[Reports of 12 Cases of Stanford Type A Acute Aortic Dissection Emergent Surgery for Jehovah's Witnesses patients].

The Jehovah's Witnesses (JW) is well known for declining blood transfusions. Especially, cardiovascular surgery on JW poses unique challenges. We herein report 12 JW emergent cases of Stanford type A acute aortic dissection which underwent graft replacement between 2003 and 2019. Graft replacement of ascending aorta was performed in all cases. Operative time and anesthetic time were 344±100 and 396±109 minutes respectively. The mean intraoperative hemoglobin nadir was 4.9±1.2 g/dl. The postoperative hemoglobin nadir was 6.3 ±2.4 g/dl. There were 2 deaths within 24 hours after surgery. We did not transfuse any packed red blood cells, fresh frozen plasma or platelets for JW patients of Stanford type A acute aortic dissection surgery.

Acorbine, a Corbicula japonica-derived tripeptide containing non-proteinogenic amino acids, suppresses ethanol-induced liver injury.

Since ancient times, Corbicula extract has been believed in Japan to have hepatoprotective effects, but it remains unclear whether these claims are true, and if so, which component is responsible for hepatoprotection. In this study, we showed that Corbicula extract exerted a protective effect against liver damage. Recent work identified acorbine (ß-alanyl-ornithyl-ornithine), a novel tripeptide containing non-proteinogenic amino acids, in the extract of Corbicula japonica. Synthesized acorbine cured alcohol-induced liver damage in mice. In addition, acorbine purified from Corbicula extract exerted a protective effect against alcohol-induced hepatotoxicity in a culture liver model derived from mouse ES/iPS cells. Thus, acorbine is one of the components of Corbicula extract that protects hepatocytes against ethanol-induced death.

Beneficial effects of restrictive annuloplasty on subvalvular geometry in patients with functional mitral regurgitation and advanced cardiomyopathy.

OBJECTIVES: The effects of restrictive mitral annuloplasty (RMA) on subvalvular geometry remains unknown. We evaluated changes in left ventricular (LV) function, severity of mitral regurgitation (MR), and leaflet tethering parameters after RMA and clarified their associations. METHODS: In 44 patients with clinically relevant functional MR who underwent RMA, distances between papillary muscle (PM) tips and anterior mitral annulus (PM tethering distance), leaflet angles relative to lines connecting annuli, and interpapillary muscle distance (IPMD) were serially quantified. RESULTS: One month after surgery, LV function and MR severity improved with decreased anterior (34 ± 5 to 30 ± 4 mm) and posterior PM tethering distance (37 ± 4 to 32 ± 4 mm), anterior leaflet angle (32 ± 8° to 22 ± 7°), and IPMD (31 ± 6 to 25 ± 5 mm), whereas these variables remained abnormal and posterior leaflet angle increased (34 ± 8° to 48 ± 14°; P < .01 for all). During follow-up (66 ± 37 months), these effects were maintained in 33 patients without MR recurrence, whereas 11 with it showed worsened tethering with less LV function recovery. Multiple linear regression analyses identified that change in MR severity from baseline to 12-month examination independently associated with corresponding change in IPMD (parameter estimate of 0.100 with standard error of 0.039; P = .019) and that in posterior PM tethering distance (parameter estimate of -0.104 with standard error of 0.045; P = .035), whereas not with change in posterior-leaflet angle. The IPMD change was independently associated with change in LV end-systolic dimension (parameter estimate of 0.299 with standard error of 0.110; P = .013). CONCLUSIONS: The RMA procedure partially relieved leaflet tethering, evidenced by decreased tethering distances and IPMD; the latter was the main determinant of MR. These beneficial effects might be mainly attributed to post-RMA reverse LV remodeling, potentially offsetting the negative effect of augmented posterior leaflet angle in selected patients.

Dilated left atrium as a predictor of late outcome after pulmonary vein isolation concomitant with aortic valve replacement and/or coronary artery bypass grafting†.

