Results of a phase I trial evaluating a liver support device utilizing albumin dialysis.

BACKGROUND: We have previously reported the clearance of protein-bound and water-soluble hepatic toxins, in vitro and in an animal model, using albumin dialysis as an extracorporeal hepatic support (ECHS) device. OBJECTIVE: The objective of this study was to evaluate albumin dialysis through a phase I clinical trial. We hypothesized that albumin dialysis would (1) decrease elevated levels of hepatic toxins, (2) increase the Fischer ratio, and (3) decrease hepatic encephalopathy (HES) and intracranial pressure (ICP), while (4) maintaining stable hemodynamics. METHODS: Patients with acute liver failure were treated with an ECHS device utilizing continuous hemodiafiltration with continuous albumin dialysis. Mean arterial blood pressure (MAP), heart rate (HR), systemic venous oxygen saturation (Svo(2)), ICP, and HES were recorded. Blood samples were evaluated for hepatic toxins and factor VII levels. RESULTS: Nine patients were enrolled (status I, n = 5; status IIA, n = 4). There was no significant change in MAP, HR, or Svo(2) (MAP: Pre = 81 +/- 5.6 mm Hg, Post = 79 +/- 5.9 mm Hg, P =.70; HR: Pre = 104 +/- 5.2 bpm, Post = 107 +/- 6.2 bpm, P =.62; Svo(2): Pre = 72 +/- 3.5, Post = 71 +/- 1.7, P =.77). There was a decrease in the ammonia and total bilirubin levels (NH(3): Pre = 129.8 +/- 23.8 mg/dL, Post = 63.9 +/- 16.1 mg/dL, P =.01; total bilirubin: Pre = 20.3 +/- 2.5 mg/dL, Post = 17.6 +/- 2.7 mg/dL, P =.4). There was a significant increase of the Fischer ratio and factor VII levels (Fischer ratio: Pre = 0.98 +/- 0.2, Post = 2.17 +/- 0.5, P =.038; factor VII: Pre = 13.9 +/- 4.9, Post = 23.2 +/- 4.8, P =.015). There was a significant decrease in the HES and ICP (HES: Pre = 3.8 +/- 0.1, Post = 2 +/- 0.7, P =.02; ICP: Pre = 37 +/- 3.9, Post = 13.3 +/- 2.8, P =.048). Of 5 status I patients, 1 recovered native hepatic function and 3 were bridged to transplantation. CONCLUSIONS: This phase I study suggests that albumin dialysis as a liver support device is safe and effective in clearing hepatic toxins, with an associated decrease in the HES and ICP. This encouraging efficacy data warrant further investigation with a phase II/III trial.

The use of extracorporeal life support in adult patients with primary cardiac failure as a bridge to implantable left ventricular assist device.

BACKGROUND: Extracorporeal life support (ECLS) is an effective technique for providing emergent circulatory assistance, and may represent a life-saving option in patients who might not initially be considered a candidate for other forms of circulatory support (extracorporeal or implantable left ventricular assist device [LVAD]). In the setting of cardiac arrest, ECLS represents the only viable method of initiating circulatory support. However, ECLS has a number of disadvantages that include high complication rates (eg, stroke, bleeding) and a limited duration of potential support, which have prevented its widespread acceptance, particularly in the adult population. With the increased successful application of long-term implantable LVADs as a bridge to transplant, the major limitation of ECLS could be overcome by bridging patients to a long-term implantable LVAD ("bridge to bridge"), thereby reducing the reluctance to utilize ECLS when indicated. After acquisition of the HeartMate LVAD (Thermo Cardiosystems, Inc, Woburn, MA) we investigated the use of ECLS as a bridge to an implantable LVAD and subsequent transplantation in selected high-risk patients. METHODS AND RESULTS: From Oct 1, 1996 to Sept 30, 2000, 33 adult patients presenting with cardiac arrest or severe hemodynamic instability were placed on ECLS for the bridge to bridge indication. Of the 33 patients, 10 patients survived to LVAD implant, 1 was bridged directly to transplant, 5 weaned from ECLS, and 16 died on ECLS. Overall, 12 patients survived to discharge. One-year actuarial survival from the initiation of ECLS was 36%. One-year actuarial survival from the time of LVAD implant, conditional on surviving ECLS, was 80%. CONCLUSIONS: The 1-year survival of adult patients placed on ECLS and who subsequently survived to an implantable LVAD was favorable. These data support a strategy of ECLS to implantable LVAD bridge to heart transplant in adult patients who are in need of circulatory support and who are not initially candidates for other forms of mechanical support. The favorable results of this strategy support utilization of ECLS even in situations where myocardial recovery is thought to be unlikely.

