Influence of gastric acid on gastric emptying and gastric distension-induced pain response in rats--effects of famotidine and mosapride.

BACKGROUND: Gastroduodenal acidification has been reported to aggravate upper abdominal discomfort and pain that are symptoms suffered by functional dyspepsia (FD) patients. Delayed gastric emptying and hypersensitivity to gastric distension (GD) contribute importantly to the pathophysiology of FD. METHODS: In the present study, we determined the influence of pentagastrin-stimulated endogenous gastric acid on gastric emptying and GD-induced pain responses using rat model systems. Moreover, we evaluated the effects of famotidine and mosapride on changes in gastric emptying and the GD-induced pain response to gastric acid hypersecretion. Gastric emptying was measured by excretion of glass beads that had been intragastrically administered with a liquid nutrient, and gastric pain response was evaluated by observing whether a GD-induced increase in mean blood pressure occurred. KEY RESULTS: Pentagastrin (2 mg kg(-1), s.c.) which markedly and continuously stimulated gastric acid secretion, significantly delayed and enhanced respectively, gastric emptying and pain compared with saline-injected groups. Oral famotidine (0.1-3 mg kg(-1)) and mosapride (0.3-3 mg kg(-1)) administration in a dose-dependent manner accelerated the delay of gastric emptying. Furthermore, famotidine (0.3-3 mg kg(-1)) significantly alleviated the aggravation of the GD-induced pain response, but mosapride (10 mg kg(-1)) did not. CONCLUSIONS & INFERENCES: We established rat models to evaluate the effect of gastric acid hypersecretion on gastric emptying and the GD-induced pain response. In these models, acid hypersecretion delayed gastric emptying and aggravated the pain response. Furthermore, we showed that famotidine ameliorated both delayed gastric emptying and gastric hypersensitivity, whereas mosapride only improved delayed gastric emptying.

An adult form of Alexander disease: a novel mutation in glial fibrillary acidic protein.

Glial fibrillary acidic protein (GFAP) mutation has been reported in Alexander disease. We report a patient with the adult form of Alexander disease who shows a novel mutation in GFAP. This case presented with progressive dysarthria, dysphagia and spastic gait on the right side. Brain and spinal cord MRI showed marked atrophy of the medulla oblongata and spinal cord. Abnormal high signal intensities in the ventral medulla oblongata were detected bilaterally. There were no white matter lesions or contrast enhancing lesions. Recently, there have been reports of patients with a juvenile form of Alexander disease presenting with atrophy or signal abnormalities of the medulla or spinal cord. Atrophy of the medulla and spinal cord have specifically been described as suggestive of Alexander disease [1]. Sequence analysis of the GFAP gene of this patient showed a heterozygous c.221T>C mutation, predicting a p.M74T amino acid change. In all patients suspected of Alexander disease on the basis of MRI findings, GFAP analysis is necessary to confirm the diagnosis.

Gastric emptying in diabetic gastroparetic dogs: ffects of SK-951,a novel prokinetic agent.

We examined whether delayed gastric emptying could be produced by diabetes in dogs. Diabetes was produced by a single injection of streptozotocin (30 mg/kg i.v.), and diabetic hyperglycemia was observed from 2 to 15 months after injection. The plasma acetaminophen concentration, which is an indirect indicator of the gastric emptying rate, was delayed in 2 of 5 diabetic dogs from 15 months after the induction of diabetes. The effects of SK-951, a benzofuran derivative, on delayed gastric emptying were also examined in diabetic gastroparetic dogs in comparison with those of cisapride. SK-951 (1 mg/kg i.v.) significantly enhanced delayed gastric emptying in diabetic dogs, but cisapride (1 mg/kg i.v.) had no effect. In addition, SK-951 increased the plasma glucose levels in a manner correlated with its effect on gastric emptying. The present study suggested that SK-951 may be useful in the treatment of diabetic gastroparesis.

Pharmacological profile of YM-31636, a novel 5-HT3 receptor agonist, in vitro.

