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This study was carried out to assess the quality properties, components associated with taste and aroma of beef as a function of breed. For this purpose, steers from four Korean native cattle breeds: Hanwoo (n=10), Chikso (n=10), black Hanwoo (n=12, BHW) and Jeju black cattle (n=12, JBC) were used. The steers all were raised under identical conditions and finished at a similar age of around 30-months old. Following 24 h of slaughter, all longissimus lumborum muscles were collected and used for analysis of meat quality, fatty acids, and flavor-related components (metabolic compounds, free amino acids, and aroma volatiles). The Hanwoo presented a significantly higher intramuscular fat content (IMF, 22.85%) than the BHW (11.78%), Chikso (9.25%), and JBC (9.14%; p<0.05). The meat of Hanwoo breed showed lighter and redder color, and lower shear force value (p<0.05). The JBC presented a "healthier" fatty acid profiles as it had a higher total unsaturated fatty acids content (p<0.05). With regard to flavor-related components, Hanwoo also had higher total contents of free amino acids and metabolites associated with umami and sweet tastes, and fat-derived volatile compounds (aldehydes, alcohols, and ketones) associated with fatty aroma. It may be concluded that there was a considerable difference in the meat quality properties among breeds. The variations of IMF content and flavor-related components may be the main factors contributing to the typical flavors of beef among the four Korean native cattle breeds.
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BACKGROUND: Atrial functional mitral regurgitation (AFMR) is a newly discovered condition associated with longstanding atrial fibrillation. This retrospective study aimed to analyze the outcomes of the maze procedure and mitral regurgitation (MR) surgery in AFMR and atrial fibrillation in comparison with those in degenerative MR (DMR). METHODS: Patients who underwent mitral valve repair/replacement with a maze procedure at a hospital (July 2012-August 2021) were included. We excluded patients aged below 18 years undergoing concomitant coronary artery bypass grafting or atrial septal defect repair and those with MR etiology other than ARMR or DMR. RESULTS: We included 35 patients with AFMR and 50 patients with DMR. Patient characteristics and postoperative outcomes were not significantly different between the two groups. Long-term outcomes revealed no significant differences in the ratio of cardiac mortality, stroke, or hospital readmission. However, after the maze procedure, the sinus rhythm restoration rate was significantly lower (62% vs. 28.5%, p < 0.001), a junctional rhythm state (p < 0.001) and permanent pacemaker insertion for sick sinus syndrome (SSS) (p = 0.03) were significantly more common in AFMR than DMR. On postoperative transthoracic echocardiography (TTE), the pulmonary artery systolic pressure was significantly less decreased in the AFMR group than in the DMR group compared with that on preoperative TTE (p = 0.04). CONCLUSIONS: AFMR showed excellent mitral valve surgery outcomes, similar to DMR, but had a significantly higher risk of pacemaker insertion for SSS after the maze procedure.
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Fibrilación Atrial , Procedimiento de Laberinto , Insuficiencia de la Válvula Mitral , Válvula Mitral , Humanos , Insuficiencia de la Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/fisiopatología , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Fibrilación Atrial/cirugía , Fibrilación Atrial/fisiopatología , Resultado del Tratamiento , Válvula Mitral/cirugía , Válvula Mitral/fisiopatología , Anciano , Implantación de Prótesis de Válvulas Cardíacas/métodos , Ecocardiografía , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/epidemiologíaRESUMEN
OBJECTIVE: To analyze and compare the outcomes of mitral valve surgery for atrial functional mitral regurgitation (AFMR) and for degenerative mitral regurgitation (DMR). METHODS: Patients with AFMR or DMR who underwent mitral valve repair/replacement at 2 institutions between January 2012 and December 2022 were included. Patients <18 years of age and patients undergoing concomitant cardiac surgery (except for the maze procedure or tricuspid annuloplasty) were excluded. Propensity score analysis was used to adjust for baseline differences. RESULTS: A total of 642 patients were enrolled. After propensity score analysis, 164 patients were classified into the DMR group, and 82 patients were classified into the AFMR group. All matched patients in both groups had atrial fibrillation. In DMR and AFMR, the 5-year freedom from readmission for heart failure and cardiac death was 96.3% in the DMR group versus 88.6% in the AFMR group (P = .045) and freedom from readmission for cardiac death in the 2 groups was 100% and 90.0%, respectively (P = .002). The recurrence rate of significant mitral regurgitation (MR) after mitral valve repair was not significantly different between the 2 groups (P = .699, log-rank test), and the 5-year freedom from MR recurrence (moderate or greater) was 89.8% and 93.0%, respectively. After the maze procedure, significantly more patients in the AFMR group than the DMR group were in junctional rhythm (49.1% vs 3.3%; P < .001) and required permanent pacemaker insertion during the follow-up period (11.4% vs 1.5% after 5 years; P = .041, log-rank test). CONCLUSIONS: AFMR was associated with acceptable outcomes of mitral valve surgery, and mitral valve repair is a good treatment option. However, significantly more patients were in junctional rhythm after the maze procedure, needing more permanent pacemaker insertion.
