Non-prompt surgery for patients with acute type A aortic dissection without pre-operative shock and malperfusion.

Background: Acute type A aortic dissection (ATAAD) requires urgent surgical treatment. However, during daily practice, there were some patients with ATAAD sought for medical attention several days after symptoms occurred and some other patients hesitated to receive aortic surgery after the diagnosis of ATAAD was made. This study aims to investigate the surgical outcomes of non-prompt aortic surgery (delayed diagnosis caused by the patient or delayed surgery despite immediate diagnosis) for ATAAD patients. Methods: From November 2004 to June 2020, of more than 200 patients with ATAAD patients who underwent aortic surgery at our hospital, there were 30 patients without pre-operative shock and malperfusion who sought for medical attention with symptoms for several days or delayed aortic surgery several days later despite ATAAD was diagnosed. Of the 30 patients (median age 60.9, range 33.4~82.5 years) in the study group, there were 18 patients undergoing surgery when they arrived at our hospital (delayed diagnosis by the patient) and 12 patients receiving surgery days later (delayed surgery despite immediate diagnosis). Patients with prompt surgery after symptom onset (control group) were matched from our database by propensity score matching. The surgical mortality rate and post-operative morbidities were compared between the study group and control group. Results: The in-hospital mortality was 3.3% for the study group and 6.7% for the control group (p = non-significant). The incidence of post-operative cerebral permanent neurological defect was 0% for the study group and 13.3% for the control group (p = 0.112). There were three patients receiving aortic re-intervention or re-do aortic surgery during follow-up for the study group and two patients for the control group. Conclusion: Prompt surgery for ATAAD is usually a good choice if everything is well prepared. Besides, urgent but non-prompt aortic surgery could also provide acceptable surgical results for ATAAD patients without pre-operative shock and malperfusion who did not seek medical attention or who could not make their minds to undergo surgery immediately after symptom onset. Hospitalization with intensive care is very important for pre-operative preparation and monitoring for the patients who decline prompt aortic surgery.

Diabetes associated with hypertension exacerbated oxidative stress-mediated inflammation, apoptosis and autophagy leading to erectile dysfunction in rats.

BACKGROUND: Diabetes or hypertension contributes to erectile dysfunction (ED). We hypothesized that excess reactive oxygen species (ROS) production evoked by diabetes combined with hypertension may further suppress endothelial nitric oxide (NO) expression/activity and promote oxidative stress in the ED penis. METHODS: Twenty-four adult male Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were divided into four groups: normal WKY, diabetic WKY, normal SHR and diabetic SHR. Intraperitoneal streptozotocin (65 mg/kg) was applied to induce type I diabetes. After 4-week diabetes and/or hypertension induction, we determined the intra-cavernous pressure (ICP) using electrical stimulation of cavernous nerves, intra-cavernosum NO amount using an electrochemical NO probe, and blood ROS using an ultrasensitive chemiluminescence-amplified analyzer. Western blot analysis and immunohistochemistry were used to explore the pathophysiologic mechanisms of inflammation, apoptosis and autophagy in the penis. A novel NO donor, CysaCysd Lu-5 (CCL5, (RCH2CH2S)(R'R"CHCH2S)Fe(NO)2, 1-4 µg), was intravenously administered to these ED rats for evaluating their ICP responses. RESULTS: In the baseline status, the lucigenin- and luminol-amplified blood ROS were significantly enhanced in the diabetic SHR rats vs normal WKY rats. Significantly decreased ICP, eNOS expression and NO amount were found in the normal SHR, diabetic WKY, and diabetic SHR vs normal WKY rats. Intravenous NO donor L-Arginine markedly increased ICP and NO amount, whereas eNOS inhibitor, Nω-Nitro-L-Arginine methyl ester hydrochloride depressed ICP in all four groups. Diabetes and/or hypertension alone increased fibrosis, proinflammatory NF-kB/ICAM-1 expression, mast cell numbers, CD68 expression and infiltration, Caspase 3-mediated apoptosis, Beclin-1/LC3-II-mediated autophagy and mild Nrf-2/HO-1 expression and depressed eNOS expression in the ED penis. The novel NO donor, CCL5, was more efficient than L-arginine to improve diabetes and/or hypertension-induced ED by the significant increase of ICP. CONCLUSION: Diabetes combined with hypertension synergistically exacerbated ED through enhanced oxidative stress, inflammation, apoptosis and autophagy and depressed eNOS activity and NO production.

