Redo ileal pouch-anal anastomosis for malfunctioning pouches-acceptable alternative to permanent ileostomy?

BACKGROUND: Pouch complications after ileal pouch-anal anastomosis (IPAA) can result in morbidity and pouch loss. Recent reports describe success with redo IPAA. This study was conducted to assess the outcome of malfunctioning pouches treated by redo IPAA. METHODS: All patients undergoing redo IPAA between 1983 and 1999 were identified and clinical records studied. Redo IPAA was defined as an operation for malfunctioning pouch with pelvic dissection and disconnection, pouch revision, and reanastomosis. Analyzed were etiology, presentation, diagnostic modalities, surgical management, pouch loss, and outcome. Follow-up was obtained by telephone or mailed survey. RESULTS: Between 1983 and 1999, 650 IPAA procedures were performed, 6 (0.9%) of which required redo IPAA. Ten referred patients required redo IPAA. These 16 cases included 7 anastomotic disruptions, 3 pouch-vaginal fistulae, 2 recurrent polyps after stapled IPAA, 2 megapouches, 1 cuff abscess, and 1 straight pullthrough. All patients underwent redo IPAA with pouch salvage 100% in this series. Twelve had the original pouch repaired and 4 new pouches. Six patients (37%) had complications and outcome was acceptable with 7.8 stools per day and nighttime incontinence "rarely" or "never" in 7 patients. Eight described results as "good," 6 as "fair.". CONCLUSION: Redo IPAA can be performed with few complications, an acceptable outcome, and should result in low pouch loss.

1',1'-Dimethylheptyl-delta-8-tetrahydrocannabinol-11-oic acid: a novel, orally effective cannabinoid with analgesic and anti-inflammatory properties.

1',1'-Dimethylheptyl-Delta-8-tetrahydrocannabinol-11-oic acid (CT-3) is a novel cannabinoid that is under development by Atlantic Pharmaceuticals as an anti-inflammatory and analgesic drug. The objective of the study was to investigate the effects of CT-3 on overt symptom complex (Irwin's test), nociception, gastrointestinal (GI) ulceration, and pharmacological availability after intragastric (i.g.) and intraperitoneal (i.p.) administration. Analgesic studies were assessed in the hot-plate (55 degrees C) and the tail clip tests in mice and in the tail clip test in rats. In addition, pharmacological interaction of CT-3 with the solvent dimethyl sulfoxide (DMSO) was investigated in rats. In mice, CT-3 decreased spontaneous motor activity and induced dose-dependent, analgesic activity in the tail clip and hot-plate tests, with potency similar to morphine sulfate after i.g. and i.p. administration. However CT-3 showed more prolonged duration of analgesic action than morphine. In rats, CT-3 showed marked analgesia in the tail clip test and had similar i.p. and i.g. median effective dose (ED(50) values; 5 mg/kg). CT-3 was devoid of GI ulceration when administered with DMSO either acutely at doses below 100 mg/kg or chronically at a dosage of 30 mg/kg/day for 5 days. In contrast, indomethacin induced GI ulceration and deaths. The concurrent use of DMSO with CT-3 decreased its analgesic action, increased its adverse central nervous system effects, and induced GI ulceration. The evidence indicates that CT-3 exhibits a large dissociation between its anti-inflammatory/analgesic effects and its ulcerogenic actions. CT-3 warrants clinical development as a novel anti-inflammatory and analgesic drug.

A new model for recognizing and rewarding the educational accomplishments of surgery faculty.

