The matricellular protein CCN5 prevents anti-VEGF drug-induced epithelial-mesenchymal transition of retinal pigment epithelium.

Age-related macular degeneration (AMD) is one of the major causes of blindness in the elderly worldwide. Anti-vascular endothelial growth factor (VEGF) drugs have been widely used to treat the neovascular type of AMD (nAMD). However, VEGF acts not only as a pro-angiogenic factor but also as an anti-apoptotic factor in the eyes. In this study, we found that anti-VEGF drugs, including bevacizumab (Bev), ranibizumab (Ran), and aflibercept (Afl), induced epithelial-mesenchymal transition (EMT) in ARPE-19 cells in vitro, accompanied by the induction of CCN2, a potent pro-fibrotic factor. Similarly, intravitreal injection of Afl into mouse eyes resulted in EMT in the retinal pigmented epithelium (RPE). Co-treatment with CCN5, an anti-fibrotic factor that down-regulates CCN2 expression, significantly attenuated the adverse effects of the anti-VEGF drugs both in vitro and in vivo. Inhibition of the VEGF signaling pathway with antagonists of VEGF receptors, SU5416 and ZM323881, induced EMT and up-regulated CCN2 in ARPE-19 cells. Additionally, knock-down of CCN2 with siRNA abolished the adverse effects of the anti-VEGF drugs in ARPE-19 cells. Collectively, these results suggest that anti-VEGF drugs induce EMT in RPE through the induction of CCN2 and that co-treatment with CCN5 attenuates the adverse effects of anti-VEGF drugs in mouse eyes.

Phytogenic feed additives alleviate pathogenic Escherichia coli-induced intestinal damage through improving barrier integrity and inhibiting inflammation in weaned pigs.

BACKGROUND: This study was conducted to investigate the effects of each phytogenic feed additive (PFA; PFA1, bitter citrus extract; PFA2, a microencapsulated blend of thymol and carvacrol; PFA3, a mixture of bitter citrus extract, thymol, and carvacrol; PFA4, a premixture of grape seed, grape marc extract, green tea, and hops; PFA5, fenugreek seed powder) on the growth performance, nutrient digestibility, intestinal morphology, and immune response in weaned pigs infected with Escherichia coli (E. coli). RESULTS: A total of 63 4-week-old weaned pigs were placed in individual metabolic cages and assigned to seven treatment groups. The seven treatments were as follows: 1) NC; basal diet without E. coli challenge, 2) PC; basal diet with E. coli challenge, 3) T1; PC + 0.04% PFA1, 4) T2; PC + 0.01% PFA2, 5) T3; PC + 0.10% PFA3, 6) T4; PC + 0.04% PFA4, 7) T5; PC + 0.10% PFA5. The experiments lasted in 21 d, including 7 d before and 14 d after the first E. coli challenge. In the E. coli challenge treatments, all pigs were orally inoculated by dividing a total of 10 mL of E. coli F18 for 3 consecutive days. The PFA-added groups significantly increased (P < 0.05) average daily gain and feed efficiency and decreased (P < 0.05) the fecal score at d 0 to 14 post-inoculation (PI). Tumor necrosis factor α was significantly lower (P < 0.05) in the PFA-added groups except for T1 in d 14 PI compared to the PC treatment. The T3 had a higher (P < 0.05) immunoglobulin G and immunoglobulin A concentration compared to the PC treatment at d 7 PI. Also, T3 showed significantly higher (P < 0.05) villus height:crypt depth and claudin 1 expression in ileal mucosa, and significantly down-regulated (P < 0.05) the expression of calprotectin compared to the PC treatment. CONCLUSIONS: Supplementation of PFA in weaned pigs challenged with E. coli alleviated the negative effects of E. coli and improved growth performance. Among them, the mixed additive of bitter citrus extract, thymol, and carvacrol showed the most effective results, improving immune response, intestinal morphology, and expression of tight junctions.

Matricellular Protein CCN5 Gene Transfer Ameliorates Cardiac and Skeletal Dysfunction in mdx/utrn (±) Haploinsufficient Mice by Reducing Fibrosis and Upregulating Utrophin Expression.

Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration due to dystrophin gene mutations. Patients with DMD initially experience muscle weakness in their limbs during adolescence. With age, patients develop fatal respiratory and cardiac dysfunctions. During the later stages of the disease, severe cardiac fibrosis occurs, compromising cardiac function. Previously, our research showed that the matricellular protein CCN5 has antifibrotic properties. Therefore, we hypothesized that CCN5 gene transfer would ameliorate cardiac fibrosis and thus improve cardiac function in DMD-induced cardiomyopathy. We utilized mdx/utrn (±) haploinsufficient mice that recapitulated the DMD-disease phenotypes and used an adeno-associated virus serotype-9 viral vector for CCN5 gene transfer. We evaluated the onset of cardiac dysfunction using echocardiography and determined the experimental starting point in 13-month-old mice. Two months after CCN5 gene transfer, cardiac function was significantly enhanced, and cardiac fibrosis was ameliorated. Additionally, running performance was improved in CCN5 gene-transfected mice. Furthermore, in silico gene profiling analysis identified utrophin as a novel transcriptional target of CCN5. This was supplemented by a utrophin promoter assay and RNA-seq analysis, which confirmed that CCN5 was directly associated with utrophin expression. Our results showed that CCN5 may be a promising therapeutic molecule for DMD-induced cardiac and skeletal dysfunction.

Effects of different Bacillus licheniformis and Bacillus subtilis ratios on nutrient digestibility, fecal microflora, and gas emissions of growing pigs.

The objective of this study was to evaluate the effects of different mixing ratios of Bacillus licheniformis and Bacillus subtilis in diets on nutrient digestibility, fecal microflora, and odor gas emissions of growing pigs. A total of four crossbred ([Landrace × Yorkshire] × Duroc) barrows with average body weight (BW) of 41.2 ± 0.7 kg were randomly allotted four diets over four periods in a 4 × 4 Latin square design. Treatments were as follows: Control (CON, basal diet), CON + 0.2% probiotic complex (L4S6, B. licheniformis and B. subtilis at a 4:6 ratio), CON + 0.2% probiotic complex (L5S5, B. licheniformis and B. subtilis at a 5:5 ratio), CON + 0.2% probiotic complex (L6S4, B. licheniformis and B. subtilis at a 6:4 ratio). Dietary probiotic supplementation showed higher crude protein (CP) digestibility values and lower Escherichia coli counts in fecal samples than the CON group (p < 0.05). There was no significant difference in NH3 or H2S emission until day 3. The positive effect of H2S and NH3 emissions was detected earlier with the L4S6 and L5S5 compared to the L6S4, which had a lower ratio of B. subtilis. Both the L4S6 and L5S5 probiotic complexes significantly decreased the fecal H2S and NH3 emission in days 4 and 6 (p < 0.05). On day 7, all probiotic complexes decreased (p < 0.05) H2S and NH3 emissions than the CON group. Our results agreed that the dietary supplementation of Bacillus licheniformis and Bacillus subtilis complexes in growing pigs can significantly improve CP digestibility and reduce fecal E. coli counts, NH3 and H2S emissions. Notably, the higher mixing ratio of Bacillus subtilis in probiotic supplementation is more effective in reducing the odor of manure.

Anticancer Potential of Lipophilic Constituents of Eleven Shellfish Species Commonly Consumed in Korea.

The present study was aimed to investigate the composition and contents and the major lipophilic compounds, including the sterols, fatty acids, and tocols of shellfish species. Moreover, to explore the antitumor activity of these lipophilic constituents, their cytotoxicity potentials were determined against five different human cancer cells, including colon carcinoma (HCT116), epithelial melanoma (A2058), glioblastoma multiforme (T98G), lung carcinoma (A549), and adenocarcinoma (HeLa). The results show a significant variation in the contents and composition of lipophilic constituents among the studied species. The highest omega-3 (n-3) polyunsaturated fatty acids (PUFAs) were recorded from arrow squid and pacific oysters, accounting for 53.2% and 53.0% of their total fatty acids, respectively. However, the highest cholesterol content was also recorded in arrow squid (154.4 mg/100 g; 92.6% of total sterols). In contrast, in the Japanese littleneck, Yesso scallop, and common orient clam, cholesterol was just 17.1%, 18.3%, and 18.9% of total sterols, respectively, making them the richest source of non-cholesterol sterols (NCS). Lipids extracted from shellfish species showed ABTS+•- and DPPH•-scavenging activities. In the cytotoxicity analysis, lipids extracted from the Argentine red shrimp showed the highest cytotoxicity against glioblastoma multiforme T98G cells, with an IC50 value of 12.3 µg/mL. The composition and cytotoxicity data reported herein may help explore the nutritional and anticancer potentials of shellfish species.

