Endosurgery and the senior pediatric surgeon.

BACKGROUND: Endosurgery is difficult for the senior pediatric surgeon to master because the technique has a steep learning curve, lacks tactile sense, uses elongated instruments, and is ergonomically tiring. METHODS: The senior author, starting at age 53, has performed more than 300 endoscopic procedures at both children and community hospitals. A full year was required to master laparoscopic Nissen fundoplications. Conversion to open procedures from bleeding and enterotomies were committed in the first year of endosurgery. Facility with endosurgery is gained by performing common and frequent procedures as appendectomies. CONCLUSION: The advantages of endosurgery in pain control and shortened hospitalization make the technique deserving of commitment by the senior pediatric surgeon.

Evaluation of minimally invasive approaches to achalasia in children.

BACKGROUND: Achalasia is an uncommon disease in children, but when present can result in severe disabling symptoms often requiring surgical intervention. This report describes the authors' experience with thoracoscopic (TH) and later laparoscopic Heller (LH) myotomy for definitive treatment of this disease. METHODS: Nine patients with achalasia were referred for surgical therapy. Ages ranged from 5 to 17 years and weight from 23 to 78 kg. All had undergone at least one dilatation with recurrence of symptoms. The first 4 were treated by TH and the last five by LH. The 5 LH procedures also included a partial fundoplication. RESULTS: All procedures were completed successfully using minimally invasive techniques. Operating times averaged 95 minutes for TH and 62 minutes for LH. One patient undergoing TH had a small esophageal perforation repaired primarily. The other 3 TH patients were started on clear liquids within 1 day and discharged on day 2. One patient had recurrent symptoms at 6 months and underwent a LH for an incomplete TH. All 5 LH patients were discharged on postoperative day 1. One had an esophageal perforation 4 days after operation requiring laparoscopic repair. Seven of 9 patients are asymptomatic. Studies of pH levels in 2 asymptomatic TH patients show mild gastroesophageal reflux (GER). CONCLUSIONS: Minimally invasive Heller myotomy is a safe and effective procedure in children. TH results in a slightly longer operating time and hospital stay and, without a partial fundoplication, also may be associated with a higher incidence of silent GER. From these results, we prefer LH with a Dor fundoplication for treatment of achalasia in children.

Primary laparoscopic placement of gastrostomy buttons for feeding tubes. A safer and simpler technique.

BACKGROUND: During a 4-year period, 240 gastrostomy buttons were placed in children, as the initial surgical feeding tube, using laparoscopic techniques. MATERIALS AND METHODS: The technique requires the use of a minilaparoscope (1.6-mm) and a single 5-mm trocar placed at the exit site for the gastrostomy button. It can also be performed in addition to a laparoscopic fundoplication using the same trocar sites. The technique requires no special instrumentation or kits. When performed alone, operative times average 15 min. When performed with fundoplication, it adds approximately 5-10 min to the time for the procedure. RESULTS: There were no intraoperative complications and five (2.1%) postoperative complications. CONCLUSIONS: This technique has proven to be simple and effective. It allows primary placement of a gastrostomy button that is cosmetically and functionally superior to a gastrostomy tube.

Shock after blast wave injury is caused by a vagally mediated reflex.

OBJECTIVE: Bomb blast survivors occasionally suffer from profound shock and hypoxemia without signs of external injury. We hypothesize that a vagally mediated reflex such as the pulmonary defensive reflex is the cause of shock from blast wave injury. This study was a prospectively randomized, controlled animal study. METHODS: By using a previously described model of blast wave injury, we randomized rats to one of four groups: control, blast-only, bilateral cervical vagotomy plus atropine 200 microg/kg i.p. only, and bilateral cervical vagotomy plus atropine 200 microg/kg i.p. before blast injury. Cardiopulmonary parameters were recorded for 90 minutes after the blast or until death. RESULTS: Bradycardia, hypotension, and absence of compensatory peripheral vasoconstriction, typically seen in animals subjected to a blast pressure injury, were prevented by bilateral cervical vagotomy and intraperitoneal injection of atropine methyl-bromide. Hypoxia and lung injury were not statistically significant between the blasted groups, suggesting equivalent injury. CONCLUSION: Our data implicate a vagally mediated reflex such as the pulmonary defensive reflex as the cause of shock seen immediately after a blast pressure wave injury.

Treating the snakebitten child in North America: a study of pit viper bites.

