Rise and fall of cyclic AMP required for onset of lymphocyte DNA synthesis.

The adenosine 3',5'-monophosphate (cyclic AMP) levels of mouse lymphocytes rose and fell sharply 10 hours after stimulation with concanavalin A. Treatment of the cells with indomethacin reversibly prevented the increase in cyclic AMP and the subsequent onset of DNA synthesis. When the heightened cyclic AMP before S phase was maintained by either inhibiting phosphodiesterase or by adding the 8-bromo derivative of cyclic AMP, DNA synthesis was also blocked. Both the increase and decrease in cyclic AMP appear to be required for progression of lymphocytes into the S phase of growth.

31P NMR measurement of ATP synthesis rate in perfused intact rat hearts.

Using 31P NMR and the saturation-transfer method, the unidirectional rate of ATP synthesis was measured in isolated, Langendorff-perfused, isovolumic rat hearts operating at a rate pressure product of 25.6 +/- 2.5 (SE) X 10(3) mmHg X min-1 and consuming O2 at a rate of 35 +/- 2 mumol O2 X min-1 X (g dry wt)-1, at 37 degrees C. This rate was 7.2 +/- 0.9 mumol X s-1 X (g dry wt)-1 and was related to the rate of oxygen atom consumption by a ratio of 6.3 +/- 0.9. These data show that in the intact heart the unidirectional rate of ATP synthesis exceeds the net rate of ATP synthesis and consumption by approximately a factor of 2.

Inhibitors of polyamine biosynthesis. 9. Effects of S-adenosyl-L-methionine analogues on mammalian aminopropyltransferases in vitro and polyamine biosynthesis in transformed lymphocytes.

Seven analogues of S-adenosyl-L-methionine were studied as inhibitors or substrates for mammalian spermidine and spermine synthases. One of these, S-(5'-deoxy-5'-adenosyl)-(+/-)-1-methyl-3-(methylthio)propylamine (5), showed a unique spectrum of activities on the polyamine biosynthesis enzymes. It was an inhibitor of S-adenosyl-L-methionine decarboxylase from rat liver and spermine synthase from bovine brain and rat ventral prostate. This compound was a substrate for the spermidine synthases from bovine brain and rat ventral prostate but not a substrate for the spermine synthases from these same sources. At concentrations of 0.2 mM and higher, compound 5 blocked the increases in polyamine levels and in [3H]thymidine incorporation induced by concanavalin A in cultured mouse lymphocytes. At approximately a 0.5 mM concentration of 5, the cellular polyamine levels and the rate of thymidine incorporation were similar to those of the unstimulated lymphocytes. Lower concentrations of 5 (0.02-0.1 mM) produced a dose-dependent increase in thymidine incorporation. A dose-dependent decrease in the cellular polyamine levels was observed in the range of 0.05-0.5 mM of the inhibitor. These results suggest that the effects of 5 on transformed lymphocytes are complex and may not be solely due to the inhibition of polyamine biosynthesis by this compound.

Echocardiographic versus cardiac catheterization diagnosis of infants with congenital heart disease requiring cardiac surgery.

The success of noninvasive preoperative evaluation of infants with congenital heart disease using cardiac ultrasound depends not only on diagnostic accuracy, but also on risk of morbidity and mortality as compared with infants who undergo cardiac catheterization. Fifty-six infants (age 10 weeks or younger) with coarctation of the aorta (n = 16), coarctation with ventricular septal defect (n = 12), valvar aortic stenosis (n = 10) or total anomalous pulmonary venous connection (n = 18) were examined. Thirty-one underwent noninvasive preoperative assessment and 25 underwent evaluation including cardiac catheterization. Age, level and duration of support, pH, renal function, mortality, complications of cardiac catheterization and errors of diagnosis were compared. Significant differences between the 2 groups were more frequent preoperative use of prostaglandin E1 and shorter hospital stay in the noninvasively evaluated coarctation group. Of the infants with coarctation and ventricular septal defect, 1 who had cardiac catheterization required renal transplantation and 1 evaluated noninvasively required surgery at age 3 months for mitral stenosis not discovered on preoperative evaluation. One noninvasively evaluated infant with total anomalous pulmonary venous connection had a stenotic communication between the pulmonary venous confluence and the left atrium not detected by ultrasound. Surgery was successful in the latter 2 infants. Noninvasive preoperative diagnosis of some infants with congenital heart disease can be performed without increasing the risk of operative morbidity and mortality. Eliminating cardiac catheterization reduces hospital costs, decreases total numbers of catheterizations performed and influences the structure of training programs.