Percutaneous cannulation for pediatric venovenous extracorporeal life support.

BACKGROUND/PURPOSE: The objective of this study was to show the safety and efficacy of a method of percutaneous cannulation for venovenous extracorporeal life support (ECLS) access in nonneonatal (>10 kg) pediatric patients. METHODS: Between June 1992 and October 1998, 26 pediatric patients (age range, 3 to 17 years; weight range, 19 to 100 kg) underwent attempted percutaneous cannulation for venovenous ECLS at our institution. Venous drainage access was attempted using a modified Seldinger technique via the right internal jugular vein (RIJ, n = 22) or right femoral vein (RFV, n = 4). Reinfusion access was attempted via the RFV (n = 19), RIJ (n = 4), or left femoral vein (n = 3). RESULTS: The percutaneous technique was successful in 24 of 26 patients (92.3%). Maximum blood flow during ECLS was 80.1 +/- 30.0 mL/kg/min, generating a postmembrane lung outlet pressure of 138 +/- 54.8 mm Hg. Adequate gas exchange was achieved in all patients, and survival to discharge was 79.2%. There was no procedure-related mortality. Complications potentially related to the percutaneous technique included RIJ thrombosis (n = 1) detected after decannulation and cannula site bleeding (n = 3). CONCLUSION: Percutaneous access may be used safely and effectively for venovenous ECLS in pediatric patients.

Extracorporeal life support outcome for 128 pediatric patients with respiratory failure.

PURPOSE: The aim of this study was to describe a single-center experience with pediatric extracorporeal life support (ECLS) and to determine variables predictive of outcome in pediatric patients, both before the institution of ECLS and while on support. METHODS: From October 1985 to September 1998 the authors supported 128 children with severe acute hypoxemic respiratory failure(n = 121, Pao2/FIo2 ratio = 58+/-29) or acute hypercarbic respiratory failure (n = 7, Paco2 = 128+/-37), despite maximal conventional ventilation. Mode of access included venoarterial bypass (VA, n = 64), venovenous bypass (VV, n = 53), and VV to VA bypass (n = 11). The techniques used included lung rest, pulmonary physiotherapy, diuresis to dry weight using hemofiltration if needed, minimal anticoagulation, and optimal systemic oxygen delivery. RESULTS: The median age was 1.4 years (range, 2 weeks to 17 years). The mean duration of ECLS was 288+/-240 hours (range, 4 to 1148 hours or 0.2 to 47.8 days). Lung compliance increased from 0.32+/-0.02 mL/cm H2O/kg to 0.59+/-0.03 mL/cm H2O/kg in survivors, but only increased from 0.34+/-0.02 mL/cm H2O/kg to 0.35+/-0.02 mL/cm H2O/kg in nonsurvivors (P<.002 comparing change between survivors and nonsurvivors). Mean body weight decreased from 9%+/-2% over dry weight to 4%+/-2% in survivors, whereas in nonsurvivors the mean body weight increased from 25%+/-5% over dry weight to 35%+/-7% (P<.001). Outcome results by diagnosis were pneumonia, 73%; acute respiratory distress syndrome, 67%; and airway support, 60%, with overall lung recovery occurring in 77%, and hospital survival in 71%. Multivariate logistic regression modelling of patients with hypoxemic respiratory failure found the only pre-ECLS variable significantly associated with outcome to be pH (P<.05). Variables during the course of ECLS significantly associated with decreased survival were the presence of creatinine greater than 3.0 (P<.01), the need for inotropes (P<.04), failure to return the patient to dry weight (P<.04), and lung compliance that did not improve significantly. (P<.01). CONCLUSIONS: ECLS provides life support in severe respiratory failure in children, allowing time for injured lungs to recover. Pre-ECLS predictors, such as pH and variables during ECLS, such as presence of renal failure, improvement in compliance, return to dry weight, and the need for inotropes on ECLS, may be useful for predicting outcome.