Surgical or interventional treatment for adult patients with atrial septal defect and atrial fibrillation: A systemic review and meta-analysis.

The prevalence of atrial fibrillation (AFib) in adult patients with atrial septal defect (ASD) who did not undergo ASD repair in the childhood is higher than that in general population. The primary aim of this study is to collect various related articles published in the literature and to compare the clinical outcomes with different treatment strategies by systemic reviews and meta-analyses. Of the 1299 initially screened articles, 13 studies with 213 patients were included in this study. All the patients were adults and the mean age at presentation was 55.7 years (range 34-79 years) and 47.8% of the patients were male. Regarding the types of the AFib, there were paroxysmal AFib in 62 patients, persistent AFib in 40 patients and long-standing persistent AFib in 111 patients. For adult patients with ASD and AFib, ASD closure is beneficial for most of the patients if significant left-to-right shunt exists but risk stratification cannot be overlooked because worsening of the functional class may be experienced by some patients post-operatively, especially for the patients with advanced age (>75 years). Reduction of prevalence of AFib could be observed after ASD closure alone which is mainly effective for paroxysmal AFib but not for persistent or long-standing persistent AFib. The successful ablation rate of paroxysmal AFib by catheter ablation is similar to that of all kinds of AFib by surgical ablation. Regarding AFib recurrence, bi-atrial surgical ablation is better than right-atrial ablation for the adult patients with ASD and AFib.

Association of Region-Specific Cardiac Adiposity With Dysglycemia and New-Onset Diabetes.

Background Visceral adipose tissue is assumed to be an important indicator for insulin resistance and diabetes beyond overweight/obesity. We hypothesized that region-specific visceral adipose tissue may regulate differential biological effects for new-onset diabetes regardless of overall obesity. Methods and Results We quantified various visceral adipose tissue measures, including epicardial adipose tissue, paracardial adipose tissue, interatrial fat, periaortic fat, and thoracic aortic adipose tissue in 1039 consecutive asymptomatic participants who underwent multidetector computed tomography. We explored the associations of visceral adipose tissue with baseline dysglycemic indices and new-onset diabetes. Epicardial adipose tissue, paracardial adipose tissue, interatrial fat, periaortic fat, and thoracic aortic adipose tissue were differentially and independently associated with dysglycemic indices (fasting glucose, postprandial glucose, HbA1c, and homeostasis model assessment of insulin resistance) beyond anthropometric measures. The superimposition of interatrial fat and thoracic aortic adipose tissue on age, sex, body mass index, and baseline homeostasis model assessment of insulin resistance expanded the likelihood of baseline diabetes (from 67.2 to 86.0 and 64.4 to 70.8, P for ∆ ꭕ2: <0.001 and 0.011, respectively). Compared with the first tertile, the highest interatrial fat tertile showed a nearly doubled risk for new-onset diabetes (hazard ratio, 2.09 [95% CI, 1.38-3.15], P<0.001) after adjusting for Chinese Visceral Adiposity Index. Conclusions Region-specific visceral adiposity may not perform equally in discriminating baseline dysglycemia or diabetes, and showed differential predictive performance in new-onset diabetes. Our data suggested that interatrial fat may serve as a potential marker for new-onset diabetes.

Perceptions of medical students towards and effectiveness of online surgical curriculum: a systematic review.

BACKGROUND: Online education has been used as an adjunct modality for teaching and it attracts attention in recent years as many medical students can not accomplish their clerkship in the hospital due to COVID-19 pandemic. This study aims to collect the articles related to online surgical education for medical students, and to analyze the effectiveness of online education and the perceptions of the medical students. METHOD: We performed a systemic literature search in PubMed, MEDLINE, EMBASE, ERIC and Cochrane library. Keywords used for searching included "medical student", "online education", "online teaching", "online learning", "distance learning", "electronic learning", "virtual learning" and "surgical". Medical education research study quality instrument (MERSQI) was used for the evaluation of the quality of the searched articles. RESULTS: From 1240 studies retrieved from the databases, 13 articles were included in this study after screening. The publication year was from 2007 to 2021. The mean MERSQI score of the 13 searched articles was 12.5 +/- 1.7 (range 10.0-14.5). There were totally 2023 medical students who attended online surgical curriculum. By online course, improvement of understanding and knowledge on the studied topics could be reached. The confidence in patient encounters could be improved by online curriculum with sharing experiences, discussing, and role playing. However, students felt concentration was poor during online course. Medical students studying through video platform could get better test scores than those studying with textbooks. Regarding basic surgical skills, online teaching of suturing and knot-tying could be possible and was appreciated by the students who could practice away from the hospital and get feedbacks by instructors through online environment. The scores for the clinical competence assessment for incision, suturing and knot-tying were found to be no significant difference between the online teaching group and face-to-face teaching group. CONCLUSION: Online surgical curriculum for medical students is not easy but inevitable in the era of COVID-19 pandemic. Although online course is not the same as physical course, there are some efforts which could be tried to increase the effectiveness. Basic surgical skills could also be taught effectively through online platform. Even if the COVID-19 pandemic is over in the future, online curriculum could still be a helpful adjunct for surgical education.