Repair of type B interruption of the aortic arch. Results and follow-up.

Surgical repair of type B interruption of the aortic arch and ventricular septal defect (VSD) in the newborn period is difficult and the optimal approach is controversial. We report here our early and late results using a two-staged approach in the repair of these lesions in seven consecutive neonates whose weights ranged from 2.9 to 3.8 kg and who were all less than 21 days of age. Each underwent aortic arch reconstruction off cardiopulmonary bypass with placement of a large (6 to 10 mm) polytetrafluoroethylene (PTFE) graft and pulmonary artery banding for interruption of the aortic arch (six) or extreme hypoplasia (one) of the arch. All seven (100%) survived the first-stage operation. No significant (greater than 10 mm Hg) conduit gradient was found in the seven patients studied 3 to 18 months postoperatively. One death occurred in a patient at 1 year of age with severe subaortic stenosis. Six patients subsequently underwent closure of VSD and removal of a pulmonary artery band, with five survivors (83%). The operative death occurred in an infant in whom pulmonary hypertension developed from an inadequate pulmonary artery band. One late death occurred at home when a tracheostomy tube, required because of severe tracheomalacia, became plugged. The long-term survival rate for completion of both stages is 57%. We conclude: (1) Aortic arch reconstruction and pulmonary artery banding can be reliably performed even in critically ill infants, and the 8 or 10 mm grafts should be adequate for several years. (2) Significant subaortic stenosis occurred in only one patient. (3) Pulmonary artery banding was the greatest source of difficulty, and distortion of the pulmonary arteries, inadequate banding, and compression of the trachea were all seen. Therefore, the staged repair will provide good results with this complex anomaly, and most of the problems associated with this approach may be eliminated by early second-stage repair.

Nissen fundoplication for gastroesophageal reflux in infants.

Some degree of gastroesophageal reflux is very common in infants and tends to reverse with time. Therefore, the indications for an antireflux operation are not well defined. Furthermore, the complication rate and the ability of the fundoplication to grow remain to be determined. To answer these questions, we reviewed the records of patients 6 months of age or younger who underwent a Nissen fundoplication with gastrostomy tube placement between 1979 and 1985. There were 45 patients (25 boys and 20 girls) with birth weights of 0.65 to 4.3 kg. The consequences of gastroesophageal reflux were more varied than in older children. Severe respiratory problems were common, including recurrent aspiration or bronchopulmonary dysplasia in 60% and frequent apneic and bradycardiac spells in 17%. Failure to gain weight was present in 20% and intractable vomiting in 2.0%. As expected, 78% of these patients had congenital anomalies or acquired problems which, in many cases, were important to the prognosis. The diagnosis was confirmed by barium swallow in all but one patient in whom gross reflux during feedings was present. Initially, medical management was tried for 3 to 4 weeks. In one patient, however, the severity of the respiratory problems precluded trial beyond 12 days. The recommendation for operation was based only on the severity of symptoms attributed to gastroesophageal reflux. All patients underwent Nissen fundoplication with gastrostomy tube placement at 2 weeks to 6 months of age and weighing 1.02 to 6.95 kg. The only surgical complication was one gastrostomy leak. Prematurity or preexisting anomalies led to a 20% incidence of late unrelated deaths between 2 weeks and 23 months postoperatively. Improvement in symptoms occurred in our survivors with follow-up of 5 to 72 months. We conclude: Significant gastroesophageal reflux in infancy most frequently produces respiratory problems that can be life threatening. Nissen fundoplication can be a safe and effective procedure in infants 6 months of age or younger. Fundoplication appears to have good growth potential, and no late complications or feeding problems have occurred. Consequently, surgical correction can be recommended for infants not responding to conservative medical therapy.

Central aorta-pulmonary artery shunts in neonates with complex cyanotic congenital heart disease.

