Robot-assisted endoscopic removal of a huge tricuspid valve myxoma: case report.

BACKGROUND: Cardiac myxoma is the most common benign cardiac tumor. Its tremendous size and fragile character severely bother the surgeons. Several minimal invasive approaches had been applied for radical tumor excision. The wound was forcibly enlarged for en-bloc specimen removal and prevention of debris sputtering. CASE PRESENTATION: We reported a case of huge tricuspid valve (TV) myxoma managed by robot-assisted endoscopic tumor resection and TV repair, with initial presentation of worsening shortness of breath for two months. The tumor was downsized with a morcellator and removed through a keyhole wound (1.1 cm in diameter). The patient recovered uneventfully and was discharged after four days. CONCLUSIONS: With the first morcellator application, this might be the smallest surgical wound reported after the removal of a huge cardiac myxoma. The ICU and hospital stays were shortened. This might be effectively applied to further minimally invasive surgeries for cardiac tumor excision.

Right ventricular reserve post mitral valve repair is associated with heart failure hospitalization.

Right ventricular impairment is a predictor of cardiovascular outcomes in patients with degenerative mitral regurgitation. However, the time course of right ventricular functional changes post-surgical mitral valve repair remains largely unknown. Herein, using right ventricular-focused echocardiography, we aimed to investigate right ventricular reserve and its impact on hospitalization for heart failure after mitral valve repair. In this prospective study, we enrolled 108 patients scheduled to undergo surgical repair of degenerative mitral regurgitation. Echocardiography, including right ventricular strain analysis, was performed prior to, and one month and six months post mitral valve repair. Right ventricular strain that improved one month post-surgery was defined as reserved right ventricular. In addition, any cardiovascular outcomes comprising heart failure that required admission were recorded. The median follow-up duration is 31 months. Despite a significant improvement in mitral valve regurgitant volume post-operatively, left ventricular ejection fraction (LVEF) at six months was similar to LVEF at baseline. There was a transient decrease in LV longitudinal strain at one month that was recovered six months post mitral valve repair. Regarding the right ventricular, in contrast with conventional right ventricular parameters, including right ventricular tissue Doppler S', fractional area change and tricuspid annular plane systolic excursion (TAPSE), only resolution of right ventricular strain at one month predicted the subsequent myocardial recovery. Furthermore, patients with reserved right ventricular had a lower risk of hospitalization for heart failure compared to those with non-reserved right ventricular. Collectively, the early resolution of right ventricular strain is associated with the improvement in right ventricular function (measured by TAPSE) and in heart failure hospitalization in patients who had undergone surgical mitral valve repair for degenerative mitral regurgitation.

Influence of warfarin on cardiac and cerebrovascular events following bioprosthetic aortic valve replacement: A nationwide cohort study.

OBJECTIVE: The need for anticoagulation treatment following bioprosthetic aortic valve replacement remains controversial. We investigated the associations of warfarin treatment with the risks of major adverse cardiac and cerebrovascular events, including mortality, bleeding incidents, and reoperation requirement after bioprosthetic aortic valve replacement surgery. METHODS: We identified 1086 patients who received first bioprosthetic aortic valve replacement between 2001 and 2010 using Taiwan's National Health Insurance Database. Patients were excluded for prior use of warfarin, warfarin use for >3 months, dual valve procedures, prior valve surgeries, or concomitant surgeries. Enrolled patients were divided into 2 groups according to whether they were warfarin-naïve or received warfarin for <3 months postsurgery. After propensity score matching, 282 patients not receiving warfarin were matched to 282 patients receiving warfarin for <3 months. Patients were followed-up for minimum 36 months. RESULTS: Patients receiving warfarin were younger and showed less frequent kidney disease than those who did not use warfarin. The warfarin group demonstrated a gross decrease in major adverse cardiac and cerebrovascular events. Patients receiving warfarin for <30 days were at an even lower risk for major adverse cardiac and cerebrovascular events than those treated for ≥30 days. No significant difference in bleeding or reoperation risk was observed between warfarin users and warfarin nonusers. Similar findings remained after propensity-score matching but the benefit of short-term warfarin use diminished in a younger population. CONCLUSIONS: Short-term use of postoperative warfarin (especially <30 days) following bioprosthetic aortic valve replacement may be associated with a reduction in MACCE compared with nonuse.