Surgical Strategies for Cardiac Perforation After Catheter Ablation or Electrophysiology Study.

Catheter ablation is a treatment modality which has been increasingly used for cardiac arrhythmias. However, it is not complication-free, and cardiac perforation is one of its most life-threatening complications. As surgery is usually not the first-line treatment for this emergent episode, there were only very few sporadic surgical reports in the literature. This systemic review primarily aims to collect different surgical approaches for catheter-induced cardiac perforation to help surgeons manage this kind of uncommon and critical patients. Of the 452 initially screened articles, 22 studies (38 patients) were included in the systemic review. Of all the included patients, 84% (32/38) were found to have pericardial effusion acutely following catheter-related procedures, and 16% (6/38) experienced delayed-onset episodes. Regarding the surgical procedures, four patients underwent removal of clots only, eight patients underwent suture repair of the left ventricle (LV), nine patients underwent suture repair of the right ventricle (RV), five patients underwent suture repair of the LA, and four patients underwent sutureless repair of the LV and pulmonary vein (LV 1, RV 1, pulmonary vein 1). In addition to repair of perforation sites, the concomitant combined procedures included repair of intercostal vessels (complication of pericardiocentesis) for one patient, cryoablation for two patients, and maze procedure for one patient. For cardiac perforation following catheter ablation or electrophysiology study, although the majority of the patients are treated with pericardiocentesis and medical management at first, cardiovascular surgeons have to prepare to take over if the bleeding is persistent or if the cardiac tamponade is not relieved.

Thoracic Aortic Calcification and Pre-Clinical Hypertension by New 2017 ACC/AHA Hypertension Guidelines.

The recently revised 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension (HTN) guidelines employ a lower blood pressure threshold to define HTN, aiming for earlier prevention of HTN-related cardiovascular diseases (CVD). Thoracic aortic calcification (TAC), a new surrogate marker of aging and aortic medial layer degeneration, and different stages of HTN, according to the 2017 ACC/AHA HTN guidelines, remain unknown. We classified 3022 consecutive asymptomatic individuals enrolled into four HTN categories using the revised 2017 ACC/AHA guidelines: normal blood pressure (NBP), elevated blood pressure (EBP), and stage 1 (S1) and stage 2 (S2) HTN. The coronary artery calcification score and TAC metrics (total Agaston TAC score, total plaque volume (mm3), and mean density (Hounsfield units, HU)) were measured using multi-detector computed tomography. Compared to NBP, a graded and significant increase in the TAC metrics was observed starting from EBP and S1 and S2 HTN, using the new 2017 ACC/AHA guidelines (NBP as reference; all trends: p < 0.001). These differences remained consistent after being fully adjusted. Older age (>50 years), S1 and S2 HTN, prevalent diabetes, and chronic kidney disease (<60 mL/min/1.73 m2) are all independently contributing factors to higher TAC risk using multivariate stepwise logistic regressions (all p ≤ 0.001). The optimal cutoff values of systolic blood pressure, diastolic blood pressure, and pulse pressure were 121, 74, and 45 mmHg, respectively, for the presence of TAC after excluding subjects with known CVD and ongoing HTN medication treatment. Our data showed that the presence of TAC starts at a stage of elevated blood pressure not categorized as HTN from the updated 2017 ACC/AHA hypertension guidelines.

Green Tea Polyphenol Catechins Inhibit Coronavirus Replication and Potentiate the Adaptive Immunity and Autophagy-Dependent Protective Mechanism to Improve Acute Lung Injury in Mice.