Assessment of an extracorporeal life support to LVAD bridge to heart transplant strategy.

BACKGROUND: Extracorporeal life support (ECLS) is an effective technique for providing emergent circulatory assistance. However, its use in adult patients is associated with poor survival when myocardial function fails to recover. Due to the prolonged waiting times for heart transplantation, ECLS as a bridge to transplant is associated with poor survival. In addition, ECLS has been reported to be a significant risk factor for death after bridging to an implantable left ventricular assist device (LVAD). After acquisition of the HeartMate LVAD (Thermo Cardiosystems, Inc) in October 1996, we began using ECLS as a bridge to an implantable LVAD and subsequently transplantation in selected high-risk patients. METHODS: From October 1, 1996 to December 1, 1999, 60 adult patients presenting with cardiogenic shock were evaluated for circulatory assistance. RESULTS: Twenty-five patients (group 1) with cardiac arrest or severe hemodynamic instability and multiorgan failure were placed on ECLS. Eight patients survived to LVAD implant, 1 was bridged directly to transplant, and 4 weaned from ECLS. Nine patients in group 1 survived to discharge. Thirty patients (group 2) underwent LVAD implant without ECLS. Twenty-three were bridged to transplant, with 22 surviving to discharge. Five patients (group 3) were placed on extracorporeal ventricular assist with 3 bridged to transplant and all surviving to discharge. One-year actuarial survival from the initiation of circulatory support was 36% (group 1), 73% (group 2), and 60% (group 3). One-year actuarial survival from the time of LVAD implant in group 1, conditional on surviving ECLS, was 75% (p = NS compared with group 2). CONCLUSIONS: In selected high-risk patients, LVAD survival after initial ECLS was not different from survival after LVAD support alone. An initial period of resuscitation with ECLS is an effective strategy to salvage patients with cardiac arrest or extreme hemodynamic instability and multiorgan injury.

Extracorporeal life support to left ventricular assist device bridge to heart transplant: A strategy to optimize survival and resource utilization.

BACKGROUND: The use of extracorporeal life support (extracorporeal membrane oxygenation [ECMO]) as a direct bridge to heart transplant in adult patients is associated with poor survival. Similarly, the use of an implantable left ventricular assist device (LVAD) to salvage patients with cardiac arrest, severe hemodynamic instability, and multiorgan failure results in poor outcome. The use of LVAD implant in patients who present with cardiogenic shock who have not been evaluated for transplantation or who have sustained a recent myocardial infarction also raises concerns. ECMO may provide reasonable short-term support to patients with severe hemodynamic instability, permit recovery of multiorgan injury, and allow time to complete a transplant evaluation before long-term circulatory support with an implantable LVAD is instituted. After acquisition of the HeartMate LVAD (Thermo Cardiosystems, Inc), we began using ECMO as a bridge to an implantable LVAD and, subsequently, to transplantation in selected high-risk patients. METHODS AND RESULTS: From October 1, 1996, through September 30, 1998, 32 adult patients who presented with refractory cardiogenic shock (cardiac index <2.0 L. min(-1). m(-2), with systolic blood pressure <100 mm Hg and pulmonary capillary wedge pressure >/=24 mm Hg and dependent on >/=2 inotropes with or without intra-aortic balloon pump) were evaluated and accepted as candidates for mechanical assistance as a bridge to transplant. Of the 32 patients, 14 (group I) had a cardiac arrest or severe hemodynamic instability (systolic blood pressure 3 mg/dL or oliguria; international normalized ratio >1.5 or transaminases >5 times normal or total bilirubin >3 mg/dL; and needing mechanical ventilation). Group I patients were placed on ECMO support; 7 underwent subsequent LVAD implant and 1 was bridged directly to transplant. Six patients in group I survived to transplant hospitalization discharge. The remaining 18 patients (group II) underwent LVAD implant without ECMO support; 12 survived to transplant hospitalization discharge and 2 remained alive with ongoing LVAD support and awaited transplant. One-year actuarial survival from the initiation of circulatory support was 43% in group I and 75% in group II. One-year actuarial survival from the time of LVAD implant in group I, conditional on surviving ECMO, was 71% (P=NS compared with group II). CONCLUSIONS: In appropriately selected high-risk patients, the rate of LVAD survival after initial ECMO support was not significantly different from the survival rate after LVAD support alone. An initial period of resuscitation with ECMO is an effective strategy to salvage patients with extreme hemodynamic instability and multiorgan injury. Use of LVAD resources is improved by avoiding LVAD implant in a very-high-risk cohort of patients who do not survive ECMO.

