Toru Okamura

Surgical Results for Functional Univentricular Heart With Total Anomalous Pulmonary Venous Connection Over a 25-Year Experience

BACKGROUND Surgical results for functional univentricular heart with total anomalous pulmonary venous connection (TAPVC) have been unsatisfactory to date. METHODS During a 25-year period until December 2009, 207 TAPVC patients underwent surgical repair at our institute, including 56 with a univentricular heart. The 10-year survival rate was 51.1% with univentricular heart and 84.7% with biventricular heart (p<0.0001; log-rank, 27.6). Surgical outcomes and risk factors for early and late death after TAPVC repair in univentricular hearts were retrospectively analyzed. RESULTS Patients were aged 3.8±4.3 years and weighed 12.3±10.7 kg at operation. Preoperative diagnoses included heterotaxy syndrome in 55, asplenia in 48, preoperative pulmonary venous obstruction in 35, and pulmonary atresia in 20. TAPVC was classified as I in 22, II in 26, III in 5, and IV in 3. Concomitant procedures included Fontan procedure in 29, bidirectional Glenn procedure in 5, systemic-pulmonary shunt in 11, and pulmonary artery banding in 5. There were 17 hospital deaths and 11 late deaths. Fontan completion was undertaken in 31 (55.3%). Postoperative pulmonary venous obstruction was found in 15. Multivariate analysis identified TAPVC III and IV and pulmonary atresia as risk factors for hospital death. Univariate analysis identified postoperative pulmonary venous obstruction and concomitant systemic-pulmonary shunt as risk factors for hospital and late death. CONCLUSIONS TAPVC III, IV, and pulmonary atresia are risk factors for early postoperative death. Intensive intervention, including perioperative management and operation, is required in these complex patients.

Cardiopulmonary Bypass Increases Permeability of the Blood-Cerebrospinal Fluid Barrier

BACKGROUND The integrity of the blood-cerebrospinal fluid (CSF) barrier during cardiopulmonary bypass (CPB) with hypothermic circulatory arrest (HCA) has not been systematically studied, especially in children. We tested the hypothesis that the blood-CSF barrier is disrupted by CPB. METHODS The study randomized 25 piglets (mean weight, 11 kg) to five groups (5 per group): anesthesia alone (control); CPB at 37 degrees C with full-flow (FF); CPB at 25 degrees C with very low flow (LF); and HCA at 15 degrees C and 25 degrees C. pH-stat strategy was applied during CPB. An epidural catheter was inserted into the cisterna magna for collection of CSF. CSF and blood samples were collected at seven points: after induction of anesthesia (baseline), at 10, 50 and 115 minutes after start of CPB, just before the end of CPB, and at 30 and 120 minutes after CPB. Albumin levels in CSF and plasma were measured to assess blood-CSF barrier integrity and the albumin ratio (CSF/plasma) was calculated (Q(Alb)). RESULTS In both HCA groups, the Q(Alb) was significantly higher than in the control and 37 degrees C FF groups (all p < 0.05), whereas Q(Alb) in the 37 degrees C group was not significantly different vs control. CONCLUSIONS The blood-CSF barrier is impaired by CPB with 1 hour of 15 degrees C or 25 degrees C HCA. Further investigations are needed to understand the behavior of the blood-CSF barrier during CPB and its role in neuroprotection.

Hypothermic Circulatory Arrest Increases Permeability of the Blood Brain Barrier in Watershed Areas

BACKGROUND The integrity of the blood brain barrier (BBB) after cardiopulmonary bypass (CPB) with hypothermic circulatory arrest (HCA) is controversial in children. We tested the hypothesis that the BBB is disrupted by HCA. METHODS Forty-one piglets (mean weight 11 kg) were randomly allocated to acute and survival experiments. Five groups (25 piglets, 5 per group) underwent acute studies: anesthesia alone (control); CPB at 37°C with full-flow (FF); CPB at 25°C with very low flow (LF); HCA at 15°C, and HCA at 25°C. Two groups (16 piglets, 8 per group) underwent survival studies: CPB at 25°C with LF and HCA. In the acute studies, Evans blue dye (EBD) extravasation through the BBB into the brain was measured using two methods: EBD absorbance of homogenized brain, and immunohistochemical localization of EBD-linked albumin for cortex, caudate nucleus, thalamus, hippocampus, and cerebellum. In the survival studies, cerebral histology was assessed with hematoxylin-eosin stain after sacrifice at 4 days after surgery. RESULTS The BBB disruption was clearly observed around watershed areas for 25°C HCA compared with other conditions. Microscopic data showed that leakage of EBD in 25°C HCA was more severe than control in all brain areas (p < 0.05), and EBD and albumin were colocalizing. Histologic damage scores were significantly higher in watershed areas with 25°C HCA. CONCLUSIONS The BBB was impaired around watershed areas by 25°C HCA for 1 hour according to both macroscopic and microscopic data. An increase in permeability of the BBB may be both a sign and a mechanism of brain damage.