OBJECTIVES: Left atrial (LA) dimension can predict atrial fibrillation (AF) recurrence after catheter-based or surgical ablation. Pulmonary vein isolation (PVI) may be a surgical option during aortic valve replacement (AVR) and/or coronary artery bypass grafting (CABG), though consensus regarding patient selection and late outcome is lacking. METHODS: We studied 160 patients (mean age 70 ± 9 years) with paroxysmal AF who underwent radiofrequency-based PVI during AVR and/or CABG, and were followed up postoperatively for at least 6 months. Mean preoperative LA dimension was 44 ± 7 mm. Serial echocardiography was performed to evaluate left ventricular (LV) and LA dimensions, E/e', estimated systolic pulmonary artery (PA) pressure and degree of valvular regurgitation. Follow-up was completed with a mean duration of 47 ± 25 months. RESULTS: At the latest follow-up, 133 patients (83%) remained in sinus rhythm. Preoperative LA dimension was independently associated with increased risk of AF recurrence at 6 months after surgery [adjusted odds ratio 1.3 per 1-mm increase in LA dimension, 95% confidence interval (CI) 1.1-1.6, P < 0.001]. Receiver-operating characteristic curve analysis demonstrated an optimal cut-off value for preoperative LA dimension of 45 mm to predict sinus rhythm restoration (98% for <45 mm vs 55% for ≥45 mm, P < 0.001). Patients with LA dimension ≥45 mm had a significantly lower 5-year survival rate (62 ± 7 vs 82 ± 7%, P = 0.025) and freedom from adverse events defined as cerebral infarction/haemorrhage, admission for heart failure, catheter ablation and permanent pacemaker implantation (58 ± 7 vs 91 ± 4%, P < 0.001). Multivariate analysis showed that preoperative LA dimension ≥45 mm was independently associated with adverse events (adjusted hazards ratio 2.4, 95% CI 1.2-5.1, P = 0.019). Serial echocardiography demonstrated improvement in LV systolic function irrespective of LA dimension, whereas patients with LA dimension ≥45 mm showed less improvement in LA dimension and systolic PA pressure (interaction effect P < 0.001) and persistent higher E/e' (group effect P < 0.001), along with aggravated tricuspid regurgitation. CONCLUSIONS: In patients with paroxysmal AF related to aortic valve disease and/or coronary artery disease, a dilated left atrium (≥45 mm) was associated with inferior AF- and event-free survival after PVI, accompanied by persistent abnormalities in cardiac and haemodynamic function. These findings may assist patient selection for PVI during AVR and/or CABG.

Total synthesis of pectenotoxin-2.

Pectenotoxin-2 (PTX2) is a shellfish toxin and has a non-anomeric spiroacetal, which is not stabilized by an anomeric effect. The selective construction of the non-anomeric spiroacetal has been a major problem in the synthesis of PTX2. Described herein is the stereoselective total synthesis of PTX2 via the isomerization of anomeric spiroacetal pectenotoxin-2b (PTX2b). The synthesis of PTX2b was achieved by a simple process including sulfone-mediated assembly of spirocyclic and bicyclic acetals and subsequent macrocyclization by ring-closing olefin metathesis. Finally, the selective construction of PTX2 was accomplished by the early termination of a dynamic transition process to equilibrium in the acid-catalyzed isomerization of anomeric PTX2b. [6,6]-Spiroacetal pectenotoxin-2c (PTX2c) was also synthesized from PTX2b. The cytotoxicity assay of the synthetic compounds against HepG2 and Caco2 cancer cells showed a potency of the order: PTX2≫PTX2b>PTX2c.

p-terphenyl derivatives from the mushroom Thelephora aurantiotincta suppress the proliferation of human hepatocellular carcinoma cells via iron chelation.