Extracorporeal resuscitation of cardiac arrest.

OBJECTIVE: Extracorporeal support of heart and lung function (venoarterial perfusion) during cardiac arrest (ECPR) has been advocated as a means of improving survival following cardiac arrest. The authors retrospectively reviewed their institution's seven-year experience with this intervention. METHODS: Emergency department patients and inpatients in cardiac arrest or immediately postarrest were considered candidates. ECPR was instituted using venoarterial bypass and was continued until patients regained sufficient cardiopulmonary function to allow weaning from the device or until their condition was deemed irrecoverable. RESULTS: ECPR was attempted in 25 patients and successfully instituted in 21. Four patients (16%) were converted from ECPR to ventricular assist devices, two of whom survived and await transplantation. Seven additional patients were discharged from the hospital, resulting in an overall survival of 36%. Because none of the children treated survived, there was a trend toward higher age among survivors (survivors 40 +/- 14 yr, nonsurvivors 33 +/- 15 yr, p = 0.29). The duration of conventional CPR was shorter among survivors (survivors 21 +/- 16 min, nonsurvivors 43 +/- 32 min, p = 0.04), as was the duration of extracorporeal support (survivors 44 +/- 21 hr, nonsurvivors 87 +/- 96 hr, p = 0.18). Survival was seen only in patients whose conditions were amenable to a definitive therapeutic intervention, particularly cardiac arrest due to respiratory or pulmonary embolic disease. While four of the five patients treated in the ED were successfully supported, none survived to discharge. CONCLUSION: In select patients with reversible disease, extracorporeal CPR can be used to successfully treat cardiac arrest. Further investigation into its most appropriate application is warranted.

The utility of technetium 99m pertechnetate scintigraphy in the evaluation of patients with Meckel's diverticulum.

PURPOSE: The aim of this study was to assess the utility of technetium (Tc) 99m pertechnetate scintigraphy in the diagnostic workup of the pediatric patient with gastrointestinal (GI) bleeding and a suspected Meckel's diverticulum. METHODS: The charts of 235 consecutive patients evaluated with a Meckel's scan (n = 165) or with the discharge diagnosis of Meckel's diverticulum (n = 70) between January 1975 and October 1997 were reviewed for presenting symptoms, bleeding characteristics, diagnostic studies and pathological diagnosis. Those patients with lower GI bleeding and a serum hemoglobin level less than 11.0 g/dL who underwent a 99mTc pertechnetate scan (n = 43) were assessed for utility of the scan. RESULTS: In all patients the Meckel's scan had a positive and negative predictive value of 0.93. However, in patients with lower GI bleeding and a hemoglobin less than 11.0 g/dL the Meckel's scan had a sensitivity of 0.60, a positive predictive value of 1.0, a specificity of 0.96, but only a negative predictive value of 0.74. As such, the probability that a child who presents with GI bleeding and a serum hemoglobin less than 11 g/dL will have a Meckel's diverticulum despite a negative Meckel's scan of 0.26. We further evaluated the eight patients with a false-negative scan: ectopic gastric mucosa was present on pathological examination in all eight patients. Pentagastrin stimulation was performed at the time of scintigraphic study in three of eight. Six of these eight patients had duplicate scans that also were negative. Patients with a false-negative (FN) scan had significantly increased hospital charges when compared with those with a true positive (TP) scan (TP = $5012 +/- 1992; FN = $8554 +/- 1506; P = .0001). Clinical suspicion had a major effect on the decision-making process in these patients independent of the results of the Meckel's scan, and all eight patients ultimately underwent exploratory laparoscopy-laparotomy with Meckel's diverticulectomy despite the scan results. CONCLUSIONS: The relatively low negative predictive value of the Meckel's scan may result in the need for operative evaluation despite the scan data. As such, the contribution of the scan to clinical decision making is low. These findings suggest that exploratory laparotomy or laparoscopy may be indicated instead of scintigraphic scanning in the assessment of the anemic (hemoglobin less than 11 g/dL) pediatric patient with lower GI bleeding, especially in patients in whom a high suspicion for a bleeding Meckel's diverticulum exists.

