Flow Energy Loss as a Predictive Parameter for Right Ventricular Deterioration Caused by Pulmonary Regurgitation After Tetralogy of Fallot Repair.

The optimal timing for pulmonary valve replacement after Tetralogy of Fallot (TOF) repair remains controversial. In this study, we estimated the feasibility of using flow energy loss (FEL) to predict right ventricular (RV) deterioration due to pulmonary regurgitation after TOF repair. We examined RV outflow tract (RVOT) flow in nine patients who underwent TOF or double-outlet right ventricle repair in the intervention group (Group I) and compared them with three healthy children in the control group (Group C). We evaluated flow across the RVOT and pulmonary valve by vector flow mapping (VFM) on echocardiography and by phase contrast-magnetic resonance imaging (PC-MRI). Next, we calculated FEL and analyzed the relationship between FEL and clinical parameters of RV function. The mean FEL was significantly greater in Group I than in Group C (p = 0.002). Flow pattern and FEL were comparable by VFM and PC-MRI at the same phase 14.6 years after TOF repair. There was a significant positive correlation for the cardiothoracic ratio with both the mean FEL [correlation coefficient (r) = 0.78; p = 0.012] and the diastolic peak FEL (r = 0.75; p = 0.021) in Group I. There was also a significant positive correlation between the serial change in QRS duration with both the mean FEL (r = 0.82; p = 0.014) and the diastolic FEL (r = 0.70; p = 0.052) in Group I. FEL by VFM is an effective tool for evaluating ventricular deterioration caused by RV workload.

Daily transient discontinuation of extracorporeal LVAD to prevent thromboembolism of mechanical aortic valve prosthesis.

Patients with mechanical aortic valves are generally contraindicated for left ventricular assist device (LVAD) insertion because the prosthetic valve often becomes fixed in closed position. A 41-year-old woman with mechanical aortic valve prosthesis experienced sudden chest pain and developed cardiogenic shock. A paracorporeal pulsatile LVAD and a monopivot centrifugal pump as a right VAD (RVAD) were implanted. The mechanical aortic valve was intentionally left in place. Soon after the operation, LVAD support was discontinued daily for few seconds to allow the mechanical aortic valve to open and to avoid thrombus formation. The patient was successfully weaned off RVAD and received anticoagulation therapy with warfarin. On postoperative day 141, she was transferred to a university hospital where a HeartMate II LVAD was implanted, and the aortic valve was successfully replaced with a bioprosthetic valve. The patient is currently awaiting heart transplantation.

Norwood Procedure Performed on a Patient With Trisomy 13.

Trisomy 13 is associated with a variety of congenital anomalies, some of which are life-threatening and related to poor prognosis. Therefore, cardiac surgery is rarely offered to these patients, especially to those with complex cardiac anomalies. We report the case of a neonate weighing 2324 g who was born with severe congenital heart defects. Transthoracic echocardiography revealed the diagnoses of asplenia, single ventricle, aortic stenosis, coarctation of the aorta, hypoplastic aortic arch, and total anomalous pulmonary venous return. She was hemodynamically unstable. Palliative Norwood procedure with right ventricle-pulmonary artery conduit (RV-PA conduit) was performed at the age of 1 day to save her life. On postoperative day 7, chromosome analysis revealed trisomy 13. Echocardiography revealed good heart function; stable hemodynamic status was achieved with minimal amounts of inotropic agents. However, she developed anuria, which did not improve despite situational possible interventions, including peritoneal dialysis and continuous hemodiafiltration. On postoperative day 37, she succumbed to sudden cardiorespiratory failure. Nevertheless, this case indicates that a neonate with trisomy 13 can have a better chance at survival with cardiac surgery such as the Norwood procedure with an RV-PA conduit.

Seventeen-month-long paracorporeal biventricular mechanical support as a bridge to transplantation for severe dilated cardiomyopathy.

The long-term management of paracorporeal biventricular assist devices (BiVAD) is difficult because of significant risks of bleeding, thrombosis, and infection. Here we report the case of a 41-year-old woman with severe dilated cardiomyopathy who developed serious cerebral bleeding after receiving a paracorporeal BiVAD but recovered well after treatment. She eventually underwent cardiac transplantation 17 months after implantation of the paracorporeal BiVAD.

