As originally published in 1992: new surgical technique for total-defect aortopulmonary window. Updated in 1999.

A new technique is described to repair aortopulmonary window with total defect in an 8-day-old baby. Because we expected the future growth of aorta, we used the anterior wall of the pulmonary artery as a large flap to reconstruct the posterolateral aortic wall. An equine pericardial patch was used to repair the defect in the pulmonary artery. This is a logically effective method for aortic reconstruction in a neonate with a large aortopulmonary septal defect.

Elevation of antioxidant potency in the brain of mice by low-dose gamma-ray irradiation and its effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced brain damage.

The elevation of endogenous thiol-related antioxidants and free radical scavenging enzymes in the brain of C57BL/6 female mice after low-dose gamma-ray irradiation and its inhibitory effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced brain damage were investigated. The brain level of the reduced form of glutathione (GSH) increased soon after irradiation with 50 cGy of gamma-rays, reached a maximum at 3 h post-treatment, and remained elevated until 12 h. Thioredoxin (TRX) was also transiently increased after irradiation. The activities of free radical scavenging enzymes, including Cu/Zn-superoxide dismutase, catalase and glutathione peroxidase, were significantly induced after irradiation as well. Cerebral malondialdehyde was remarkably elevated by MPTP treatment, and this elevation was suppressed by pre-irradiation (50 cGy). The contents of GSH and TRX were significantly decreased by MPTP treatment in comparison with those of the control group. These reductions both seemed to be attenuated by pre-irradiation with gamma-rays. These results suggest that low-dose gamma-ray irradiation induces endogenous antioxidative potency in the brain of mice and might be effective for the prevention and/or therapy of various reactive oxygen species-related neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease.

Localization of glutathione and induction of glutathione synthesis-related proteins in mouse brain by low doses of gamma-rays.

First, we determined the cerebral localization of reduced glutathione (GSH) in normal mice by means of autoradiography using 99mTc-meso-hexamethyl propylene oxime. A highly specific localization of GSH in the cerebellum and hippocampus was observed. Secondly, we measured the elevation of GSH level in the brain after low-dose gamma-irradiation. The cerebral GSH levels increased soon after irradiation with 50 cGy of gamma-rays, reaching a maximum at 3 h post-treatment, then remaining significantly higher than that of the non-irradiated control until 12 h and returning to the control level by 24 h. Thirdly, we examined the induction of the activities and the mRNAs of proteins involved in the synthesis and regeneration of GSH in the brain of mice subjected to low-dose gamma-ray irradiation. The level of mRNA for gamma-glutamylcysteine synthetase was significantly increased at 0.5 h, and remained high until 2 h post-irradiation (50 cGy). The level was transiently lowered to the non-irradiated control level at 3 h and slightly increased again after 6 h post-irradiation. gamma-Glutamylcysteine synthetase activity was significantly increased 3 h after irradiation, and remained high up to 24 h post-irradiation. As for glutathione reductase, the mRNA level was increased at 0.5 h, and peaked strongly at 2 h, while the enzyme activity was significantly increased at 6 h after irradiation, and continued to increase up to 24 h. The level of mRNA for thioredoxin, which contributes to GSH biosynthesis by supplying cysteine to the de novo pathway, peaked between 0.5 h and 2 h post-irradiation, and rapidly declined thereafter. The content of thioredoxin showed a transient decrease immediately after irradiation, but was then remarkably elevated, reaching a maximum at 3 h, and thereafter declining sharply. These results indicate that the increase in endogenous GSH in mouse brain soon after low-dose gamma-ray irradiation is a consequence of the induction of GSH synthesis-related proteins and occurs via both the de novo synthesis and the regeneration pathways.

Induction of mRNAs for glutathione synthesis-related proteins in mouse liver by low doses of gamma-rays.