Venovenous extracorporeal life support via percutaneous cannulation in 94 patients.

STUDY OBJECTIVE: The objective of this study was to demonstrate the safety and utility of a method of percutaneous access for cannulation of adult patients for venovenous extracorporeal life support (ECLS). DESIGN: A retrospective review of a patient series. SETTING: A surgical ICU at a university teaching hospital. PATIENTS: The study group consisted of 94 adults > 17 years old with respiratory failure who were placed on venovenous ECLS by means of percutaneous cannulation. INTERVENTIONS: The cannulation of the internal jugular and femoral veins (FVs) using the Seldinger technique for venovenous ECLS. MEASUREMENTS AND RESULTS: Between May 1992 and November 1997, we performed percutaneous cannulation for venovenous ECLS in 94 adult patients with respiratory failure. The mean (+/- SD) age was 36.1+/-12.7 years old (range, 17 to 65 years). The mean (+/-SD) weight was 80.7+/-22.3 kg (range, 36 to 156 kg). The right internal jugular vein (RIJV) was used for venous drainage access in all but four cases. The right FV (n = 86), the left FV (n = 3), or the RIJV (n = 4) was utilized for venous reinfusion. The maximum blood flow (+/-SD) during ECLS was 57.6+/-17.5 mL/kg/min (range, 22.4 to 127.8 mL/kg/min), with a postmembrane outlet pressure (+/-SD) of 146+/-43 mm Hg (range, 56 to 258 mm Hg) at the maximum flow rate. There were 11 unsuccessful percutaneous cannulation attempts. In three patients (3%), the complications consisted of arterial injury requiring operative cutdown and repair. In six patients (6%), cannula-site bleeding required pursestring suture reinforcement of the cannula site. One patient died from the perforation of the superior vena cava during cannulation. CONCLUSIONS: Based on these data, we conclude that percutaneous cannulation may be utilized to provide venovenous ECLS in adults.

Relationship of esophageal anastomotic tension to the development of gastroesophageal reflux.

BACKGROUND/PURPOSE: Gastroesophageal reflux (GER) is a common occurrence after repair of congenital esophageal atresia and is believed to be more frequent when the esophageal anastomosis is performed under tension. This study documents that esophageal anastomotic tension correlates directly with the severity of acid reflux into the esophagus in the rabbit model. METHODS: Eight adult rabbits underwent complete esophageal transection with immediate reanastomosis (EA) and 12 underwent resection of a 1-cm segment of the midesophagus with reanastomosis under mild tension (EAT). Three-weeks postoperation continuous lower esophageal pH (LEpH) values were recorded for a 24-hour period for each rabbit, and compared with five normal unoperated rabbits. RESULTS: The normal rabbit's average LEpH is 7.7. EA rabbits had LEpH values below 5.0 for a mean of 56 min/24 hr (3.8% of monitored time). EAT rabbits had LEpH values below 5.0 for a mean of 328 min/24 hr (25.5% of monitored time; P < .05). EA rabbits had a mean of 8.8 reflux episodes under 5.0/24 hr, whereas EAT rabbits had a mean of 29.6 reflux episodes under 5.0. All EAT rabbits had moderate to severe anastomotic strictures; no EA rabbits had strictures. There were no anastomotic leaks. CONCLUSIONS: Esophageal anastomosis with mild tension in the rabbit causes severe GER with resultant anastomotic strictures in almost all rabbits, in contrast to rabbits undergoing esophageal anastomosis without tension in whom strictures did not develop and had only small reduction in esophageal pH values.