Optimal Graft Size of Modified Blalock-Taussig Shunt for Biventricular Circulation in Neonates and Small Infants.

The modified Blalock-Taussig shunt (mBTS) is one of the most important palliative procedures in congenital heart surgery. However, in neonates and small infants, operative mortality and morbidity due to excessive pulmonary blood flow or shunt failure remains high. In this study, a small shunt graft (3.0-mm diameter) was estimated to determine the optimal shunt graft size of BTS as an initial palliation for ultimate biventricular circulation. Eighteen patients weighing an average 3.5 kg who underwent mBTS from July 2004 to January 2013 at our institute were reviewed. We divided the study cohort into two groups: group S (n = 10) included patients with 3.0-mm diameter shunt grafts, and group L (n = 8) included patients with 3.5-mm diameter shunt grafts. There were no hospital deaths or shunt occlusion in either group. One group L patient (12.5%) had cardiogenic shock due to excessive pulmonary blood flow. There were no differences in postoperative arterial oxygen saturation (SaO2) between the groups. There were no differences in body weight at intracardiac repair (ICR) between the groups. During the interstage to ICR, body weight gain was significantly greater in group S than in group L (P = 0.008). The small shunt graft (3.0-mm diameter) in BTS was safe, provided adequate pulmonary blood flow, and led to significant weight gain between mBTS and ICR for ultimate biventricular circulation in neonates and small infants with low body weight.

GABA type B receptor signaling in proopiomelanocortin neurons protects against obesity, insulin resistance, and hypothalamic inflammation in male mice on a high-fat diet.

There is evidence suggesting that the GABA system in the arcuate nucleus, where orexigenic neuropeptide Y and agouti-related peptide as well as anorexigenic proopiomelanocortin (POMC) are expressed, plays an important role in energy balance. In this study, we generated POMC-specific GABAB receptor-deficient [knock-out (KO)] mice. Male KO mice on a high-fat diet (HFD) showed mild increases in body weight (BW) at the age of 9 weeks compared to wild-type (WT) mice, and the differences remained significant until 16 weeks old. However, there was no difference in BW in females between genotypes. While food intake was similar between genotypes, oxygen consumption was significantly decreased in the male KO mice. The insulin tolerance test revealed that the male KO mice were less insulin sensitive compared to WT mice at the age of 8 weeks, when there was no significant difference in BW between genotypes. Despite increased BW, POMC mRNA expression in the arcuate nucleus was significantly decreased in the KO mice compared to WT mice at the age of 16 weeks. Furthermore, the expression of TNFα as well as IL-6, proinflammatory markers in the hypothalamus, was significantly increased in the KO mice on a HFD compared to WT mice. This demonstrates that the deletion of GABAB receptors in POMC neurons in the male mice on a HFD results in obesity, insulin resistance, and hypothalamic inflammation. Furthermore, the decreased POMC expression in the obese KO mice suggests that the regulation of POMC expression through GABAB receptors is essential for proper energy balance.

Five-week use of a monopivot centrifugal blood pump as a right ventricular assist device in severe dilated cardiomyopathy.

Right heart failure is a critical complication in patients requiring mechanical ventricular support. However, it is often difficult to provide adequate right ventricular support in the acute phase. A 41-year-old woman diagnosed with dilated cardiomyopathy with severe right heart failure underwent implantation of a paracorporeal pulsatile left ventricular assist device (LVAD, Nipro Corporation, Tokyo, Japan) and a MERA monopivot centrifugal pump (Senko Medical Instrument Manufacturing Co., Ltd., Tokyo, Japan) as a right ventricular assist device (RVAD). The patient developed ischemic enteritis 3 weeks after surgery, necessitating fasting and reversal of anticoagulation therapy. A target international normalized ratio of 1.5 was selected, and aspirin administration was discontinued. Following recovery without thromboembolic events, the patient failed the RVAD discontinuation test. Five weeks after surgery, the monopivot centrifugal pump was exchanged for a pulsatile pump. No thrombus was evident on the centrifugal pump. The patient was undergoing cardiac rehabilitation at the time of this writing and awaiting heart transplantation.

A case of thrombosis of intra-atrial extracardiac conduit and left pulmonary artery due to infective endocarditis after modified Fontan operation.