Simultaneous repair of pectus excavatum and congenital heart defect in adults by using the convex bar

Simultaneous repair of pectus excavatum and cardiac lesions remains technically difficult. In adults, most repairs of pectus deformity and heart lesions have been performed through long incisions, sternal splits, excision of deformed cartilages, and sternal turnover, which can result in poor cosmetic appearance because of sternal devascularization. We performed concomitant repair of pectus excavatum and an atrial septal defect through a short midline incision in an adult. The sternum was fixed by using absorbable plates and screws and was supported by a convex steel bar. The cosmetic appearance remained excellent after the operation. The technique and a review of the literature are included.

Optimal dose of aprotinin for neuroprotection and renal function in a piglet survival model

OBJECTIVE The efficacy of aprotinin in reducing blood loss after cardiopulmonary bypass is well established, although its neuroprotective potential is less well known. Furthermore, there is controversy regarding optimal dosing and possible renal complications. METHODS Fifty-four piglets were randomized to one of 3 cardiopulmonary bypass groups designed to carry the risk of postoperative cerebral and renal dysfunction: circulatory arrest at 25 degrees C and ultra-low flow bypass (10 mL x kg(-1) x min(-1)) at either 25 degrees C or 34 degrees C. Animals were randomized to the following groups: control (no aprotinin), low dose (30,000 KIU/kg into prime only), standard full dose (30,000 KIU/kg bolus administered intravenously into prime plus 10,000 KIU/kg infusion), and double full dose. The tissue oxygenation index was monitored by means of near-infrared spectroscopy. Neurologic functional and histologic scores and creatinine and blood urea nitrogen values were outcomes of interest. RESULTS Aprotinin significantly improved neurologic scores on postoperative day 1 after ultra-low-flow bypass at 25 degrees C or 34 degrees C (P < .01) but not after hypothermic circulatory arrest (P = .57). Linear regression indicated a strong dose-response relationship, with higher aprotinin doses having the best neurologic scores. During low-flow bypass, a higher tissue oxygenation index was correlated with a higher aprotinin dose (P < .05). Aprotinin dose had no significant effect on creatinine or blood urea nitrogen values on day 1. Low body weight was the only predictor of high blood urea nitrogen values (r = -0.39, P < .01). CONCLUSION Aprotinin significantly improves neurologic recovery without compromising renal function in the young piglet.

Ibuprofen for neuroprotection after cerebral ischemia

OBJECTIVE Ibuprofen has been shown to reduce cerebral ischemic injury, such as may occur after deep hypothermic circulatory arrest. We investigated whether ibuprofen has direct protective effects against excitotoxic neuronal injury, as may be seen after cerebral ischemia, by using a cell culture model. METHODS Mixed cortical cultures containing neuronal and glial cells were prepared from fetal mice at 13 to 15 days gestation, plated on a layer of confluent astrocytes from 1- to 3-day-old postnatal pups. Near-pure neuronal cultures containing less than 5% astrocytes were obtained from mice of the same gestational stage. Slowly triggered excitotoxic injury was induced at 37 degrees C by 24-hour exposure to 12.5 micromol/L N-methyl-D-aspartate or 50 micromol/L kainate. Neuronal death was quantified by release of lactate dehydrogenase from damaged cells. Data were analyzed using 1-way analysis of variance with Tukey post hoc multiple comparisons. RESULTS In mixed cultures, ibuprofen concentrations of 25 microg/mL, 50 microg/mL, and 100 microg/mL all significantly reduced N-methyl-D-aspartate-induced neuronal cell death from 74.5% to 56.1%, 38.7%, and 12.3%, respectively, revealing a strong dose response (P < .001). In near-pure cultures, ibuprofen at a concentration of 25 microg/mL failed to protect neurons, indicating that the neuroprotective effects of ibuprofen require interaction with glial cells. Furthermore, ibuprofen at 100 microg/mL was not protective against neuronal cell death induced by kainate excitotoxicity in near-pure culture but was effective in mixed cultures. CONCLUSION Ibuprofen provides neuroprotection through glial cells against excitotoxic neuronal injury caused by glutamatergic excitotoxicity after cerebral ischemia as demonstrated by reduced neuronal cell death in mixed cell cultures. Further studies are needed to evaluate the potential of ibuprofen to reduce neurologic injury in patients experiencing an hypoxic/ischemic insult.