We examined the elevation of the reduced form of glutathione (GSH)level and the induction of MRNAs for proteins involved in the synthesis and regeneration of GSH in the liver of mice after low-dose gamma-ray irradiation. The liver GSH level increased soon after irradiation with 50 cGy of gamma-rays, reached a maximum at around 12 h post-treatment. The mRNA of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme for de novo synthesis for GSH, showed a small increase that peaked at 6 h after gamma-ray irradiation at a dose of 50 cGy. Only a small increase in gamma-GCS activity was observed throughout the 24-h post-irradiation period. In the case of glutathione reductase (GR), which is involved in the regeneration of GSH from the oxidized form (GSSG), the mRNA level peaked strongly at 1 h, while the activity peaked at twice the control level 12 h after irradiation. The level of mRNA for thioredoxin (TRX), which contributes to GSH biosynthesis by supplying cysteine to the de novo pathway, peaked at 1 h and declined thereafter, while the activity peaked at 3 h and then declined sharply. These results indicate that the increase in endogenous GSH immediately following low-dose gamma-ray irradiation is predominantly due to operation of the regeneration cycle and not de novo synthesis. We also examined the dependence of mRNA induction on the gamma-ray dose.

Elevation of mouse liver glutathione level by low-dose gamma-ray irradiation and its effect on CCl4-induced liver damage.

We examined the elevation of glutathione (GSH) levels in the liver of C57BL/6 female mice after low-dose r-ray irradiation and its inhibitory effect on CClI4-induced liver damage. The liver GSH level increased soon after irradiation with 50 cGy of gamma-rays, reached a maximum at around 12 post-treatment, and returned almost to the control level by 24 h. The activities of glutathione reductase, and glutathione peroxidase also showed the same pattern of change, while the activity of gamma-glutamylcysteine synthetase showed a gradual increase up to 24 h. The effect of pre-irradiation on CCl4-induced liver damage was also investigated. The activities of glutamic oxaloacetic transaminase and glutamic pyruvic transaminase in serum were markedly increased 12 h post-treatment with CCl4. Both increases were significantly suppressed by a single low-dose pre-irradiation. Malondialdehyde, a marker of lipidperoxidation, was also greatly elevated after CCl4 treatment, and its increase was suppressed by irradiation. These results suggest low-dose gamma-ray irradiation might be effective for the prevention of and/or therapy of various reactive oxygen species-related diseases including cancer.

Does small-dose gamma-ray radiation induce endogenous antioxidant potential in vivo?

The induction of in vivo antioxidant potential following small doses of gamma-ray irradiation was investigated in C57BL/6 mice. The antioxidant capacity of various organs was assessed in terms of the scavenging activity of cytosol fractions against 1,1-diphenyl-2-picrylhydrazyl (DPPH), a chemically stable radical. Significant elevations in the scavenging activity were recognized in several organs, including the liver, pancreas and brain, soon after post-irradiation with 50 cGy of gamma-ray. These increases persisted for 24 h. gamma-Radiation of the liver at 25-50 cGy elevated its cytosolic antioxidant capacity, but this was lowered at 200 cGy. In order to assess which antioxidants underlie this phenomenon, the content of a reduced form of glutathione (GSH) in liver was assayed as a function of time after gamma-irradiation at a dose of 50 cGy. The GSH content was significantly increased from 6 h after irradiation, and this change was consistent with that of the total radical scavenging potency of the liver against DPPH. Further, the elevation of GSH content was accompanied by elevated GSSG reductase activity induced by gamma-irradiation.

Unifocalization for pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries.

To extend the indications for corrective operation in patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries, surgical procedures were done to unify the blood sources for pulmonary perfusion. Since December 1985, 50 patients have undergone unifocalization at ages from 2 months to 26 years with a mean of 6 +/- 7 years. In total, 84 staged unifocalization procedures and 5 other palliative procedures were done in 49 patients. These included several operative procedures: simple ligation of major aortopulmonary collateral arteries in 8; pulmonary angioplasty in 29 including reconstruction of the pulmonary arterial tree by direct anastomosis or interposition between the central pulmonary arteries and the intrapulmonary arteries; construction of artificial central pulmonary arteries with use of a xenograft pericardial tube graft in 36 with no native central pulmonary arteries detected; and construction of supplemental central pulmonary arteries also with use of a pericardial tube graft in 10. The pericardial tube graft, if used, was anastomosed to the intrapulmonary arteries on one end and connected to a prosthetic tube on the other end so as to perfuse the reconstructed pulmonary arteries. The anastomosis was made inside the lung through the divided interlobar fissure. Five patients died after operation among those undergoing these 89 preparative operative procedures. Deaths were related either to bleeding caused by anticoagulation therapy administered to prevent thrombosis within the xenograft pericardial tube graft used or to progressive congestive heart failure as a result of an excessive amount of pulmonary blood flow. Twenty-six patients have undergone intracardiac repair after previous unifocalization. In 16 patients the artificial central pulmonary arteries surgically constructed were connected to each other and then an external conduit was placed. In another patient, intracardiac repair and unifocalization could be concomitantly achieved via a median sternotomy. The right ventricle to left ventricle systolic pressure ratio immediately after intracardiac repair in 27 patients ranged from 0.24 to 0.91 with a mean of 0.54 +/- 0.17. One patient (4%) died shortly after intracardiac repair because of thrombosis within the pulmonary arteries. Postoperative catheterization showed that pulmonary vascular resistance was correlated significantly with the number of pulmonary vascular segments functioning rather than with the condition of the central pulmonary arteries. We conclude that surgical unifocalization is a feasible procedure before subsequent intracardiac repair, even in patients with critically hypoplastic or absent central pulmonary arteries.