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Hyperinflammation occurs in sepsis, especially in the early phase, and it could have both positive and negative effects on sepsis. Previously, we showed that a new concept of NF-κB inhibitor, exosome-based super-repressor IκBα (Exo-srIκB) delivery, has a beneficial effect on sepsis. Here, we further investigate the therapeutic effects of Exo-srIκB at different severities and phases of sepsis using an animal polymicrobial intra-abdominal infection model. We used a rat model of fecal slurry polymicrobial sepsis. First, we determined the survival effects of Exo-srIκB on sepsis according to the severity. We used two different severities of the animal sepsis model. The severe model had a mortality rate of over 50%. The mild/moderate model had a less than 30% mortality rate. Second, we administered the Exo-srIκB at various time points (1 h, 6 h, and 24 h after fecal slurry administration) to determine the therapeutic effect of Exo-srIκB at different phases of sepsis. Lastly, we determined the effects of the Exo-srIκB on cytokine production, arterial blood gas, electrolyte, and lactate. The survival gain was statistically significant in the severe sepsis model when Exo-srIκB was administered 6 h after sepsis. Interleukin 6 and interleukin-10 were significantly decreased in the kidney when administered with Exo-srIκB. The laboratory data showed that lactate, glucose, and potassium levels were significantly lowered in the NF-κB inhibitor group. In conclusion, Exo-srIκB exhibited a beneficial therapeutic effect when administered 6 h post fecal slurry administration in a severe sepsis model.
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A 62-year-old woman who had undergone mitral valve replacement 24 years ago was admitted to the hospital with congestive heart failure. She needed heart transplantation for stage D heart failure. Preoperative cardiac computed tomographic scans showed a severely calcified left atrium and a large right atrium. Given that the left atrium's calcification was too severe to suture, the calcified left atrial wall was broadly resected, and the resected left atrial wall was reconstructed with a bovine pericardial patch for anastomosis with the donor's left atrial wall. The operation was completed without heavy bleeding, and the patient was discharged from the hospital with no complications.