The matricellular protein CCN5 prevents adverse atrial structural and electrical remodelling.

Atrial structural remodelling including atrial hypertrophy and fibrosis is a key mediator of atrial fibrillation (AF). We previously demonstrated that the matricellular protein CCN5 elicits anti-fibrotic and anti-hypertrophic effects in left ventricles under pressure overload. We here determined the utility of CCN5 in ameliorating adverse atrial remodelling and arrhythmias in a murine model of angiotensin II (AngII) infusion. Advanced atrial structural remodelling was induced by AngII infusion in control mice and mice overexpressing CCN5 either through transgenesis (CCN5 Tg) or AAV9-mediated gene transfer (AAV9-CCN5). The mRNA levels of pro-fibrotic and pro-inflammatory genes were markedly up-regulated by AngII infusion, which was significantly normalized by CCN5 overexpression. In vitro studies in isolated atrial fibroblasts demonstrated a marked reduction in AngII-induced fibroblast trans-differentiation in CCN5-treated atria. Moreover, while AngII increased the expression of phosphorylated CaMKII and ryanodine receptor 2 levels in HL-1 cells, these molecular features of AF were prevented by CCN5. Electrophysiological studies in ex vivo perfused hearts revealed a blunted susceptibility of the AAV9-CCN5-treated hearts to rapid atrial pacing-induced arrhythmias and concomitant reversal in AngII-induced atrial action potential prolongation. These data demonstrate the utility of a gene transfer approach targeting CCN5 for reversal of adverse atrial structural and electrophysiological remodelling.

Pro-Oxidant Actions of Carotenoids in Triggering Apoptosis of Cancer Cells: A Review of Emerging Evidence.

Carotenoids are well known for their potent antioxidant function in the cellular system. However, in cancer cells with an innately high level of intracellular reactive oxygen species (ROS), carotenoids may act as potent pro-oxidant molecules and trigger ROS-mediated apoptosis. In recent years, the pro-oxidant function of several common dietary carotenoids, including astaxanthin, ß-carotene, fucoxanthin, and lycopene, has been investigated for their effective killing effects on various cancer cell lines. Besides, when carotenoids are delivered with ROS-inducing cytotoxic drugs (e.g., anthracyclines), they can minimize the adverse effects of these drugs on normal cells by acting as antioxidants without interfering with their cytotoxic effects on cancer cells as pro-oxidants. These dynamic actions of carotenoids can optimize oxidative stress in normal cells while enhancing oxidative stress in cancer cells. This review discusses possible mechanisms of carotenoid-triggered ROS production in cancer cells, the activation of pro-apoptotic signaling by ROS, and apoptotic cell death. Moreover, synergistic actions of carotenoids with ROS-inducing anti-cancer drugs are discussed, and research gaps are suggested.

Effect of glucose, soya oil and glutamine on protein expression and mammalian target of rapamycin complex 1 pathway of jejunal crypt enterocytes in weaned piglets.

The present study was conducted to evaluate the effects of glucose, soya oil or glutamine on jejunal morphology, protein metabolism and protein expression of the mammalian target of rapamycin complex 1 (mTORC1) signalling pathway in jejunal villus or crypt compartment of piglets. Forty-two 21 d-weaned piglets were randomly allotted to one of the three isoenergetic diets formulated with glucose, soya oil or glutamine for 28 d. On day 14 or 28, the proteins in crypt enterocytes were analysed with isobaric tags for relative and absolute quantification and proteins involved in mTORC1 signalling pathway in villus or crypt compartment cells were determined by Western blotting. Our results showed no significant differences (P > 0·05) in jejunal morphology among the three treatments on day 14 or 28. The differentially expressed proteins mainly took part in a few network pathways, including antimicrobial or inflammatory response, cell death and survival, digestive system development and function and carbohydrate metabolism. On day 14 or 28, there were higher protein expression of eukaryotic initiation factor-4E binding protein-1 in jejunal crypt compartment of piglets supplemented with glucose or glutamine compared with soya oil. On day 28, higher protein expression of phosphor-mTOR in crypt compartment was observed in piglets supplemented with glucose compared with the soya oil. In conclusion, the isoenergetic glucose, soya oil or glutamine did not affect the jejunal morphology of piglets; however, they had different effects on the protein metabolism in crypt compartment. Compared with soya oil, glucose or glutamine may be better energy supplies for enterocytes in jejunal crypt compartment.

Matricellular Protein CCN5 Reverses Established Cardiac Fibrosis.