BACKGROUND/PURPOSE: Snakebite envenomation is a potentially life-threatening form of trauma, the dangers of which are amplified in children because their smaller size increases the relative dose of venom received. The authors reviewed a large series of snakebitten children to address the medical and fiscal issues of treating these patients. METHODS: The records of 37 snakebitten children (1987 through 1997) were analyzed for demographic data, signs of envenomation, use of specific therapies (antivenin, blood products, or surgery), length of hospitalization, complications, and cost of care. RESULTS: Fifty-four percent of the children had a major envenomation demonstrated by systemic symptomatology, laboratory analysis, or need for surgery. All children made full recoveries with most receiving only supportive care (92%). The average time to emergency department presentation was 8 hours, where all children with major envenomations and those requiring specific therapies (surgery, clotting factors) were identified. Cost analysis showed an average of $2,450 dollars per child with the majority of expenses attributable to length of hospitalization. CONCLUSIONS: Most snakebitten children completely recover with minimal supportive care, and they can be cared for safely and cost effectively as outpatients if no signs of major envenomation are noted within 8 hours of the bite.

Global primary blast injury: a rat model.

Blast wave injury from bombs cause a unique but poorly understood spectrum of injuries. Previous blast wave models involved high energy explosives detonated in an open field without the sophisticated monitoring of laboratory equipment. We characterized a rodent model that produces a global blast injury in a safe laboratory environment. Male rats, prospectively randomized to four groups of ten, were anesthetized and subjected to a blast at 2.0 cm, 2.5 cm, or 3.5 cm from the blast nozzle. The control group received no blast. Intensity of the blast (80-120 psi peak pressure, 1-2 msec duration) was controlled by varying the distance of the blast wave generator to the rat. The rats were monitored for three hours following the blast and then euthanized. Bradycardia was an immediate but transient response to blast injury. Mean arterial pressure was bimodal with severe hypotension occurring immediately after the blast and, again, two to three hours later. The characteristic injuries from a blast wave, such as pulmonary hemorrhage with increased lung weight, intestinal serosal hemorrhage, and hemoperitoneum, were found in the rats subjected to the blast pressure wave. In conclusion, our rodent model accurately reproduces the clinical spectrum of injuries seen in blast victims and will provide a powerful tool for studying the pathophysiology and potential treatments of bomb blast victims.

Experience with minimally invasive surgery in infants.

BACKGROUND: This study evaluates the feasibility, safety, and efficacy of performing advanced endoscopic procedures in infants under 5 kg. METHODS: Over a 51-month period 183 infants weighing 1.3 to 5.0 kg underwent 195 procedures using minimally invasive techniques. The majority of the procedures were performed using 3.5-mm instruments and 2.7-mm scopes. Procedures include Nissen fundoplication, pyloromyotomy, colon pull-through, patent ductus arteriosus closure, Ladd's procedure, colon resection, congenital diaphragmatic hernia repair, ovarian cyst excision, and exploration. RESULTS: All but two procedures were completed successfully endoscopically. There were two intraoperative complications and no mortality. Days to discharge for patients admitted for their specific procedure were Nissen 2.1, patent ductus arteriosus 2, pyloromyotomy 1, and pull-through 3.4. CONCLUSIONS: This study demonstrates that advanced endosurgical techniques in infants is safe, effective, and associated with the same benefit as that seen in older patients.

Extracorporeal life support for nonimmune hydrops fetalis.

BACKGROUND/PURPOSE: Most babies born with idiopathic nonimmune hydrops fetalis (NIHF) suffer generalized cardiopulmonary collapse and die despite maximal medical therapy. With reported survival rates of less than 10%, many centers consider NIHF an unsalvageable situation and the babies who have this condition, untreatable. In this study, the authors questioned if the aggressive use of extracorporeal life support (ECLS) could salvage this condition and improve the chances of survival for babies born with NIHF. METHODS: The Extracorporeal Life Support Organization's (ELSO) neonatal registry was searched for all available information on babies treated for hydrops fetalis. The ELSO records of all hydropic babies were then reviewed to exclude those babies who had identifiable causes of hydrops. Survival statistics were then calculated for the remaining core group of idiopathic NIHF babies before separating them into two groups based on survival. A detailed analysis comparing the survivors with nonsurvivors was then performed. RESULTS: A total of 28 hydropic babies were identified in the ELSO registry. Four babies were excluded from analysis because of identifiable causes of hydrops (two with congenital diaphragmatic hernia, one with Rh incompatibility, and one with fetal anemia). Of the remaining 24 babies who had NIHF, 54% (13 babies) survived the neonatal period and were discharged from the hospital. Analysis comparing the survivors with the nonsurvivors in our study showed that the groups were similar in their gestational ages, birth weights, Apgar scores and the time to initial intubation. The most distinguishing factor of survival in our study was that the survivors, on average, received ECLS support 3 days sooner than nonsurvivors (mean, 17.5 +/- 1.3 hours of life for survivors v 105 +/- 36.6 hours for nonsurvivors, P < or = .05). CONCLUSION: Idiopathic NIHF should no longer be considered an untreatable condition but a new indication for ECLS that, when begun early, may significantly improve the chances of survival for these babies previously considered "unsalvageable."