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Calcinosis , Atrios Cardíacos , Insuficiencia Cardíaca , Trasplante de Corazón , Cardiopatía Reumática , Tomografía Computarizada por Rayos X , Humanos , Femenino , Cardiopatía Reumática/cirugía , Cardiopatía Reumática/complicaciones , Cardiopatía Reumática/diagnóstico , Trasplante de Corazón/métodos , Persona de Mediana Edad , Calcinosis/cirugía , Calcinosis/diagnóstico , Calcinosis/complicaciones , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/cirugía , Insuficiencia Cardíaca/cirugía , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/diagnóstico , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Implantación de Prótesis de Válvulas Cardíacas/métodos , Pericardio/trasplante , Pericardio/cirugíaRESUMEN
Background: Pump-controlled retrograde trial off (PCRTO) is a safe, simple, and reversible method for weaning patients from veno-arterial extracorporeal membrane oxygenation (VA-ECMO). However, few studies have compared PCRTO to conventional weaning methods. This retrospective study aimed to compare PCRTO to non-PCRTO methods. Methods: This study included patients who were weaned from VA-ECMO from January 2016 to December 2022 at our medical center. Demographic data, ECMO management, ECMO complications, survival to discharge, and cardiogenic shock after VA-ECMO weaning were compared between the 2 groups. Results: Seventy patients who were weaned from VA-ECMO using PCRTO and 85 patients who were weaned with conventional methods were compared. Patient characteristics were not significantly different between the 2 groups. The rate of survival to discharge was significantly higher in the PCRTO group than in the non-PCRTO group (90% vs. 72%, p=0.01). The rates of freedom from all-cause mortality at 10, 30, and 50 days after weaning from ECMO were 75%, 55%, and 35% in the non-PCRTO group and 62%, 60%, and 58% in the PCRTO group, respectively (p=0.1). The incidence of cardiogenic shock after weaning from VA-ECMO was significantly higher in the non-PCRTO group (16% vs. 5%, p=0.04). In logistic regression analysis, PCRTO was a significant factor for survival to discharge (odds ratio, 2.42; 95% confidence interval, 1.29-5.28; p=0.02). Conclusion: Compared to conventional methods, PCRTO is a feasible and reversible method, and it serves as a useful predictor of successful VA-ECMO weaning through a preload stress test.
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Endoplasmic reticulum (ER) stress plays a crucial role in liver diseases, affecting various types of hepatic cells. While studies have focused on the link between ER stress and hepatocytes as well as hepatic stellate cells (HSCs), the precise involvement of hepatic macrophages in ER stress-induced liver injury remains poorly understood. Here, we examined the effects of ER stress on hepatic macrophages and their role in liver injury. Acute ER stress led to the accumulation and activation of hepatic macrophages, which preceded hepatocyte apoptosis. Notably, macrophage depletion mitigated liver injury induced by ER stress, underscoring their detrimental role. Mechanistic studies revealed that ER stress stimulates macrophages predominantly via the PERK signaling pathway, regardless of its canonical substrate ATF4. hnRNPA1 has been identified as a crucial mediator of PERK-driven macrophage activation, as the overexpression of hnRNPA1 effectively reduced ER stress and suppressed pro-inflammatory activation. We observed that hnRNPA1 interacts with mRNAs that encode UPR-related proteins, indicating its role in the regulation of ER stress response in macrophages. These findings illuminate the cell type-specific responses to ER stress and the significance of hepatic macrophages in ER stress-induced liver injury. Collectively, the PERK-hnRNPA1 axis has been discovered as a molecular mechanism for macrophage activation, presenting prospective therapeutic targets for inflammatory hepatic diseases such as acute liver injury.
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Rationale: The surge of severe liver damage underscores the necessity for identifying new targets and therapeutic agents. Endoplasmic reticulum (ER) stress induces ferroptosis with Gα12 overexpression. NF-κB essential modulator (NEMO) is a regulator of inflammation and necroptosis. Nonetheless, the regulatory basis of NEMO de novo synthesis and its impact on hepatocyte ferroptosis need to be established. This study investigated whether Nrf2 transcriptionally induces IKBKG (the NEMO gene) for ferroptosis inhibition and, if so, how NEMO induction protects hepatocytes against ER stress-induced ferroptosis. Methods: Experiments were conducted using human liver tissues, hepatocytes, and injury models, incorporating NEMO overexpression and Gα12 gene modulations. RNA sequencing, immunoblotting, immunohistochemistry, reporter assays, and mutation analyses were done. Results: NEMO downregulation connects closely to ER and oxidative stress, worsening liver damage via hepatocyte ferroptosis. NEMO overexpression protects hepatocytes from ferroptosis by promoting glutathione peroxidase 4 (GPX4) expression. This protective role extends to oxidative and ER stress. Similar shifts occur in nuclear factor erythroid-2-related factor-2 (Nrf2) expression alongside NEMO changes. Nrf2 is newly identified as an IKBKG (NEMO gene) transactivator. Gα12 changes, apart from Nrf2, impact NEMO expression, pointing to post-transcriptional control. Gα12 reduction lowers miR-125a, an inhibitor of NEMO, while overexpression has the opposite effect. NEMO also counters ER stress, which triggers Gα12 overexpression. Gα12's significance in NEMO-dependent hepatocyte survival is confirmed via ROCK1 inhibition, a Gα12 downstream kinase, and miR-125a. The verified alterations or associations within the targeted entities are validated in human liver specimens and datasets originating from livers subjected to exposure to other injurious agents. Conclusions: Hepatic injury prompted by ER stress leads to the suppression of NEMO, thereby facilitating ferroptosis through the inhibition of GPX4. IKBKG is transactivated by Nrf2 against Gα12 overexpression responsible for the increase of miR-125a, an unprecedented NEMO inhibitor, resulting in GPX4 induction. Accordingly, the induction of NEMO mitigates ferroptotic liver injury.