We investigated the in vitro pharmacological profile of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate). In cloned human 5-HT3A receptors, YM-31636 had a pKi value of 9.67 vs. ramosetron and pKi values for other 5-HT3 receptor agonists were less than 7. YM-31636 showed very low affinities for other receptors. YM-31636 induced contraction of isolated guinea pig distal colon. The intrinsic activity was approximately 0.90 compared with 5-hydroxytryptamine's (5-HT) 1.0, and the potency was 26 times greater than that of 5-HT. YM-31636 increased short-circuit current (Isc) in the isolated guinea pig distal colon. In this case, the relative intrinsic activity was approximately 0.19. In isolated guinea pig right atrium, YM-31636 induced tachycardia with the relative intrinsic activity of approximately 0.23. All these effects of YM-31636 were antagonized by ramosetron, a selective 5-HT3 receptor antagonist. These results suggest that YM-31636 is a potent and selective 5-HT3 receptor agonist, preferentially acting on the contraction of the colon.

Stroke after coronary artery bypass grafting in patients with cerebrovascular disease.

BACKGROUND: Stroke has been associated with a significantly increased mortality from coronary artery bypass grafting (CABG). To determine the predictors of stroke in patients undergoing CABG, we collected data on 472 consecutive patients. METHODS: From March 1991 to March 1999, all patients undergoing CABG at our institution underwent routine duplex scanning of the extracranial carotid and vertebral arteries. Seven patients with symptomatic carotid stenosis were treated by carotid endarterectomy (CEA) before CABG. RESULTS: There was a 10-fold increase in mortality (12.5%) associated with postoperative stroke. Many variables were analyzed by a multivariate technique and the severity of extracranial carotid artery stenosis was determined to be the only independent predictor of postoperative stroke (p < 0.01). None of the patients with carotid artery occlusion and none of the patients who underwent CEA before CABG experienced a stroke. CONCLUSIONS: To reduce the stroke rate, the indications for prophylactic CEA may be extended for asymptomatic patients with carotid artery stenosis greater than 75%.

The effect of SK-896 on post-operative ileus in dogs: gastrointestinal motility pattern and transit.

The aim of this study was to investigate the effect of SK-896 (Phe-Val-Pro-Ile-Phe-Thr-Try-Gly-Glu-Leu-Gln-Arg-Leu-Gln-Glu-Lys-Glu- Arg-Asn-Lys-Gly-Gln-Hse), a new motilin analogue, on gastrointestinal motility and transit in dogs with post-operative ileus, and to compare the effects of this agent on these parameters with the effects of prostaglandin F(2alpha), a well-known gastroprokinetic agent. We used chronically implanted force transducers to measure motility and radiography of radio-opaque markers to measure transit. Infusion of SK-896 1 microgram/kg/h, for 20 min twice a day induced interdigestive migrating contractions-like motility. Infusion of prostaglandin F(2alpha), 20 microgram/kg/h, for 1 h twice a day induced continuous contractions in the distal part of the small intestine. The time of first appearance of interdigestive migrating contractions in the stomach (gastric-interdigestive migrating contractions) and the gastric emptying time of the solid marker with the administration of SK-896 were significantly less than those noted with the administration of prostaglandin F(2alpha). It appears that gastric-interdigestive migrating contractions play an important role in the transit of substances, especially solid substances, in the gastrointestinal tract. We conclude that SK-896, which induced gastric-interdigestive migrating contractions, is effective to induce early recovery from post-operative ileus.

Different amounts of K-ras mutant epithelial cells in pancreatic carcinoma and mass-forming pancreatitis.