Effective antiviral therapeutics are urgently required to fight severe acute respiratory syndrome (SARS) caused by a SARS coronavirus (SARS-CoV). Because polyphenol catechins could confer antioxidative, anti-inflammatory, antiviral, and antimicrobial activities, we assessed the therapeutic effects of catechins against SARS-CoV replication in Vero E6 cells, the preventive effect of catechins on CD25/CD69/CD94/CD8+ cytotoxic T lymphocytes-mediated adaptive immunity, and the protective effect on lipopolysaccharide-induced acute lung injury (ALI) in mice. We found that catechins containing 32.8% epigallocatechin gallate, 15.2% epicatechin gallate, 13.2 epicatechin, 10.8% epigallocatechin, 10.4% gallocatechin, and 4.4% catechin directly inhibited SARS-CoV replication at sub-micromolecular concentrations. Four-week catechins ingestion increased CD8+ T cell percentage, upregulated CD69+/CD25+/CD94-NKG2A/CD8+ T lymphocytes-mediated adaptive immunity, and increased type I cytokines release responding to ovalbumin/alum. Catechins significantly reduced lipopolysaccharide-induced cytokine storm and oxidative stress and ALI by inhibiting PI3K/AKT/mTOR signaling to upregulate Beclin-1/Atg5-Atg12/LC3-II-mediated autophagy mechanism. Pretreatment of autophagy inhibitor 3-Methyladenine reversed the inhibiting effects of catechins on the cytokines and oxidative stress levels and ALI. In conclusion, our data indicated that catechins directly inhibited SARS-CoV replication, potentiated the CD25/CD69/CD94/CD8+ T lymphocytes-mediated adaptive immunity and attenuated lipopolysaccharide-induced ALI and cytokine storm by PI3K/AKT/mTOR-signaling-mediated autophagy, which may be applied to prevent and/or treat SARS-CoV infection.

Retrograde cerebral perfusion for surgery of type A aortic dissection.

BACKGROUND: For type A aortic dissection (TAAD), antegrade cerebral perfusion (ACP) was proposed as a more physiological method than retrograde cerebral perfusion (RCP) for intra-operative brain protection, but it is still debatable whether antegrade cerebral perfusion (ACP) or retrograde cerebral perfusion (RCP) is related to the better clinical outcome. The present study was undertaken to compare the results in our patients receiving surgery for TAAD with ACP or RCP. The primary aim of this study was focused on the incidence of and the factors associated with surgical mortality, post-operative neurological outcomes and long-term survival. METHODS: From February 2001 to March 2019, there were 223 consecutive patients with TAAD treated surgically at our hospital. The median age at presentation was 56 years (range 29-88 years) and 70 patients (31.4%) over 65 years of age. There were 168 patients treated with RCP and 55 patients treated with ACP. The primary endpoints were surgical mortality and neurological outcome. Propensity score matching was used to compare the treatment results of surgeries with RCP or ACP. The long-term survival was also analyzed. RESULTS: The overall in-hospital mortality rate and the overall 30-day mortality rate were 15.6% and 14.3% respectively. For the patients without pre-operative shock (n = 184), the in-hospital mortality rate was 10.3% and the 30-day mortality rate was 8.7% and higher long-term survival rates (88.3% for 5 years, 86.5% for 10 years, 86.5% for 15 years) were documented for this patient group. There was no significant difference on the surgical mortality between the ACP group and the RCP group. In the entire cohort, there were 23 patients (10.3%) who suffered from post-operative neurological deficits (PND) and there were less PND for the patients with RCP than the patients with ACP (7.7% vs 18.1%, p = 0.027). After propensity score matching, there was still higher incidence of PND in the ACP group than in the RCP group but without statistical significance (18.5% vs 11.1%, p = 0.279). CONCLUSIONS: Aortic surgery carries high risk for the patients with TAAD and PND is not an unusual post-operative morbidity. In our series, pre-operative shock, pre-operative CPR, CRI, past history with CAD are related to higher surgical mortality. The younger patients (<65 years old) without pre-operative shock got better surgical outcome and long-term survival. RCP could provide acceptable cerebral protection during aortic surgery for the TAAD patients. Old age, pre-operative shock, CRI and past history of CAD are independent risk factors for long-term survival.