Cardiopulmonary physiology of primary blast injury.

OBJECTIVE: Bomb blast survivors are occasionally found in profound shock and hypoxic without external signs of injury. We investigated the cardiovascular and pulmonary responses of rats subjected to a blast pressure wave. DESIGN: Prospectively randomized, controlled animal study. MATERIALS AND METHODS: Rats were instrumented and subjected to a blast pressure wave of different intensities from a blast wave generator. Cardiopulmonary parameters were recorded for 3 hours or until death. MEASUREMENTS AND MAIN RESULTS: The cardiovascular response to a blast pressure wave was immediate bradycardia, hypotension, and low cardiac index. Three hours later, the rats developed hypotension, low cardiac index, and low stroke volume. Interestingly, systemic vascular resistance remained unchanged. The pulmonary response was a decreased PaO2 and stable PacO2, suggesting a ventilation-perfusion mismatch from massive pulmonary hemorrhage. CONCLUSIONS: Blast-induced circulatory shock resulted from immediate myocardial depression without a compensatory vasoconstriction. Hypoxia presumably resulted from a ventilation-perfusion mismatch caused by pulmonary hemorrhage.

Chorioamniotic membrane separation: a potentially lethal finding.

Sonographic detection of chorioamniotic membrane separation (CMS) has been considered a benign incidental finding. We now report 6 cases of CMS identified by prenatal ultrasound; 1 in an otherwise normal pregnancy and 5 following fetal surgery. Following membrane separation, amniotic bands formed and compromised the umbilical cord in 4 cases leading to 2 fetal deaths. In the first case, CMS was detected by ultrasound at 22 weeks' gestation in an otherwise uncomplicated pregnancy. Because CMS was considered benign and umbilical cord blood flow was ample, the mother was followed by intermittent sonographic examinations. Fetal demise occurred 2 weeks later, clearly due to umbilical cord strangulation by an amniotic band. Surprised by this unexpected outcome, we reviewed our experience with CMS after hysterotomy for fetal surgery. Out of more than 40 fetal surgical cases, we have 5 cases in which CMS was recognized after hysterotomy. Three of these fetuses had umbilical cord compromise by a band of amniotic membrane leading to 1 fetal death. This experience demonstrates that membrane separation may be associated with amniotic band formation which can lead to cord strangulation and fetal compromise. Following fetal surgery, serial ultrasound evaluation and close fetal monitoring are indicated. In otherwise unremarkable pregnancies, clinician awareness of the possibility of amniotic band formation following CMS should be heightened. In either situation, knowledge of this potential life-threatening complication may identify cases in which cord compromise requires emergent delivery or fetoscopic release of the strangulating amniotic band.

Operating on placental support: the ex utero intrapartum treatment procedure.

While treating eight fetuses with predictable airway obstruction, the authors developed a systematic approach, the ex utero intrapartum treatment procedure, to secure the airway during delivery. Six patients had their trachea plugged or clipped in utero for treatment of congenital diaphragmatic hernia, and two patients had prenatally diagnosed cystic hygroma of the neck and oropharynx. The ex utero intrapartum treatment procedure was performed by using high doses of inhaled halogenated agents to facilitate uterine relaxation during cesarean section, securing the fetal airway while feto-placental circulation remained intact, and then dividing the umbilical cord. A variety of procedures were performed during the ex utero intrapartum treatment procedure including bronchoscopy, orotracheal intubation, tracheostomy, tracheostomy with retrograde orotracheal intubation, tracheoplasty, removal of internal tracheal plug, removal of external tracheal clip, central line placement, and instillation of surfactant. There were minimal maternal or fetal complications during the procedure. This approach requires the coordinated efforts of pediatric surgeons, obstetricians, anesthesiologists, sonographers, and neonatologists. The combination of intensive maternal-fetal monitoring, cesarean section with maximal uterine relaxation, and maintenance of intact feto-placental circulation provides a controlled environment for securing the airway in babies with prenatally diagnosed airway obstruction.