Clinically, differential diagnosis of pancreatic carcinoma (PC) and so-called "mass-forming pancreatitis (MFP)" is difficult. We analyzed the amount, ductal level, and K-ras mutation of ductal hyperplasia and intraductal carcinoma in surgically resected cases of MFP (n = 18) and PC (n = 16). DNAs extracted from microdissected epithelial foci were analyzed for K-ras codon 12 mutation by nested polymerase chain reaction and restriction fragment length polymorphism. The histology of MFP showed severe destruction of exocrine tissue and pancreatic stones and/or protein plugs (72%, 13 of 18 cases) in mostly peripheral ducts. The average basal membrane lengths of nonpapillary and papillary hyperplasia in cases of carcinoma were about 4 and 15 times more than those of MFP, respectively. The frequency of K-ras mutation in hyperplastic foci increased from nonpapillary [six (27%) of 22] to papillary foci [16 (64%) of 25] in K-ras mutant PCs, but there was no difference between nonpapillary [one (6%) of 18] and papillary foci (none of 19) in K-ras wild-type PCs, and also between nonpapillary (none of 24) and papillary foci [one (7%) of 14] in MFPs.

Genetic progression and divergence in pancreatic carcinoma.

Genetic alterations of pancreatic intraductal lesions adjacent to invasive ductal carcinoma were investigated. We submitted nine foci of ordinary epithelium, 12 foci of nonpapillary hyperplasia, 12 foci of papillary hyperplasia (pap HP), 66 foci of severe ductal dysplasia, and 27 invasive foci from a total of 10 pancreatic carcinomas for genetic analysis. All foci were individually microdissected and allelic losses of 3p, 4q, 5q, 6q, 8p, 9p, 10q, 11q, 13q, 16q, 17p, and 18q were studied. All invasive and severely dysplastic intraductal foci exhibited loss of heterozygosity (LOH) at more than one chromosomal locus. For each case, allelic loss was frequently observed on 9p (severe ductal dysplasia 90%, invasion 100%), 17p (severe ductal dysplasia 80%, invasion 80%), and 18q (severe ductal dysplasia 88%, invasion 88%). Ninety-four percent of severe ductal dysplasia and 96% of invasive foci had multiple LOH. Seventeen percent of nonpapillary hyperplasia and 33% of pap HP showed LOH. Only one focus of pap HP showed multiple LOH. The patterns of allelic loss identified in severe ductal dysplasia were generally conserved in synchronous infiltrating tumors, supporting the paradigm that infiltrating tumors are clonally derived from severe ductal dysplasia. In eight of 10 cases, however, we found frequent genetic heterogeneity in the intraductal lesion, suggestive of genetic progression or diversion. These findings indicate that invasive pancreatic carcinoma evolves through successive and divergent genetic changes with selection of aggressive subclones in the intraductal component.

In vitro pharmacological profile of SK-896, a new human motilin analogue.

SK-896 ([Leu(13)]motilin-Hse) is a new human motilin analogue synthesized by Escherichia coli using a biotechnological method. We investigated the binding of SK-896 to motilin receptors and the contractile effect of SK-896 on smooth muscle preparations isolated from the gastrointestinal tract and various regional organs in order to clarify its in vitro pharmacological profile. SK-896 inhibited the binding of (125)I-human motilin to rabbit gastroduodenal motilin receptors with the same potency as unlabeled human motilin. The IC(50) values of SK-896 and human motilin were 3.5 +/- 1.5 and 3.1 +/- 1.8 nmol/l, respectively. The K(d) of human motilin was 3.0 +/- 1.5 nmol/l, and the Ki of SK-896 was 3.4 +/- 1.5 nmol/l. SK-896 induced contraction of smooth muscle preparations isolated from rabbit duodenum in a concentration-dependent manner. However, there was no effect of SK-896 on duodenal preparations isolated from the dog and the rat. SK-896 thus exhibited species specificity in its contractile effect. We next investigated the effect of SK-896 on various smooth muscle preparations isolated from rabbit gastrointestinal tract, trachea, bladder, gallbladder, uterus, vas deferens and artery. Results showed that SK-896 induced contraction of smooth muscle preparations isolated from gastrointestinal tract, with potencies in the order duodenum > gastric pylorus = jejunum = descending colon > ascending colon >/= ileum. However, there was no effect of SK-896 on smooth muscle preparations from gastric fundus and other regional organs. SK-896 thus exhibited regional specificity in its contractile effect. Moreover, the effects of SK-896 on smooth muscle preparations from rabbit duodenum were the same as those of human motilin, and were not inhibited by pretreatment with tetrodotoxin and atropine but were inhibited by verapamil. These findings indicate that SK-896 has the same pharmacological profile as human motilin. They suggest that SK-896 acts on gastrointestinal smooth muscle isolated from rabbit directly and specifically.

