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Mycotic thromboaneurysmal disease of the abdominal aorta in preterm infants: Its natural history and its management

Five infants with mycotic complications of umbilical artery catheterization were evaluated with abdominal ultrasound and followed serially to document their natural history. Methicillin-resistant Staphylococcus aureus was always the infecting organism. There were one female and four male infants and they weighed between 900 and 1,200 g at birth. While two of the catheters were positioned in the abdominal aorta, three were located above the diaphragm. The predominate signs and symptoms included: thrombocytopenia, unexplained anemia, renal failure, hypertension, and embolic phenomena to the toes. Real-time ultrasound always proved sufficient for diagnosis. Serial studies detected the initial aortic thrombosis in three patients and accurately documented its progression to aneurysmal disease over 10 days in one patient and 17 days in another. Three of the infants were diagnosed with aneurysms at their initial examination. Of the five patients, three were treated nonoperatively and died of complications of their aortic disease. One patient was discovered at operation to have necrotic ischemic intestine. Aortic repair was postponed and he died of septic complications. The remaining patient underwent a PTFE interposition graft and survived for 6 months, dying of pulmonary failure with autopsy confirmed graft patency.

Vascular sling with tracheomalacia: surgical management

Surgical repair of pulmonary artery sling without concomitant correction of associated tracheal abnormalities has yielded poor results in the past. We combined vascular sling repair done during cardiopulmonary bypass through a median sternotomy incision with tracheopexy for severe associated tracheomalacia in 2 infants. Neither experienced substantial postoperative respiratory difficulties and both had patent vascular anastomoses at 1 year after repair, thus supporting this approach when this combination of lesions is present.

Evaluation of Hexosaminidase Activity as a Potential Biochemical Marker in Serum for Necrotizing Enterocolitis

The presence of increased serum activity of the lysosomal hydrolase hexosaminidase has been suggested to be potentially useful in the diagnosis of neonatal necrotizing enterocolitis (NEC). In the present study, serum activity of hexosaminidase was measured in 19 neonates with NEC and compared to developmental patterns of enzyme activity determined in 61 neonates without NEC. Infants with NEC were studied at intervals starting at the onset of disease and continuing until 6 weeks after diagnosis. In normal infants, serum activity of hexosaminidase increases with increasing gestational and postnatal ages. However, infants with NEC had relatively lower serum hexosaminidase activity than these control infants of similar gestational and postnatal ages. Necrotizing enterocolitis is not associated with increased serum activity of hexosaminidase.

Development of Serum Hexosaminidase Activity in Infants

Serum activity of hexosaminidases A and B has been measured to identify patients with Tay-Sachs and Sandhoff diseases, and may also be influenced by other clinical conditions including neonatal necrotizing enterocolitis. We have characterized the normal developmental pattern of hexosaminidase activity in serum by measuring this enzyme activity in 61 neonates of 27-40 weeks gestation who were followed from birth to age 4-8 weeks. Total serum hexosaminidase activity significantly increased with postnatal and gestational age, and with initiation of enteral feeding. We conclude that serum hexosaminidase activity in infants with clinical conditions that may influence serum activity of this enzyme must be compared to that in normal infants of similar gestational and postnatal ages.

312 DEVELOPMENT OF SERUM HEXOSAMINIDASE (HEX) IN INFANTS

Serum activity of hexosaminidases A and B has been measured to identify patients with Tay-Sachs and Sandhoffs diseases, and may also be affected in other clinical conditions including neonatal necrotizing enterocolitis (NEC). Data utilizing serum HEX as a marker for NEC is difficult to interpret because normal developmental patterns have not been characterized. We have measured serum activity of total HEX and Hex B in 61 neonates of 27 to 40 weeks gestation who did not have NEC. These infants were followed from birth until 4 to 8 weeks of age. The infants were divided into 2 gestational age groups (≤34 weeks and >35 weeks) since enzyme activities were similar within each of these 2 groups. Total serum HEX activity, increased with postnatal (PN) age and was greater in the older gestational age group (ANOVA p<0.01). Factors associated with increased total serum HEX include enteral feeding, parenteral nutrition and unexplained hematochezia.Serum HEX activity in infants with clinical conditions that may influence serum activity of this enzyme must be compared to that in normal infants of similar gestational and postnatal ages.

