First-in-human left atrial appendage closure using the WATCHMAN FLX Pro device: a case report.

Background: Device-related thrombosis (DRT) is a known complication to left atrial appendage closure (LAAC). The surface of a LAAC device should ideally have antithrombotic properties. The novel WATCHMAN FLX Pro (WFP) incorporates a fluoropolymer-coated fabric membrane designed to increase thromboresistance and facilitate endothelialization. Such features could potentially allow for a minimal post-procedural antithrombotic regimen. Radiopaque platinum markers at the device shoulders and a large 40 mm device are other novel features of the WFP. Case summary: A 75-year-old man with atrial fibrillation was referred for LAAC due to prior subdural haemorrhage during direct-acting anticoagulation treatment. He underwent the first-in-human WFP implantation as part of the WATCHMAN FLX Pro CT study (NCT05567172). Computed tomography (CT) was used for pre-planning, and the procedure was performed under local analgesia guided by intracardiac echocardiography from the left atrium (LA) without any complications. Post-procedural antithrombotic treatment consisted of acetylsalicylic acid 75 mg/day only, and 45-day CT, transoesophageal echocardiography (TEE), and magnetic resonance imaging demonstrated optimal device position with complete LAAC. Hypoattenuated thickening (6 mm) appeared on the device as a smooth surface in continuity with the left atrial wall on CT and TEE. A specific magnetic resonance T1-weighted scan, used for visualization of fresh thrombus, suggested this to represent tissue ingrowth rather than thrombus. Discussion: The advanced follow-up imaging protocol suggested a good WFP implantation result with signs of tissue ingrowth at 45 days. The added radiopaque markers facilitated optimal deployment, evaluation of device stability during tug test, and assessment of device protrusion into the LA.

Increasing Levels of Positive End-expiratory Pressure Cause Stepwise Biventricular Stroke Work Reduction in a Porcine Model.

BACKGROUND: Positive end-expiratory pressure (PEEP) is commonly applied to avoid atelectasis and improve oxygenation in patients during general anesthesia but affects cardiac pressures, volumes, and loading conditions through cardiorespiratory interactions. PEEP may therefore alter stroke work, which is the area enclosed by the pressure-volume loop and corresponds to the external work performed by the ventricles to eject blood. The low-pressure right ventricle may be even more susceptible to PEEP than the left ventricle. The authors hypothesized that increasing levels of PEEP would reduce stroke work in both ventricles. METHODS: This was a prospective, observational, experimental study. Six healthy female pigs of approximately 60 kg were used. PEEP was stepwise increased from 0 to 5, 7, 9, 11, 13, 15, 17, and 20 cm H2O to cover the clinical spectrum of PEEP. Simultaneous, biventricular invasive pressure-volume loops, invasive blood pressures, and ventilator data were recorded. RESULTS: Increasing PEEP resulted in stepwise reductions in left (5,740 ± 973 vs. 2,303 ± 1,154 mmHg · ml; P < 0.001) and right (2,064 ± 769 vs. 468 ± 133 mmHg · ml; P < 0.001) ventricular stroke work. The relative stroke work reduction was similar between the two ventricles. Left ventricular ejection fraction, afterload, and coupling were preserved. On the contrary, PEEP increased right ventricular afterload and caused right ventriculo-arterial uncoupling (0.74 ± 0.30 vs. 0.19 ± 0.13; P = 0.01) with right ventricular ejection fraction reduction (64 ± 8% vs. 37 ± 7%, P < 0.001). CONCLUSIONS: A stepwise increase in PEEP caused stepwise reduction in biventricular stroke work. However, there are important interventricular differences in response to increased PEEP levels. PEEP increased right ventricular afterload leading to uncoupling and right ventricular ejection fraction decline. These findings may support clinical decision-making to further optimize PEEP as a means to balance between improving lung ventilation and preserving right ventricular function.

Detection of brain lesions after catheter ablation depends on imaging criteria: insights from AXAFA-AFNET 5 trial.