BACKGROUND: Cardiac fibrosis (CF) is associated with increased ventricular stiffness and diastolic dysfunction and is an independent predictor of long-term clinical outcomes of patients with heart failure (HF). We previously showed that the matricellular CCN5 protein is cardioprotective via its ability to inhibit CF and preserve cardiac contractility. OBJECTIVES: This study examined the role of CCN5 in human heart failure and tested whether CCN5 can reverse established CF in an experimental model of HF induced by pressure overload. METHODS: Human hearts were obtained from patients with end-stage heart failure. Extensive CF was induced by applying transverse aortic constriction for 8 weeks, which was followed by adeno-associated virus-mediated transfer of CCN5 to the heart. Eight weeks following gene transfer, cellular and molecular effects were examined. RESULTS: Expression of CCN5 was significantly decreased in failing hearts from patients with end-stage heart failure compared to nonfailing hearts. Trichrome staining and myofibroblast content measurements revealed that the established CF had been reversed by CCN5 gene transfer. Anti-CF effects of CCN5 were associated with inhibition of the transforming growth factor beta signaling pathway. CCN5 significantly inhibited endothelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation, which are 2 critical processes for CF progression, both in vivo and in vitro. In addition, CCN5 induced apoptosis in myofibroblasts, but not in cardiomyocytes or fibroblasts, both in vivo and in vitro. CCN5 provoked the intrinsic apoptotic pathway specifically in myofibroblasts, which may have been due the ability of CCN5 to inhibit the activity of NFκB, an antiapoptotic molecule. CONCLUSIONS: CCN5 can reverse established CF by inhibiting the generation of and enhancing apoptosis of myofibroblasts in the myocardium. CCN5 may provide a novel platform for the development of targeted anti-CF therapies.

A learning curve in aortic dissection surgery with the use of cumulative sum analysis.

This study demonstrates the risk adjusted cumulative sum analysis of an individual surgical learning curve for acute type A aortic dissection surgery. Thirty consecutive patients were operated by a single surgeon for acute type A aortic dissection from April 2001 to March 2008. Operative variables, mortality, and major morbidities were analyzed. The learning curve was calculated by cumulative sum analysis. The anticipated 30-day operative mortality rate was 20.2 +/- 12.7% (range, 3.3-56.7%) and the expected 30-day mortality and morbidity rate was 47.0 +/- 13.3% (range, 21.7-70.6%) according to the Japan SCORE calculator. The observed operative and in-hospital mortality rate was 6.67% (two patients), and the observed major postoperative morbidity rate was 10.0% (three patients). Risk-adjusted cumulative sum analysis revealed that no excess deaths occurred beginning at the seventh case and thereafter. The surgeries for acute type A aortic dissection could be performed at the professionally permissive level from the beginning. Risk-adjusted cumulative sum analysis was a useful tool to monitor the performance of the surgical procedure.

Risk-adjusted mortality rate cumulative sum analysis based on the Japan SCORE represents a learning curve in mitral valve reparative surgery.

PURPOSE: We calculated the cumulative sum analysis of an individual surgical learning curve for mitral valve reconstructive surgery to monitor quality control. METHODS: Between April 2003 and March 2009, 25 consecutive patients underwent mitral valve reconstructive surgery for mitral regurgitation (MR). All operations were performed by a single surgeon. We analyzed the operative variables, mortality, and major morbidities and calculated the learning curve, using descriptive statistics and cumulative sum analysis based on the Japan SCORE calculator. RESULTS: In this series, the Japan SCORE calculator predicted a 30-day operative mortality rate of 3.07 ± 3.48 % and a 30-day operative mortality and morbidity rate of 14.9 ± 9.58 %s. In reality, there was no operative or in-hospital death and the major postoperative morbidity rate was 6.0 % (two patients). The risk-adjusted cumulative sum analysis revealed that the learning curve for mortality and morbidity shifted downward below the lower confident interval for all the patients, on completion of mitral valve repair. Coefficient analysis revealed a significant negative correlation between the aortic cross-clamp time and the cardiopulmonary time and case load. There was no correlation between the operation time and the case load. CONCLUSIONS: Routine reconstructive mitral valve surgery for MR can be performed at the professionally permissive level from the beginning, even in low-volume case loads.

t10,c12 conjugated linoleic acid upregulates hepatic de novo lipogenesis and triglyceride synthesis via mTOR pathway activation.