Delayed effects of epidermal growth factor after extensive small bowel resection.

Epidermal growth factor (EGF) is produced in the gastrointestinal tract and has been shown to have a transient stimulatory effect on mucosal growth and uptake of glutamine. This study investigated the delayed effects of EGF on mucosal brush-border membrane enzymes and glutamine uptake after extensive small bowel resection. Twenty-four New Zealand White rabbits underwent a 50% to 60% midjejunoileal enterectomy. One group of 12 had a subcutaneous osmotic pump inserted, delivering EGF at 0.3 microgram/kg/h for the first 7 postoperative days. The other group of 12 served as controls. Six rabbits from each group were killed at 3 weeks, and the remaining 12 were killed at 6 weeks. Six additional rabbits served asd nonsurgical controls. There was a twofold increase in mucosal dry weight at 3 weeks without EGF, and an almost fourfold increase with EGF, over control rabbits. This effect of EGF on the mucosa persisted for 6 weeks. Enzymatic activity per gram of protein in each group of rabbits was similar between the four groups of rabbits, although maltase activity increased approximately fourfold over that of nonoperative control animals. However, enzyme capacity of maltase and aminooligopeptidase (AOP) increased threefold and twofold (respectively) at 3 weeks without EGF, and sixfold and fourfold with EGF. Functional capacity is a measure of the load of nutrients that the intestine can digest and absorb, and therefore the derivable benefit to the animal. Glutamine uptake capacity increased 60% in 3 weeks without EGF, then declined by 6 weeks. However with EGF it increased 200% by 3 weeks, and further increased 400% by 6 weeks over control levels. The authors conclude that EGF markedly increases the functional capacity of the small intestine in rabbits that have undergone extensive small bowel resection; this effect persists for up to 6 weeks after a small initial dosage of EGF.

Superior and inferior vena caval occlusion in infants receiving total parenteral nutrition.

During the past 23 1/2 years, 510 infants under 12 months of age had 756 Broviac central venous catheters inserted. At first catheter insertion 51 per cent of patients were less than 1 month old. Catheter function ranged from 3 to 1080 days (mean = 90 days). Sites of insertion were saphenous 85 per cent, external jugular 7 per cent, internal jugular 5 per cent, subclavian 2 per cent, cephalic 0.7 per cent, and transthoracic azygos 0.5 per cent. Eighty-nine patients had malabsorption syndromes, 86 had short bowel syndrome, 74 had intractable diarrhea, and 261 required nutritional support for other reasons. Vena caval thrombosis developed in 35 infants; 23 had inferior vena cava (IVC) occlusion (4.5% at risk); six had isolated superior vena cava (SVC) occlusion (11% at risk), and six had both SVC and IVC thrombosis. No major symptoms or complications resulted from isolated IVC thrombosis, whereas all infants with SVC occlusion developed head and neck swelling, 50 per cent developed pleural effusions, and two died. Each of six infants with combined IVC and SVC occlusion died within 6 months. We conclude that SVC occlusion is a very serious complication in infants receiving total parenteral nutrition (TPN) solutions and that infusion via the IVC has fewer and less serious complications.

Adaptation of rabbit small intestinal brush-border membrane enzymes after extensive bowel resection.

Short lengths of small intestine may be resected without significantly affecting the digestive and absorptive capacity; however, extensive resection produces varying degrees of malnutrition. This study was undertaken to define the adaptive changes in the remaining small intestine of two of the jejunal and ileal mucosal brush-border membrane enzymes after extensive small bowel resection in rabbits. Thirty adult New Zealand White rabbits underwent a 50% to 60% jejuno-ileal-enterectomy with end-to-end anastomosis. Maltase activity (UE/g protein) increased from 152 (preoperative) to 392 at 3 weeks in the proximal segment and from 85 to 259 in the distal segment; these levels decreased to 222 and 155 in the respective segments at 6 weeks. AOP activity (UE/g protein) increased from 154 (preoperative) to 171 in the proximal segment and 171 to 256 in the distal segment at 3 weeks, and was 131 and 288 in the respective segments at 6 weeks. This marked increase in the mucosal brush-border enzymatic activities at 3 weeks postoperatively was associated with a 28% increase in bowel length. By 6 weeks the enzyme levels had decreased slightly; however, there was a persistent 41% increase in bowel length over that immediately postoperation. The mucosal surface area increased from 295 mm2 immediately postoperation to 5,337 mm2 at 3 weeks and 7,635 mm2 at 6 weeks, a 250% increase. The authors conclude that there is an immediate compensatory increase in villus length as well as brush-border enzymatic expression in the remaining intestine that gradually declines as the small intestinal surface area continues to increase and the bowel lengthens with time.