197 NALOXONE INDUCED GUT ISCHEMIA DURING RESUSCITATION OF EXPERIMENTAL NEONATAL SEPTIC SHOCK

Naloxone has been recommended for use in neonatal septic shock. To evaluate its effectiveness in peritonitis-induced septic shock, anesthetized newborn pigs were monitored and peritonitis was induced by intraperitoneal injection of E.coli and sterile pig feces. All pigs received fluid resuscitation, gentamicin, and bicarbonate to correct acidemia. When shock was evident, the pigs either received an initial IV bolus of naloxone (2 mg/kg) followed by a 2 mg/kg.hr infusion (Group I, n=9), or received no additional pharmacological intervention (Group II, n=7). Hemodynamic parameters assessed included mean arterial, pulmonary arterial, and central venous pressures; cardiac, stroke volume, and left ventricular stroke work indices; and systemic and pulmonary vascular resistance indices. There were no significant differences in any of the parameters measured between Groups I and II, although peripheral vascular resistance in Group I was transiently elevated acutely after naloxone infusion began. Mean survival times in the two groups were similar. Five of 9 Group I animals (56%), demonstrated gross and histologically proved intestinal ischemia (p<.02) while none of the animals in Group II demonstrated any notable sequelae. The data demonstrate that naloxone resuscitation results in an increase in vascular resistance without concomitant improvement in cardiac performance. These changes are associated with significant intestinal ischemia in this model.

Treatment of Intestinal Ischemia with Oxygenated Intraluminal Perfluorocarbons

Liquid perfluorocarbons are biologically inert compounds capable of dissolving up to 40 percent oxygen by volume. This remarkable and reversible oxygen solubility has encouraged investigations into therapeutic application in situations where tissue oxygen delivery is impaired. One such setting is intestinal ischemia. Identically prepared devascularized segments of rat intestine were treated with either intraluminal oxygenated perfluorocarbon (perfluorotributylamine) or physiologic saline solution. After timed sacrifice, blinded quantitative histologic evaluation for ischemic injury was performed. The perfluorotributylamine treatment groups had histologic scores indicative of less severe injury between 1 and 4 hours. These scores achieved statistical significance (p less than 0.05). We conclude that intraluminal oxygenated perfluorocarbons have a significant protective effect in this model of intestinal ischemia. This quantitative analysis is unique and is an important aspect of the preclinical evaluation of the perfluorocarbon preparations.

693 HEXOSAMINIDASE: A MARKER FOR HEALING AFTER ISCHEMIC GUT INJURY

Serum hexosaminidase activity (HEX) is elevated with ischemic gut injury. To determine if subsequent decreases in HEX correlate with gut healing, 97 weanling rats were subjected to laparotomy at which alternate vascular bundles were ligated along the base of the entire anterior mesenteric artery arcade. Fifteen rats served as pre-operative controls. After recovery, rats were allowed ad lib food and water. Groups were then killed at intervals, blood was drawn for HEX determination, and samples of small bowel were taken for histological evaluation. DATA:Microscopically, focal ischemic necrosis began at 6 hours. Between 12 and 48 hrs, cellular changes were consistent with progressive ischemic injury. Evidence of healing was apparent beginning at 5 days and these histological changes correlated with changes in HEX. Thus HEX proves useful as a marker for healing gut in this model.

1520 HEXOSAMINIDASE: A MARKER FOR NECROTIZING ENTEROCOLITIS

Hexosaminidase (HEX) activity in serum is used to diagnose Tay-Sachs and Sandhoffs Diseases, and has been suggested as a marker for diagnosis of neonatal necrotizing enterocolitis (NEC). In this study, serum HEX activity was determined in 19 neonates with NEC. Ten infants, gestational age ≤34 weeks, had onset of NEC at 18.5±12 days (mean ± SD) and 20% mortality. Nine infants, gestational age ≥35 weeks had onset of NEC at 3±1 days and 22% mortality. Infants with NEC had lower serum HEX activity than controls. Because of possible association of NEC with perinatal asphyxia (PA) we examined the relationship among HEX, NEC and asphyxia. Serum HEX activity was lowest in infants of ≤34 weeks gestation with both NEC and PA. In contrast, infants ≥35 weeks gestation who had NEC but no PA had lower serum HEX activity than control infants or infants with PA and NEC.Earlier reports of increased serum HEX activity in infants with NEC did not consider normal developmental increases of enzyme activity with increasing gestational and postnatal age.

709 Use of Superoxygenated Intraluminal Fluorocarbons in the Treatment of Experimental Intestinal Ischemia

Direct amelioration of intestinal ischemia using an inert intraluminal oxygen carrier is an appealing concept. The perfluorocarbons are biologically inert substances known to reversibly bind oxygen such that passive local delivery of oxygen to tissues is theoretically feasible. 75-100 gram weanling male Sprague-Dawley rats (n=46) were divided into timed study groups from 0.5 to 5 hours. All underwent laparotomy with identical complete de-vascularization of two adjacent 5 cm segments of terminal ileum. Each intestinal segment was treated with a single intraoperative instillation of either; Superoxygenated FC-43 (initial pO2596) or physiologic saline. Timed sacrifice was performed and tissue taken for light and electron microscopy. Blinded (norwai) histologic evaluation was performed in triplicate using a scoring system to quantitate the ischemic injury. (0= normal to 6= full thickness necrosis).The fluorocarbon treatment group has a significantly (p<.01) lower histologic score than the saline treated controls at comparable time points; indicating a cytoprotective effect in the treatment group. (Wilcoxian sign rank test). The utility of this preliminary observation will require further laboratory and clinical experience.