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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. We reported a case of huge tricuspid valve (TV) myxoma managed by robot-assisted endoscopic tumor resection and TV repair. 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.

BackgroundMitral regurgitation (MR) is a major contributor for heart failure (HF) and atrial fibrillation. Despite the advancement of MR surgeries, an effective medical therapy to mitigate MR progression is lacking. Sodium glucose cotransporter 2 inhibitors, a new class of antidiabetic drugs, has shown measurable benefits in reduction of HF hospitalization and cardiovascular mortality but the mechanism is unclear. We hypothesized that dapagliflozin (DAPA), a sodium glucose cotransporter 2 inhibitor, can improve cardiac hemodynamics in MR‐induced HF.Methods and ResultsUsing a novel, mini‐invasive technique, we established a MR model in rats, in which MR induced left heart dilatation and functional decline. Half of the rats were randomized to be administered with DAPA at 10 mg/kg per day for 6 weeks. After evaluation of electrocardiography and echocardiography, hemodynamic studies were performed, followed by postmortem tissue analyses. Results showed that DAPA partially rescued MR‐induced impairment including partial restoration of left ventricular ejection fraction and end‐systolic pressure volume relationship. Despite no significant changes in electrocardiography at rest, rats treated with DAPA exhibited lower inducibility and decreased duration of pacing‐induced atrial fibrillation. DAPA also significantly attenuated cardiac fibrosis, cardiac expression of apoptosis, and endoplasmic reticulum stress‐associated proteins.ConclusionsDAPA was able to suppress cardiac fibrosis and endoplasmic reticulum stress and improve hemodynamics in an MR‐induced HF rat model. The demonstrated DAPA effect on the heart and its association with key molecular contributors in eliciting its cardio‐protective function, provides a plausible point of DAPA as a potential strategy for MR‐induced HF.

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.

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.

Supplemental material, sj-pdf-2-pul-10.1177_2045894020943858 for Right ventricular reserve post mitral valve repair is associated with heart failure hospitalization by Wei-Ting Chang, Nan-Chun Wu, Jhih-Yuan Shih, Chih-Hsin Hsu, Zhih-Cherng Chen and Bor-Chih Cheng in Pulmonary Circulation

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.

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.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 for3 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 for3 months postsurgery. After propensity score matching, 282 patients not receiving warfarin were matched to 282 patients receiving warfarin for3 months. Patients were followed-up for minimum 36 months.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 for30 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.Short-term use of postoperative warfarin (especially30 days) following bioprosthetic aortic valve replacement may be associated with a reduction in MACCE compared with nonuse.

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.

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).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.The viability of H9c2 cells was temperature-dependently (40-44 °C) and time-dependently (90-180 min) significantly (p0.05) 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.We conclude that pre-inducing HSP70 attenuates heat-stimulated cell autophagy, apoptosis and damage in the heart. However, this requires in vivo confirmation.

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.

Objective We attempted to test the hypothesis that preinduction of heat shock protein (HSP) 72 in the heart would improve left ventricular performance in rat heatstroke. Methods Cardiac expression of HSP 72 was quantitatively evaluated by western blot analysis in rats 0h, 12h, or 72h after mild heat preconditioning (MHP; 43°C for 30min). They were subjected to severe heat stress (SHS; 43°C for 70min) to induce heatstroke. A 1.2F catheter-tip pressure transducer was inserted into the left ventricle of these group rats under general anesthesia to record hemodynamic in the closed chest with a pressure–volume loop module data recording and analysis system. Results At the time point of heatstroke onset, compared with normothermic controls, group rats with 12h post-MHP had significantly increased cardiac HSP 72, decreased hyperthermia, decreased hypotension, decreased bradycardia, increased end-systolic pressure, increased end-diastolic pressure, increased stroke volume, decreased end-systolic volume, decreased end-diastolic pressure, increased cardiac output, increased ejection fraction, increased stroke work, increased arterial elastance, and decreased time constant of fall in ventricular pressure by Glantz-methods. With the loss of cardiac HSP 72 expression observed at 72h in post-MHP group rats, an insignificant protection against left ventricular performance was observed. Conclusion Preinduction of cardiac HSP 72 may improve hypotension in heatstroke rats by increasing both cardiac mechanical efficiency and arterial elastance.

Hemorphins, a family of atypical endogenous opioid peptides, are produced by the cleavage of hemoglobin β-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.

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.

