Motility abnormality in intestinal atresia

Motility Abnormality in Intestinal Atresia By E d w a r d J. Doolin, Herbert S. Ormsbee, and J. Laurance Hill Baltimore, Maryland 9 This study was designed to investigate the motility of the small bowel of the lamb under the conditions of experimental intestinal atresia. Of 26 fetal lambs operated upon (50 to 90 days gestation), 13 came to term. All t e r m lambs exhibited a type 3a atresia. Six w e r e successfully repaired and had intestinal myoelectric activity monitored for periods from 2 to 27 hours. A slow w a v e pattern (12 to 13/rain) was present in the bowel of control lambs and in the proximal dilated bowel and the microbowel of atretic lambs, confirming the presence of functional smooth muscle. Spike potentials, which indicated circular muscular contractions, occurred 1 0 % of the time in the control intestine, 5% in the proximal dilated gut (P < .2), and 0 % in the microbowel (P < .001). A previously undescribed myoelectric transient of variable amplitude and frequency (6 to 2 4 / m i n ) was identified in all lambs studied. Histologic evaluation demonstrated villous hyperplasia in the microbowel and mucosal flattening in the distended bowel. The data suggest that the quiescent microbowel distal to the atresia contributes significantly to the functional obstruction. 9 1 9 8 7 by Grune & Stratton. Inc.

remove or modify this segment of gut. T M The function of the microbowel has not been evaluated. The purpose of this investigation was to study the intestinal motor activity of both the dilated proximal segment and the distal microbowel in the newborn lamb.

INDEX W O R D S : Intestinal atresia; intestinal motility.

Study Procedure

ARLY C L I N I C A L E X P E R I E N C E S in neonates with intestinal atresia were plagued with significant morbidity and mortality. 1'2 After operative correction of the atresia, the debilitated infant could not withstand the malnutrition and the prolonged clinical course produced by abnormal gastrointestinal function. Today, with improved medical management, the use of stomas when indicated, and especially with the advent of total parenteral nutrition, survival is improved. 35 However, the underlying functional defect in intestinal atresia is not thoroughly understood. In addition to the observed anatomic abnormalities, a functional obstruction is characteristic. The poor transit may be due to dysmotility of the dilated proximal segment or the distal microbowel, or to a combination of the two. Investigations of intestinal atresia in animals to date have focused on the proximal dilated bowel and have suggested a decreased ability to propel its contents distally. 6'7 This has led to attempts to

The lambs were delivered at term (145 days) either vaginally (4) or by cesarean section (9). Through a laparotomy, the intestinal atresia was repaired with primary anastomosis. Pairs of bipolar electrodes, 60 ~m in diameter, (made of either silver or stainless steel) were implanted in the seromuscular layer of the dilated proximal jejunum and the distal microbowelJ 3 At birth, the lamb was supported one of two ways: (1) with mechanical ventilation and intravenous (IV) hydration, or (2) the lamb's connection to the ewe via the umbilical cord was maintained during the surgical procedure (Fig 2). Following surgical implantation of electrodes and repair of the atresia, all lambs were supported by endotracheal intubation, intravenous fluids, and mechanical ventilation (Engstrom). ECG, arterial pressure, and temperature were monitored. The electrode wires were connected to bioelectric preamplifiers with a lower cutoff frequency of 1.5 Hz on a HewlettPackard 7758A recorder (Hewlett-Packard Co, Palo Alto, CA) to measure the small bowel motility. Myoelectric activity of the intestine was recorded in the conscious lambs for 2 to 27 hours to determine the frequency and incidence of slow waves and spike potentials from each site. Seven unfed normal newborn lambs (delivered vaginally) also underwent laparotomy with local anesthesia for the implantation of recording electrodes on the jejunum and ileum similar to those placed in the experimental group. The myoelectric activity was recorded for six hours in the control lambs.

E

From the Department of Surgery, Universityof Maryland School of Medicine, Baltimore. Address reprint requests to Edward J. Doolin, MD, Department of Surgery, Cooper Medical Arts Building, 300 Broadway, Camden, NJ 08103. 9 1987 by Grune & Stratton, Inc. 0022-3468/87/2204-0006503.00/0

320

MATERIALS AND METHODS

The M o d e l o f Intestinal Atresia Twenty-six adult ewes, 50 to 90 days gestation, were anesthetized with 2.5% thiamyl sodium (titrated) and 1.5% halothane inhalation anesthesia. Through a midline laparotomy and hysterotomy, the hind half of the fetus was delivered. Care assured conservation of the amniotic fluid and protection of the umbilical cord. A small (1 to 2 cm) left flank incision exposed the small intestine. To produce intestinal atresia as described by Abrams, the mesentery was avulsed from a 10-cm segment of proximal jejunum, rendering this segment ischemic 12 (Fig 1). The fetal laparotomy was then repaired in one layer followed by closure of the hysterotomy and maternal laparotomy.