Transcatheter atrioventricular valve-in-valve implantation for Fontan circulation and dextrocardia.

Transcatheter heart valve-in-valve implantation in failed surgical bioprosthetic valves has shown promising outcomes, prompting the stepwise expansion of their applications in different clinical scenarios. Recently, there is increased interest in valve-in-valve techniques for the treatment of patients with complex congenital heart disease. Herein, we report a case of successful transapical transcatheter atrioventricular valve-in-valve implantation in a patient with Fontan circulation and dextrocardia. The patient was previously treated with total cavopulmonary connection and atrioventricular valve replacement with recurrent prosthesis dysfunction.

Robotic mitral valve replacements with bioprosthetic valves in 52 patients: experience from a tertiary referral hospital.

OBJECTIVES: Robotic mitral valve replacement (MVR) emerged in the late 1990s as an alternative approach to conventional sternotomy. With the increased use of bioprosthetic valves worldwide and strong patient desire for minimally invasive procedures, the safety and feasibility of robotic MVRs with bioprosthetic valves require investigation. METHODS: Between January 2013 and May 2017, 52 consecutive patients underwent robotic MVRs using the da Vinci Si surgical system (Intuitive Surgical Inc., Sunnyvale, CA, USA). Their mean age was 55.1 ± 13.8 years, and mean EuroSCORE II was 2.25% ± 1.25%. Among the enrolled patients, 32 (61.5%) patients presented with preoperative atrial fibrillation, 6 (11.5%) patients had experienced embolic stroke and 5 (9.6%) patients had undergone previous cardiac surgery. The operations were performed using cardiopulmonary bypass (CPB) under an arrested heart status. RESULTS: Five porcine valves and 47 bovine valves were implanted. A total of 38 (73.1%) patients received concomitant cardiac procedures, including 26 Cox-maze IV procedures, 12 tricuspid valve repairs and 5 atrial septal defect repairs. The mean aortic cross-clamp and CPB times were 141.3 ± 34.3 min and 217.1 ± 42.0 min, respectively. There was no operative mortality. During the mean follow-up of 29 ± 15 months, no prosthesis degeneration was noted. The average left atrial dimension exhibited a significant decrease from 51.4 ± 11.5 mm to 42.6 ± 10.1 mm. CONCLUSIONS: Robotic MVR with bioprosthetic valves is safe, feasible and reproducible. Mid-term results are encouraging. Both aortic cross-clamp and CPB times can be improved with experience.

Robotic totally endoscopic coronary artery bypass for isolated ostial stenosis of the left coronary artery.

Isolated ostial stenosis (IOS) is a rare disease that encroaches on aorto-coronary junction of uncertain etiology. All distal coronary vessels present normally. IOS occurs predominantly in premenopausal young women with few risk factors for atherosclerotic disease. Here, we report a 40-year-old woman who had experienced crescendo angina for 4 months. Surgical revascularization was achieved by robotic totally endoscopic coronary artery bypass (TECAB) with left internal thoracic artery (LITA) graft. She resumed her daily tasks without difficulties 1 week after the operation. Postoperative computed tomographic angiography disclosed good opacification of the LITA graft and distal runoff. Robotic TECAB is a potentially feasible alternative for IOS patients, particularly in premenopausal young woman, with obvious benefits of cosmetic appearance and speedy recovery.

Totally Endoscopic Coronary Artery Bypass for Anomalous Origin of Right Coronary Artery.