Background Herein, we compared the effectiveness of different small volume resuscitation in a rat model of heatstroke. Methods Anesthetized rats, immediately after the onset of heatstroke, were randomizedly divided into 5 groups and given the following: ( a ) nothing; ( b ) 0.9% NaCl (1-10 mL/kg of body weight, i.v.); ( c ) hydroxyethyl starch (HAES) (6%, 1-10 mL/kg of body weight, i.v.); ( d ) 7.2% NaCl (1-10 mL/kg of body weight, i.v.); and ( e ) hyper-HAES (6% HAES plus 7.2% NaCl, 1-10 mL/kg of body weight, i.v.). Results When the untreated or 0.9% NaCl (1-5 mL/kg of body weight)-treated rats underwent heat stress, their survival time values were found to be 20 to 22 minutes. Resuscitation with 10 mL/kg of body weight of 0.9% NaCl, 6% HAES, 7.2% NaCl, or hyper-HAES, their survival time values, respectively, are 93 ± 6, 101 ± 12, 154 ± 18, or 286 ± 21. Apparently, the order of effectiveness in resuscitation of heatstroke is hyper-HAES > 7.2% NaCl > 0.9% NaCl or 6% HAES. The heatstroke-induced hypotension, cerebral ischemia and hypoxia, hypercoagulable state, activated inflammation, and hepatic and renal dysfunction can be significantly reduced by hyper-HAES. Conclusions Our results suggest that hyper-HAES seems superior to 7.2% NaCl or HAES alone in resuscitation of heatstroke. The benefit of hyper-HAES during heatstroke is related to restoration of normal multiorgan function.

β-amyloid (Aβ)-mediated neuronal apoptosis contributes to the pathogenesis of Alzheimer's disease (AD). This study aimed to investigate whether astragalosides (AST) could inhibit Aβ-induced apoptosis in vivo and in vitro and to explore the underlying mechanisms. Amyloid β-protein fragment 25-35 (Aβ25-35) 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 Aβ25-35-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 Aβ-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 Aβ-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.

Interleukin (IL)-19, IL-20, and IL-22, three novel cytokines in the IL-10 family, have recently been discovered. The biological functions and clinical implications of these cytokines are not clear. We aimed to analyze if serum levels of these cytokines were altered in inflammatory responses of postoperative cardiopulmonary bypass (CPB) and investigate the molecular mechanism involved in cytokine induction.Twenty-five patients undergoing elective aortic-coronary bypass grafting with CPB were enrolled in this study. Blood samples withdrawn at (T1) before anesthesia, (T2) CPB start, (T3) CPB end, (T4) 4 hours post-CPB, (T5) 8 hours post-CPB, (T6) 12 hours post-CPB, (T7) 24 hours post-CPB, and (T8) 48 hours post-CPB were assayed for IL-6, IL-10, IL-19, IL-20, IL-22, and tumor necrotic factor-alpha (TNF-alpha). Transcripts of IL-19, IL-20, and IL-22 from monocytes were analyzed. In vitro, levels of IL-19, IL-20, and IL-22 production in monocytes incubated with IL-6 and TNF-alpha were determined.The serum levels of IL-19 and IL-22 significantly increased at T3, peaked at T5, and remained increased at T8 (p0.001). Induction of IL-19 and IL-22 was concomitant with the change in IL-10, IL-6, and TNF-alpha levels. Interleukin-19, IL-20, and IL-22 transcripts in monocytes from patients increased after CPB. In vitro experiments showed that IL-6 and TNF-alpha upregulated IL-19 protein expression in monocytes.Serum IL-19 and IL-22 were induced in cardiac surgery with CPB and concomitant with induction of IL-6 and TNF-alpha. The IL-19 and these proinflammatory cytokines may interactively contribute to systemic inflammatory responses after CPB.

IL-20 belongs to the IL-10 family and is involved in the pathogenesis of keratinocyte hyperproliferation in vivo. Endothelial cells express IL-20 receptors. To explore the function of IL-20 on endothelial cells, we treated human umbilical vein endothelial cells (HUVECs) and human microvascular endothelial cells (HMECs) with human IL-20 and analyzed its effect on endothelial cells. IL-20 induced proliferation of endothelial cells and the activity was specifically blocked by anti-human-IL-20 monoclonal antibody and soluble (s)IL-20 receptor (R)1 and sIL-20R2. An alternatively spliced variant of IL-20 was isolated and also was shown to induce proliferation of HUVECs and HMECs. Treatment of HUVECs with both IL-10 and IL-20 demonstrated that IL-10 antagonized the activity of IL-20 because it diminished IL-20-induced proliferation of HUVECs. IL-20 significantly induced HUVECs migration and vascular tube formation on Matrigel in vitro. In vivo, IL-20 also enhanced tumor angiogenesis. Incubation of IL-20 with HUVECs induced transcripts of bFGF, VEGF, MMP-2, MMP-9, and IL-8. Furthermore, incubation of HUVECs with IL-20 induced phosphorylation of ERK1/2, p38, and JNK. Thus, IL-20 is a pleiotropic cytokine and promotes angiogenesis.