Fetal endoscopic tracheal occlusion ('Fetendo-PLUG') for congenital diaphragmatic hernia.

Despite recent advances in surgical technique, posthysterotomy preterm labor remains a major determinant of postoperative fetal morbidity and mortality after in utero repair of congenital diaphragmatic hernia (CDH). Temporary fetal tracheal occlusion, or "PLUG" (Plug the Lung Until it Grows), reverses the pulmonary hypoplasia seen in experimental models of CDH and provides an alternative treatment strategy for some fetuses with CDH. Adaptation of current, minimally invasive surgical technology to the PLUG technique allows treatment of CDH without opening the uterus. In this report the authors describe a video-fetoscopic, intrauterine technique of tracheal occlusion (called Fetendo-PLUG) that could be used in human fetuses with CDH. The technique was developed in four fetal lambs that underwent video-fetoscopic intervention at 110 days' gestation (full term, 145 days), having undergone open creation of diaphragmatic hernias at 75 days. After maternal laparotomy and uterine exposure, the fetal head was located and a 5-mm curved, balloon-cuffed trocar was introduced through a uterine puncture directly into the fetal oral cavity. A steerable "bronchoscope" (with an instrument channel) was used to endoscopically intubate the trachea through the trocar, and the trocar was advanced over the bronchoscope and its balloon inflated to provide secure tracheal access below the vocal cords. Next, a 10-mm trocar was placed directly over the fetal neck, and the amniotic space was expanded with warm saline. A 5-mm laparoscope was introduced, and under simultaneous, dual video-fetoscopic (endotracheal and endoamniotic) visualization, a 1-mm nephrostomy puncture wire was advanced along the instrument channel of the bronchoscope, through the anterior wall of the trachea and fetal neck, into the amniotic space, then through the uterine wall to the outside. Withdrawal of the bronchoscope over the wire left a 5-mm endotracheal "trocar channel" along which a compressed, gelatin-encapsulated, polymeric foam insert (outer diameter, 4.8 mm) could be delivered by suture attachment to the guide wire. Once the foam was in its final endotracheal position, dissolution of the gelatin membrane allowed expansion of the foam to produce a water impervious tracheal occlusion. This two-trocar video-fetoscopic PLUG technique was performed successfully in all four fetuses, with a sequential decrease in operating time (median, 3.5 hours). Although two fetuses aborted postoperatively, the other two were carried successfully to term and demonstrated the anticipated physiological effects of adequate tracheal occlusion at the time of delivery.

Correction of congenital diaphragmatic hernia in utero VIII: Response of the hypoplastic lung to tracheal occlusion.

Most fetuses with congenital diaphragmatic hernia (CDH) diagnosed before 24 weeks' gestation die despite optimal postnatal care. In fetuses with liver herniation into the chest, prenatal repair has not been successful. In the course of exploring the pathophysiology of CDH and its repair in fetal lambs, the authors found that obstructing the normal egress of fetal lung fluid enlarges developing fetal lungs, reduces the herniated viscera, and accelerates lung growth, resulting in improved pulmonary function after birth. They developed and tested experimentally a variety of methods to temporarily occlude the fetal trachea, allow fetal lung growth, and reverse the obstruction at birth. The authors applied this strategy of temporary tracheal occlusion in eight human fetuses with CDH and liver herniation at 25 to 28 weeks' gestation. With ongoing experimental and clinical experience, the technique of tracheal occlusion evolved from an internal plug (two patients) to an external clip (six patients), and a technique was developed for unplugging the trachea at the time of birth (Ex Utero Intrapartum Tracheoplasty [EXIT]). Two fetuses had a foam plug placed inside the trachea. The first showed dramatic lung growth in utero and survived; the second (who had a smaller plug to avoid tracheomalacia) showed no demonstrable lung growth and died at birth. Two fetuses had external spring-loaded aneurysm clips placed on the trachea; one was aborted due to tocolytic failure, and the other showed no lung growth (presumed leak) and died 3 months after birth. Four fetuses had metal clips placed on the trachea. All showed dramatic lung growth in utero, with reversal of pulmonary hypoplasia documented after birth. However, all died of nonpulmonary causes. Temporary occlusion of the fetal trachea accelerates fetal lung growth and ameliorates the often fatal pulmonary hypoplasia associated with severe CDH. Although the strategy is physiologically sound and technically feasible, complications encountered during the evolution of these techniques have limited the survival rate. Further evolution of this technique is required before it can be recommended as therapy for fetal pulmonary hypoplasia.