Faculty members' educational endeavors have generally not received adequate recognition. The Association for Surgical Education in 1993 established a task force to determine the magnitude of this problem and to create a model to address the challenges and opportunities identified. To obtain baseline information, the task force reviewed information from national sources and the literature on recognizing and rewarding faculty members for educational accomplishments. The group also developed and mailed to surgery departments at all U.S. and Canadian medical schools a questionnaire asking about the educational endeavors of the surgery faculty and their recognition for such activities. The response rate after two mailings was only 56%, but the responses reaffirmed the inadequacy of systems for rewarding and recognizing surgeon-teachers and surgeon-educators, and confirmed that the distinction between the roles of teacher and educator was rarely made. The task force created a four-tier hierarchical model based on the designations teacher, master teacher, educator, and master educator as a framework to offer appropriate recognition and rewards to the faculty, and endorsed a broad definition of educational scholarship. Criteria for various levels of achievement, ways to demonstrate and document educational contributions, appropriate support and recognition, and suggested faculty ranks were defined for these levels. The task force recommended that each surgery department have within its faculty ranks a cadre of trained teachers, a few master teachers, and at least one educator. Departments with a major commitment to education should consider supporting a master educator to serve as a resource not only for the department but also for the department's medical school and other medical schools. Although this model was created for surgery departments, it is generalizable to other disciplines.

Effects of tolcapone, a catechol-O-methyltransferase inhibitor, and Sinemet on intestinal electrolyte and fluid transport in conscious dogs.

Tolcapone (T) is a novel catechol-O-methyltransferase (COMT) inhibitor recently introduced for the treatment of Parkinson's disease. In clinical efficacy studies, T has been associated with a low incidence of diarrhea. The objectives of the study were to examine whether T and its adjunctive drug Sinemet (S) could influence intestinal fluid and electrolyte transport as a possible cause for the diarrhea. The studies were conducted in conscious dogs surgically prepared with Thiry-Vella loops constructed from a 40-cm jejunal segment. A physiologically buffered test solution was perfused into the orad stoma and collected from the caudad stoma. Secretions were collected at 15-min intervals and analyzed for volume, electrolytes, lipid phosphorus, and protein. The acute oral administration of T (10 and 30 mg/kg doses) was well tolerated. Concurrent acute administration of S (25 mg/kg) with T (30 mg/kg) was also well tolerated. The acute oral administration of T induced a dose-dependent efflux of intestinal fluid and electrolytes (sodium, potassium, chloride, and bicarbonate) secretion (P < 0.05). The oral coadministration of S (25 mg/kg) with T (30 mg/kg) accelerated the onset of the stimulation of intestinal secretion. Despite the significant stimulation of intestinal secretion, none of the dogs developed diarrhea, indicating the importance of intestinal compensatory mechanisms. Neither T nor T&S affected calcium, lipid, or protein efflux rates, suggesting that the stimulated secretion was not a consequence of intestinal mucosal injury. The chronic (seven-day) administration of T and T&S was associated with reduced intestinal secretory responses when compared with the acute administration of the same drugs; S enhanced the T-induced tolerance development. The basis for such tolerance is unknown. In conclusion, the stimulatory systemic actions of tolcapone on intestinal secretion may, under certain conditions, contribute to the induction of diarrhea in susceptible patients.

Outcome of pouch-related complications after ileal pouch-anal anastomosis.

BACKGROUND: Creation of a small intestinal reservoir after ileal pouch-anal anastomosis (IPAA) results in an improved quality of life because of significantly diminished stool frequency. However, a number of complications associated with the pouch may jeopardize these sphincter-sparing procedures and occasionally result in permanent ileostomy. This study was conducted to assess the incidence, risk factors, clinical characteristics, management strategies, and outcome of pouch-related complications after IPAA. METHODS: Data on all patients undergoing IPAA with a J pouch between 1983 and Spring 1997 were prospectively gathered. Patients with pouch-specific complications were identified, and both inpatient and outpatient records analyzed in detail. When necessary, telephone contact was made to update functional data. Other parameters evaluated included age, gender, diagnosis, medication history, diagnostic modalities, laboratory values, time course, management strategies, reoperative procedures, and final results. RESULTS: Some 510 IPAA procedures were performed between 1983 and Spring 1997; 87% of patients had inflammatory bowel disease. Operative mortality was 0%. In the entire series, 27 (5.3%) had complications related to the J pouch. Of those, 22 (81%) had ulcerative colitis and were on a mean dose of 32 mg/day of prednisone. Computed tomography scan made the diagnosis in 18 (67%) and the mean white blood cell count on admission was 14,400. In 11 (41%), the complications occurred after IPAA whereas in the other 16 (59%) it occurred after ileostomy closure. In 5 (19%), the complication resolved with intravenous antibiotics and percutaneous drainage, and 22 (81%) required reoperation. Proximal (11, or 41%) and distal (8, or 30%) pouch leaks or cuff abscesses were the most common complication and accounted for 19 (70%) of the complications observed. In this series, 3 patients (11%) had complications severe enough to warrant J pouch excision, and 1 patient had a permanent ileostomy without excision. Overall pouch excision/ failure in this series was 0.78%. CONCLUSION: Complications involving the J pouch are a seemingly unavoidable part of sphincter-sparing surgery for colonic mucosal diseases. However, if therapy is timely, aggressive, and judicious for these complex patients, pouch loss should be uncommon and long-term results acceptable.