Ischemic and oxidative damage to the hypothalamus may be associated with decreased heat tolerance as well as heatstroke formation. The present study explores the hypothalamic proteome mechanisms associated with heatstroke-mediated hypothalamic ischemia, and oxidative damage. Heatstroke rats had hypotension, hypothalamic ischemia, and lethality. In addition, they had hyperthermia and hypothalamic blood-brain-barrier disruption, oxidative stress, activated inflammation, and neuronal apoptosis and degeneration. 2DE combined LC-MS/MS revealed that heatstroke-induced ischemic injury and apoptosis were associated with upregulation of L-lactate dehydrogenase but downregulation of both dihydropyriminase-related protein and 14-3-3 Zeta isoform protein. Heat-induced blood-brain-barrier disruption might be related to upregulation of glial fibrillary acidic protein. Oxidative stress caused by heatstroke might be related to upregulation of cytosolic dehydrogenase-1. Also, heat-induced overproduction of proinflammatory cytokines might be associated with downregulation of stathmin 1. Heat-induced hypothalamic ischemia, apoptosis, injury (or upregulation of L-lactate dehydrogenase), blood-brain-barrier disruption (or upregulation of glial fibrillary acidic protein), oxidative stress (or upregulation of cytosolic dehydrogenase-1), and activated inflammation (or downregulation of stathmin 1) were all significantly reversed by whole body cooling. Our data indicate that cooling therapy improves outcomes of heatstroke by modulating hypothalamic proteome mechanisms.

It remains unclear whether etanercept penetrates directly into the contused brain and improves the outcomes of TBI by attenuating brain contents of TNF-αand/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-αor 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-αcontents 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-αand by stimulating newly formed neurogenesis.

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.

Objective We sought to assess the effect of therapeutic hypothermia on the autophagy that occurred in ischemia-reperfused (IR) H9c2 cardiomyocytes. Methods In control studies, the H9c2 cells at a density of 1×10 5 per culture dish in six-well plate were exposed to normoxic culture medium at 37°C for 12h. All assays contained appropriate controls and were performed in triplicate and repeated on three separately initiated cultures. In hypothermia-treated group, the ischemic and hypoxic cells were maintained in a 32°C incubation. The trypan blue exclusion method was used to assess the cell viability. Autophagy was evaluated by determining both the microtubule-associated protein 1 light chain 3 [LC3] levels and punctuate distribution of the autophagic vesicle associated form [LC3-II]. Results The results were mean±standard error of mean of triplicates. The viable cell percentage for control group, IR group, and IR group treated with hypothermia at the start of ischemia, or reperfusion were 100%±9%, 20%±1%, 32%±3%, and 41%±3%, respectively. The cell death in I/R H9c2 cells was positively associated with increased LC3 levels and punctuate distribution of (LC3-II). Mild hypothermia adopted at the start of ischemia or reperfusion significantly reduced both the cell death and the autophagy in H9c2 cells. Conclusion Our data indicate that in H9c2, IR stimulates cell autophagy and causes cell death, which can be attenuated by mild hypothermia. Our results, if further confirmed in vivo, may have important clinical implications during IR injury.

Objective— Atherosclerosis is a chronic inflammatory disease with immune cell infiltration. Various cytokines and chemokines have been characterized as pro- or antiatherogenic factors. Interleukin-20 (IL-20) belongs to the IL-10 family and is a proinflammatory cytokine involved in the pathogenesis of psoriasis. However, the association between IL-20 and atherosclerosis is undetermined. Therefore, we sought to investigate whether IL-20 is associated with atherosclerosis. Methods and Results— We examined the expression of IL-20 and its receptor complex IL-20R1/IL-20R2 in atherosclerotic lesions of humans and mice using immunohistochemical staining. IL-20 was expressed in macrophage-rich areas. Both IL-20 and IL-20R1/IL-20R2 were expressed by endothelial cells lining the intimal microvessels, vasa vasorum, but rarely in nonatherosclerotic arteries. We used reverse-transcription polymerase chain reaction to analyze gene expression. IL-20 transcripts increased in hypoxic monocytes and monocytes treated with oxidized low-density lipoprotein. The expression of IL-20R1 and IL-20R2 was also upregulated by human umbilical vein endothelial cells in response to hypoxic treatment. Incubating IL-20 with human umbilical vein endothelial cells upregulated CXCL9 and CXCL11 transcripts. Furthermore, in vivo administration of IL-20 expression vector using intramuscular electroporation promoted atherosclerosis in apolipoprotein E-deficient mice. Conclusions— Our data suggest that IL-20 is a proatherogenic cytokine that contributes to the progression of atherosclerosis.