[Should arterial grafts be used for urgent coronary artery bypass surgery?].

It is not clear whether arterial grafts should be used for emergency or urgent coronary artery bypass grafting (CABG) because harvest of internal thoracic arteries (ITAs) is not easy under urgent conditions and the blood flow through the ITAs may be inadequate immediately after CABG. The purpose of this study was to assess whether the use of arterial grafts in urgent CABG affects the outcome adversely or not. Twenty consecutive patients who underwent urgent CABG within 48 hours following coronary angiography at our institute between July 1991 and October 1998 were reviewed. The patients who underwent CABG with associated procedures were excluded. Among these subjects, 11 patients received at least one arterial graft. Only 1 patient died of subarachnoidal hemorrhage, and the hospital mortality rate was 5.0%. According to the overall survival rate, cardiac-death-free rate, and cardiac-event-free rate, the long-term outcome was much better in the patients with arterial grafts than those with saphenous vein grafts alone. We suggest that arterial grafts should be used even for urgent CABGs since the use of arterial grafts may not affect operative results adversely and will confer better long-term benefits.

Corticotropin-releasing hormone receptors mediate consensus interferon-alpha YM643-induced depression-like behavior in mice.

Depression-like behavior induced by YM643, a consensus interferon-alpha (IFN-alpha), was evaluated with the tail-suspension test in mice and compared with depression-like behavior induced by sumiferon, a natural IFN-alpha. To investigate the mechanism of IFN-alpha-induced depression-like behavior, the effects of the tricyclic antidepressant imipramine, the cyclooxygenase inhibitor indomethacin, the opioid receptor antagonist naloxone, and the selective corticotropin-releasing hormone receptor antagonist CP-154, 526 on IFN-alpha-induced depression-like behavior were evaluated. Intravenously injected YM643 (2 x 10(8)-2 x 10(9) U/kg) and sumiferon (2 x 10(6)-2 x 10(7) I.U./kg) dose-dependently increased immobility time. Repeated s.c. injection of either YM643 (6 x 10(6)-6 x 10(8) U/kg) or sumiferon (6 x 10(4)-6 x 10(6) I.U./kg) for 7 days also dose-dependently increased immobility time. After i.c.v. injection of either YM643 (2 x 10(6) U/mouse) or sumiferon (6 x 10(4) I.U./mouse), significant prolongation of immobility time also was observed. Pretreatment with imipramine (30 mg/kg s.c.) significantly reduced the YM643- or sumiferon-induced increases in immobility time. CP-154,526 (0.3-3 mg/kg s.c.) dose-dependently reduced YM643- or sumiferon-induced increases in immobility time with ID(50) values of 0.6 mg/kg against YM643 and 1.3 mg/kg against sumiferon. However, neither indomethacin (10 mg/kg s.c.) nor naloxone (3 mg/kg s.c.) had any effect on YM643- or sumiferon-induced increases in immobility time. These results suggest that IFN-alpha centrally induces depression-like behavior in mice that can be alleviated with imipramine. The results also suggest that activation of corticotropin-releasing hormone receptors is involved in IFN-alpha-induced depression-like behavior, but the prostaglandin and opioid systems do not participate in this process.

Protective effect of thiopental against cerebral ischemia during circulatory arrest.