Methods of palliating critical pulmonary oligemia in neonates with complex cyanotic congenital heart disease continue to evolve. Pulmonary artery distortion and other complications of the use of native vessels to increase pulmonary blood flow has led to the more frequent use of polytetrafluoroethylene shunts either in a central position or as a modified Blalock-Taussig shunt. Central aorta-pulmonary artery shunts have largely fallen into disfavor because of previously reported unacceptably high incidences of complications such as shunt thrombosis, congestive heart failure, and pulmonary artery distortion. This report details our experience palliating 23 neonates with pulmonary atresia or severe pulmonary stenosis by placing central aorta-pulmonary artery shunts utilizing a short segment (less than 1 cm) of polytetrafluoroethylene. Although three of the 23 died postoperatively, none of the 23 patients had evidence of shunt thrombosis. Congestive heart failure, a potential complication of any pulmonary artery shunt, was present in eight of the 20 survivors but did not require shunt takedown and was readily controlled by digoxin. Repeat catheterization was performed in 12 patients; pulmonary angiography showed good growth of both pulmonary arteries and there was no evidence of pulmonary artery hypertension. Although minor pulmonary artery distortion was present in two patients, this distortion was centrally located and easily remedied at the time of total correction. Thus we have found the central aorta-pulmonary artery shunt to be an extremely effective and reliable means of palliating pulmonary artery hypoplasia as a result of pulmonary atresia or severe pulmonary stenosis in neonates.

Correction of esophageal atresia with distal tracheoesophageal fistula.

Correction of the full spectrum of esophageal atresia with tracheoesophageal fistula (TEF) remains controversial. Circular myotomy and other lengthening procedures have shown promise to reduce tension when a relatively wide gap exists between esophageal segments; nevertheless a relatively high complication rate persists. We believe anastomotic tension is commonly found with repair of this anomaly. Therefore, the construction of the anastomosis will be a primary determinant of success. Twenty-four infants with TEF were admitted, 12 (50%) weighing 2.5 kg, nine (37%) 1.8 to 2.5 kg, and three (13%) 1.8 kg. All underwent gastrostomy and end-to-end single-layer anastomosis. Gaps of up to 4.5 cm were encountered, and in one case a cervical incision was necessary for mobilization of the upper pouch. For eight patients (33%) the gap was at least 2.5 cm and significant anastomotic tension was generated. For the series, there were no anastomotic leaks (all confirmed by barium swallow), reoperations, or surgical complications (there were two late, unrelated deaths). Prophylactic dilation was routinely performed 6 weeks and 3 months postoperatively. Subsequently, seven of the 24 (29%) required additional (one to five) dilatations but are now asymptomatic at least 2 years later. Follow-up for the entire series is 5 months to 5 years. Three infants (13%) required fundoplication for reflux without stricture and two infants (8%) an aortopexy. For successful esophageal anastomosis we consider the following technical points important: (1) no-touch technique to minimize tissue damage, (2) generous (5 to 7 mm) full-thickness suture depth, (3) fine (6/0) monofilament suture to reduce tissue reactivity, and (4) in cases of significant tension, the sutures are preplaced and used to provide traction to eliminate tension during tying. Tension is often unavoidable in TEF, yet a carefully constructed anastomosis will withstand this stress. This approach provides results at least as satisfactory as the reported experience with a variety of techniques.

Comparison of catecholamine effects on canine myocardial metabolism and regional blood flow during and after cardiopulmonary bypass.

The acute metabolic and hemodynamic effects of dopamine, dobutamine (both at 10 micrograms . kg-1 . min), and isoproterenol (at 0.05 or 0.1 micrograms . kg-1. min) were determined in dogs following 20 minutes of normothermic global myocardial ischemia. The catecholamines were started 10 minutes before cardiopulmonary bypass (CPB) was discontinued and were continued for 1 hour after bypass. Regional myocardial and systemic blood flow distribution was measured by means of the radioactive microsphere technique. On bypass all catecholamines sharply increased heart rate, myocardial oxygen consumption, and left ventricular blood flow (p less than 0.01). Because the hearts were unloaded, these data suggest that velocity of contraction is an important component of myocardial oxygen consumption. Although these drugs did not lower myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) levels, the significant rise in oxygen consumption suggested that inotropic treatment on bypass may not be beneficial. Furthermore, renal blood flow was diminished in dobutamine-treated dogs (p less than 0.01) and tended to decrease with isoproterenol infusion. No change was seen with dopamine infusion. After bypass, dobutamine treatment increased cardiac output (p less than 0.01) and stroke volume (p = 0.017) with no change in heart rate, myocardial oxygen consumption, high-energy phosphate levels, and total or transmural distribution of left ventricular blood flow. Dopamine infusion did not change cardiac output but did increase oxygen consumption (p less than 0.01). Isoproterenol showed a slight inotropic effect, but frequent ventricular arrhythmias were present during weaning from bypass. In all treatment groups, blood flow in the other systemic beds (cerebral, gastrointestinal, and renal) was similar to that in control dogs. These data suggest that dobutamine is the most efficient of the drugs tested for support of the heart following global myocardial ischemia but, when given during bypass, it appears to decrease renal blood flow.