A novel 2',3'-dihydroxy-p-terphenyl derivative, thelephantin O (TO), which has cancer-selective cytotoxicity, was isolated. This study investigated the underlying basis of the cytotoxicity of 2',3'-dihydroxy-p-terphenyl compounds in view of their ability to chelate metal ions. FeCl(2) significantly reduced TO-induced cytotoxicity, whereas several other salts of transition metals and alkaline-earth metals did not. A structure-activity relationship study using newly synthesized p-terphenyl derivatives revealed that o-dihydroxy substitution of the central benzene ring was necessary for both the cytotoxicity and Fe(2+) chelation of the compounds. Real-time PCR array and cell cycle analysis revealed that the TO-induced cytotoxicity was attributed to cell cycle arrest at the G1 phase via well-known cell cycle-mediated genes. The TO-induced changes in the cell cycle and gene expression were completely reversed by the addition of FeCl(2). Thus, it was concluded that Fe(2+) chelation occurs upstream in the pivotal pathway of 2',3'-dihydroxy-p-terphenyl-induced inhibition of cancer cell proliferation.

Analysis of the sternum for sternal closure with bioabsorbable sternal pins.

PURPOSE: Poly-L-lactide sternal pins have been reported to be beneficial for sternal closure. However, we sometimes experience a small sternum, and the size characteristics of the sternum have not been fully investigated. We analyzed size features of the sternum to determine the optimal size of sternal pin for sternal closure. METHODS: Chest computed tomography scans were preoperatively obtained in 144 patients undergoing major cardiovascular surgery. We reviewed all scans at the level of the sternum, and measured the width of the bone marrow of the sternum on each computed tomography slice. RESULTS: The mean values of bone marrow width of the sternal manubrium and body of male patients were significantly higher than those of females (manubrium: 38.6 ± 3.9 mm in males, 34.5 ± 3.3 mm in females, p < 0.0001; body: 23.4 ± 3.7 mm in males, 20.8 ± 2.8 mm in females, p < 0.0001). There was no correlation between the bone marrow width of the sternal body and body surface area in either males or females (males: r = 0.08, p = 0.45, females: r = 0.08, p = 0.58). CONCLUSION: To select the appropriate size of sternal pin, preoperative measurement of the bone marrow width of the sternum is recommended because it cannot be predicted from body size.

Total synthesis of thelephantin O, vialinin A/terrestrin A, and terrestrins B-D.

The first total synthesis of natural, unsymmetrical 2',3'-diacyloxy-p-terphenyls, thelephantin O (1) and terrestrins C and D (2 and 3, respectively), was achieved via a practical route which was also applicable to the synthesis of the symmetrical diesters vialinin A/terrestrin A (4) and terrestrin B (5). Compounds 1-5 exhibited cytotoxicity against cancer cells (HepG2 and Caco2) with IC(50) values of 13.6-26.7 µmol/L.

Restrictive mitral annuloplasty with or without surgical ventricular restoration in ischemic dilated cardiomyopathy with severe mitral regurgitation.

BACKGROUND: We assessed changes in left ventricular (LV) volume and function and in regional myocardial wall stress in noninfarcted segments after restrictive mitral annuloplasty (RMA) with or without surgical ventricular restoration (SVR). METHODS AND RESULTS: Thirty-nine patients with ischemic cardiomyopathy (ejection fraction ≤ 0.35) and severe mitral regurgitation (≥ 3) were studied before and 2.8 months after surgery with cine-angiographic multidetector computed tomography (cine-MDCT). Eighteen underwent RMA alone (RMA group) and 21 underwent RMA and SVR (RMA+SVR group). In addition to measuring conventional parameters (LV end-diastolic volume index [LVEDVI], LV end-systolic volume index [LVESVI], and LV ejection fraction), we evaluated the regional circumferential end-systolic wall stress and mean circumferential fiber shortening in both the basal and mid-LV regions using 3-dimensional cine-MDCT images. LV end-diastolic and end-systolic volume indexes were significantly greater in the RMA+SVR group than in the RMA group preoperatively, but these values did not differ significantly postoperatively. LV end-diastolic and end-systolic volume indexes decreased significantly, by 21% and 27% after RMA and by 35% and 42% after RMA and SVR, and the percent reductions in LV end-diastolic and end-systolic volume indexes were significantly larger in the RMA+SVR group. Regional end-systolic wall stress decreased and circumferential fiber shortening increased significantly in the noninfarcted regions after RMA with or without SVR. CONCLUSIONS: RMA plus SVR showed a potentially greater reduction of LV end-diastolic and end-systolic volume indexes than RMA alone. In selected patients with more advanced LV remodeling, concomitant SVR may favorably affect the LV reverse-remodeling process induced by RMA.