Results of unifocalization for pulmonary atresia, ventricular septal defect and major aortopulmonary collateral arteries: patency of pulmonary vascular segments.

Unifocalization, a surgical technique to unifocalize the pulmonary blood supply in patients with pulmonary atresia, ventricular septal defect and major aortopulmonary collateral arteries, is a useful preparative operation to extend the indication for corrective surgery. The preoperative and postoperative pulmonary angiograms of 51 patients (aged 3 months-26 years at first unifocalization, 29 males, 22 females), who underwent a total of 96 unifocalizations from December 1985 to July 1994, were studied to assess the effectiveness of each procedure of unifocalization. The procedures of unifocalization were ligation (9), angioplasty (6), direct anastomosis (25), bridging (6), additional central pulmonary artery creation (9), central pulmonary artery creation (36) and thrombectomy (5). Altogether 125 anastomoses were made, and the patency of 101 (80.2%) anastomoses was confirmed, 24 (19.2%) were shown to be occluded. The patency rate of the anastomoses between xenograft rolls and intrapulmonary arteries was 79.5% (70/88), while that between native central pulmonary arteries and intrapulmonary arteries was 83.8% (31/37; N. S.). The patency rate of the anastomoses involving intrahilar arteries was 88.0% (44/50), while that for the group involving extrahilar arteries only was 71.9% (46/64; P < 0.05). It is concluded that 1) unifocalization with the reconstruction of central pulmonary arteries using a pericardial roll is a useful method for patients with absent or hypoplastic central pulmonary arteries, 2) it is preferable to divide the fissures of lung in anastomosing pulmonary arteries of arborization abnormalities.

What factors affect ventricular performance after a Fontan-type operation?

Postoperative conditions after a Fontan-type operation, particularly as they affect results in the early term, are thought to depend on factors such as the state of pulmonary circulation and ventricular function. In this study, we attempted to determine the factors that influence ventricular characteristics in the middle term after Fontan-type procedures. Catheterization was performed at a mean of 15 months after operation in 57 patients with univentricular atrioventricular connection who underwent the operation between 1.0 and 22.6 years of age. End-diastolic volume, end-systolic volume, ejection fraction, and end-diastolic pressure of the systemic ventricle were analyzed together with an estimation of the systemic flow index. These parameters were influenced significantly by the presence of atrioventricular valve insufficiency. The morphologically left ventricle showed a better ejection fraction than did the morphologically right ventricle, whereas the systemic flow index was greater in patients undergoing total cavopulmonary connection than in those receiving an atriopulmonary connection. Young age was significantly associated with a better postoperative contractility, whereas the potential for impaired ventricular compliance was suggested in several patients undergoing operation after 4 years of age. On the basis of our results, we conclude that total cavopulmonary connection performed at a young age should be the surgical procedure of choice and that atrioventricular insufficiency must be treated properly at, and even after, the initial definitive repair.

Biventricular repair in cardiac isomerism. Report of seventeen cases.

Ninety-three patients with cardiac isomerism were treated surgically from July 1985 to June 1991. Among them, three patients with right and 14 with left isomerism underwent biventricular repair. Ages ranged from 4 months to 41 years (mean 4.8 years). Anatomic repair was accomplished in 15 patients and functional repair with the right ventricle used as the systemic ventricle in two patients. Methods of atrial septation to separate pulmonary venous flow from systemic venous flow included atrial partition with a straight patch in seven patients, intraatrial rerouting with a tailored baffle in five, and a Mustard-type atrial switch in five. One hospital death (5.8%) and two late deaths (12%) occurred. Two patients required reoperation (12%), one reconstruction of a stenotic systemic venous connection and one mitral valve replacement because of incompetence. Surgically induced complete atrioventricular block was not observed in any of the patients. Optimal atrial septation offers the possibility of biventricular repair for patients with acceptable intraventricular structure.