Management of intracardiac fungal masses in premature infants.

Intracardiac fungal masses can develop following episodes of candidemia in premature infants with indwelling right atrial lines. We report the first premortem diagnosis and successful surgical removal of Candida-containing intracardiac masses in three premature infants. All had central venous lines and had been on systemic antibiotics prior to the development of candidemia. By echocardiography, two were pedunculated, solitary masses within the right atrium. Amphotericin B and 5-flucytosine for 21 to 42 days controlled the Candida sepsis, but the masses became increasingly mobile and did not decrease in size. In the third infant, large, irregular masses extended from the right atrium to the main pulmonary artery, and surgical removal was recommended 4 days after the start of antifungal therapy. In all three patients, the masses were nearly the size of the main pulmonary artery and presumably contained viable organisms. Removal was accomplished with the aid of cardiopulmonary bypass for two and inflow stasis for one infant weighing only 1,300 gm. The masses were filled with viable Candida organisms. All patients tolerated the operation well and have been followed up for 1 to 3.6 years without evidence of recurrent Candida infection. The case of a fourth infant, weighing 1,320 gm, is also reported. This infant had a bacteria-containing intra-atrial mass, which was removed successfully with the aid of inflow occlusion. This report documents the following points: (1) Echocardiography provides a noninvasive method of diagnosing the development of intracardiac masses and should be performed in infants who have had candidemia and a central venous line. (2) Prolonged systemic antifungal therapy does not appear to either sterilize or promote regression of the masses. (3) The masses can be safely removed, even in the premature infant, with either inflow stasis or cardiopulmonary bypass. (4) Surgical removal is an effective component of the treatment of infection in these infants.

Esophageal replacement with jejunum in children: an 18 to 33 year follow-up.

Since 1947 a total of 32 staged jejunal interpositions have been performed in children for total esophageal replacement. There have been no failures of the jejunum to reach the neck, no loss of graft, and no deaths. The first 16 of these 32 children have now reached adulthood and form the basis for this report on the late functional results of staged jejunal interposition. Among these 16 patients there occurred four cervical fistulas which healed without sequelae (25%), one cervical stricture which necessitated dilatation but not revision (6%), one early cervical revision for necrosis of the distal tip of the graft (6%), and no complications related to the distal anastomosis. Long-term follow-up (range 18 to 33 years; mean 27 years) was obtained in 100% (16/16) of patients. A barium swallow was obtained in 81% (13/16) at a mean of 25 years following initial reconstruction (range 14 to 33 years). The fact that all patients could eat a regular diet at normal speeds indicates satisfactory long-term function. Two patients (13%) reported mild cervical dysphagia. A barium swallow in one of these patients revealed no abnormalities. The other was found to have an apparent esophageal diverticulum which resulted because the jejunum was end-to-side to the esophagus. This was recently corrected 27 years after the initial reconstruction and represented the only late complication of the procedure. There were no late strictures or peptic ulcerations. Motility of the jejunal limb was normal in 12 of the 13 patients studied. These results demonstrate that staged jejunal interposition can be accomplished reliably and safely in children with excellent long-term functional results and a minimum of late complications. The jejunum should be considered as an alternative to colon and gastric tubes for total esophageal replacement in children.

Management of pulmonary atresia with intact ventricular septum.