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Ferroptosis , Hepatopatías , MicroARNs , Humanos , Estrés del Retículo Endoplásmico/genética , Ferroptosis/genética , Quinasa I-kappa B/genética , Quinasa I-kappa B/metabolismo , MicroARNs/genética , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Quinasas Asociadas a rhoRESUMEN
OBJECTIVE: Beef of Jeju black cattle (JBC) is considered as a healthy meat type due to its significantly higher unsaturated fatty acids (UFA). Lipid (e.g., UFA) is highly susceptible to oxidizing agents, which results in the quality deterioration and economic value loss of meat products. Therefore, development and application of novel preservative techniques is necessary to improve the shelf-life stability of high-UFA beef. The objective of this study was to assess the applicability of chitosan-based coatings in preservation of JBC beef. METHODS: Different coating solutions: 2% chitosan alone, and 2% chitosan containing 0.1% or 0.3% gallic acid were prepared to investigate their applicability in preservation of fresh beef during storage. Jeju black cattle beef (2-cm thick steaks) were non-coated (control) or coated with the above coating solutions, placed on trays, over-wrapped with plastic film and stored at 4°C. The microbiological indices, color, total volatile basic nitrogen (TVBN) and lipid oxidation of the beef were investigated after 1, 10, and 21 days of storage. RESULTS: Coating with 2% chitosan alone reduced the spoilage bacteria count, TVBN and thiobarbituric acid reactive substances levels in the beef compared with control during storage (p<0.05). Noticeably, coating with 2% chitosan containing 0.1% or 0.3% gallic acid was more effective on retardation of spoilage bacteria growth, lipid oxidation and discoloration in the beef compared to the chitosan coating alone over the storage period (21 days) (p<0.05). CONCLUSION: Taken together, the combined chitosan and gallic acid coating could be used as a bio-preservative technique in the meat industry.
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Previously, we demonstrated that mitochondrial transplantation has beneficial effects in a polymicrobial sepsis model. However, the mechanism has not been fully investigated. Mitochondria have their own genes, and genomic changes in sepsis are an important issue in terms of pathophysiology, biomarkers, and therapeutic targets. To investigate the changes in transcriptomic features after mitochondrial transplantation in a polymicrobial sepsis model, we used a rat model of fecal slurry polymicrobial sepsis. Total RNA from splenocytes of sham-operated (SHAM, n = 10), sepsis-induced (SEPSIS, n = 7), and sepsis receiving mitochondrial transplantation (SEPSIS + MT, n = 8) samples was extracted and we conducted a comparative transcriptome-wide analysis between three groups. We also confirmed these results with qPCR. In terms of percentage of mitochondrial mapped reads, the SEPSIS + MT group had a significantly higher mapping ratio than the others. RT1-M2 and Cbln2 were identified as highly expressed in SEPSIS + MT compared with SEPSIS. Using SHAM expression levels as another control variable, we further identified six genes (Fxyd4, Apex2l1, Kctd4, 7SK, SNORD94, and SNORA53) that were highly expressed after sepsis induction and observed that their expression levels were attenuated by mitochondrial transplantation. Changes in transcriptomic features were identified after mitochondrial transplantation in sepsis. This might provide a hint for exploring the mechanism of mitochondrial transplantation in sepsis.