Extent of aortopulmonary collateral blood flow as a risk factor for Fontan operations.

Between November 1987 and January 1990, 33 patients (tricuspid atresia, 9 patients; mitral atresia, 3; single ventricle, 15; others, 6) underwent Fontan operations. The rate of blood flow returning to the heart during aortic cross-clamping was measured as an indication of the extent of development of aortopulmonary collateral arteries. Percent cardiac return (calculated by dividing the blood flow rate returning to the heart by the cardiopulmonary bypass blood flow rate and expressing the value as a percentage), were 1% to 9%, 7 patients; 10% to 19%, 11; 20% to 29%, 9; 30% to 39%, 4; 40% to 49%, 1; and 50% to 59%, 1 patient. Percent cardiac return showed a significant correlation with postoperative mean systemic venous pressure (r = 0.6, p < 0.01). In those patients in whom percent cardiac return was more than 33%, the mean systemic venous pressure after operation was high (more than 17 mm Hg), and none of these patients survived. To predict percent cardiac return preoperatively, the conventional indices of systemic ventricular volume, pulmonary artery area index, arterial blood oxygen saturation, pulmonary blood flow index, and pulmonary vascular resistance were analyzed. None of these showed significant correlation with percent cardiac return. However, all the patients who had a high percent cardiac return (more than 30%) also had both high arterial blood oxygen saturation (more than 75% in room air) and small pulmonary artery area index (less than 55%). In addition, the age at operation showed good correlation (r = 0.6, p < 0.01) to percent cardiac return.(ABSTRACT TRUNCATED AT 250 WORDS)

A bicuspid pulmonary valve is not a contraindication for the arterial switch operation.

There are no obvious criteria concerning the optimal repair for complete transposition with bicuspid pulmonary valve if neither the organic changes in the valve nor the pressure gradient between the left ventricle and the pulmonary trunk are severe. Instead of intraatrial switching or intraventricular rerouting in such circumstances, we have proceeded to the arterial switch procedure in 6 patients with an adequate diameter of the pulmonary valve (greater than 100% of the calculated normal aortic orifice). Postoperative catheterization (at approximately 8 months after the procedures) showed no pressure gradient between the left ventricle and the neoaorta except for a finding of 34 mm Hg difference in 1 patient who had undergone simultaneous subpulmonary myotomy. Echocardiography (7 years later in the longest follow-up) has shown no more than slight regurgitation across the bicuspid neoaortic valve, with no progressive increase of blood velocity across the valve. From these results in the middle term, we conclude that the arterial switch procedure remains an option of choice for patients with initially bicuspid pulmonary valve, providing there is no severe subpulmonary stenosis.

[Inhaled nitric oxide after Fontan type operation].

The indication of Fontan type operation has been extending, but some cases on the boundary of the indication resulted in low cardiac output syndrome (LOS) postoperatively. Recently the inhalation of nitric oxide (NO) has been revealed to produce selective pulmonary vasodilatation, and it has come to be applied in the clinical setting. We experienced a case of 6-year-old boy with complex cardiac anomaly in whom the inhalation of nitric oxide was remarkably effective for the LOS caused by increased pulmonary vascular resistance after Fontan type operation. In the case various conventional treatments failed to improve his LOS during the weaning from a respirator on the second postoperative day. After the initiation of the inhalation of nitric oxide at a concentration of 6ppm, a rapid decreasing of pulmonary artery pressure concomitant with an improvement of hemodynamics were obtained. We concluded that the inhalation of nitric oxide is an effective strategy for the increased pulmonary resistance after Fontan type operation.

[Successful aortic root replacement with pulmonary autograft in two infants].