Infants with pulmonary atresia and intact ventricular septum pose a difficult clinical problem. Pulmonary valvotomy has been widely recommended for relief of the right ventricular obstruction, and most infants also have had an aortopulmonary shunt placed to ensure pulmonary blood flow. We have evolved a different approach that includes placement of a right ventricular outflow tract patch initially and continuation of prostaglandin E1 infusion postoperatively until the need for a shunt can be determined. We report here our management of 15 neonates with this diagnosis and suprasystemic right ventricular pressures. All of the infants were placed on a regimen of prostaglandin E1 before the operation to improve pulmonary blood flow, and all had an outflow patch placed early in life. Satisfactory postoperative right ventricular function, which would allow both outflow patching and ductus ligation, could be confidently predicted in only two of the 15 patients. For nine of the 15 an outflow patch was placed and prostaglandin was infused postoperatively to provide pulmonary blood flow until right ventricular function became adequate. Early in the series, three other infants were judged to need an aortopulmonary shunt in addition to decompression by an outflow patch, and one infant had only a shunt placed. Postoperatively, adequate pulmonary blood flow was present in all, and 11 of the 15 (73%) survived. Three of the deaths (average 2.8 days) after the outflow patch operation probably resulted from premature cessation of the prostaglandin infusion. One neonate with an outflow patch and a shunt died of myocardial ischemia because of coronary artery steal through right ventricular sinusoids. One late death occurred suddenly in the child with only a shunt, presumably because of an arrhythmia. The remaining survivors (10/15, 67%) are alive and have had complete repair. Study of these patients has also revealed that the definition of adequate right ventricular size needs to be more liberal. Five of the 10 surviving patients had a residual atrial septal defect with a right-to-left shunt at the ages of 1 to 3 years, but balloon occlusion of the atrial septal defect during cardiac catheterization revealed that the right ventricle in these patients was functionally adequate. These five children subsequently underwent closure of the atrial septal defect, and in two the aortopulmonary shunt was also taken down. In summary, correction was achieved in all survivors, in contrast to reported studies in which many patients are living with shunts.(ABSTRACT TRUNCATED AT 400 WORDS)

Management of congenital stenosis of a branch pulmonary artery with balloon dilation angioplasty. Report of 52 procedures.

Twenty-four children, aged 4 months to 16 years (nine patients 2 years old or younger), underwent balloon dilation angioplasty of hypoplastic or stenotic branch pulmonary arteries between July, 1981, and April, 1984. Most children had tetralogy of Fallot, with or without pulmonary atresia, or isolated peripheral pulmonary artery stenosis. Fifty-two dilations were attempted, 44 in the catheterization laboratory and eight in the operating room. Of these, 26 (50%) were judged successful; the average vessel diameter on angiogram increased from 4.1 +/- 0.3 to 7.2 +/- 0.3 mm (76%), the gradient across the narrowed segment fell from 60 +/- 10 to 36 +/- 5 mm (40%), pressure in the main pulmonary artery or right ventricle proximal to the obstruction decreased from 83 +/- 10 to 66 +/- 6 mm Hg (20%), and the radionuclide-determined fraction of cardiac output directed to the lung ipsilateral to the dilated pulmonary artery increased from 40 +/- 4 to 51 +/- 4 (28%). All changes were significant at the p less than 0.005 level. Reasons for failure included inadequate technique (balloon too small, inability to position balloon or wire) in 14 and the refractory nature of the lesion itself in 11. Technical failures were age independent. Nondilatable lesions were more common in children more than 2 years old (10/25 versus 1/10) or with isolated peripheral pulmonary artery stenosis (5/7). Five of seven stenoses near previous shunts were nondilatable. One child exsanguinated when the pulmonary artery ruptured during dilation, but other complications were few. Eight dilations, followed up for an average of 6 months after dilation, showed angiographic persistence of improvement; two of four lesions were successfully redilated to a larger size. Balloon dilation angioplasty appears beneficial, both short and long term, for some patients with hypoplastic or stenotic branch pulmonary arteries, especially if performed early in life.

The changing spectrum of cystic pulmonary lesions requiring surgical resection in infants.