Anticancer activities of thelephantin O and vialinin A isolated from Thelephora aurantiotincta.

Thelephora aurantiotincta is an edible mushroom belonging to the genus Thelephora; it grows in symbiosis with pine trees. Recently, phytochemical investigations have revealed that the genus Thelephora is an abundant source of p-terphenyl derivatives. However, their bioactivity has not yet been well characterized. In screening for natural materials with anticancer activity, a T. aurantiotincta ethanol extract (TAE) was found to decrease cell viability in human hepatocellular carcinoma cells (HepG2). In this study, a new p-terphenyl derivative, thelephantin O, and a known compound, vialinin A, were isolated as the principal bioactive components of TAE. These compounds decreased cell viability in HepG2 and human colonic carcinoma cells (Caco2), but not in noncancerous human hepatocytes. This is the first report of the isolation from T. aurantiotincta of selective cytotoxic agents against cancer cells.

Novel software package for quantifying local circumferential myocardial stress.

Local myocardial stress is an important index of ventricular loading conditions. We developed a novel software package to provide estimation of local circumferential stress in the entire left ventricle (LV) based on Janz's method using contemporary LV imaging techniques. The aim of this study was to confirm the validity of our novel software by comparing local circumferential stress (local σ) with global equatorial stress (global σ) values. We acquired 30° right anterior oblique LVG images in 74 patients (aortic regurgitation; n = 48, aortic stenosis; n = 26) and 26 healthy subjects, then analyzed them using Janz's method to elucidate local σ in segment #12 (mid-anterolateral) based on AHA/ASE segmentation criteria. Global σ was obtained using Mirsky's formula. A highly significant correlation was found between local σ and global σ (r = 0.99, p < 0.001). Bland-Altman analysis also showed good agreement between the two methods (mean bias 2.4 kdyn/cm(2), limits of agreement 9.3 kdyn/cm(2)/-4.6 kdyn/cm(2)). There were good correlations for both intra-observer and inter-observer agreement. Our novel software package was shown useful to assess local circumferential stress with contemporary cardiovascular imaging techniques.

A simplified echocardiographic measurements of direct effects of restrictive annuloplasty on mitral valve geometry.

OBJECTIVE: The purpose of this study was to evaluate the direct effects of restrictive mitral annuloplasty on mitral valve geometry. METHODS: We studied 23 patients (mean age: 63 ± 5 years) with functional mitral regurgitation (moderate to severe) and advanced cardiomyopathy (ejection fraction: 25 ± 8%) with ischemic (n = 15) or nonischemic (n = 8) conditions, who underwent restrictive annuloplasty. We determined annular septal-lateral diameter, tenting height, tenting area, vertical length of coaptation of the mitral leaflets (coaptation length), and ratio of coaptation length to septal-lateral diameter (coaptation length index) at end-systole, before and after surgery, using transthoracic echocardiography. RESULTS: Annular septal-lateral diameter, tenting height, and tenting area were significantly decreased (34 ± 7 to 20 ± 5 mm, P < 0.05; 9 ± 4 to 5 ± 2 mm, P < 0.05; 210 ± 120 to 80 ± 50 mm(2) , P < 0.05, respectively), whereas coaptation length and coaptation length index were significantly increased (3.4 ± 1.3 to 6.5 ± 2.9 mm, P < 0.05; 0.11 ± 0.06 to 0.33 ± 0.15, P < 0.05, respectively). Spearman's rank correlation analysis revealed that these five variables had a statistically significant correlation with the degree of mitral regurgitation. Furthermore, stepwise regression analysis showed that coaptation length index, in contrast to coaptation length, was the most important correlate with the degree of mitral regurgitation. CONCLUSION: Our simplified parameters were useful for quantitative and geometrical descriptions of mitral valve geometry, and may also provide important information for developing a surgical strategy for functional mitral regurgitation.

Mechanism of beneficial effects of restrictive mitral annuloplasty in patients with dilated cardiomyopathy and functional mitral regurgitation.