Previous studies have reported that the extracardiac Fontan procedure has excellent outcomes and a lower incidence of postoperative complications than the lateral tunnel procedure. However, thromboembolic events that occur after the Fontan procedure are a well-known cause of morbidity. We experienced a case of thrombosis of intra-atrial extracardiac conduit and the left pulmonary artery 2 years after a modified Fontan operation due to infective endocarditis (IE) despite prophylactic antiplatelet therapy. The patient underwent reoperation. The conduit in the right atrium (RA) was excised, and the thrombus in the vessels was removed. Because the fibrous tissue in the RA around the conduit was firm, the tissue was used as the "tunnel" for the Fontan route between the IVC and the ePTFE graft outside the RA instead of replacement using another alien graft. He was discharged on postoperative day 45 and was medicated with coumadin and aspirin. He is now being followed in our outpatient clinic and is still without any sign of infection.

A case report of persistent fifth aortic arch presenting with severe left ventricular dysfunction.

According to several previous reports on persistent fifth aortic arch (PFAA), the presentation of the patients was usually either very mild when diagnosed by physical examination including upper body systemic hypertension and systolic murmur, or severe with ductal shock in the neonatal period. In our case, the clinical course was unique with relatively mild narrowing at the distal PFAA and an interrupted fourth aortic arch. It can be classified as medium severity based on the timing of presentation to the hospital. In the present case, severe LV dysfunction suggested sustained narrowing at the junction between the PFAA and the descending aorta and insufficient development of collateral arteries.We experienced a case with PFAA with severe LV dysfunction. These findings suggest another differential diagnosis for severe LV dysfunction in infancy.

Aortic arch rerouting and OPCAB in a patient with situs inversus totalis.

Endovascular therapy approaches for aortic aneurysm have lowered the mortality and morbidity rates even in high-risk patients; moreover, these approaches are applied in the management of aortic arch pathologies by transposition of the supra-aortic branches. We present the case of a 75-year-old female patient with situs inversus totalis on hemodialysis. The patient underwent off-pump aortic arch rerouting and thoracic endovascular aortic repair concomitant with coronary artery bypass grafting for distal aortic arch aneurysm and ischemic heart disease.

[Bilateral pulmonary artery banding using ligation clips and facile Norwood-Glenn procedure].

Bilateral pulmonary artery banding( BPAB), though a less-invasive surgical option for hypoplastic left heart syndrome (HLHS), entails considerable risk of residual pulmonary artery stenosis after de-banding. Autologous aortic reconstruction in Norwood procedure is attractive in terms of growth potential, but technically demanding. To overcome these drawbacks, we modified the 2 techniques. Eight patients with HLHS underwent BPAB whereby ligation clips were half-closed into rhombic shape to deform bilateral pulmonary arteries. The arterial duct was kept patent by prostaglandin E1 infusion. One patient died of sepsis( age 8 months), while the 7 survivors underwent Norwood-Glenn procedure. Both pulmonary arteries were excised from the pulmonary trunk with minimal cuffs. Resultant defect in the pulmonary trunk was longitudinally closed. After arterial duct excision, pulmonary trunk-to descending aorta continuity was reconstructed by end-to-end anastomosis. Ascending aorta-to-aortic arch complex was anastomosed to the pulmonary trunk in a side-to-side fashion. After bilateral pulmonary artery continuity was reconstructed, Glenn anastomosis was made. One patient died of pneumonia(age 5 months). Currently, the 6 surviving patients(age 4∼30 months), enjoy good health. Four of them have completed Fontan procedure. Our modified techniques are facile, reproducible, and pose low risk of residual pulmonary artery stenosis or aortic stenosis.

[Outcomes of the surgical treatment of infectious endocarditis in a single institute for 13-years].

Recently, due to the progress in patient managements with antibiotics, the prognosis of the active phase infectious endocarditis (IE) has improved, but in some cases, urgent or emergent surgical treatment is inevitable because of the uncontrollable acute heart failure due to valve regurgitation, uncontrollable infection with circulatory collapse, or high embolization risk. We reviewed the outcomes of the 57 IE patients who underwent surgical treatment in our hospital from January, 2000 to April, 2012. Preoperative state including inflammatory responses, bacterial blood culture, antibiotic administration, and surgical procedures were examined. No statistical significances were detected in the mortalities between elective cases (n=43)and urgent or emergent cases (n=14). Totally, mortality was 5.3% including one case in prosthetic valve endocarditis, and was satisfactory.