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Sepsis , Transcriptoma , Ratas , Animales , Mitocondrias/genética , Mitocondrias/metabolismo , Perfilación de la Expresión Génica , Sepsis/genética , Sepsis/metabolismoRESUMEN
Background: There is not sufficient evidence of the superiority of hybrid procedures over total arch replacement (TAR) for the aortic arch aneurysm of an elderly patients. This retrospective study aimed to compare total arch replacement and hybrid procedures for treatment of aortic arch aneurysms in patients aged ≥75. Methods: This study was a multicenter retrospective investigation of peri-operative outcomes of patients undergoing aortic arch aneurysm repair using either TAR or hybrid procedures between January 2012 and May 2021. Risk factors for mortality were evaluated using multivariate analyses. Results: This study included 90 patients, of which 28 underwent hybrid procedures (hybrid group: frozen elephant trunk =9, zone 0 =6, zone 1 =1, zone 2 =12), and 62 underwent TAR (TAR group), and the mean duration of follow-up was 27.0±28.8 months. In patient characteristics, the incidence of chronic obstructive lung disease and chronic kidney disease in the TAR group was significantly higher than in the hybrid group, and other operative risk factors were not significantly different in both groups. No significant differences in the incidence of post-operative complications and mortality on hospitalization. Survival rates of both groups were not significantly different (P=0.31). However, re-intervention rates after aortic arch aneurysm repair were significantly higher in the hybrid group compared to the TAR group (freedom from re-intervention rates at 1, 3, 5 years: 100%, 93%, 93% in the TAR group, and 90%, 80%, 80% in the hybrid group, P=0.04). Conclusions: There was no definitive evidence of the superiority of hybrid procedures over TAR, although the risk of re-intervention was higher in the former group. The surgical strategy for aortic arch aneurysms should be selected based on the patient's demographic and anatomical characteristics.
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BACKGROUND: There is ongoing debate regarding the diagnostic criteria for chronic obstructive pulmonary disease (COPD); recent studies have focused on the early COPD detection and management. Here, we compared clinical features and prognosis in patients with FEV1/FVC<0.70 at baseline, according to normalized airflow obstruction status during follow-up. METHODS: We used the Korea COPD Subgroup Study (KOCOSS) cohort database, a prospective nationwide observational COPD study. Normalized obstruction (NO) was defined as FEV1/FVC ≥0.7 in the 2-year follow-up period, whereas fixed obstruction (FO) was defined as FEV1/FVC <0.7. Demographic and clinical data, 1-year exacerbation risk and difference in FEV1 decline over 2 years were compared between NO and FO groups. RESULTS: Among the 670 COPD patients with post-bronchodilator FEV1/FVC <0.7 in this study, 95 (14.2%) displayed NO. Compared with the FO group, the NO group had higher FEV1, and DLCO, body mass index, as well as lower Saint George Respiratory Questionnaire, Beck Depression Index, and Beck Anxiety Index. Blood eosinophil count, IgE level, and FeNO did not significantly differ between two groups. There was no significant difference in exacerbation frequency between the two groups, but the NO group had a significant increase in FEV1 compared with the FO group during follow-up. CONCLUSION: Transient airflow obstruction in the NO group may represent a clinical manifestation of early COPD; close monitoring is needed for such patients.