Gastroschisis increases small bowel nitric oxide synthase activity.

In gastroschisis, the eviscerated fetal bowel frequently is damaged and this results in hypoperistalsis and malabsorption. The mechanistic link that ties gastroschisis-induced intestinal damage to dysfunction may be nitric oxide (NO) and the enzyme responsible for producing it, NO synthase. Using a fetal rabbit model, the authors investigated the hypothesis that the hypoperistalsis and malabsorption associated with gastroschisis may be attributable to abnormal small bowel NO synthase activity. Using the 3H-arginine-to-3H-citrulline conversion assay, they measured NO synthase activity in the small bowel of full-term fetal rabbits with and without gastroschisis. The mean total small bowel NO synthase activity of fetal rabbits with gastroschisis was 2.5 times greater than that of control littermates without gastroschisis (n = 6; 5,726 +/- 834 v 2,208 +/- 537 mean pmol/mg protein/min; P = .004). This increased NO synthase activity also was studied by measuring the individual isoforms of NO synthase, and the site of increased NO synthase activity was localized to the small bowel epithelium and neurons. After detecting and localizing the gastroschisis-induced increase in NO synthase activity, the authors explored the mechanism of this increase using NADPH-diaphorase staining. With this histological staining technique, no quantitative increase was found in the small bowel NO synthase of the rabbits with gastroschisis. This suggests that the increased NO synthase activity found in these rabbits is the result of accelerated enzyme kinetics. These findings suggest that the increased NO synthase activity caused by gastroschisis may contribute to the common clinical sequelae of malabsorption and intestinal dysmotility.

The incidence and spectrum of neurological injury after open fetal surgery.

A preterm infant's immature brain is susceptible to both anoxic and hemorrhagic injury during periods of physiological stress. The advent of in utero surgery has created a new population of premature patients at risk for central nervous system (CNS) injury. The aim of this study was to evaluate the frequency and nature of CNS injuries in fetal surgical patients. Of 33 fetuses with known neurological outcome after fetal surgery, CNS injuries were identified in seven (21%). Of the seven, four had significant episodes of fetal bradycardia (3) or neonatal hypotension (1), which suggests that asphyxia contributed to the neurological injury. The CNS injuries in the other three patients occurred unexpectedly and without associated signs of fetal distress. The authors speculate that these injuries may have been caused by sudden fluxes in cerebral blood flow, induced by maternal hypoxia (1) or by maternally administered tocolytic drugs (2) used to treat postoperative preterm labor.

Fetal endoscopic ('Fetendo') surgery: the relationship between insufflating pressure and the fetoplacental circulation.

Application of video-endoscopic surgery to the gravid uterus provides a new treatment option for the fetus with a correctable congenital anomaly. "Fetendo" surgery requires temporary enlargement of the uterine cavity to create a working space. Volume expansion of the amniotic space raises intrauterine pressure, which could increase placental vascular resistance and thereby reduce placental blood flow. To test this hypothesis, the authors developed a fetal sheep model to examine the relationship between insufflating pressure and flow in the placental circulation. Fetoplacental blood flow was measured via ultrasonic flow probes placed around the fetal common umbilical artery and the maternal uterine artery in five anesthetized 120-day-gestation ewes. Invasive feto-maternal monitoring permitted synchronous measurement of fetal mean arterial pressure, fetal central venous pressure, maternal mean arterial pressure, amniotic pressure, and fetal oxygen saturation, with calculated values for fetal and maternal placental vascular resistance. Amniotic pressure was raised from 10 mm Hg to 40 mm Hg in 5-mm Hg increments by a combination of saline amnioinfusion and external uterine compression. At amniotic pressures of 20 mm Hg or less, placental blood flow was preserved; however, elevation of amniotic pressure above 20 mm Hg resulted in a significant decrease in placental flow, with concomitant fetal hypoxia. The authors conclude that the relationship between intrauterine pressure, flow in the placental circulation, and fetal oxygen delivery must be considered when selecting intrauterine insufflation pressures for hysteroscopic intervention.