Should older patients undergo ileal pouch-anal anastomosis?

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is a technically demanding, lengthy procedure with substantial associated morbidity. Some have suggested that this procedure should not be performed in older patients. This study was conducted to evaluate whether older patients have a poorer functional outcome and higher complication rate than younger patients who undergo IPAA. METHODS: The 455 patients who have undergone IPAA at this institution were stratified according to age (< 55 versus > 55) to compare functional outcome and complication rates. The data were prospectively collected. The groups included 32 patients > 55 (7%) and 423 patients < 55. Comparisons were made with regard to stool frequency, incontinence rates, post-IPAA complications, postileostomy closure complications, and results 12 months postileostomy closure. RESULTS: Preoperative anal sphincter resting and squeeze pressures were significantly lower in the > 55 group. Most complication rates were similar after IPAA except dehydration rates, which were higher in the older patients than the younger ones (27% versus 11%, respectively). Pre-ileostomy closure anal sphincter resting and squeeze pressures were not significantly lower in patients older than 55. Twenty-four hour daytime and nighttime stool frequencies were significantly higher in the > 55 group, as were daytime and nighttime stool incontinence. CONCLUSION: Although functional outcome is poorer and some complications are higher in the > 55 group, the procedure can be safely performed with acceptable results and is greatly preferred by this population over permanent ileostomy.

Prevention of postoperative abdominal adhesions by a sodium hyaluronate-based bioresorbable membrane: a prospective, randomized, double-blind multicenter study.

BACKGROUND: Postoperative abdominal adhesions are associated with numerous complications, including small bowel obstruction, difficult and dangerous reoperations, and infertility. A sodium hyaluronate and carboxymethylcellulose bioresorbable membrane (HA membrane) was developed to reduce formation of postoperative adhesions. The objectives of our prospective study were to assess the incidence of adhesions that recurred after a standardized major abdominal operation using direct laparoscopic peritoneal imaging and to determine the safety and effectiveness of HA membrane in preventing postoperative adhesions. STUDY DESIGN: Eleven centers enrolled 183 patients with ulcerative colitis or familial polyposis who were scheduled for colectomy and ileal pouch-anal anastomosis with diverting-loop ileostomy. Before abdominal closure, patients were randomly assigned to receive or not receive HA membrane placed under the midline incision. At ileostomy closure eight to 12 weeks later, laparoscopy was used to evaluate the incidence, extent, and severity of adhesion formation to the midline incision. RESULTS: Data were analyzed for 175 assessable patients. While only five (6 percent) of 90 control patients had no adhesions, 43 (51 percent) of 85 patients receiving HA membrane were free of adhesions (p < 0.00000000001). The mean percent of the incision length involved was 63 percent in the control group, significantly greater than the 23 percent observed in patients who received HA membrane (p < 0.001). Dense adhesions were observed in 52 (58 percent) of the 90 control patients, but in only 13 (15 percent) of the 85 receiving HA membrane (P < 0.0001). Comparison of the incidence of specific adverse events between the groups did not identify a difference (P > 0.05). CONCLUSIONS: This study represents the first controlled, prospective evaluation of postoperative abdominal adhesion formation and prevention after general abdominal surgery using standardized, direct peritoneal visualization. In this study, HA membrane was safe and significantly reduced the incidence, extent, and severity of postoperative abdominal adhesions.