In mice, supplementation of t10,c12 conjugated linoleic acid (CLA) increases liver mass and hepatic steatosis via increasing uptake of fatty acids released from adipose tissues. However, the effects of t10,c12 CLA on hepatic lipid synthesis and the associated mechanisms are largely unknown. Thus, we tested the hypothesis that gut microbiota-producing t10,c12 CLA would induce de novo lipogenesis and triglyceride (TG) synthesis in HepG2 cells, promoting lipid accumulation. It was found that treatment with t10,c12 CLA (100 micrometer) for 72 h increased neutral lipid accumulation via enhanced incorporation of acetate, palmitate, oleate, and 2- deoxyglucose into TG. Furthermore, treatment with t10,c12 CLA led to increased mRNA expression and protein levels of lipogenic genes including SREBP1, ACC1, FASN, ELOVL6, GPAT1, and DGAT1, presenting potential mechanisms by which CLA may increase lipid deposition. Most strikingly, t10,c12 CLA treatment for 3 h increased phosphorylation of mTOR, S6K, and S6. Taken together, gut microbiota-producing t10,c12 CLA activates hepatic de novo lipogenesis and TG synthesis through activation of the mTOR/SREBP1 pathway, with consequent lipid accumulation in HepG2 cells.

Advantage of a more central incision onto left atrium by using ultrasonic scalpel.

Exposure of the mitral valve is of critical importance in mitral valve surgery. The mitral valve is located near the interatrial groove. As we accumulated experience and learned from embryology, we found that a more central left atriotomy was advantageous, and was made possible by interatrial groove dissection using an ultrasonic scalpel. This crucial finding prompted us to report the technique.

Injection of vessel-derived stem cells prevents dilated cardiomyopathy and promotes angiogenesis and endogenous cardiac stem cell proliferation in mdx/utrn-/- but not aged mdx mouse models for duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy. DMD patients lack dystrophin protein and develop skeletal muscle pathology and dilated cardiomyopathy (DCM). Approximately 20% succumb to cardiac involvement. We hypothesized that mesoangioblast stem cells (aorta-derived mesoangioblasts [ADMs]) would restore dystrophin and alleviate or prevent DCM in animal models of DMD. ADMs can be induced to express cardiac markers, including Nkx2.5, cardiac tropomyosin, cardiac troponin I, and α-actinin, and adopt cardiomyocyte morphology. Transplantation of ADMs into the heart of mdx/utrn(-/-) mice prior to development of DCM prevented onset of cardiomyopathy, as measured by echocardiography, and resulted in significantly higher CD31 expression, consistent with new vessel formation. Dystrophin-positive cardiomyocytes and increased proliferation of endogenous Nestin(+) cardiac stem cells were detected in ADM-injected heart. Nestin(+) striated cells were also detected in four of five mdx/utrn(-/-) hearts injected with ADMs. In contrast, when ADMs were injected into the heart of aged mdx mice with advanced fibrosis, no functional improvement was detected by echocardiography. Instead, ADMs exacerbated some features of DCM. No dystrophin protein, increase in CD31 expression, or increase in Nestin(+) cell proliferation was detected following ADM injection in aged mdx heart. Dystrophin was observed following transplantation of ADMs into the hearts of young mdx mice, however, suggesting that pathology in aged mdx heart may alter the fate of donor stem cells. In summary, ADMs delay or prevent development of DCM in dystrophin-deficient heart, but timing of stem cell transplantation may be critical for achieving benefit with cell therapy in DMD cardiac muscle.

A learning curve in Bentall and De Bono procedure with the use of the risk-adjusted cumulative sum analysis based on the Japan SCORE.

OBJECTIVE: The risk-adjusted cumulative sum analysis of an individual surgical learning curve for the Bentall and De Bono procedure on aortic root pathologies was used to monitor and enhance quality control. METHODS: From April 2004 to March 2009, 20 consecutive patients were operated upon by a single surgeon for aortic root pathologies by means of the Bentall and De Bono procedure. Operative variables, mortality, and major morbidities were analyzed. The learning curve was calculated using descriptive statistics and cumulative sum failure observed minus expected failure rate derived from the Japan SCORE calculator. RESULTS: In this series, the Japan SCORE calculator expected 3.91% ± 5.14% of 30-day operative mortality rate and 16.74 ± 13.47% of 30-day operative mortality and morbidity. In reality, there was no operative and in-hospital death. Major postoperative morbidity rate was 15.0% (3 patients). The risk-adjusted cumulative sum analysis revealed that the learning curve of mortality was downward below the lower 95% confidence interval throughout all the patients and that of morbidity was upward till the seventh case and remained downward thereafter. The polynomial approximation coefficient analysis revealed a significant negative correlation between aortic cross-clamp time, cardiopulmonary time, and operation time and case load. CONCLUSIONS: The Bentall and De Bono procedure for aortic root pathologies was performed at the professionally permissive level from the beginning, even in a low-volume environment. It showed one good example of a learning curve. The risk-adjusted cumulative sum analysis based on the Japan SCORE was a very useful tool for monitoring the performance.