Anomalous origin of the right coronary artery (ARCA) from the left Valsalva sinus is a rare but known cause of sudden cardiac death. Surgical revascularization techniques include coronary artery bypass grafting, unroofing, and reimplantation. We report 4 patients who underwent robot-assisted totally endoscopic coronary artery bypass (TECAB) for ARCA as an alternative surgical option. In 3 patients, a single aortocoronary saphenous vein bypass was performed, and in 1 patient the right internal mammary artery was used. All grafts are patent as shown by computed tomographic angiography or cardiac catheterization. We claim that totally endoscopic coronary artery bypass is feasible and safe for anomalous origin of the right coronary artery.

Beneficial Effect of Astragaloside on Alzheimer's Disease Condition Using Cultured Primary Cortical Cells Under ß-amyloid Exposure.

ß-amyloid (Aß)-mediated neuronal apoptosis contributes to the pathogenesis of Alzheimer's disease (AD). This study aimed to investigate whether astragalosides (AST) could inhibit Aß-induced apoptosis in vivo and in vitro and to explore the underlying mechanisms. Amyloid ß-protein fragment 25-35 (Aß25-35) was administered to cerebral lateral ventricle of rats to make the AD models in vivo. AST was able to attenuate both cortical cell degeneration and memory deficits in the AD rats. AST also inhibited Aß25-35-induced cytotoxicity (e.g., decreased cell viability); apoptosis (e.g., increased caspase-3 expression, increased DNA fragmentation, and Tau hyperphosphorylation); synaptotoxicity (e.g., increased loss of both a dendritic marker, microtubule-associated protein 2 (MAP-2) and synaptic proteins, synaptophysins); and mitochondrial dysfunction (e.g., increased mitochondrial membrane potential) in cultured primary rat cortical cells. The beneficial effect of AST in reducing Aß-induced cytotoxicity, apoptosis, and mitochondrial dysfunction in cortical cells were blocked by inhibition of phosphoinositide 3-kinase (PI3K)-dependent protein kinase B (PKB, as known as AKT) activation with LY294002. In addition, inhibition of extracellular protein kinase (ERK) with U0126 shared with the AST the same beneficial effects in reducing Aß-induced apoptosis. Our data suggest that the cortical PI3K/AKT and MAPK (or ERK) pathways as appealing therapeutic targets in treating AD, and AST may have a positive impact on AD treatment via modulation of both PI3K/AKT and ERK pathways.

Attenuating systemic inflammatory markers in simulated high-altitude exposure by heat shock protein 70-mediated hypobaric hypoxia preconditioning in rats.

BACKGROUND/PURPOSE: The primary goal of this study was to test whether high-altitude exposure (HAE: 0.9% O(2) at 0.47 ATA for 24 hours) was capable of increasing the systemic inflammatory markers as well as the toxic organ injury indicators in rats, with a secondary goal to test whether preinduction of heat shock protein (HSP) 70 by hypobaric hypoxia preconditioning (HHP: 18.3% O(2) at 0.66 ATA for 5 h/day on 5 days consecutively for 2 weeks) attenuated the proposed increased serum levels of both the systemic inflammatory markers and the toxic organ injury indicators. METHODS: Rats were assigned to: (1) non-HHP (21% O(2) at 1.0 ATA)+non-HAE (21% O(2) at 1.0 ATA) group; (2) non-HHP+HAE group; (3) HHP+non-HAE group; (4) HHP+HAE group; and (5) HHP+HSP70 antibodies (Ab)+HAE group. For the HSP70Ab group, a neutralizing HSP70Ab was injected intravenously at 24 hours prior to HAE. All the physiological and biochemical parameters were obtained at the end of HAE or the equivalent time period of non-HAE. Blood samples were obtained for determination of both the systemic inflammatory markers (e.g., serum tumor necrosis factor-α, interleukin-1ß, E-selectin, intercellular adhesion molecule-1, and liver myeloperoxidase activity) and the toxic organ injury indicators (e.g., nitric oxide metabolites, 2,3-dihydroxybenzoic acid, and lactate dehydrogenase). RESULTS: HHP, in addition to inducing overexpression of tissue HSP70, significantly attenuated the HAE-induced hypotension, bradycardia, hypoxia, acidosis, and increased tissue levels of both the systemic inflammatory markers and the toxic organ injury indicators. The beneficial effects of HHP in inducing tissue overexpression of HSP70 as well as in preventing the HAE-induced increased levels of the systemic inflammatory markers and the toxic organ injury indicators could be significantly reduced by HSP70Ab preconditioning. CONCLUSION: These results suggest that HHP may downgrade both the systemic inflammatory markers and the toxic organ injury indicators in HAE by upregulating tissue HSP70.