Data Analysis After completion of the experiments, necropsy was performed and intestinal specimens were evaluated histologically. The microscopic characteristics of the animal model were compared with the specimen of a human patient with intestinal atresia. For each recording site, the myoelectric activity was evaluated for the presence and frequency of slow waves and the incidence of spike

Journal of Pediatric Surgery, Vol 22, No 4 (April), 1987: pp 320-324

MOTILITY IN INTESTINAL ATRESIA

321

Table 1. Optimal Age for the Induction of Intestinal Atresia in the Fetal Lamb

Fig 1. The technique of fetal mesenteric avulsion eliminates vascular collaterals to the intestine and produces atresia.

potentials. Comparisons among the dilated gut, microbowel, and normal intestine were compiled by the Student's t-test with statistical significance accepted when P < .05.

RESULTS

Gestational A ~ (d)

Abortion Ra~ (%)

50-60 60-70 70-80 80-100

50 25 60 100

animal model. Four of these animals delivered vaginally; all died in the immediately postpartum period. Nine lambs were delivered by cesarean section. The first three were separated from the ewe and supported mechanically, but died during the surgical repair of the experimental atresia and could not be studied. Six lambs underwent repair of the experimental atresia and electrode implantation while supported by the ewe via the umbilical cord. These six were successfully repaired and studied. The experimental intestine of the lamb was histologically similar to that of the human lesion. In both the

Thirteen of 26 fetuses spontaneously aborted (50%) and, therefore, could not be studied. When the fetuses were grouped by gestational age at the time of operation, the optimal age for survival following the induction of atresia was determined to be 60 to 70 days (Table 1). This group had the lowest abortion rate (25%). Thirteen lambs (50%) were delivered at term. All of the lambs that came to term exhibited a type 3a atresia, hence a 100% development of atresia in the

\

,J Fig 2. The lamb is depicted in continuity w i t h the e w e via t h e umbilical cord. Surgery can be performed in a stable subject w i t h o u t cumbersome support apparatus.

Fig 3.

Photomicrograph of the gut proximal to t h e atresia

shows characteristic mucosal flattening and submucosal inflammation in both the human (A) and animal (B) specimens ( x 4 0 } .

322

DOOLIN, ORMSBEE, AND HILL

human and lamb, the proximal jejunum exhibited flattened mucosa with submucosal inflammation (Fig 3). The microbowel demonstrated a narrowed lumen, thickened muscularis, and villous hyperplasia in both cases (Fig 4), as previously described) 4 Six lambs survived to be recorded for 2 to 27 hours. All were supported by the umbilical cord during operative repair. The recordings were analyzed for slow waves (Fig 5A), indicating the presence of intact smooth muscle cells, and for spiking potentials (Fig 5B), indicating contractions. In normal lambs, and in both the proximal intestine and microbowel of atretic lambs, slow waves were observed with a frequency of approximately 13/min (Table 2). The slow wave frequency was not significantly different between the two sites proximal and distal to the atretic intestine, or between the experimental and normal lamb small intestine. Spike potentials clearly were observed in the normal lamb intestine and in the proximal segment of the atretic lamb intestine, but at no time in the distal microbowet (Table 2). An additional myoelectric sig-

!l!

I

L

: LJ :::L~ ~

Fig 5. (A) Typical slow wave pattern during myoelectric recording proximal and distal to the atrasia. (B) Spiking potentials, which are here superimposed upon slow wave patterns, are never seen in the microbowel.

nal of unknown origin was also observed during these experiments. The signal was characterized by a myoelectric transient of variable amplitude and frequency (6 to 24/min), which could be differentiated from the typical slow waves and spike potentials and from electrical "noise" (Fig 6). It was observed at each recording location during these experiments. The presence of the spike potential was quantitated as a percentage of the slow wave tracings. The myoelectric transient was not included in the calculations. The incidence of spike potentials in the normal intesTable 2. Characteristics of Intestinal Myoelectric Activity From Normal Lambs and Lambs W i t h Experimental Intestinal Atresia Experimental Atresia Characteristic No.