Cyclic GMP relaxes the internal anal sphincter in Hirschsprung's disease.

In Hirschsprung's disease (HD), the aganglionic colon and internal anal sphincter (IAS) fail to relax. Aganglionic colon of HD patients relaxes in response to exogenous nitric oxide (NO), whereas the IAS from HD patients does not relax. The authors hypothesized that the failure of IAS relaxation is caused by a local deficiency of cyclic guanosine monophosphate (cGMP), the final metabolite in NO-mediated smooth muscle relaxation. To test this hypothesis, the authors measured the isometric tension of smooth muscle strips taken from the IAS and aganglionic colon of patients with HD before and after exposure to cGMP and compared this with ganglionic colon and IAS from normal controls. In HD patients both the IAS and aganglionic colon relaxed in response to cGMP (P < .05). The amount of relaxation observed in both the aganglionic colon and IAS was comparable to that measured in the normal controls. The observation that exogenous cGMP relaxes the IAS, whereas exogenous NO does not, suggests that mechanisms for relaxation may be different than those in the aganglionic colon and may explain persistent IAS dysfunction after resection of aganglionic colon. The defect of the IAS in HD may be the inability of the NO/cGMP pathway to induce smooth muscle cell relaxation rather than a defect in the smooth muscle cell.

The 'PLUG' odyssey: adventures in experimental fetal tracheal occlusion.

In animal experiments, it has been shown that tracheal occlusion counteracts the pulmonary hypoplasia associated with congenital diaphragmatic hernia (CDH). Successful clinical implementation requires a reliable, reversible, and atraumatic technique of occluding the fetal trachea. With this clinical goal in mind, the authors evaluated the following three methods of tracheal occlusion in a fetal lamb CDH model: (1) an occluded foam-cuffed endotracheal tube, (2) a foam-cuffed endotracheal tube with a magnetically controlled flow valve, and (3) a tracheal insert constructed of a water-impermeable, expandable, polymeric foam, which is placed by a translaryngeal approach. The foam-cuffed endotracheal tube did not provide consistently reliable fetal tracheal occlusion. Although the magnetically triggered flow valve functioned well, it was not necessary to open the valve in utero (to prevent overdistension of the lungs), and the presence of the valve contributed to several occlusive failures. In contrast, the foam insert was easy to position and to remove from the trachea, while providing reliable tracheal occlusion for several weeks with consequent enlarged fetal lungs, increased lung fluid volumes, complete reduction of abdominal viscera, and improved pulmonary gas exchange after birth. Bronchoscopic evaluation of the foam-occluded neonatal tracheas showed little or no tracheal damage, which was confirmed during necropsy by gross and histological examination. Translaryngeal placement of a compressible, water-impermeable polymeric foam appears to be a simple and safe technique to achieve fetal tracheal occlusion.

Effect of nitric oxide on the colonic smooth muscle of patients with Hirschsprung's disease.

Hirschsprung's disease results in bowel obstruction because of a failure of smooth muscle relaxation in both the aganglionic segment of bowel and the internal anal sphincter (IAS). Nonadrenergic noncholinergic (NANC) nerves, which use nitric oxide (NO) as their chemical messenger, are responsible for relaxing smooth muscle in normal bowel and the IAS. Previous work indicates that the cause of the aganglionic colon's inability to relax may be a lack of NANC nerves. To test this hypothesis, the authors compared the effect of an exogenous source of NO, S-nitroso-N-acetylpenicillamine (SNAP), on the isometric tension of smooth muscle strips taken from the ganglionic colon, aganglionic colon, and IAS of patients with Hirschsprung's disease. Exposure of ganglionic and aganglionic colon specimens to SNAP (10(-3) to 10(-5) mol/L) resulted in up to 70% reduction of resting tension. This relaxation occurred in a dose-dependent fashion and could be promptly reversed by the addition of the NO antagonist methylene blue. However, SNAP had no demonstrable effect on the smooth muscle strips taken from the IAS of patients with Hirschsprung's disease. This finding suggests that, in the aganglionic colon, a deficiency of NANC nerves contributes to the development of bowel obstruction. However, the failure of the IAS to relax in Hirschsprung's disease appears to be unrelated to NO and the NANC nervous system.