BACKGROUND: One of the most important disadvantages of the hypothermic circulatory arrest technique is the limited time allowable for circulatory arrest. Thiopental is usually used to protect the brain against ischemic injuries. However, it remains uncertain how well thiopental reduces cerebral metabolism. We investigated its effectiveness by comparing outcomes after different doses. METHODS: Fifty patients who underwent aortic arch repair with hypothermic circulatory arrest had their records reviewed. Electroencephalograms (EEG) and partial pressures of oxygen in the internal jugular vein (PjO2) were monitored. Following confirmation of total disappearance of EEG activity, 15 or 30 mg/kg thiopental was administered before circulatory arrest Th duration of circulatory arrest ranged from 16 to 77 min. RESULTS: Hospital mortality rate was 10% and 4 (8%) patients developed neu-rologic complications, but 3 of them were transient. After thiopental infusion, PjO2 increased significantly from 430 to 499mmHg (p <0.01), indicating that thiopental reduces cerebral oxygen consumption. The rate of the decrease in PjO2 during circulatory arrest was slower with the higher thiopental dose, suggesting that thiopental lowered the cerebral metabolic rate of oxygen during circulatory arrest. CONCLUSION: It appears that thiopental has protective effects against cerebral ischemia under profound hypothermia.

Multiple K-ras mutations in hyperplasia and carcinoma in cases of human pancreatic carcinoma.

Mucous cell hyperplasia (MCH) has been considered an important precursor of pancreatic ductal carcinoma based on histological and molecular research, although various K-ras mutations rates are seen among cases with pancreatic carcinoma, chronic pancreatitis and normal pancreas, with a wide range of histological characters. To investigate the premalignant potential of MCH and the multicentricity of pancreatic carcinoma, we analyzed K-ras mutation at codon 12 in carcinoma foci of 82 cases of surgically-resected pancreatic carcinoma [67 solid-type carcinomas (SCs) and 15 ductectatic-type carcinomas (DCs)], as well as in both MCH and carcinoma foci in 42 cases (30 SCs and 12 DCs), using an enriched polymerase chain reaction (PCR)-enzyme linked mini-sequence assay (ELMA). K-ras mutation was recognized in 85% (57/67) of SCs and 73% (11/15) of DCs, and multiple K-ras mutations in 12% (8/67) of SCs and in 20% (3/15) of DCs. Multiple K-ras mutations were also recognized in MCHs in 47% (14/30) of SCs and in 42% (5/12) of DCs. Moreover, the same sequence at K-ras codon 12 in MCH and carcinoma was identified in 76% (32/42) of carcinoma cases and it was more frequently recognized in hyperplasias with histological atypia (51%, 37 of 72 foci) than those without atypia (24%, 16 of 68 foci) (P<0.0007). These results further support the idea of multicentric carcinogenesis and premalignant potential of atypical hyperplasia in the human pancreas, although about half of the hyperplasias around carcinomas were not thought to be direct precursors.

Histological and genetic changes in malignant transformation of gallbladder adenoma.

DESIGN: Elucidate the histological and genetic changes in malignant transformation of adenoma of the gallbladder. MATERIALS AND METHODS: Forty-three adenomas and 20 intramucosal tumors of carcinoma-in-adenomas were studied for histological and genetic changes (particularly K-ras mutation and p53 protein overexpression by immunohistochemistry) in malignant transformation. The genetic changes were compared with those of 164 carcinomas without anomalous union and 17 carcinomas with anomalous union of pancreatico-biliary duct. RESULTS: Atypical cell foci, i.e. spindle cell foci, were observed only in the adenoma area, with a frequency of 23% in 39 adenomas, and of 45% in 20 tumors of carcinoma-in-adenoma. 129 of 130 spindle cell foci examined were negative for Ki-67 staining and all the spindle cell foci were negative for p53 stain. K-ras mutation and p53 overexpression were not found in all adenomas, pure and with carcinoma i.s., and only one carcinoma (1/16, 6%) with adenoma showed p53 overexpression. K-ras mutation was low (10%, 4/40) in carcinomas without adenoma, but high in carcinomas with anomalous union of pancreatico-biliary duct. While, p53 overexpression was high and similar in carcinomas with and without anomalous union. CONCLUSIONS: These results suggest that there are three distinct pathways in gallbladder carcinogenesis; that is, de novo carcinoma develops from a predominant p53 alteration with low K-ras mutation, de novo carcinoma with anomalous union from K-ras mutation and p53 mutation, and carcinoma-in-adenoma from K-ras-, p53-, and probably APC-gene-related, as yet unknown, alteration.