Evaluation of scheduled J-pouch irrigations on decreasing stool frequency after ileoanal pull-through and ileostomy closure.

This study was intended to determine whether J-pouch irrigations through the efferent limb of the protective ileostomy stoma after ileoanal pull-through are effective in decreasing high stool frequency after ileostomy closure. Patients undergoing ileoanal pull-through may have high stool frequency after ileostomy closure. J-pouch irrigations through the efferent ileostomy stoma may decrease stool frequency by increasing J-pouch volume, improving storage capacity. The study used a randomized, prospective design in a university hospital outpatient setting. Participants (N = 58) were randomly assigned to control and experimental groups. Effectiveness of irrigation was determined by stool frequency. Both groups were taught Kegel exercises (anal muscle strengthening exercises). The experimental group was taught how and when to irrigate the J-pouch daily; the control group was not. Forty-seven subjects, 25 men and 22 women ranging in age from 15 to 65 years, completed the study. Results of MANOVA indicated no significant between-group difference in the average number of times that subjects performed Kegel exercises; however, there was a significant decrease during the 4-week study period (p < 0.001). There was no significant difference between groups in stool frequency, which decreased with time. There also was no significant effect on nocturnal leakage or satisfaction with surgical outcome. Additional clinical variables that were measured but had no significant effect included eating late, pouch size, and intake of sugar, fiber, bulk-forming products, and antidiarrheal agents. The study did not support the effectiveness of J-pouch irrigation in decreasing stool frequency after ileostomy closure. The cost, time commitment, and burden of performing daily irrigations are not warranted in this patient group.

The occurrence of colon cancer in patients with known premalignant colonic mucosal diseases.

Both ulcerative colitis and familial polyposis are colonic mucosal diseases which are known to predispose to colon cancer. While colonoscopy is an accurate modality used in screening and surveillance for patients with these two diseases, patients continue to present with colon cancer with these known premalignant diseases. This study was conducted to ascertain why patients with known premalignant disease still develop life-threatening colon cancer and to assess the clinical profile and prognosis of patients with known ulcerative colitis (UC) and familial polyposis coli (FPC) who subsequently develop colon cancer. Total colectomy, mucosal proctectomy, and ileoanal pullthrough was performed on 367 patients with UC and FPC between January 1982 and March 1993 at our institution. Of these, 15 had invasive adenocarcinoma of the colon (4.1%) in addition to the primary disease. These 15 patients were studied in detail. The average duration of disease from diagnosis to definitive treatment of cancer was 17 years. Thirteen of the patients in this series had UC (87%), while only 2 had FPC (13%). Colonoscopy was used to make the diagnosis in 11 patients (73%), while the diagnosis was made only at the time of surgery in 3 (20%). Nine of the patients presented with a Dukes' B2 cancer or worse, representing 60% of the series. A high percentage had synchronous invasive cancers in this series--6 patients (40%). Despite the relatively high percentage of advanced cancers in this series, at a mean follow-up of 47.1 months, 14 of the 15 patients are still living. One patient has known recurrent disease while 1 has an elevated CEA with no other evidence of recurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Asynchrony in circadian rhythms of gastric function in the rat. A model for gastric mucosal injury.