Moderate prosthesis-patient mismatch may be negligible in elderly patients undergoing conventional aortic valve replacement for aortic stenosis.

Together with aging of the Japanese population, aortic valve replacement (AVR) for aortic stenosis (AS) is now becoming more and more common in the elderly. When the aortic annulus is too small to allow an adequate sized prosthetic valve, aortic root enlargement is required to avoid prosthesis-patient mismatch (PPM). However, age-related comorbidities including aortic root calcification bring significant risk in performing aortic root enlargement. In the present study, 40 patients aged 75 years or more who underwent AVR for AS were reviewed to determine whether moderate PPM has a negative impact on the long-term results. Operative mortality occurred in 2 patients (5%) and moderate PPM occurred in 8 patients. There was no significant difference in survival between cases with and without PPM (P = 0.87). Both aortic pressure gradient (PG) and left ventricular mass index (LVMI) measured by echocardiography were signifi cantly decreased in patients with and without PPM. Reduction of PG was significantly greater in patients with PPM than without PPM (P = 0.02). Reduction of LVMI was not different between the groups (P = 0.58). Moderate PPM did not negatively influence survival or reduction of PG or LVMI in patients aged 75 years or older who underwent AVR for AS.

Relationship between pellet formation by Aspergillus oryzae strain KB and the production of ß-fructofuranosidase with high transfructosylation activity.

Aspergillus oryzae KB produces two ß-fructofuranosidases (F1 and F2). F1 has high transfructosylation activity (Ut) to produce fructooligosaccharides. F2 has high hydrolysis activity (Uh), releasing glucose and fructose. It is desirable to selectively produce F1, which can be used for production of fructooligosaccharides. Here, the relationship between filamentous pellet size and selective production of F1 in liquid culture was investigated. Our finding revealed that: (i) The mean particle size of pellets (5.88 ± 1.36 mm) was larger, and the ratio of Ut to Uh was improved (Ut/Uh = 5.0) in 10% sucrose medium compared with 1% sucrose medium (pellet size = 2.60 ± 0.37 mm; Ut/Uh = 0.96). (ii) The final culture pH of the 1% sucrose medium was 8.7; on controlling the pH of 1% sucrose medium at 5.0, increased pellet size (9.69 ± 2.01 mm) and Ut/Uh (7.8) were observed. (iii) When 3% glycerin was used as carbon source, the pellet size decreased to 1.09 ± 0.33 mm and Ut/Uh was 0.57. (iv) In medium containing 1% sucrose, the pellet size was dependent on the number of spores used in the culture inoculum, but, in these experiments, Ut/Uh was almost constant (1.05 ± 0.08). Collectively, the data show that the value of Ut/Uh is proportional to the pellet size when liquid culture of A. oryzae strain KB is performed in some conditions (such as in the presence of high sucrose concentration, low pH, or added Tween surfactant), but in other conditions Ut/Uh is independent of pellet size.

Effects of nonionic surfactants on pellet formation and the production of ß-fructofuranosidases from Aspergillus oryzae KB.

Aspergillus oryzae KB produces two ß-fructofuranosidases (F1 and F2). F1 has high transferring activity and produces fructooligosaccharides from sucrose. Mycelial growth pellets were altered by the addition of Tween 20, 40 and 80 (HLB=16.7, 15.6 and 15.0, respectively) in liquid medium cultures to form small spherical pellets. The particle size of the pellets decreased with the HLB value, which corresponds to an increase in surfactant hydrophobicity. Selective F1 production and pellet size were maximized using Tween 20. Adding polyoxyethylene oleyl ethers (POEs) with various degrees of polymerization (2, 7, 10, 20 and 50: HLB=7.7, 10.7, 14.7, 17.2 and 18.2, respectively) was investigated. A minimum mean particle size was obtained using a POE with DP=10, HLB=14.7. The POE surfactants had little effect on the selective production of F1. The formation of filamentous pellets depended on the surfactant HLB value, and F1 enzymes were produced most efficiently using Tween 20.