Cathepsin B is involved in the heat shock induced cardiomyocytes apoptosis as well as the anti-apoptosis effect of HSP-70.

Cathepsin B is one of the major lysosomal cysteine proteases that plays an important role in apoptosis. Herein, we investigated whether Cathepsin B is involved in cardiomyocyte apoptosis caused by hyperthermic injury (HI) and heat shock protein (HSP)-70 protects these cells from HI-induced apoptosis mediated by Cathepsin. HI was produced in H9C2 cells by putting them in a circulating 43 °C water bath for 120 min, whereas preinduction of HSP-70 was produced in H9C2 cells by mild heat preconditioning (or putting them in 42 °C water bath for 30 min) 8 h before the start of HI. It was found that HI caused both cardiomyocyte apoptosis and increased Cathepsin B activity in H9C2 cells. E-64-c, in addition to reducing Cathepsin B activity, significantly attenuated HI-induced cardiomyocyte apoptosis (evidenced by increased apoptotic cell numbers, increased tuncated Bid (t-Bid), increased cytochrome C, increased caspase-9/-3, and decreased Bcl-2/Bax) in H9C2 cells. In addition, preinduction of HSP-70 by mild heat preconditioning or inhibition of HSP-70 by Tripolide significantly attenuated or exacerbated respectively both the cardiomyocyte apoptosis and increased Cathepsin B activity in H9C2 cells. Furthermore, the beneficial effects of pre-induction of HSP-70 by mild heat production in reducing both cardiomyocyte apoptosis and increased Cathepsin B activity caused by HI can be significantly reduced by Triptolide preconditioning. These results indicate that Cathepsin B is involved in HI-induced cardiomyocyte apoptosis in H9C2 cells and HSP-70 protects these cells from HI-induced cardiomyocyte apoptosis through Cathepsin B pathways.

Etanercept attenuates traumatic brain injury in rats by reducing brain TNF- α contents and by stimulating newly formed neurogenesis.

It remains unclear whether etanercept penetrates directly into the contused brain and improves the outcomes of TBI by attenuating brain contents of TNF- α and/or stimulating newly formed neurogenesis. Rats that sustained TBI are immediately treated with etanercept. Acute neurological and motor injury is assessed in all rats the day prior to and 7 days after surgery. The numbers of the colocalizations of 5-bromodeoxyuridine and doublecortin specific markers in the contused brain injury that occurred during TBI were counted by immunofluorescence staining. Enzyme immunoassay for quantitative determination of TNF-α or etanercept in brain tissues is also performed. Seven days after systemic administration of etanercept, levels of etanercept can be detected in the contused brain tissues. In addition, neurological and motor deficits, cerebral contusion, and increased brain TNF-α contents caused by TBI can be attenuated by etanercept therapy. Furthermore, the increased numbers of the colocalizations of 5-bromodeoxyuridine and doublecortin specific markers in the contused brain tissues caused by TBI can be potentiated by etanercept therapy. These findings indicate that systemically administered etanercept may penetrate directly into the contused brain tissues and may improve outcomes of TBI by reducing brain contents of TNF- α and by stimulating newly formed neurogenesis.