Midterm results of surgical box line ablation for atrial fibrillation by bipolar radiofrequency.

OBJECTIVES: The surgical box lesion isolation of pulmonary veins and left atrium is recently reported to be superior to the conventional Cox maze IV procedure. The aim of this study is to investigate the midterm results of surgical box lesion ablation with the use of the bipolar radiofrequency energy performed at our institution. METHODS: From April 2004 to December 2008, 35 patients underwent the surgical box lesion ablation using bipolar radiofrequency and were followed for mean 31 months ranging from 3 to 58 months. RESULTS: There was no operative mortality. One patient (2.86%) needed electric cardioversion before discharge. One patient (2.86%) needed pacemaker implantation. At discharge, all patients were in normal sinus rhythm. During the follow-up period, the rate of sinus rhythm maintenance was 100%, the rate of freedom from antiarrhythmic medication was 42.9%, and the rate of freedom from thromboembolic episodes was 100%. CONCLUSIONS: The surgical box lesion ablation was a safe and effective procedure to terminate atrial fibrillation and restore sinus rhythm.

Successful repair of atrial fibrillation by surgical ablation in a patient with persistent left superior vena cava and mitral stenosis.

We recently cared for a woman who had mitral stenosis, atrial fibrillation, absent right superior vena cava, and persistent left superior vena cava. She underwent mitral valve replacement and surgical ablation of the pulmonary vein, and conjunction of the coronary sinus and left superior vena cava. Her atrial fibrillation was cured and successfully restored to sinus rhythm postoperatively.

Hemoptysis as a presenting symptom of a distal aortic arch aneurysm and its repair via an L-shaped thoracotomy.

A 61-year-old man presented with multiple episodes of hemoptysis. A computed tomography scan revealed a 70-mm saccular aneurysm of the distal aortic arch. During a surgical repair via a midline sternotomy and a left thoracotomy, a saccular aneurysm was found to protrude into the lung, which had chronically healed. The patient underwent replacement of the Dacron graft, and he recovered well postoperatively. This experience prompted us to report the findings of this unique case.

Intraoperative heart rate variability of a cardiac surgeon himself in coronary artery bypass grafting surgery.

The mental strain of a cardiac surgeon may differ when he performs coronary surgery from and when he only assists in performing coronary surgery. In 50 selected cases of on-pump heart arrested coronary artery bypass grafting (CABG), an attending-consultant surgeon performed 30 procedures of CABG (Group A) and an attending-consultant surgeon supervised the remaining 20 cases of CABG performed by two resident surgeons (Group B). Intraoperative Holter electrocardiograms of the attending-consultant surgeon were recorded and analyzed for heart rate variability (HRV). In Group A, the ratio of low frequency to high frequency was at a peak in the beginning of the operation and gradually decreased toward the end of the operation. In Group B, the ratio of low frequency to high frequency was at a peak in the phase of aortic cross-clamp, coronary anastomosis, and unclamping. When an attending-consultant surgeon performed the operation himself, the most anxious part of the operation was at the beginning and thereafter the level of anxiety gradually declined. In contrast, when he assisted a resident, the highest level of anxiety was when the aortic cross-clamp was in place and out of place and during the coronary anastomosis.

Asymptomatic severe carotid stenosis undergoing staged carotid artery stent and coronary artery bypass grafting: decisive role of brain single photon emission computed tomography.

Effort angina of a 70-year-old man was diagnosed as due to triple coronary vessel disease, and he was scheduled to undergo coronary artery bypass surgery. Preoperative carotid duplex scan revealed more than 75% stenosis of the right internal carotid artery, which was functionally proven to be significantly ischemic on brain single photon emission computed tomography. Although he was neurologically asymptomatic, we chose staged surgery for fear of stroke during coronary artery bypass surgery. He had successful carotid artery stenting first by neurosurgeons; then, 2 months later he underwent uneventful coronary artery bypass surgery. This experience prompted us to report the case.