Effects of coronary artery bypass grafting using internal mammary arteries for diabetic patients.

OBJECTIVES: In our institute, internal mammary arteries (IMAs) have been preferred for coronary artery bypass grafting (CABG) in diabetic patients. The purpose of this study was to evaluate the influence of diabetes and IMA grafting on survival after CABG. BACKGROUND: The influence of diabetes on the results of CABG is not well documented, and there is controversy about whether the use of IMAs conveys greater survival benefits to diabetic patients. METHODS: A total of 420 consecutive patients who underwent CABG from April 1990 to July 1998 were reviewed; 211 of these patients had diabetes mellitus at the time of surgery. Internal mammary artery grafts have been used with increasing frequency, and bilateral IMAs have been used when possible since 1993. Internal mammary artery grafts were used in 164 nondiabetic patients (78%) and in 155 diabetic patients (73%). Seventy-eight nondiabetic patients and 74 diabetic patients received bilateral IMA grafts. RESULTS: The postoperative mortality was 2.4% in the nondiabetic and 2.8% in the diabetic group. With regard to postoperative complications, diabetic patients had a significantly higher rate of chest wound infection (p < 0.05), irrespective of whether IMAs were used or not. The use of bilateral IMAs did not increase the risk of chest wound infection in nondiabetic or diabetic patients. Overall survival curve, cardiac death-free curve and cardiac event-free curve were not affected adversely by diabetes, and in diabetic patients, CABG with saphenous veins alone conveyed significantly (p < 0.01) less long-term benefit than did CABG with at least one IMA graft. CONCLUSIONS: It was suggested that IMA grafts should be preferred in diabetic patients.

Coronary-coronary bypass using the internal thoracic artery: a sparing procedure of the arterial conduit.

BACKGROUND: The internal thoracic artery (ITA) is well known to be the best conduit for coronary artery bypass grafting. However, the bilateral use of ITAs remains limited because in situ right ITAs (RITAs) do not possess an adequate length to be directed to the posterolateral myocardium. We thus considered using free ITAs for conduits between the two segments of the same coronary artery. METHODS: From March 1997 to May 1999, 17 patients underwent coronary-coronary bypass grafting (C-CBG) using free ITAs. Early operative results were analyzed. C-CBG was indicated when the right ITA had an inadequate length or when a distal part of the ITA was left unused. RESULTS: No patient died after C-CBG and none have experienced angina since C-CBG (mean follow-up period 27.3 +/- 19.8 months). Postoperative angiography was performed in all subjects at discharge. Only one coronary-coronary bypass graft was occluded, the other grafts were patent, and there were no stenotic changes. Bilateral ITAs were used in 75% of the patients undergoing CABG during the period of this study. CONCLUSIONS: C-CBG can expand the use of bilateral ITAs and can provide an alternative method for revascularization of the posterolateral myocardium.

Effects of SK-951, a benzofuran derivative, as a prokinetic agent in rats and dogs.