Slow wave (cycles per

Normal Intestine

Proximal Intestine

Microbowel

7

6

5

13 + 3

13 • 2

12 • 3

10

5

O*

355

560

306

min)

Fig 4. Similar villous hyperplasia and muscularis thickening is seen in the human (upper) and animal (lower) specimens of the microbowel distal to the atresia ( x 4 0 ) .

Spike potentials (% slow waves with spike potentials) Pooled recording time

* P < .001 compared with normal intestine.

MOTILITY IN INTESTINAL ATRESIA

Fig 6.

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Transient wave with no consistent pattern.

tine was 10%. The dilated proximal atretic intestine demonstrated a 5% incidence of spike potentials, which was not significantly different from the controls (P < .2). The absence of spike potentials in the distal microbowel revealed significant lack of contractile activity (P < .001). DISCUSSION

At present, the etiology of the functional obstruction observed in neonates after operative repair of intestinal atresia is thought to be altered motility of the dilated proximal bowel. This hypothesis and operative techniques to alleviate the problem have been suggested by Gross, Nixon, and Santulli et al) '4"6 The data of this study suggests a slight depression of smooth muscle function in the proximal gut. More significantly, contractile activity in the distal microbowel is absent. The basic cause of the pathology of the microbowel is not known. If one accepts that the gut is small because of the lack of passage of contents, perhaps the motility problem is secondary to a lack of conditioning. The data of this study suggests the distal intestine is unable to accept the fluid delivered to it, thus resulting in a functional obstruction. Therefore, a major defect in intestinal atresia is distal to the anastomosis and not only a consequence of the proximal intestine. Based on these observations, a new valid approach to the problem of delayed function in atresia would be an attempt to alter the microbowel. Either mechanical

treatments, such as intubation, infusion, and dilatation, or pharmacologic manipulation might improve the patient's progress. Identifying the defect in the microbowel explains, in part, the resistance of this problem to the various modalities currently invoked. Several technical aspects of the investigation deserve comment. First, this technique appears to duplicate what is postulated as the in utero cause of this lesion. 5'12'15 By both gross and histologic evaluation, the lesion is similar to the human disorder. Thus, experimental intestinal atresia in the lamb is a useful model of human intestinal atresia. Future long-term studies on surviving lambs may lend further insight into this disorder and present the next experimental challenge. In these studies, lambs maintained by umbilical support were the only survivors. This was an effective technique for maintaining the animals during surgery. This technique may be applicable to other manipulations of newborn lambs. The slow wave frequency recorded in the normal atretic lambs was 13/min. This agrees well with the work of Bueno and Ruckebusch who demonstrated an increasing slow wave frequency in normal fetal and neonatal dogs and sheep. 16 During the first day of neonatal life, the slow wave frequency they recorded in the lamb was similar to the findings herein, and then gradually reached the typical adult frequency over a ten-day period. Bueno and Ruckebusch also observed a 40% incidence of spike potentials during the first day after birth in the lamb) 6 This incidence is considerably higher than that observed in the control lambs of this study. At present we have no explanation for this difference. Finally, a previously undescribed electrical pattern was evident in these recordings. This electrical transient may represent disorganized smooth muscle activity. Such asynchronous activity may be characteristic of undeveloped gut and contribute to the functional problem. Alternatively, this electrical pattern could represent a poor recording. However, it is identifiably different from electrical interference, and not characteristic of recordings from the small intestine of mature animals made by others using this technique) 7,18

REFERENCES

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Daniel EE (ed): Proceedings of the Fourth International Symposium on Gastrointestinal Motility. Vancouver, Mitchell Press, 1974, pp 427-434 14. Touloukian R J: Antenatal intestinal adaptation with experimental jejunoileal atresia. J Pediatr Surg 13:468-474, 1978 15. Louw JH, Barnard CN: Congenital intestinal atresia, observations on its origin. Lancet 2:1065-1067, 1955 16. Bueno L, Ruckebusch Y: Perinatal development of intestinal myoelectrical activity in dogs and sheep. Am J Physio1237:E61-E67, 1979 17. Ruckebusch Y, Bueno L: Electrical activity of the ovine jejunum and changes due to disturbances. Am J Dig Dis 20:10271034, 1975 18. Fleckenstein P, Bueno L, Fioramoni D, et al: Minute rhythm of electrical spike burst of small intestine in different species. Am J Physiol 242:G654-659, 1982