A model for gastric mucosal injury is proposed in which a key pathogenetic event is the disruption in the normal relationships among several circadian rhythms of gastric function. In the rat a circadian rhythm in acid secretion was found to be out of phase with a circadian rhythm in gastric pepsin secretion, another aggressive factor, and several mucosal defensive factors (mucus and bicarbonate efflux and tissue prostacyclin content). Gastric corpus mucosal blood flow circadian patterns paralleled the the rhythmicity in acid secretion and, therefore, was out of phase with the other measured mucosal defensive factors. Thus, gastric mucosal defense was maintained by different mechanisms over the 24-hr cycle. During the dark phase, when this species was active and when acid secretion was highest, enhanced damage by topical acidified aspirin was documented, despite increased mucosal blood flow. Natural asynchrony in circadian rhythms of gastric function can be protective of gastric mucosal integrity but disruption of this circadian interplay of gastric aggressive and defensive factors could theoretically lead to greater vulnerability to damage. In the human, a circadian rhythm in basal gastric acidity has been described but no information exists as to the possibility of similar rhythmic variation in other gastric factors (aggressive and defensive) and possible disruption of these rhythms in disease.

Effect of constant light on rhythmic gastric functions in fasting rats.

The effects of four weeks of continuous illumination (LL), a subacute stress, on gastric mucosal endogenous aggressive and defensive factors were studied. Young male Sprague-Dawley rats were used with two different illumination regimens: LL and 12 hr light/12 hr dark (LD). At the end of three to four weeks of either regimen of illumination, gastric acid secretion, pepsin secretion, mucus secretion, and potential difference (PD) were studied. All gastric parameters, except mucus secretion, were significantly reduced by LL. The reduction in acid secretion (13.3%) was not significant after Bonferroni correction for the four t tests Pepsin secretion and PD were 27.9% and 24.6% less, respectively. These differences were significant after Bonferroni correction. The LD rats showed significant circadian rhythms for acid, mucus, and pepsin secretion. The LL rats showed significant rhythmicity for these same parameters with period lengths different from 24 hr. Gross inspection of the gastric mucosa indicated that 69.8% of the LL rats had lesion scores of 1.0 or higher, while none of the LD rats had scores above 0.5.

Circadian rhythm of pepsin efflux in the fasting rat stomach.

Gastric pepsin efflux, a putative aggressive factor because of its proteolytic activity, was examined to determine if it displays circadian rhythmicity as has been shown for other factors such as acid, bicarbonate, mucus, blood flow, potential difference, and tissue prostacyclin activity. Ninety-six fasted Sprague-Dawley male rats, 6-7 weeks of age were acclimated in sound-attenuating, light-proof chambers on a 12/12 light/dark schedule. They were studied in groups of 12 at 3-h intervals. After anesthesia and minor surgery, the stomach was cannulated and filled with 2 ml of saline for two sequential periods of 30 min. The samples were tested for pepsin according to the modified hemoglobin substrate colorimetric method. The data were analyzed with cosinor rhythmometric techniques. Pepsin efflux displayed significant (p < 0.05) circadian rhythmicity with an acrophase value or peak time at 06:49 h after lights on, during the lights-on resting phase. In contrast, the acrophase for acid secretion in the same model occurs during the dark period, when the rats are normally active. We postulate that differences in the circadian patterns of acid and pepsin may be protective.

Circadian rhythm in aspirin (ASA)-induced injury to the stomach of the fasted rat.

Circadian rhythms exist in several gastric parameters affecting ulcerogenesis. This study investigated possible circadian rhythmicity in observed aspirin (ASA)-induced gastric lesions in the rat. In five experiments 183 rats were studied at 14 time points over a 24-hr period. Rats were adapted for three weeks on a 12-hr light schedule, fasted 18 hr, then given oral acidified ASA. One hour later, the rats were sacrificed, the stomachs were removed, stretched flat, photographed, scanned, and measured for percent area of gross lesions in the gastric corpus by computer planimetry. Cosinor rhythmometric analysis showed a significant (P < 0.001) rhythm. Mean of rhythm (MESOR) was 5.60 +/- 0.25% of total corpus. Amplitude was 25.89 +/- 6.07% of MESOR. Peak time (acrophase) was 1909 +/- 0101 hr after lights on. Thus, gastric vulnerability to ASA injury exhibited circadian rhythmicity with peak injury during the dark period in this species.

Gastric potential difference in fasted rats: circadian studies.