Congenital labor emphysema and cystic adenomatoid malformation have been the most common surgically treatable cystic lesions of the lung. With the successful treatment of newborn respiratory distress syndrome, an increased frequency of an acquired form of cystic disease, interstitial pulmonary emphysema, has been observed. Some degree of interstitial pulmonary emphysema is relatively common, and during the years 1980 to 1983 this disease was diagnosed in 372 infants. Seven of these infants, all premature, underwent resection of relatively localized areas of persistent cystic interstitial pulmonary emphysema. Lobectomy or wedge resection was performed in five patients because of their inability to be weaned from the ventilator. A sixth patient with this disease underwent lobectomy for recurrent pneumothoraces. A seventh patient underwent lobectomy because the cystic interstitial pulmonary emphysema produced atelectasis and recurrent infections. All seven patients were extubated by the fourth postoperative day, have been discharged, and are showing respiratory improvement. Within the same period, four infants had congenital lobar emphysema and two had congenital cystic adenomatoid malformation. They were gestational age 36 weeks or older and, although respiratory distress was present to some degree in all six, only one was ventilator dependent at operation. All underwent lobectomy and one infant had a left upper lobe resection and right middle lobectomy on separate occasions for bilateral congenital cystic adenomatoid malformation. All patients with congenital labor emphysema and congenital cystic adenomatoid malformation have been discharged and are doing well. Our results suggest the following conclusions: Persistent interstitial pulmonary emphysema is now the most common indication for pulmonary resection in the newborn period. The anatomic distribution of resected interstitial pulmonary emphysema is similar to that of congenital lobar emphysema. Although only a small fraction (less than 2%) of patients with interstitial pulmonary emphysema require operation, the development of relatively large discrete cystic areas that (1) significantly decrease effective lung volume and produce respirator dependence, (2) produce atelectasis and recurrent infections, or (3) lead to pneumothoraces may make pulmonary resection beneficial. Finally, despite the presence of generalized lung disease in patients with interstitial pulmonary emphysema, these patients can be expected to improve significantly after resection, and the long-term outcome is generally good.

The ivory tower from outside and in: a survey of Minnesota surgeons.

BACKGROUND: Increasing competition has eroded the patient base of many university hospitals and may jeopardize their teaching programs. METHODS: We questioned all private surgeons (PS), university surgeons (US), and resident surgeons (RS) in our state. Chi-squared analysis was used. RESULTS: Most PS, US, and RS, respectively, answered "yes" when asked to respond to the following items: whether teaching hospitals were the best way to educate new surgeons (77% versus 96% versus 87%), whether surgery residencies should be based at a university hospital (72% versus 96% versus 91%), and whether PS should refer complicated clinical cases for teaching purposes (75% versus 87% versus 68%). Differences appeared when the groups were asked whether the university should take the lead in guaranteeing the quality of surgical care in the state (67% versus 100% versus 77%, p = 0.002) and whether PS are better teachers of surgery than US (40% versus 4% versus 59%, p = 0.0001). An unexpected and disturbing trend was observed in RS when groups were asked whether practicing surgeons had any obligation to the state's university (57% versus 74% versus 22%, p = 0.0001) and whether surgeons had an obligation to repay society for their education (77% versus 83% versus 56%, p = 0.005). CONCLUSIONS: Despite recent changes in medical economics, most PS still feel residency programs should be university based. A significantly smaller percentage of RS feel an obligation to their university and to society than do either PS or US.

Alterations in amino acid clearance during ischemia predict hepatocellular ATP changes.

Although decreases in hepatic adenosine triphosphate (ATP) levels during ischemia are thought to reflect loss of hepatic energy reserves and decreased viability, such changes have not been correlated with a clinically relevant index of hepatic function or viability. Ability to clear amino acids from plasma has been shown to correlate with function of the allograft in hepatic transplantation and survival after portal decompression in patients with hepatic cirrhosis. The effects of 60 minutes of warm ischemia in two groups of mongrel dogs were studied to assess the relationship between loss of ATP and amino acid clearance. One group (shunted) had portal decompression during the ischemic period and the other (portal stasis) did not. There was a significant correlation between loss of ATP and amino acid clearance after ischemia. Although the effects of ischemia on the liver were similar in both groups, the portal stasis group demonstrated significantly elevated SGOT levels during reperfusion that were related to impaired net adenine monophosphate synthesis and suggestive of ongoing injury. These data support the contention that loss of ATP during ischemia is associated with reduced functional capacity. In addition, they suggest that portal stasis produces toxic products that can impede hepatic recovery from ischemia.

Recovery of adenine nucleotide levels after global myocardial ischemia in dogs.