Epicardial Adiposity in Relation to Metabolic Abnormality, Circulating Adipocyte FABP, and Preserved Ejection Fraction Heart Failure.

Epicardial adipose tissue (EAT) as a source of pro-inflammatory cytokines tightly linked to metabolic abnormalities. Data regarding the associations of EAT with adipocyte fatty acid-binding protein (A-FABP), a cytokine implicated in the cardiometabolic syndrome, might play an important part in mediating the association between EAT and cardiac structure/function in preserved ejection fraction heart failure (HFpEF). We conducted a prospective cohort study comprising 252 prospectively enrolled study participants classified as healthy (n = 40), high-risk (n = 161), or HFpEF (n = 51). EAT was assessed using echocardiography and compared between the three groups and related to A-FABP, cardiac structural/functional assessment utilizing myocardial deformations (strain/strain rates) and HF outcomes. EAT thickness was highest in participants with HFpEF (9.7 ± 1.7 mm) and those at high-risk (8.2 ± 1.5 mm) and lowest in healthy controls (6.4 ± 1.9 mm, p < 0.001). Higher EAT correlated with the presence of cardiometabolic syndrome, diabetes and renal insufficiency independent of BMI and waist circumference (pinteraction for all > 0.1), and was associated with reduced LV global longitudinal strain (GLS) and LV mass-independent systolic/diastolic strain rates (SRs/SRe) (all p < 0.05). Higher A-FABP levels were associated with greater EAT thickness (pinteraction > 0.1). Importantly, in the combined control cohort, A-FABP levels mediated the association between EAT and new onset HF. Excessive EAT is independently associated with the metabolic syndrome, renal insufficiency, and higher A-FABP levels. The association between EAT and new onset HF is mediated by A-FABP, suggesting a metabolic link between EAT and HF.

Diabetes Upregulates Oxidative Stress and Downregulates Cardiac Protection to Exacerbate Myocardial Ischemia/Reperfusion Injury in Rats.

Diabetes exacerbates myocardial ischemia/reperfusion (IR) injury by incompletely understood mechanisms. We explored whether diabetes diminished BAG3/Bcl-2/Nrf-2/HO-1-mediated cardioprotection and overproduced oxidative stress contributing to exaggerated IR injury. Streptozotocin-induced diabetes enhanced hyperglycemia, cardiac NADPH oxidase p22/p67 expression, malondialdehyde amount and leukocyte infiltration, altered the mesenteric expression of 4-HNE, CaSR, p-eNOS and BAG3 and impaired microvascular reactivity to the vasoconstrictor/vasodilator by a wire myography. In response to myocardial IR, diabetes further depressed BAG3/Bcl-2/Nrf-2/HO-1 expression, increased cleaved-caspase 3/poly(ADP-ribose) polymerase (PARP)/TUNEL-mediated apoptosis and exacerbated IR-induced left ventricular dysfunction characterized by further depressed microcirculation, heart rate, left ventricular systolic pressure and peak rate of pressure increase/decrease (±dp/dt) and elevated left ventricular end-diastolic pressure (LVEDP) and Evans blue-2,3,5-triphenyltetrazolium chloride-stained infarct size in diabetic hearts. Our results implicated diabetes exacerbated IR-induced myocardial dysfunction through downregulated BAG3/Bcl-2/Nrf-2/HO-1 expression, increased p22/p67/caspase 3/PARP/apoptosis-mediated oxidative injury and impaired microvascular reactivity.

Application and Comparison of Different Prognostic Scoring Systems in Patients Who Underwent Cardiologist-Managed Percutaneous Cardiopulmonary Support.