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Relevancia Clínica , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Estudios Prospectivos , Volumen Espiratorio Forzado , Capacidad Vital , EspirometríaRESUMEN
BACKGROUND AND OBJECTIVES: The left atrial appendage (LAA) can contribute significantly to LA mechanical contraction. Nevertheless, the preventive effect of LAA occlusion during the maze procedure against cerebral infarction remains controversial. In this study, we compared the surgical, cardiac hemodynamic, and neurologic outcomes between LAA preservation and occlusion performed during the maze procedure. METHODS: Between January 2015 and August 2021, 252 patients underwent the maze procedure using cryoablation at our medical center. After excluding patients according to our exclusion criteria (i.e., mechanical prosthesis implantation, preexisting LAA thrombus), LAA was preserved in 113 patients (non-occlusion group) and occluded in 75 patients (occlusion group). Outcomes were compared using propensity score matching (PSM). RESULTS: PSM did not reveal significant intergroup differences in baseline characteristics between the non-occlusion (n=53) and occlusion (n=53) groups. During a median follow-up of 44 months, 2 patients in the non-occlusion group (3.8%) experienced ischemic strokes. There was no significant difference in the rate of freedom from stroke (p=0.19) and major adverse cardiac events (p=0.43) between the 2 groups. Through echocardiography at 1-year follow-up, a statistically significant difference in LA mechanical contraction was observed between the non-occlusion group and occlusion group (24 of 33 [72.7%] vs. 18 of 37 [48.6%], respectively; p=0.04). CONCLUSIONS: In this study, preservation of the LAA during the maze procedure resulted in better LA function than LAA occlusion, with similar rates of stroke.
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Background: Superior vena cava (SVC) stenosis during follow-up is a major concern after heart transplantation, and many technical modifications have been introduced. We analyzed the surgical results of the SVC intima layer-only suture technique in heart transplantation. Methods: We performed SVC anastomosis with sutures placed only in the intima during heart transplantation. We measured the area of the SVC at 3 different points (above the anastomosis, at the anastomosis, and below the anastomosis) in an axial view by freely drawing regions of interest, and then evaluated the degree of stenosis. Patients who underwent cardiac computed tomography (CT) at 2 years postoperatively between June 2017 and May 2020 were included in this study. Results: We performed heart transplantation in 41 patients. Among them, 24 patients (16 males and 8 females) underwent follow-up cardiac CT at 2 years postoperatively. The mean age at operation was 49.4±4.9 years. The diagnoses at time of operation were dilated cardiomyopathy (n=12), ischemic heart disease (n=8), valvular heart disease (n=2), hypertrophic cardiomyopathy (n=1), and congenital heart disease (n=1). No cases of postoperative bleeding requiring intervention occurred. The mean CT follow-up duration was 1.9±0.7 years. At follow-up, the mean areas at the 3 key points were 2.7±0.8 cm2, 2.7±0.8 cm2, and 2.7±1.0 cm2 (p=0.996). There were no SVC stenosis-related symptoms during follow-up. Conclusion: The suture technique using only the SVC intimal layer is a safe and effective method for use in heart transplantation.
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BACKGROUND: Additional retrograde cardioplegia infusion in conventional coronary artery bypass grafting (CABG) was introduced to address the concern of inappropriate cardioplegia delivery through the stenotic coronary artery. However, this method is complex and requires repeated infusions. Therefore, we investigated the surgical outcomes of only antegrade cardioplegia infusion in conventional CABG. METHODS: We included 224 patients who underwent isolated CABG between 2017 and 2019. The patients were divided into two groups according to the cardioplegia infusion method: antegrade cardioplegia infusion with del Nido solution (n=111, group I) and antegrade+retrograde cardioplegia infusion with blood cardioplegia solution (n=113, group II). RESULTS: The sinus recovery time after release of the aorta cross-clamp was shorter in group I (3.8±7.1 minutes, n=98) than in group II (5.8±4.1 minutes, n=73) (p=0.033). The total cardioplegia infusion volume was lower in group I (1,998.6±668.6 mL) than in group II (7,321.0±2,865.3 mL) (p<0.001). Creatine kinase-MB levels were significantly lower in group I than in group II (p=0.039). Newly developed regional wall motion abnormalities on follow-up echocardiography were detected in two patients (1.8%) in group I and five patients (4.4%) in group II (p=0.233). There was no significant difference in ejection fraction improvement between the two groups (3.3%±9.3% in group I and 3.3%±8.7% in group II, p=0.990). CONCLUSION: The only antegrade cardioplegia infusion strategy in conventional CABG is safe and has no harmful effects.