The present study was performed to assess the prophylactic effect of 7-nitroindazole (7-NI), an inhibitor of neuronal nitric oxide synthase (nNOS), in an animal model of heatstroke. Anesthetized rats, immediately before the start of heat stress, were divided into two major groups and given the following: vehicle solution (1 mL per kg body weight) or 7-NI (5-20mg/mL per kg body weight) intraperitoneally. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (24 degrees C) and used as normothermic controls. Their physiologic and biochemical parameters were continuously monitored. When the vehicle-pretreated rats underwent heat stress, their survival time values were found to be 21-25 min. Pretreatment with intraperitoneal doses of 7-NI significantly improved survival during heatstroke (55-164 min). As compared to those of normothermic controls, all vehicle-pretreated heatstroke animals displayed higher levels of core temperature, intracranial pressure, nitric oxide metabolite (NO(2)(-)), glutamate, glycerol, lactate/pyruvate ratio, neuronal damage score and nNOS expression in the hypothalamus, and tumor necrosis factor-alpha (TNF-alpha) in the serum. In contrast, all vehicle-pretreated heatstroke animals had lower levels of mean arterial pressure, cerebral perfusion pressure, cerebral blood flow, and brain PO(2). Administration of 7-NI before the start of heat exposure significantly reduced the hyperthermia, intracranial hypertension, nNOS-dependent NO(2)(-), glutamate, glycerol, lactate/pyruvate ratio, and neuronal damage score in the hypothalamus, as well as overproduction of TNF-alpha in the serum that occurred during heatstroke. The data show that reduction of nNOS-dependent NO(2)(-) with 7-NI causes attenuation of cerebrovascular dysfunction, hyperthermia, and TNF-alpha overproduction during heatstroke in the rat.

Heat shock protein (HSP) 72 expression protects against arterial hypotension in rat heatstroke. HSP72 can also be induced in multiple organs, including hearts from rats with endurance exercise. We validated the hypothesis that progressive exercise preconditioning may confer cardiovascular protection during heatstroke by inducing the overexpression of HSP72 in multiple organs. To deal with the matter, we assessed the effects of heatstroke on mean arterial pressure, heart rate, cardiac output, stroke volume, total peripheral vascular resistance, colonic temperature, blood gases, and serum or tissue levels of tumor necrosis factor-alpha (TNF-alpha) in urethane-anesthetized rats pretreated without or with progressive exercise training for 1, 2, or 3 weeks. In addition, HSP72 expression in multiple organs was determined in different groups of animals. Heatstroke was induced by exposing the rats to a high blanket temperature (43 degrees C); the moment at which mean arterial pressure decreased from the peak value was taken as the time of heatstroke onset. Previous exercise training for 3 weeks, but not 1 or 2 weeks, conferred significant protection against hyperthermia, arterial hypotension, decreased cardiac output, decreased stroke volume, decreased peripheral vascular resistance, and increased levels of serum or tissue TNF-alpha during heatstroke and correlated with overexpression of HSP72 in multiple organs, including heart, liver, and adrenal gland. However, 10 days after 3 weeks of progressive exercise training, when HSP72 expression in multiple organs returned to basal values, the beneficial effects exerted by 3 weeks of exercise training were no longer observed. These results strongly suggest that HSP72 preconditioning with progressive exercise training protects against hyperthermia, circulatory shock, and TNF-alpha overproduction during heatstroke.

Digital photography has become a practical alternative to conventional film photography for medical documentation, communication, and education. The use of digital cameras has become increasingly popular in recent years for documenting perioperative conditions, intraoperative findings, and imaging studies. However, taking intraoperative pictures or video clips may be technically demanding for assistants or nurses. Herein, we describe a simple and effective method for surgeons to create photographic and video records of operations under sterile conditions involving the use of a digital camera encased in commercially available protective housing.

A 44-year-old man underwent percutaneous nephrolithotomy for a left renal staghorn stone. During the procedure, the tip of the ultrasound lithotripter dislodged from the probe rod when the renal stone was being disintegrated. The tip immediately disappeared from the field of nephroscopic vision. Despite a thorough search, the tip could not be found. Postoperative chest radiography revealed a foreign body, shaped like a lithotripter probe tip, located in the lingular branch of the left pulmonary artery. Eventually, left thoracotomy was performed to remove the foreign body. To our knowledge, this rare complication has never been reported before.

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.