BACKGROUND: Temporary mechanical support, including percutaneous cardiopulmonary support (PCPS), is crucial for reversing patients' compromised hemodynamic function. Knowledge about whether cardiologists can directly manage patients receiving PCPS and about the predictive values of different prognostic scores is insufficient. METHODS: We examined the data and in-hospital mortality of 45 eligible patients receiving cardiologist-managed PCPS from July 2012 to January 2019 in our institute. We compared different prognostic scores [namely Survival After Veno-arterial ECMO (SAVE), modified SAVE, prEdictioN of Cardiogenic shock OUtcome foR acute myocardial infarction patients salvaGed by VA-ECMO (ENCOURAGE), and Sequential Organ Failure Assessment (SOFA) scores] through area under the receiver operating characteristic curve (AUC) analysis. RESULTS: The patients' mean age was 64.3 ± 11.3 years, and 71.1% were men. The overall in-hospital survival rate was 35.6%. Compared to survivors, nonsurvivors were more likely to have an ischemic etiology, cardiopulmonary resuscitation, and higher lactate levels. Survivors had higher SAVE (-5.9 vs. -11.4) and modified SAVE (4.2 vs. -7.1) scores than nonsurvivors (both p = 0.001), but SOFA (9.7 vs. 10.3) and ENCOURAGE (24.8 vs. 26.8) scores were similar (both p > 0.1). In multivariate models, only modified SAVE score remained statistically significant (hazard ratio: 0.96, 95% confidence interval: 0.93-1.00; p = 0.047). Modified SAVE score showed the best risk discrimination (AUC = 0.78). CONCLUSIONS: Establishing regular and continual training protocols can enable cardiologists to perform emergency PCPS (without on-site surgery) and daily care for patients with refractory cardiogenic shock. The modified SAVE score facilitates risk stratification and future decision-making processes.

Circulating Monocyte Count as a Surrogate Marker for Ventricular-Arterial Remodeling and Incident Heart Failure with Preserved Ejection Fraction.

Among 2085 asymptomatic subjects (age: 51.0±10.7 years, 41.3% female) with data available on common carotid artery diameter (CCAD) and circulating total white blood cell (WBC) counts, higher circulating leukocytes positively correlated with higher high sensitivity C-reactive protein (hs-CRP).Higher WBC/segmented cells and monocyte counts were independently associated with greater relative wall thicknesses and larger CCADs,which in generalweremore pronounced in men and obese subjects (body mass index ≥ 25kg/m2) (all P interaction: < 0.05). Using multivariate adjusting models, only the monocyte count independently predicted theleft ventricularmass index (LVMi) (ß-Coef: 0.06, p = 0.01). Higher circulating WBC, segmented,and monocyte counts and a greater CCAD were all independently associated with a higher risk of heart failure (HF)/all-cause death during a median of 12.1 years of follow-up in fully adjusted models, with individuals manifesting both higher CCADs and monocyte countsincurring the highest risk of HF/death (adjusted hazard ratio: 2.81, 95% CI: 1.57. -5.03, p< 0.001; P interaction, 0.035; lower CCAD/lower monocyte as reference). We conclude that a higher monocyte count is associated with cardiac remodeling and carotid artery dilation.Both an elevated monocyte count and a larger CCAD may indicate a specific phenotype that confers the highest risk of HF, which likely signifies the role of circulating monocytes in the pathophysiology of heart failure with preserved ejection fraction (HFpEF).

Staged surgical repair for infants with interrupted aortic arch.

BACKGROUND: Interrupted aortic arch (IAA) is a rare congenital cardiac anomaly, which necessitates surgical treatment. There are several surgical strategies for corrective repair of IAA, such as one-stage repair, rapid two-stage repair and two-stage repair. Here, we reported our surgical result of staged-repair policy for the patients with IAA. METHOD: From November 2003 to July 2015, there were 14 patients (8 boys, 6 girls) with IAA treated by us. Except one teenager patient, we routinely used intravenous infusion of prostaglandin E1 for all the infant patients (n = 13) to keep adequate end organ perfusion before the first surgical intervention. Surgical repair was performed after the perfusion of end organs recovered. RESULT: Two patients (1 teenager and 1 infant with one-stage surgery) were excluded from this study. At the time of the first surgery, we did the first-stage surgery with anastomosis in between aortic arch and descending aorta, division of patent ductus arteriosus and banding of pulmonary trunk through left thoracotomy. The overall surgical survival rate of the first surgery was 100% (12/12). At the time of the second surgery, corrective repair was done under cardiopulmonary bypass through median sternotomy. The surgical survival rate of the corrective surgery was also 100%. There is no late death during follow-up for 9 years (range 4.2-15.0 years). CONCLUSION: Out of several surgical strategies for the infants with IAA, staged repair still could be a treatment option to achieve satisfied surgical result.

Genetic Depletion of Thromboxane A2/Thromboxane-Prostanoid Receptor Signalling Prevents Microvascular Dysfunction in Ischaemia/Reperfusion Injury.