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Previously, we have shown that mitochondrial transplantation in the sepsis model has immune modulatory effects. The mitochondrial function could have different characteristics dependent on cell types. Here, we investigated whether the effects of mitochondrial transplantation on the sepsis model could be different depending on the cell type, from which mitochondria were isolated. We isolated mitochondria from L6 muscle cells, clone 9 liver cells and mesenchymal stem cells (MSC). We tested the effects of mitochondrial transplantation using in vitro and in vivo sepsis models. We used the LPS stimulation of THP-1 cell, a monocyte cell line, as an in vitro model. First, we observed changes in mitochondrial function in the mitochondria-transplanted cells. Second, we compared the anti-inflammatory effects of mitochondrial transplantation. Third, we investigated the immune-enhancing effects using the endotoxin tolerance model. In the in vivo polymicrobial fecal slurry sepsis model, we examined the survival and biochemical effects of each type of mitochondrial transplantation. In the in vitro LPS model, mitochondrial transplantation with each cell type improved mitochondrial function, as measured by oxygen consumption. Among the three cell types, L6-mitochondrial transplantation significantly enhanced mitochondrial function. Mitochondrial transplantation with each cell type reduced hyper-inflammation in the acute phase of in vitro LPS model. It also enhanced immune function during the late immune suppression phase, as shown by endotoxin tolerance. These functions were not significantly different between the three cell types of origin for mitochondrial transplantation. However, only L6-mitochondrial transplantation significantly improved survival compared to the control in the polymicrobial intraabdominal sepsis model. The effects of mitochondria transplantation on both in vitro and in vivo sepsis models differed depending on the cell types of origin for mitochondria. L6-mitochondrial transplantation might be more beneficial in the sepsis model.
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Lipopolisacáridos , Sepsis , Humanos , Lipopolisacáridos/metabolismo , Mitocondrias/metabolismo , Sepsis/metabolismo , Inflamación/metabolismo , Monocitos/metabolismoRESUMEN
BACKGROUND: Due to structural valve deterioration of sutureless aortic prosthesis, there is a need for explantation of the prothesis. We introduce a surgical technique to explant sutureless aortic prosthesis, which has a self-expanding stent incorporated into the aortic wall. CASE PRESENTATION: An 82-year-old man who had undergone sutureless aortic valve replacement 6 years previously underwent redo-aortic and mitral valve replacement because of severe prosthetic aortic valve stenosis and mitral regurgitation. The sutureless prosthesis was explanted using 'lasso technique'. The patient was discharged after 7 days without complications. CONCLUSIONS: We presented a useful technique to explant a sutureless aortic prosthesis.
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Estenosis de la Válvula Aórtica , Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Insuficiencia de la Válvula Mitral , Procedimientos Quirúrgicos sin Sutura , Masculino , Humanos , Anciano de 80 o más Años , Implantación de Prótesis de Válvulas Cardíacas/métodos , Estenosis de la Válvula Aórtica/cirugía , Insuficiencia de la Válvula Mitral/cirugía , Diseño de Prótesis , Válvula Aórtica/cirugía , Resultado del Tratamiento , Procedimientos Quirúrgicos sin Sutura/métodosRESUMEN
Disturbed lipid metabolism precedes alcoholic liver injury. Whether and how AhR alters degradation of lipids, particularly phospho-/sphingo-lipids during alcohol exposure, was not explored. Here, we show that alcohol consumption in mice results in induction and activation of aryl hydrocarbon receptor (AhR) in the liver, and changes the hepatic phospho-/sphingo-lipids content. The levels of kynurenine, an endogenous AhR ligand, are elevated with increased hepatic tryptophan metabolic enzymes in alcohol-fed mice. Either alcohol or kynurenine treatment promotes AhR activation with autophagy dysregulation via AMPK. Protein Phosphatase 2 Regulatory Subunit-Bdelta (Ppp2r2d) is identified as a transcriptional target of AhR. Consequently, PPP2R2D-dependent AMPKα dephosphorylation causes autophagy inhibition and mitochondrial dysfunction. Hepatocyte-specific AhR ablation attenuates steatosis, which is associated with recovery of phospho-/sphingo-lipids content. Changes of AhR targets are corroborated using patient specimens. Overall, AhR induction by alcohol inhibits autophagy in hepatocytes through AMPKα, which is mediated by Ppp2r2d gene transactivation, revealing an AhR-dependent metabolism of phospho-/sphingo-lipids.