Two infants with congenital aortic valve stenosis underwent successful aortic root replacement with pulmonary autograft. One of the patients was 9 months and weighted 4.2 kg, and the other was 10 weeks weighing 4.6 kg. The former had undergone balloon valvotomy with a resultant severe aortic regurgitation. Operative method was basically similar to that taught by Ross. In terms of the right ventricular outflow reconstruction, however, left atrial appendage was utilized as the posterior wall while equine pericardial monocusp patch formed the anterior wall in the former patient. In the latter, morphology of the left atrial appendage was not suitable for the same kind of reconstruction, and nonvalved equine pericardial tube was used. Both of the patients eventually gained satisfactory circulatory condition. Advantages of aortic root replacement with pulmonary autograft are good competence without residual stenosis, avoidance of anticoagulation, and the high potential of future growth. So this operation is especially indicated for neonates and infants with left ventricular outflow obstruction.

Double switch operation in cardiac anomalies with atrioventricular and ventriculoarterial discordance.

Since June 1987, 10 of 19 consecutive patients with atrioventricular and ventriculoarterial discordance (average age 4 +/- 2 years) had undergone a double switch operation with the morphologically left ventricle used as a systemic ventricle. There were two combinations of procedures. Atrial switch combined with arterial switch was used in two patients who had a normal pulmonary valve. Atrial switch combined with ventriculoarterial switch by Rastelli's procedure was used in eight patients with pulmonary stenosis or atresia and a large ventricular septal defect. One early death and two late deaths have occurred in a postoperative follow-up period of up to 4 years. Subsequent problems were mainly related to the results of atrial switch procedures in patients who had a small atrium because of low pulmonary flow, especially in patients with apicocaval juxtaposition. Our experience suggested that the double switch operation would open a new era of definitive surgical treatment in half of the patients with atrioventricular and ventriculoarterial discordance.

Biventricular repair of cardiac isomerism with common atrioventricular canal with the aid of an endocardial cushion prosthesis.

Between 1983 and 1990, six patients with atrial isomerism associated with common atrioventricular canal and double-outlet right ventricle were operated on with the aid of an endocardial cushion prosthesis. This prosthesis, which has been used for the repair of common atrioventricular canal since 1975, is composed of a vertical Dacron patch and "wings" constructed from the patient's own pericardium, which are attached to both sides of the patch to compensate for the defective atrioventricular valve tissue. The ventricular portion of the patch was extended anteriorly to construct the route for blood flow from the left ventricle to the aorta. Intraventricular repair was performed through the common atrioventricular orifice in all patients and also through an additional right ventriculotomy in one patient. The complex systemic and pulmonary venous return was separated by use of the atrial part of the endocardial cushion prosthesis together with additional prosthetic materials. All patients survived the operation and were followed up from 1 to 9 years. All of them are doing well, although one patient has a significant interventricular residual shunt. Repair of atrial isomerism with common atrioventricular canal and double-outlet right ventricle with an endocardial cushion prosthesis was performed with satisfactory immediate and intermediate-term postoperative results.

Growth potential after root replacement of the right and left ventricular outflow tracts.

A successful operation for acute and severe aortic regurgitation after balloon valvuloplasty together with mitral regurgitation is described in a 9-month-old infant. Aortic root replacement was performed using a pulmonary autograft, while the right ventricular outflow tract was reconstructed with an interposed left atrial appendage posteriorly and a heterologous pericardial patch anteriorly. Mitral valve reconstruction was also effectively accomplished. This combination of right and left ventricular outflow tract reconstruction has a good potential for growth and may provide a solution for the future in infants.

Long-term performance of beta-propiolactone-treated nonviable homograft for aortic valve replacement and right ventricular outflow tract reconstruction.

The long-term performance of beta-propiolactone-treated homografts was clearly different between operative survivors of aortic valve replacement (n = 27) and those of right ventricular outflow tract reconstruction (n = 11). The reoperation-free survival rate at 20 years was 14.8 +/- 6.8 (standard error)% in the former and 77.8 +/- 13.9% in the latter. Even a nonviable aortic homograft can be favorably accepted as a material for right ventricular outflow tract reconstruction in contrast to the aortic position.

New surgical technique for total-defect aortopulmonary window.

A new technique is described to repair aortopulmonary window with total defect in an 8-day-old baby. Because we expected the future growth of aorta, we used the anterior wall of the pulmonary artery as a large flap to reconstruct the posterolateral aortic wall. An equine pericardial patch was used to repair the defect in the pulmonary artery. This is a logically effective method for aortic reconstruction in a neonate with a large aortopulmonary septal defect.