Increased transcription factor expression and permeability of the blood brain barrier associated with cardiopulmonary bypass in lambs.

BACKGROUND: The pathophysiology of neurocognitive dysfunction and developmental delay after cardiopulmonary bypass (CPB) in infants is not known. It is known that head trauma, stroke, and seizures cause dysfunction of the blood brain barrier (BBB) that is associated with increased inducible transcription factor gene expression in the cells of the barrier. The purpose of this study was to determine the effects of CPB and hypothermic circulatory arrest on expression of the transcription factor FOS and the function of the BBB in an infant animal model. METHODS: Infant lambs (n = 36; 10-12 days) were exposed to 0, 15, 30, 60, or 120 minutes of normothermic (38 degrees C) CPB or 2 hours of hypothermic circulatory arrest at 16 degrees C. After terminating bypass 15 animals had their brains perfusion-fixed and removed for immunohistochemical analysis of expression of the transcription factor FOS. The other animals were perfused with fluorescent albumin to visualize the brain microvasculature. Brain sections were analyzed with a laser scanning confocal microscope. RESULTS: Control animals (n = 6, sham operated and cannulated) exhibited normal vasculature with negligible leakage and no FOS protein expression in neurons or endothelial cells anywhere in the brain. Significant FOS expression in barrier-associated structures including the blood vessels, choroid plexus, and ependyma but not neurons occurred at all times on bypass. CPB caused leakage of fluorescent albumin from blood vessels in all animals. Two hours of normothermic CPB (n = 4) caused significant (p < 0.01) leakage in the cerebellum, cortex, hippocampus, and corpus callosum. Animals exposed to circulatory arrest experienced severe leakage throughout the brain (p < 0.001) and FOS expression in all cells. CONCLUSIONS: These experiments indicate that the BBB is dysfunctional after all time points on normothermic CPB, BBB dysfunction is worsened by hypothermic circulatory arrest, and BBB dysfunction is associated with intense molecular activity within the barrier-forming cells. Dysfunction of the BBB may contribute to neurologic complications after heart surgery.

Apical right ventriculotomy for closure of apical ventricular septal defects.

BACKGROUND: Apical ventricular septal defects (VSDs) are difficult to visualize through a transatrial approach, while the use of a left ventriculotomy may result in progressive ventricular dysfunction. Transcatheter closure has not been reliable, especially in small infants. Apical right ventriculotomy provides good exposure, preserves left ventricular function, and allows secure closure of apical VSDs. METHODS: From November 1994 through April 2002, nine children, median age 8 months (range, 74 days to 2.5 years) underwent 10 operations for VSD closure via apical right ventriculotomy (one patient with a residual defect underwent successful VSD closure via a second apical right ventriculotomy). Two patients were status post pulmonary artery banding and two patients had previous unsuccessful attempts at closure via a transatrial approach. RESULTS: There was no hospital mortality; there were 2 late deaths (78% survival; 95% confidence interval [CI], 45% to 94%), 3 months and 4 years postoperatively. Postoperative echocardiography demonstrated no residual VSDs in 3 and insignificant residual VSDs in 4 of the survivors. All survivors currently exhibit normal biventricular function during a median follow-up of 25 months (range, 11 to 104 months). CONCLUSIONS: Apical right ventriculotomy provides excellent exposure allowing safe and effective closure of apical VSDs. The observed late morbidity and mortality reflects the complexity that often exists in these cases due to additional irreparable lesions.

Results of the double switch operation for congenitally corrected transposition of the great arteries.

OBJECTIVE: To determine the outcomes for a program that utilizes the double switch operation as the primary approach for congenitally corrected transposition. METHODS: The records of 46 consecutive patients from a single institution who had undergone a double switch operation from October 1993 to March 2002 were reviewed. The records of 24 patients who were evaluated during the same period and felt not to be candidates for the double switch operation or who are awaiting double switch after pulmonary artery banding were also reviewed. RESULTS: The median age at operation was 28 months (range 2 months to 16.3 years). Associated defects included ventricular septal defect 40, pulmonic stenosis 13 and pulmonary atresia 16. Twenty-six patients underwent an arterial switch operation combined with a Senning procedure while 20 patients underwent combined Rastelli and Senning procedures. Before the double switch, 12 patients had required pulmonary artery banding and 21 patients had systemic to pulmonary artery shunts. The median duration of stay in the intensive care unit was 3.5 days (range 2-60 days) and the median duration of total hospital stay was 8 days (range 5-60 days). There were no hospital deaths; one patient died 5 months after discharge due to an arrhythmogenic cardiac arrest during a median follow-up of 24 months [long-term survival 98% (95% CI 89-100%)]. CONCLUSIONS: The double switch operation may be performed with excellent hospital and long-term survival. The theoretical advantages of this procedure which enables the morphologic left ventricle and mitral valve to support a systemic pressure load must be established by careful follow-up of these patients.

Creation of a dual-coronary system for anomalous origin of the left coronary artery from the pulmonary artery utilizing the trapdoor flap method.

OBJECTIVE: Results of the repair of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) have improved. Direct implantation of the anomalous coronary artery into the ascending aorta establishes a dual-coronary system and is the goal of current surgical approaches. We report the development of our surgical technique for ALCAPA. METHODS: Between September 1993 and December 2000, 13 patients underwent surgery for ALCAPA. There were four males and nine females. Ages ranged from 1 month to 25 years (median=3.9) and weight ranged from 2.6 to 102kg (median=16.8). One patient had previously undergone an operative procedure at an outside institution. RESULTS: Direct implantation of the anomalous coronary artery into the ascending aorta was feasible in 12 of 13 patients. In situ transfer was performed in one patient with an intramural coronary artery. The first case in the series required an intrapulmonary baffle reconstruction (Takeuchi procedure) because the coronary artery arose remotely from the ascending aorta from the left-anterior sinus of the PA. For coronary transfer, a trapdoor flap was created on the ascending aorta for the implantation of the coronary button and the sinus defect in the main PA was augmented with a pericardial patch. The left ventricular (LV) shortening fraction was improved from a median value of 27% (range 12-36%) preoperatively to 33% (range 24-45%) in the immediate postoperative period (P=0.004). The LV end-diastolic dimension decreased from a median value of 36 mm (range 22-70 mm) preoperatively to 29 mm (range 19-56 mm) in the immediate postoperative period (P=0.004). There has been no mortality or reoperation during a median follow-up of 36 months. CONCLUSIONS: Using a standard technique, direct implantation of the anomalous coronary artery into the ascending aorta was achieved in all cases but one. At intermediate follow-up, LV function had improved by echocardiography. No postoperative mechanical circulatory support was required in any of these patients. This operative technique is reproducible and is applicable to the majority of patients with ALCAPA.