The pathophysiology of gastroduodenal ulcer disease remains the subject of intense research and controversy. One model of gastric ulcerogenesis implicates a disruption of complementary circadian rhythms between protective and destructive factors. Parallel circadian rhythms have been reported between acid secretion and gastric potential difference (PD) in in vitro models. The purpose of this study was to investigate the circadian measurements of PD, a parameter of intact gastric mucosal function and thus a putative parameter of gastric protection, in intact, fasted, anesthetized rats. Sixty-four male Sprague-Dawley rats were acclimatized in sound-attenuating, lightproof chambers for 3 weeks on a 12:12-h light-dark schedule. Eight rats were fasted 18 h before being sampled at each of eight times on the circadian clock (01:00, 04:00, 07:00, 10:00, 13:00, 16:00, 19:00, and 22:00 hours after lights on) (HALO). In each rat, after anesthesia (ketamine/acepromazine) and laparotomy, the tip of a catheter (pre-filled with KCl agar) was passed into the gastric corpus through the duodenum. The tip of a second KCl-agar catheter was placed within the peritoneal cavity. The position of the intragastric catheter was gently adjusted for obtaining the highest stable PD reading. The data showed significantly higher values at 07:00 and 10:00 HALO. The lowest value was at 13:00 HALO. The difference between high (10:00 HALO) and low (13:00 HALO) values was 4.5 mV or 13% of the mean. This difference was highly significant (p = 0.003) Analysis of variance showed that the values at 07:00 and 10:00 HALO were significantly higher than the values at 01:00, 13:00, and 16:00 HALO.(ABSTRACT TRUNCATED AT 250 WORDS)

Superior results of ileoanal pull through (IAPT) in polyposis coli vs ulcerative colitis patients.

Colectomy, mucosal proctectomy, and ileoanal pull through (IAPT) have replaced proctocolectomy as the operation of choice in most patients with the colorectal mucosal diseases ulcerative colitis and polyposis coli. This study was conducted to determine whether there is any difference in postoperative morbidity and long-term functional results when IAPT is performed for polyposis coli than when it is performed for ulcerative colitis patients. Between 1982 and 1989, 277 IAPT procedures were performed at the University of Utah Medical Center, 239 for ulcerative colitis and 38 for polyposis coli syndromes. A prospective study compared polyposis and colitis patients after IAPT with regards to age, family history, preoperative findings, operative findings, postoperative complications, and long-term complications. Functional results were compared including day and night stool frequency, incidence of nighttime incontinence, and incidence of pouchitis. The incidence of postoperative complications was lower in the polyposis group than in the colitis group, but the numbers were low enough in both diseases that significant differences were not detected. However, the incidence of pouchitis (0% vs 19%), day (4.2 vs 6.0) and night (0.4 vs 0.9) stool frequency, and nighttime incontinence (5% vs 25%) was significantly lower in the polyposis group when compared to the colitis group. We conclude that IAPT performed for polyposis conditions is associated with superior results when compared with results from patients who undergo the procedure for ulcerative colitis.

Circadian rhythm in prostacyclin activity in gastric tissue of the fasting rat.

Gastroduodenal ulcer disease may result from the desynchronization of the circadian rhythms of gastric protective and destructive factors. The purpose of this study was to evaluate whether gastric tissue 6-keto prostaglandin F1 alpha (PGF1 alpha), a catabolic derivative of the putative protective factor prostacyclin, is produced in a circadian fashion in the rat model. Forty-eight male Sprague-Dawley rats were acclimatized in sound-attenuated, lightproof chambers for 3 weeks on a 12:12 hour light/dark entrainment schedule. After an 18-hour fast, six rats were killed at each of eight sampling times. The stomachs were exposed, removed, and assayed for total 6-keto PGF1 alpha content by radioimmunoassay. Cosinor analysis of the data showed significant (p = 0.0262) circadian rhythmicity in 6-keto PGF1 alpha content with an acrophase (peak time) value of 0503 HALO (hours after lights on) or in the middle of the lights-on inactive period for the rats. Hypothetically, the circadian rhythm in some gastric protective factors may render the gastric mucosa vulnerable to injury in a circadian fashion.