Loss of myocardial adenosine triphosphate (ATP) during ischemia can result in decreased cardiac function. Postischemic ATP levels remain low, and the reason for this is poorly understood. Previous attempts to enhance ATP recovery after ischemia have been only partially successful. To determine the long-term dynamics of ATP recovery and evaluate the effect of providing ATP precursors, we devised a method of obtaining sequential ventricular biopsies in dogs after 20 minutes of normothermic global ischemia on cardiopulmonary bypass. Our kinetic data show adenine (A) is metabolically favored over adenosine to regenerate ATP levels when adequate ribose (R) is present to produce phosphoribosylpyrophosphate. Therefore A (20 mM) plus R (80 mM) or saline (NS) was infused (1.0 ml X min-1) into the right atrium of dogs for 48 hours after ischemia. During A infusion myocardial tissue A was 0.19 +/- 0.07 nmol X mg-1, arterial A was 18.3 +/- 1.3 microM, coronary sinus A was 11.0 +/- 1.6 microM, and extraction of A by the myocardium was 38% +/- 10%. We found that while the decrease in ATP levels during ischemia was at least 50% in both groups, the postischemic ATP recovery rate in A/R dogs was more than eightfold greater than de novo synthesis (2.8 +/- 0.59 versus 0.34 +/- 0.06 nmoles X mg-1 X day). ATP levels in NS dogs were only 54% +/- 8% of preischemic values by 48 hours and required 9.9 +/- 1.4 days for full recovery. Recovery in A/R dogs required 1.2 +/- 0.2 days. Our results reveal that ATP recovery after a significant ischemic insult is slow, precursor availability is an important limiting factor in ATP recovery, and recovery time can be greatly shortened with precursor infusion even when started after the ischemic insult.

Staged repair of interrupted aortic arch and ventricular septal defect in infancy.

Staged repair of interrupted aortic arch and ventricular septal defect was carried out in 20 infants from 1979 through 1990. Among the important associated cardiac defects were transposition of the great arteries, truncus arteriosus, and anomalous origin of the right pulmonary artery. The first stage, usually consisting of the placement of an 8- or 10-mm polytetrafluoroethylene graft, pulmonary artery banding, and ligation of the patent ductus arteriosus, resulted in 20 survivors (100%) There were two interim deaths (10%) before the second stage of ventricular septal defect closure and pulmonary artery band removal, which had 15 survivors (83%, 15/18). Because the major morbidity and mortality early in this experience could be traced to leaving the pulmonary artery band on too long, early removal (within 2 to 3 months) was begun. Since 1985, 8 (100%) of 8 infants have survived both stages and are now doing well. Because of the relatively large polytetrafluoroethylene graft, only 1 child (aged 9 years) has experienced substantial late aortic arch obstruction and undergone placement of an 18-mm Dacron graft without difficulty. Of interest is the finding that in only 1 (5%) of the 20 patients has major (greater than or equal to 40-mm Hg gradient) left ventricular outflow tract obstruction developed. In summary, the staged repair of interrupted aortic arch with ventricular septal defect has become very reliable despite the condition of the infant or major associated cardiac anomalies and can be recommended for infants at high risk for primary repair. More long-term information will be needed to determine which approach will be the best choice for the majority of infants.

Primary repair of ultra-long-gap esophageal atresia: results without a lengthening procedure.

Ultra-long-gap esophageal atresia, defined as a gap length of 3.5 cm or greater, has proved difficult to repair. When primary repair has been attempted, even with bougienage, circular myotomy, or intraabdominal esophageal mobilization to lessen anastomotic tension, leaks, anastomotic disruptions, and recurrent tracheoesophageal fistulas are frequent. Consequently, interposition grafts are commonly used. For long-term function the intact native esophagus should be preferable to an interposition graft or the consequences of circular myotomy. Therefore, even when an ultra-long gap is present, we have carried out a primary repair using our single-layer technique without myotomies. Since 1979, 8 of 58 infants (14%) with esophageal atresia had gaps ranging from 3.5 to 6 cm. All had a primary repair with follow-up from 1 to 11 years. Despite severe anastomotic tension in all cases, there were no anastomotic leaks, disruptions, recurrent tracheoesophageal fistulas, or deaths. The tension, however, may have led to major gastroesophageal reflux in 5 of 8 patients (62.5%), all treated by a Nissen fundoplication, and a stricture in 4 of 8 infants (50%). Three strictures responded to dilation and one was resected. Now, all children are eating a normal diet for age. In conclusion, this technique has allowed primary repair of ultra-long-gap esophageal atresia. Although the severe tension may contribute to strictures needing dilation and gastroesophageal reflux requiring fundoplication, primary repair resulted in a clinically functional native esophagus.

Internal mammary artery for arterial pressure monitoring after pediatric cardiac operations.

Establishing and maintaining arterial access in pediatric cardiac operations is a frequent and sometimes frustrating problem. We have modified a procedure commonly used in our research laboratory for arterial pressure monitoring and applied it successfully to the pediatric cardiac surgical patient. The internal mammary artery can provide reliable arterial access in the postoperative period.