BACKGROUND: Restrictive mitral annuloplasty (RMA) often leads to reverse left ventricular (LV) remodeling in patients with advanced cardiomyopathy and functional mitral regurgitation. However, the mechanism responsible for its favorable effects on LV ejection performance has been poorly understood. We evaluated systolic wall stress using cineangiographic multidetector computed tomography (MDCT) and our developed software system to assess stress-shortening relations before and after RMA. METHODS AND RESULTS: Twenty-four patients with dilated cardiomyopathy underwent 64-row MDCT before and 2 months after RMA. All patients underwent stringent downsizing annuloplasty with a semirigid complete ring. Reconstructed images were used to calculate LV end-diastolic index (EDVI) and end-systolic volume index (ESVI), LV ejection fraction, and regional and global end-systolic wall stress (ESS). After RMA, LVEDVI and LVESVI decreased from 151±52 to 131±53 mL/m(2) (P=0.0001) and from 114±48 to 92±50 mL/m(2) (P=0.0001), respectively. Global ESS decreased from 157±43 to 139±50 kdyne/cm(2) (P=0.01), and LV ejection fraction improved from 27±8.0 to 33±13% (P=0.0007). There were significant correlations between change in LVEDVI and LVESVI (r=0.88, P<0.0001) and change in LVESVI and global ESS (r=0.68, P=0.0002). Moreover, the magnitude of increase in LV ejection fraction significantly correlated with the degree of reduction in global ESS (r=-0.61, P=0.002). Patients without significant reverse LV remodeling had significantly higher preoperative and postoperative global ESS than those with it. CONCLUSIONS: Our study suggests that decrease in afterload after reduction in volume overload was responsible for postoperative reverse LV remodeling process after RMA.

Assessment of regional myocardial wall stress before and after surgical correction of functional ischaemic mitral regurgitation using multidetector computed tomography and novel software system.

OBJECTIVES: The objective of this study was to assess changes in left ventricular (LV) volume, function and regional myocardial wall stress in non-infarcted segments following restrictive mitral annuloplasty (RMA) in patients with ischaemic cardiomyopathy (ICM) and severe functional mitral regurgitation (MR). PATIENTS AND METHODS: Twenty-two patients with ICM (ejection fraction <35%) and severe MR were investigated before and 3 months after RMA using cine-angiographic multidetector row computed tomography (cine-MDCT). For comparative purposes, 38 normal subjects were also studied. Cine-MDCT LV images were reconstructed in a cardiac cycle and regional circumferential wall stress (end-systolic stress (ESS)) was evaluated from the LV end-systolic image using Janz's method. The ESS was determined in six basal and six mid-LV segments of the ventricle based on AHA/ASE criteria. Five apical infarcted segments were not analysed. Mean circumferential fibre shortening (CFS) in both basal and mid-LV regions was determined as a parameter of regional systolic performance. RESULTS: Left ventricular end-diastolic volume (index) (LVEDVI) and left ventricular end-systolic volume (index) (LVESVI) decreased significantly and left ventricular ejection fraction (LVEF) increased after surgery. Neither end-systolic nor end-diastolic sphericity index changed significantly after surgery. Regional ESS significantly decreased in both basal and mid-LV regions after surgery. There was a significant inverse correlation between the change in average value of regional ESS and magnitude of increase in mean CFS of the mid-LV region (r=-0.67, p=0.0018). Postoperative reduction in ESS in the mid-LV region was also correlated with improvement in global EF (r=-0.72, p<0.01). CONCLUSION: The present cine-MDCT may be useful for assessing regional myocardial stress in patients with ICM. We found that RMA could reduce both end-diastolic and end-systolic volume leading to reduction in regional systolic wall stress, which resulted in improved ejection performance of non-infarcted myocardium in patients with functional MR and ICM.

Serious acute coronary thrombosis associated with heparin-induced thrombocytopenia in off-pump coronary artery bypass grafting.