Factors associated with nighttime incontinence following ileoanal pullthrough.

Minor nighttime incontinence following colectomy, mucosal proctectomy, and ileoanal pullthrough remains a bothersome and incompletely understood problem. Of 277 ileoanal pullthrough procedures performed at this institution between 1982 and 1989, 38 were performed on patients with polyposis coli syndrome. These 38 polyposis patients were selected to study nighttime incontinence because they represented a select population in which sphincter injury due to technically difficult mucosal stripping was minimized (compared with the difficult and hazardous mucosal stripping in inflamed tissues present in ulcerative colitis). In this series, 12 patients (32%) experienced nighttime incontinence after ileoanal pullthrough; in 9 of the 12 patients, this complication had resolved within 6 months postoperatively. Females had a significantly higher rate of minor nighttime incontinence (57%) than males (17%). Pouch size was significantly smaller in patients with nighttime incontinence (138 mL) than in continent ones (191 mL). Higher stool frequency soon after surgery also correlated with higher incontinence rates. Factors that did not show association with nighttime incontinence in this series were preoperative and postoperative resting and squeeze and sphincter pressures, disease interval, parity, and previous surgery. We conclude that nighttime incontinence is a common complication that occurs even after "technically easy" mucosal proctectomies. Further investigation will almost certainly reveal it to be multifactorial in etiology.

Circadian rhythms of gastric mucus efflux and residual mucus gel in the fasting rat stomach.

We hypothesized that two putative gastric protective factors, mucus efflux and residual mucus gel content, would manifest circadian rhythms, as reported in several other gastric functions. Rats were adapted for three weeks on a 12-hr light schedule, fasted 18-hr and studied at 3-hr intervals. Under anesthesia, the stomachs were cannulated and filled with test solution. Thirty minutes later, they were drained and the luminal fluid was analyzed for mucus content by Alcian blue binding. Residual mucus gel was determined by direct injection of dye into the lumen. Alcian blue binding of rat mucus was expressed as equivalent milligrams of porcine mucin. Both parameters showed a significant (P less than 0.001) circadian rhythm. Mucus efflux peaked at 5:03 +/- 0:52 HALO (hours after lights on), and residual mucus at 6:00 +/- 0.46 HALO. Thus, the interplay of circadian rhythms in aggressive and defensive gastric mucosal functions is supported.

Circadian rhythm in gastric mucosal blood flow in fasting rat stomach.

Circadian rhythms are present in several gastric functions including acid secretion and emptying rates. We hypothesize that aggressive and defensive factors in the gastric mucosa follow similar circadian rhythms. The purpose of this study was to determine if gastric mucosal blood flow, a known defensive factor, manifests a circadian rhythm in fasting rats. Ninety-six male Sprague-Dawley rats were light-adapted in isolation chambers for 3 weeks prior to the study. Half the rats experienced light from 6:00 AM to 6:00 PM, the other half from 6:00 PM to 6:00 AM. After an 18-hr fast, 12 rats were studied at each of eight sampling times: 0100, 0400, 0700, 1000, 1300, 1600, 1900, and 2200 hr after lights on (HALO). After anesthesia and laparotomy, the stomachs were opened along the anterior surface, gently stretched with mucosal surface upmost, and trapped between two lucite rings, with blood supply intact. Mucosal blood flow (ml/min/100 g) was measured in the forestomach, corpus, and antrum with a laser Doppler flowmeter (TSI Laserflo BPM 403). Cosinor analysis showed a significant (P less than 0.01) circadian rhythm in gastric mucosal blood flow within the corpus and antrum, but not in the forestomach. Peak time for corpus blood flow was 21:45 +/- 0:56 HALO (3:45 AM). In the antrum it was 0:51 +/- 1:08 HALO (6:51 AM). These results support the hypothesis that circadian rhythms in mucosal defensive functions are an integral part of normal gastric physiology.