AgRP Neuron-Specific Deletion of Glucocorticoid Receptor Leads to Increased Energy Expenditure and Decreased Body Weight in Female Mice on a High-Fat Diet.

Agouti-related protein (AgRP) expressed in the arcuate nucleus is a potent orexigenic neuropeptide, which increases food intake and reduces energy expenditure resulting in increases in body weight (BW). Glucocorticoids, key hormones that regulate energy balance, have been shown in rodents to regulate the expression of AgRP. In this study, we generated AgRP-specific glucocorticoid receptor (GR)-deficient (knockout [KO]) mice. Female and male KO mice on a high-fat diet (HFD) showed decreases in BW at the age of 6 weeks compared with wild-type mice, and the differences remained significant until 16 weeks old. The degree of resistance to diet-induced obesity was more robust in female than in male mice. On a chow diet, the female KO mice showed slightly but significantly attenuated weight gain compared with wild-type mice after 11 weeks, whereas there were no significant differences in BW in males between genotypes. Visceral fat pad mass was significantly decreased in female KO mice on HFD, whereas there were no significant differences in lean body mass between genotypes. Although food intake was similar between genotypes, oxygen consumption was significantly increased in female KO mice on HFD. In addition, the uncoupling protein-1 expression in the brown adipose tissues was increased in KO mice. These data demonstrate that the absence of GR signaling in AgRP neurons resulted in increases in energy expenditure accompanied by decreases in adiposity in mice fed HFD, indicating that GR signaling in AgRP neurons suppresses energy expenditure under HFD conditions.

Impact of the entry site on late outcome in acute Stanford type B aortic dissection†.

OBJECTIVES: This study aimed to investigate whether the entry site of acute type B aortic dissection affects late outcomes. METHODS: Inpatient and outpatient records were retrospectively reviewed. RESULTS: We identified 224 cases of acute type B aortic dissection between 1998 and 2013. Of these 224 patients, 168 were men and the age was 64.2 ± 12.6 (range 23-94) years, from which 130 presented with the entry at a location downstream of the distal aortic arch, 67 with the entry at the outer curvature of the distal aortic arch and 27 with the entry at the inner curvature. At the initial presentation, 127 patients had descending false lumen thrombosis. The 30-day mortality rate was 2%, and 8% of patients had malperfusion. The entry at the outer curvature was associated with a higher risk of 30-day mortality. Patients with the entry at a location downstream were significantly older, and had a higher chance for primarily thrombosed descending false lumen and a lower risk of malperfusion. At follow-up (6.0 ± 4.1 years), the actuarial survival rates were 97, 83 and 60%, freedoms from open aortic surgery were 96, 91 and 86%, aortic intervention were 73, 66 and 63% and aortic events were 71, 60 and 52% at 1, 5 and 10 years, respectively. Multivariate logistic regression analysis revealed that the outer curvature entry and maximum aortic diameter were correlated with open aortic surgery, aortic intervention and aortic events. Of the 127 patients with primarily thrombosed false lumen, the outer curvature entry was significantly correlated with aortic events. CONCLUSIONS: The primary entry at the outer curvature of the distal aortic arch, as well as the large aortic diameter, is associated with a higher risk of late open aortic surgery, aortic intervention and aortic events in acute type B aortic dissection. Thus, the entry site should be taken into consideration in the establishment of an appropriate treatment indication of type B aortic dissection.

Mitogen-activated protein kinase phosphatase 1 negatively regulates MAPK signaling in mouse hypothalamus.

Mitogen-activated protein kinase phosphatase 1 (MKP-1) is shown to negatively regulate MAPK signaling in various peripheral tissues as well as the central nervous system such as cortex, striatum and hippocampus. In this study, we examined whether MKP-1 regulates MAPK signaling in the mouse hypothalamus. Intraperitoneal injection of TNFα significantly increased MKP-1 mRNA expression in paraventricular and arcuate nuclei in the hypothalamus. TNFα treatment induced increases in MKP-1 expression at both mRNA and protein levels, accompanied by the inactivation of MAPK signaling in mouse hypothalamic explants. Inhibition of MKP-1 by its inhibitor or siRNA increased MAPK activity in the explants. Our data indicate that MKP-1 negatively regulates MAPK signaling in the mouse hypothalamus.