolol.
CHOLECYSTOKININAND GASTRIN RESPONSES DURING POSTOPERATIVElLEUS v Costas T. Frantzides, Verne E. Cowles, Mark A. Carlson, Robert E. Condon, Medical College of Wisconsin, Milwaukee, Wisconsin Administration of cholecystokinin octapeptide (OP-CCK) or pentagastrin stimulates the physiologic gastrocolic response to a meal by promoting an increase in the number of spike bursts in the colon. Administration of these drugs might facilitate recovery from postoperative ileus. Bipolar electrodes were placed on the amending and descending colon of 8 patients undergoing elective laparotomy. Myoelectric recordings were made for 2-4 hrs on each postoperative day until ileus spontaneously cleared. Following a 60-98 minute baseline recording period, OP-CCK (80 mcgkg IV over 30 minutes) was infused in 17 experiments in 5 patients, or pentagastrin (0.5 mcg/kg IVP over 1 minute) was infused in 11 experiments in 4 patients. Recording was continued following infusion for 90-120 minutes. Recordings were analyzed for slow wave and spike burst activity. Power spectrum analysis of slow wave activity showed dominant frequencies in both lower (2-9) and higher (9-14) ranges. Infusion of OP-CCK or pentagasuin dii not affect the slow wave power spectrum. Spike activity was quantified as the number of spike bursts730 min f SEM before and after drug infusion. Myoelecmc Response
(Burstsl30minJQg)
OP-CCK Pentagastrin
fi!%FtF 38*10 4MlO
kif2EYi lo=12 9&18
15428
14323
148+29
161*38
There are no differences in these responses (paired t-test). Drug infusion failed to induce flatus or a bowel movement. We conclude that OP-CCK and pentagastrin have no effect on colonic myoelectric activity in the early postoperative period.