OBJECTIVE: Activation of thromboxane A2 synthase (TXAS)/thromboxane A2 (TXA2)/thromboxane prostanoid (TP) receptor leads to arterial constriction, platelet aggregation and vascular injury. We attempted to characterize the microvascular dysfunction in ischaemia/reperfusion injury using genetically modified TXAS-/-, TP-/- and TXAS-/-TP-/- mice. APPROACH AND RESULTS: The cardiac micro-circulation and electrocardiograms were evaluated from B6, TXAS-/-, TP-/- and TXAS-/-TP-/- mice in response to intravenous saline, endothelin-1, U46619 (a TXA2 agonist) and myocardial ischaemia/reperfusion injury. Cardiac function was investigated with myocardial permeability, the troponin I concentration and the infarct size. Myocardial TXAS, TP, endothelial nitric oxide (NO) synthase (eNOS), nicotinamide adenine dinucleotide phosphate oxidase 4 (NOx4), 4-hydroxynonenal, interleukin (IL)-1ß, cell apoptosis, coronary effluent thromboxane B2 (TXB2) and superoxide anions (O2 -) and NO concentrations were measured. Mice mesenteric reactivity in response to various drugs was assessed by wire myography. In vivo fluorescent platelet adhesiveness to the mesenteric arterial endothelium after FeCl3 stimulation was examined. In B6 mice, ischaemia/reperfusion significantly increased levels of ST-segment elevation, myocardial TXAS, TP, NOx4, IL-1ß, apoptosis, coronary endothelin-1, TXB2, O2 - release and the infarct size, with concomitant decreases in eNOS, NO concentrations and cardiac micro-circulation. These effects were remarkably depressed in TXAS-/-, TP-/- and TXAS-/-TP-/- mice. Aspirin treatment or depletion of the TXAS, TP or TXAS/TP gene significantly attenuated the exaggerated vascular reactivity by vasoconstrictors and vasodilators and efficiently reduced platelet adhesion to the mesenteric endothelium under FeCl3 stimulation. CONCLUSION: Inhibiting TXAS/TXA2/TP signalling confers microvascular protection against oxidative injury in both cardiac and mesenteric arteries.

Catechins Blunt the Effects of oxLDL and its Primary Metabolite Phosphatidylcholine Hydroperoxide on Endothelial Dysfunction Through Inhibition of Oxidative Stress and Restoration of eNOS in Rats.

BACKGROUND/AIMS: We explored the effects of catechins (decaffeinated green tea extracts containing (-)-epicatechin, (-)-epigallocatechin, (-)-epicatechin gallate and (-)-epigallocatechin gallate) on atherosclerosis risk factors, oxidized low-density lipoprotein (oxLDL) and its primary metabolite, phosphatidylcholine hydroperoxide (PCOOH) induced oxidative injury in cultured endothelial cell line and rats. METHODS: We used endothelial cell line and male Wistar rats to determine the effect of catechins on oxLDL or PCOOH induced oxidative injury including apoptosis, H2O2 level, vascular responses and urinary 8-isoprostane and nitrite/nitrate concentration. Plasma catechins concentration was determined by a CoulArray HPLC. Responses of aortic and renal vasoconstriction were evaluated by a transonic meter and a full-field laser perfusion imager. RESULTS: PCOOH administration significantly increased H2O2 amounts and cell apoptosis and decreased endothelial nitric oxide synthase (eNOS) expression in the cultured endothelial cells. Catechins pretreatment significantly reduced PCOOH-elevated H2O2 amounts, endothelial cell apoptosis and partly recovered eNOS expression. Intravenous administration of oxLDL, PCOOH or H2O2, not native LDL, significantly decreased renal and aortic blood flow associated with enhanced ICAM-1 expression and 4-hydroxynoneal (4-HNE) accumulation, and decreased eNOS expression in the male Wistrar rats. One hour after oral intake of green tea extracts, 4 peaks of catechins were found in the rat plasma. The increased plasma catechins significantly inhibited oxLDL-, PCOOH- or H2O2-induced renal and aortic vasoconstriction, decreased urinary 8-isoprostane levels, renal ICAM-1 expression and 4-HNE accumulation, and restored nitrite/nitrate amounts and eNOS activity. CONCLUSIONS: Our data suggests that catechins pretreatment decrease PCOOH-induced endothelial apoptosis and arterial vasoconstriction through the action of H2O2 inhibition and eNOS restoration.