The gastrokinetic activity of SK-951 ((-)4-amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2,3-dihy dro-2-methylbenzo[b]furan-7-carboxamide hemifumarate), a benzofuran derivative with 5-hydroxytryptamine (5-HT)4-receptor agonist activity, was studied in rats and dogs. The effects of SK-951 were also investigated in a model of vagotomy-induced gastroparesis in comparison with cisapride. In rats, both SK-951 and cisapride enhanced gastric emptying of liquids (phenol red) at a dose of 1-100 mg/kg, p.o. Gastric emptying of liquid (acetaminophen) in fasted beagle dogs was enhanced significantly by SK-951 (1.0 mg/kg, i.v.), whereas the effect of cisapride (0.2-1.0 mg/kg, i.v.) was not statically significant. Similar results were found when radiopaque markers were given with standard meal to dogs with vagotomy-induced gastroparesis. The delayed gastric emptying of radiopaque markers by vagotomy was reversed by SK-951 (1.0 mg/kg, i.v.), whereas cisapride showed no effect at doses from 0.1 to 1.0 mg/kg, i.v. These results indicated that oral and intravenous administration of SK-951 accelerates gastric emptying of both liquids and solids in animal models. Thus, SK-951 may be a highly potent and useful prokinetic agent in comparison to cisapride.

The relationship between gastrointestinal transit and motility in dogs with postoperative ileus.

We investigated the relationship between gastrointestinal (GI) transit and motility during postoperative ileus in dogs undergoing a single laparotomy. We combined X-ray radiography for a GI transit study with chronically implanted force transducers (FTs) for a GI motility study. Radio-opaque markers made of polyethylene and steel wires or barium sulfate were used to examine solid substance transit or liquid substance transit. For a while after the end of the operation, postoperative ileus was observed, with weak irregular contractions of the GI tract. Transmission of the contractions to the lower GI tract was then observed. The start point of interdigestive migrating contraction (IMC)-like motility was observed in the order of small intestine (I-IMC), duodenum (D-IMC), and stomach (G-IMC), and IMC proceeded gradually after the operation. The gastric emptying time of a solid marker was 73.6 +/- 2.3 h (n = 5), and depended on the time of first occurrence of G-IMC (r = 0.674, p = 0.006). The gastric emptying of the liquid marker was finished before the time of the first occurrence of G-IMC, and its small intestinal transit time correlated with the time of the first occurrence of G-IMC (r = 0.888, p = 0.018). Using combined X-ray radiography and FTs we found that recovery from postoperative ileus was aided by GI motility in which contractions were transmitted from the stomach to the lower GI tract, like IMC.

Neurological function after deep hypothermic circulatory arrest in the rat.

BACKGROUND: Integrated neurological function, behavior, and somatic recovery were studied in 35 rats undergoing 5 to 80 minutes of hypothermic circulatory arrest (HCA). METHODS AND RESULTS: A closed extracorporeal circulation system (ECC) consisting of a miniature oxygenator and heat exchanger, primed with 6 mL of asanguinous solution, was connected to a closed-chest rat with cannulae in the right atrium for venous drainage (ID = 1.7 mm) and in the ascending aorta for arterial return (ID = 1.0 mm). The rat was surface- and core-cooled until rectal temperature reached 18 degrees C, when ECC was stopped and cardioplegic solution delivered. After 5, 10, 20, 40 (each n = 5), and 80 minutes (n = 15) of HCA, the rat was reperfused, weaned from ECC, and followed with behavioral scoring, passive avoidance tasks, and cardiopulmonary exercise testing until euthanized for morphological study. Every rat resumed weight gain in the first week after HCA and regained preoperative exercise capacity by the fourth week. Only rats undergoing 80 minutes of HCA showed behavioral abnormalities such as stereotypy and incomplete righting reflex, which eventually disappeared in the fourth week. Learning ability was preserved in all except for rats after 80 min of HCA, who failed to acquire new memory to avoid electric stimuli (n = 10) up to 3 months after HCA, when pyramidal cells were partly replaced by astroglia in the cerebral cortex and CA1 sector of hippocampus. Nonetheless, old memory established before HCA was preserved even after 80 minutes of HCA and allowed rats (n = 5) to avoid electric stimuli. CONCLUSIONS: Homogeneity of animals, miniature ECC system, and an established testing system allowed evaluation of rats after HCA, which disclosed learning disability (functional disorder) and pyramidal cell loss (organic defect) after 80 minutes of HCA despite recovery of somatic function, behavior, and growth.