A 72-year-old female underwent off-pump coronary bypass grafting one month after heparin exposure. Immediately after protamine administration, she developed hypotension due to acute graft failure. Grafting to left anterior descending branch was revised under intra-aortic balloon pump insertion and she was transferred to intensive care unit under stable hemodynamic condition. However, she gradually developed low cardiac output syndrome and echocardiography showed new onset of myocardial infarction. Coronary angiography on the first postoperative day revealed diffuse serious coronary thrombosis involving all grafts and grafted native coronary arteries. Emergent percutaneous coronary intervention (PCI) was performed for native vessels. Laboratory examination revealed severe progressive thrombocytopenia and she was clinically diagnosed as heparin-induced thrombocytopenia (HIT). After cessation of all heparins and alternative anticoagulation with argatroban, thrombocytopenia was improved and some of occluded grafts were recanalized. She was discharged on the 51st postoperative day. Acute graft thrombosis, especially caused by HIT, is a serious complication, which sometimes results in mortality. This is a successful case treated by PCI followed by an alternative anticoagulation.

Redo arch aneurysm repair for new-onset aortic arch dissection following ascending aortic surgery: long elephant trunk technique combined with trifurcate-branched graft.

Reoperative surgical intervention for a new-onset aortic arch dissection following a Bentall procedure or graft replacement for the ascending aorta is often difficult, especially in elderly patients. Herein, we report a re-do arch replacement method using a trifurcate-branched graft and long elephant trunk anastomosis at the composite root graft on the ascending aorta. The present technique is feasible as an alternative for new-onset or residual aortic arch aneurysm, as well as dissection following an operation for the ascending aorta.

Chronic ingestion of apple pectin can enhance the absorption of quercetin.

The effect of apple pectin (AP) on quercetin and rutin bioavailability was investigated. Rats received a basal (control) or AP-containing diet for 6 weeks followed by orally administered quercetin or rutin. With quercetin administration, the maximum concentration and area under the curve of concentration-time from 0 to 24 h for the sum of quercetin metabolites in the plasma were significantly higher in AP-fed rats than in the control group. However, AP did not significantly affect rutin bioavailability. The crypt depth of the jejunum and ileum and the villus thickness of the ileum of AP-fed rats were significantly greater than those of control rats. These results demonstrate that chronic AP ingestion enhances intestinal absorption of quercetin. This increase in quercetin absorption might be attributed to alteration of the absorptive capacity of the small intestine through AP-induced improvement of its morphological and physiological properties.

Use of quantitative analysis of remote myocardial fibrosis with delayed-enhancement magnetic resonance imaging to predict outcomes after surgical ventricular restoration for ischemic cardiomyopathy.

OBJECTIVE: Preserved myocardial function remote from surgical site is crucial for good outcome after surgical ventricular restoration in ischemic cardiomyopathy. We hypothesized that left ventricular scarring untouched by operation would negatively affect postoperative outcome. METHODS: In 15 consecutive patients (mean age 61 +/- 12 years, mean left ventricular ejection fraction 20% +/- 7.5%), left ventricular assessments by magnetic resonance imaging and right heart catheterization were performed before and after operation. Left ventricular basal scarring remote from surgical exclusion site was quantified from hyperenhancement area on preoperative delayed-enhancement magnetic resonance imaging as percentage of fibrosis (total infarct size relative to ventricular mass). RESULTS: Calculated percentage of fibrosis varied from 0% to 29.9% (mean 12% +/- 9.6%). Percentage of fibrosis linearly correlated with significantly worse postoperative hemodynamic variables and left ventricular function recovery: left ventricular ejection fraction (P = .0005, R = -0.79), left ventricular end-systolic volume index (P = .05, R = 0.51), mean pulmonary arterial pressure (P = .004, R = 0.70), pulmonary capillary wedge pressure (P = .009, R = 0.65), and cardiac index (P = .005, R = -0.69). At mean 30-month follow-up, 4 patients with recurrent heart failure had significantly greater percentage of fibrosis than did those without recurrence (19% +/- 8.2% vs 8.8% +/- 8.6%, P = .04). CONCLUSION: Amount of myocardial scarring at left ventricular base affected postoperative left ventricular function and hemodynamic improvements. Preoperative quantitative assessment of remote myocardial status with delayed-enhancement magnetic resonance imaging may predict outcomes for patients undergoing surgical ventricular restoration.