Remarkable giant right atrial diverticulum in asymptomatic patient

We describe the case of a 31-year-old man who had a giant right atrial diverticulum. Although he was asymptomatic, preoperative echocardiography and three-dimensional computed tomography scan found a large mass on the right atrium. He was diagnosed with a right atrial diverticulum and underwent surgical resection of the diverticulum because of the risk of thromboembolism, arrhythmia and rupture of the diverticulum. Intra-operative finding was compatible with the feature of a diverticulum which includes thin wall and large space inside the diverticulum. Postoperative pathological examination showed a thin diverticulum wall consisting of only fibrous tissue and intima without muscular tissue. We concluded that a large diverticulum should be treated surgically because of the critical complications.

Differential neuronal vulnerability varies according to specific cardiopulmonary bypass insult in a porcine survival model

OBJECTIVE We investigated whether the degree of vulnerability of different areas in the developing brain varies according to the specific mechanism of the insults caused by cardiopulmonary bypass. METHODS A meta-analysis of 2 experimental studies (n = 80) was conducted. The end points of the otherwise identical studies were tissue oxygen index in the first experiment, whereas cerebral microvessel vasoconstriction and inflammatory response of endothelial cells were directly visualized in the second study. We assigned ultra-low flow bypass at 25 °C for 60 minutes as control; circulatory arrest at 25 °C for 60 minutes as ischemic stress under circulatory arrest (ischemia-CA); and ultra-low flow bypass at 34 °C for 60 minutes as the stress under ultra-low flow bypass (ischemia-ULF). Histologic neuronal damage was the primary outcome. Secondary measures included neurologic recovery. RESULTS Vasoconstriction after ischemia and inflammation after bypass were independent predictors of severe histologic damage. The caudate nucleus was significantly vulnerable to ischemia-CA and was significantly influenced by vasoconstriction. In contrast, the hippocampus was significantly vulnerable to ischemia-ULF. The different forms of ischemic insults did not influence Purkinje cells, whereas Purkinje damage significantly correlated with inflammation. Tissue oxygen index had the ability to differentiate accurately regional damage. Neurologic recovery under ischemia-CA was significantly worse compared with ischemia-ULF. Neurologic recovery correlated with neuronal damage in the caudate nucleus, but it did not correlate with damage in the hippocampus. CONCLUSIONS Neuronal vulnerability in different areas of the developing brain varies according to mechanisms of bypass-induced ischemic stress. Certain regional damage may not be apparent in assessing acute neurologic recovery.

Aprotinin confers neuroprotection by reducing apoptotic cell death.

Aprotinin has been used in pediatric cardiac surgery for its antiinflammatory and hemostatic benefits. We have reported that aprotinin has a direct cellular neuroprotective effect through reduction of excitotoxicity. The purpose of this study was to investigate whether aprotinin is neuroprotective against apoptotic cell death. Near-pure neuronal cultures containing <5% astrocytes were obtained from fetal mice. Serum deprivation was initiated at 7 days by transferring the cultures, which are dependent on serum for survival, into growth medium lacking serum for 24 h. Neuronal cell death was assessed by phase-contrast cell counting after staining with 0.4% trypan blue dye. Aprotinin at a clinically relevant concentration of 100 KIU·mL−1 significantly reduced apoptotic neuronal cell death from 84.4% to 51.8%. This result suggests that aprotinin has the potential to reduce brain injury resulting from apoptotic cell death induced by an ischemic insult. Additional studies are needed to evaluate the potential of aprotinin to reduce neurological injury in patients at high risk of cerebral injury, including those undergoing circulatory arrest.

Cardiac perforation 6 years following the implantation of an Amplatzer septal occluder

Amplatzer vascular occluders have been used to close atrial septal defects (ASDs), ventricular septal defects, aorto-pulmonary fistulas and defects, aorto-atrial fistulas following aortic valve replacement, and left ventricular aneurysms. However, they can result in device migration resulting in cardiogenic shock and leaks resulting in perforation and pseudoaneurysm formation. We present images of an Amplatzer device which resulted in cardiac erosion and tamponade 6 years after implantation for an ASD. A 14-year-old female was admitted to an outside hospital with chest pain 6 years following repair of an ASD with an Amplatzer occluder. An echocardiogram now revealed a significant pericardial effusion with signs of tamponade. A bloody effusion was drained and she was transferred to our hospital where a repeat echocardiogram