Effect of intraamniotic dexamethasone administration on intestinal absorption in a rabbit gastroschisis model.

Infants with gastroschisis experience delayed intestinal motility and absorption for several weeks after birth. This intestinal dysfunction is believed to occur primarily in the third trimester and to be largely caused by the prolonged exposure of the intestine to amniotic fluid. Previous studies have shown that prenatal steroid administration will enhance mucosal disaccharidase activity and nutrient uptake. The present study evaluates the effects of dexamethasone on intestinal function in a rabbit fetal gastroschisis model. Thirty-four fetuses from 10 New Zealand white rabbits were divided into three groups: (1) gastroschisis group (GSC, n = 10), gastroschisis was created on gestational day (GD) 24 (term = 31 to 33 days); (2) dexamethasone group (GSD, n = 10), after the creation of gastroschisis, a small osmotic pump was placed into the rabbit doe for dexamethasone infusion into the fetal amniotic cavity for 7 days (0.2 microgram/g/d); (3) normal group (NF, n = 10), unoperated littermates from the GSC group. There were no maternal deaths, and fetal survival rate was 85%. The fetal small intestinal disaccharidase enzyme, lactase (UE/g protein), was markedly decreased in GSC fetuses. It was increased 70% in the GSD group but lower than in normal fetuses (GSC = 10.0 +/- 1.6; GSD = 17.3 +/- 1.6 [GSD versus GSC, P < .05]; NF = 48.0 +/- 6.7). Maltase activity in the GSD group was significantly increased (GSC = 7.2 +/- 1.1; GSD = 13.9 +/- 1.8 [GSD versus GSC, P < .05]; NF = 12.2 +/- 1.3).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of epidermal growth factor on mucosal function after ileal resection.

Since epidermal growth factor (EGF) enhances gut mucosal regeneration, the present study was undertaken to evaluate the effect of EGF on brush-border membrane enzyme activity and glutamine uptake in the intestinal remnant following extensive small bowel resection. Twenty-four adult male New Zealand White rabbits were divided into three groups: Group 1 (n = 12) served as controls. Groups 2 and 3 (n = 6 each) underwent a 50-60% mid-jejunoileal resection with anastomosis of the remaining intestine, leaving 90 cm between the pylorus and the ileocecal valve. Group 3 rabbits had a subcutaneous osmotic pump implanted to deliver EGF for 7 days at 0.3 micrograms/kg/hr. Rabbits from Groups 2 and 3 were sacrificed 3 weeks postoperation. Mucosa from the proximal and distal segments of the remaining intestine was analyzed for wet/dry weight, maltase and aminooligopeptidase activity, and glutamine uptake. There was a twofold increase in mucosal dry weight/cm of intestine in rabbits without EGF at 3 weeks (Group 2) and a fourfold increase in those given EGF (Group 3). The maltase enzyme capacity (UEnzyme/rabbit) increased from 37 +/- 10 in controls (Group 1) to 167 +/- 30 without EGF and 207 +/- 30 with EGF. The aminooligopeptidase enzyme capacity (UEnzyme/rabbit) increased from 55 +/- 10 to 147 +/- 20 and 226 +/- 30 in Groups 1, 2, and 3, respectively. Glutamine uptake capacity (microM glutamine/min) also increased significantly, from 63 +/- 19 in Group 1 to 88 +/- 6 without EGF and 162 +/- 18 with EGF (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)