Attenuating heat-induced cellular autophagy, apoptosis and damage in H9c2 cardiomyocytes by pre-inducing HSP70 with heat shock preconditioning.

PURPOSE: We sought to assess whether heat-induced autophagy, apoptosis and cell damage in H9c2 cells can be affected by pre-inducing HSP70 (heat shock protein 70). MATERIALS AND METHODS: Cell viability was determined using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide staining and a lactate dehydrogenase assay. Apoptosis was evidenced using both flow cytometry and counting caspase-3 positive cells, whereas autophagy was evidenced by the increased LC3-II expression and lysosomal activity. RESULTS: The viability of H9c2 cells was temperature-dependently (40-44 °C) and time-dependently (90-180 min) significantly (p < 0.05) reduced by severe heat, which caused cell damage, apoptosis and autophagy. Heat-induced cell injury could be attenuated by pretreatment with 3-methylademine (an autophagy inhibitor) or Z-DEVD-FMK (a caspase-3 inhibitor). Neither apoptosis nor autophagy over the levels found in normothermic controls was induced in heat-shock preconditioned controls (no subsequent heat injury). The beneficial effects of mild heat preconditioning (preventing heat-induced cell damage, apoptosis and autophagy) were significantly attenuated by inhibiting HSP70 overexpression with triptolide (Tripterygium wilfordii) pretreatment. CONCLUSION: We conclude that pre-inducing HSP70 attenuates heat-stimulated cell autophagy, apoptosis and damage in the heart. However, this requires in vivo confirmation.

Etanercept attenuates traumatic brain injury in rats by reducing early microglial expression of tumor necrosis factor-α.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is elevated early in injured brain after traumatic brain injury (TBI), in humans and in animals. Etanercept (a TNF-α antagonist with anti-inflammatory effects) attenuates TBI in rats by reducing both microglial and astrocytic activation and increased serum levels of TNF-α. However, it is not known whether etanercept improves outcomes of TBI by attenuating microglia-associated, astrocytes-associated, and/or neurons-associated TNF-α expression in ischemic brain. A well clinically relevant rat model, where a lateral fluid percussion is combined with systemic administration of etanercept immediately after TBI, was used. The neurological severity score and motor function was measured on all rats preinjury and on day 3 after etanercept administration. At the same time, the neuronal and glial production of TNF-α was measured by Immunofluorescence staining. In addition, TNFα contents of ischemic cerebral homogenates was measured using commercial enzyme-linked immunosorbent assay kits. RESULTS: In addition to inducing brain ischemia as well as neurological and motor deficits, TBI caused significantly higher numbers of microglia-TNF-α double positive cells, but not neurons-TNF-α or astrocytes-TNF-α double positive cells in the injured brain areas than did the sham operated controls, when evaluated 3 days after TBI. The TBI-induced cerebral ischemia, neurological motor deficits, and increased numbers of microglia-TNF-α double positive cells and increased TNF-α levels in the injured brain were all significantly attenuated by etanercept therapy. CONCLUSION: This finding indicates that early microglia overproduction of TNF-α in the injured brain region after TBI contributes to cerebral ischemia and neurological motor deficits, which can be attenuated by etanercept therapy. Studies in this model could provide insight into the mechanisms underlying neurological motor disturbance in brain-injured patients.

LVV-hemorphin 7 and angiotensin IV in correlation with antinociception and anti-thermal hyperalgesia in rats.