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Proteínas Quinasas Activadas por AMP , Receptores de Hidrocarburo de Aril , Animales , Ratones , Proteínas Quinasas Activadas por AMP/metabolismo , Autofagia , Etanol/metabolismo , Etanol/toxicidad , Quinurenina/metabolismo , Ligandos , Metabolismo de los Lípidos , Hígado/metabolismo , Fosfolípidos/metabolismo , Proteína Fosfatasa 2/genética , Proteína Fosfatasa 2/metabolismo , Receptores de Hidrocarburo de Aril/metabolismo , Triptófano/metabolismoRESUMEN
Immune suppression is known to occur during sepsis. Endotoxin tolerance is considered a mechanism of immune suppression in sepsis. However, the timing and serial changes in endotoxin tolerance have not been fully investigated. In this study, we investigated serial changes in endotoxin tolerance in a polymicrobial sepsis model. Herein, we used a rat model of fecal slurry polymicrobial sepsis. After induction of sepsis, endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was measured at various time points (6 h, 12 h, 24 h, 48 h, 72 h, 5 days, and 7 days), through the measurement of TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. At each time point, we checked for plasma tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 levels. Moreover, we analyzed reactive oxygen species (ROS) as measured by 2',7'-dichlorodihydrofluorescein, plasma lactate, serum alanine aminotransferase (ALT), and creatinine levels. Nuclear factor (NF)-κB, IL-1 receptor-associated kinase (IRAK)-M, and cleaved caspase 3 levels were measured in the spleen. Endotoxin tolerance, measured by TNF-α production stimulated through LPS in PBMCs and splenocytes, was induced early in the sepsis model, starting from 6 h after sepsis. It reached a nadir at 24 to 48 h after sepsis, and then started to recover. Endotoxin tolerance was more prominent in the severe sepsis model. Plasma cytokines peaked at time points ranging from 6 to 12 h after sepsis. ROS levels peaked at 12 h and then decreased. Lactate, ALT, and serum creatinine levels increased up to 24 to 48 h, and then decreased. Phosphorylated p65 and IRAK-M levels of spleen increased up to 12 to 24 h and then decreased. Apoptosis was prominent 48 h after sepsis, and then recovered. In the rat model of polymicrobial sepsis, endotoxin tolerance occurred earlier and started to recover from 24 to 48 h after sepsis.
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Lipopolisacáridos , Sepsis , Animales , Tolerancia a Endotoxinas , Interleucina-6 , Lactatos , Leucocitos Mononucleares , Lipopolisacáridos/farmacología , FN-kappa B , Ratas , Especies Reactivas de Oxígeno , Sepsis/patología , Factor de Necrosis Tumoral alfaRESUMEN
True aneurysms of the coronary artery after aortic root replacement in Marfan syndrome patients are very rare. An anomalous origin of the right coronary artery (RCA) from the left sinus of Valsalva adds complexity during aortic root surgery. We present a case of a 37-year-old male patient with Marfan syndrome who had an RCA anomaly and a 4.5-cm true aneurysm of the common coronary button 14 years after a previous Bentall procedure. A redo Bentall operation and hemi-arch replacement were successfully performed. The anomalous origin of the RCA from the left sinus of Valsalva was safely divided and anastomosed as separate coronary buttons to the prosthetic composite valve graft. To prevent coronary button aneurysms after aortic root surgery in Marfan patients, the coronary buttons and the corresponding side holes on the prosthetic graft must be reduced to the maximum possible extent.