Hemorphins, a family of atypical endogenous opioid peptides, are produced by the cleavage of hemoglobin ß-chain. Hemorphins were proved to bind to the µ-opioid receptors (agonist) and angiotensin IV receptors (insulin-regulated aminopeptidase; IRAP) (inhibitor). Among the hemorphins, LVV-hemorphin-7 (LVV-H7) was found to be abundant and with a longer half life in the CNS. Using intrathecal and intracerebroventricular injections, LVV-H7 and angiotensin IV were given to the rats, which were then subjected to the plantar test and the tail-flick test. Our results showed that LVV-H7 attenuated carrageenan-induced hyperalgesia at the spinal level, which could not be reversed by the co-administration of naloxone. At the supraspinal level, LVV-H7 also produced a significant anti-hyperalgesia effect but with a lower extent. Angiotensin IV showed a similar anti-hyperalgesia effect at the spinal level, but had no effect at the supraspinal level. In the tail-flick test and paw edema test, both peptides showed no effect. These results suggest that LVV-H7 mainly exert the anti-hyperalgesia effect at the spinal level, possibly through IRAP but not µ-opioid receptors. In addition, we observed the expression of IRAP in the CNS of animals with/without carrageenan-induced hyperalgesia. Our results showed a significant expression of IRAP in the spinal cord of rats. However, there was no significant quantitative change of IRAP after the development of hyperalgesia. The serum level of LVV-H7 was also found to be with no change caused by hyperalgesia. These results indicated that the endogenous LVV-H7 and IRAP may not regulate the severity of hyperalgesia through a quantitative change.

Induced interleukin-19 contributes to cell-mediated immunosuppression in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

BACKGROUND: Coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB) promotes immunosuppression, which predisposes patients to infectious complications. We investigated the role of interleukin (IL)-19 in the functions of CD4+ T cells in patients undergoing CABG with CPB. METHODS: Blood samples were withdrawn from 42 patients undergoing elective CABG with CPB. Serum levels of IL-19 were analyzed by enzyme-linked immunosorbent assay (ELISA). The CD4+/CD25+ T-cell population was determined with flow cytometry. Isolated CD4+ T cells were cultured and assayed for proliferation and cytokine production under phorbol myristate acetate/ionomycin stimulation. Cytokine production and Foxp3 mRNA expression in CD4+ T cells from healthy volunteers with or without IL-19 treatment were determined with ELISA and real-time polymerase chain reaction, respectively. RESULTS: Proliferation percentages were 162%, 48%, 34%, and 39%, and interferon (IFN)-γ production was 1.22 ng/mL, 0.56 ng/mL, 0.33 ng/mL, and 0.35 ng/mL in the CD4+ T cells of patients before CPB and at 24 hours, 48 hours, and 96 hours, respectively, after CPB. Serum levels of IL-19 were higher but negatively correlated with CD4+ T-cell proliferation and IFN-γ production. The populations of CD4+/CD25+ T cells and expression of Foxp3 mRNA in T cells were higher and were positively correlated with IL-19 levels after CPB. Treatment with IL-19 reduced T-cell proliferation and IFN-γ production, increased Foxp3 mRNA expression, and induced the regulatory activity of CD4+ T cells. CONCLUSIONS: Interleukin-19 reduces T-cell responses and promotes the regulatory activity of CD4+ T cells. Induced IL-19 in patients undergoing CABG with CPB contributes to cell-mediated immunosuppression.

Both mild hypothermia and dopamine D(2) agonist are neuroprotective against hyperthermia-induced injury in PC12 cells.

We exposed rat pheochromocytoma PC12 cells to hyperthermia or high dosage of dopamine and examined the direct effects of mild hypothermia or dopamine D(2) receptor agonist. At a hyperthermia of 42-43 degrees C for 120 min there was approximately 50% loss of cell viability accompanied by dopamine overproduction. The model of cell death due to hyperthermia in PC12 cells belonged to the necrotic and late apoptotic population. At each temperature examined below 37 degrees C, significant decrease in cytotoxicity, the percentage of necrotic and late apoptotic cells, and dopamine overproduction were observed. Cytotoxicity could also be induced by high dosages of dopamine. Both hyperthermia and dopamine induced cytotoxicity in PC12 cells could also be reduced by dopamine D(2) agonists. These results indicate the dopamine is important in hyperthermic situations. The results also indicate that mild hypothermia and dopamine D(2) receptor agonists are neuroprotective against hyperthermia-induced brain injury.