AIMS: Left atrial catheter ablation is well established in patients with symptomatic atrial fibrillation (AF) but associated with risk of embolism to the brain. The present analysis aims to assess the impact of diffusion-weighted imaging (DWI) slice thickness on the rate of magnetic resonance imaging (MRI)-detected ischaemic brain lesions after ablation. METHODS AND RESULTS: AXAFA-AFNET 5 trial (NCT02227550) participants underwent MRI using high-resolution (hr) DWI (slice thickness: 2.5-3 mm) and standard DWI (slice thickness: 5-6 mm) within 3-48 h after ablation. In 321 patients with analysable brain MRI (mean age 64 years, 33% female, median CHA2DS2-VASc 2), hrDWI detected at least one acute brain lesion in 84 (26.2%) patients and standard DWI in 60 (18.7%; P < 0.01) patients. High-resolution diffusion-weighted imaging detected more lesions compared to standard DWI (165 vs. 104; P < 0.01). The degree of agreement for lesion confirmation using hrDWI vs. standard DWI was substantial (κ = 0769). Comparing the proportion of DWI-detected lesions, lesion distribution, and total lesion volume per patient, there was no difference in the cohort of participants undergoing MRI at 1.5 T (n = 52) vs. 3 T (n = 269). CONCLUSION: The pre-specified AXAFA-AFNET 5 sub-analysis revealed significantly increased rates of MRI-detected acute brain lesions using hrDWI instead of standard DWI in AF patients undergoing ablation. In comparison to DWI slice thickness, MRI field strength had a no significant impact in the trial. Comparing the varying rates of ablation-related MRI-detected brain lesions across previous studies has to consider these technical parameters. Future studies should use hrDWI, as feasibility was demonstrated in the multicentre AXAFA-AFNET 5 trial.

Automated detection of cardiac rest period for trigger delay calculation for image-based navigator coronary magnetic resonance angiography.

BACKGROUND: Coronary magnetic resonance angiography (coronary MRA) is increasingly being considered as a clinically viable method to investigate coronary artery disease (CAD). Accurate determination of the trigger delay to place the acquisition window within the quiescent part of the cardiac cycle is critical for coronary MRA in order to reduce cardiac motion. This is currently reliant on operator-led decision making, which can negatively affect consistency of scan acquisition. Recently developed deep learning (DL) derived software may overcome these issues by automation of cardiac rest period detection. METHODS: Thirty individuals (female, n = 10) were investigated using a 0.9 mm isotropic image-navigator (iNAV)-based motion-corrected coronary MRA sequence. Each individual was scanned three times utilising different strategies for determination of the optimal trigger delay: (1) the DL software, (2) an experienced operator decision, and (3) a previously utilised formula for determining the trigger delay. Methodologies were compared using custom-made analysis software to assess visible coronary vessel length and coronary vessel sharpness for the entire vessel length and the first 4 cm of each vessel. RESULTS: There was no difference in image quality between any of the methodologies for determination of the optimal trigger delay, as assessed by visible coronary vessel length, coronary vessel sharpness for each entire vessel and vessel sharpness for the first 4 cm of the left mainstem, left anterior descending or right coronary arteries. However, vessel length of the left circumflex was slightly greater using the formula method. The time taken to calculate the trigger delay was significantly lower for the DL-method as compared to the operator-led approach (106 ± 38.0 s vs 168 ± 39.2 s, p < 0.01, 95% CI of difference 25.5-98.1 s). CONCLUSIONS: Deep learning-derived automated software can effectively and efficiently determine the optimal trigger delay for acquisition of coronary MRA and thus may simplify workflow and improve reproducibility.

Correlation between Serum Erythropoietin and Cerebral Collateral Flow in Acute Ischemic Stroke Patient.

BACKGROUND: Erythropoietin (EPO), which is associated with anemia, exerts neuroprotective effects in ischemic stroke. In cases of stenosis or narrowing of the main cerebral blood vessel, the prognosis is favorable if collateral blood circulation is well developed in acute stroke. Several studies have investigated the relationship between EPO administration and stroke outcomes. The present study investigated the correlation between serum EPO level and cerebral collateral circulation, which could result in favorable clinical outcomes. METHODS: The study subjects were patients diagnosed with acute ischemic stroke who underwent initial brain magnetic resonance imaging between January 2020 and March 2022. Following brain computed tomography perfusion for collateral flow, serum EPO levels were measured. Collaterals were assessed according to the Mass system and divided into good collateral (GC) or poor collateral (PC) groups. Serum EPO levels were determined using a chemiluminescence immunoassay method. A correlation coefficient analysis was conducted to determine the correlation between serum EPO levels and GC. A receiver operating characteristic curve analysis determined the cutoff value of EPO for GC. RESULTS: Serum EPO levels were significantly higher in the GC than that in the PC group (P<0.05). The cut-off level of serum EPO for a good outcome was 9.1 mIU/mL. CONCLUSION: A high serum EPO (>9.1 mIU/mL) could be a marker of GC in patients with acute ischemic stroke that predicts good clinical outcomes.

Myocardial infarction without obstructive coronary artery disease.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is characterized by clinical evidence of myocardial infarction with normal or near-normal coronary arteries on angiography (less-than 50% stenosis). MINOCA is a group of heterogeneous diseases with different pathophysiologic mechanism which all can cause ischaemia. MINOCA is considered a "working diagnosis" after angiography until further evaluation regarding its underlying cause is made. The aim of this review is to assess the literature on clinical features, aetiology, diagnosis, treatment and prognosis of patients with MINOCA.

Osseous metaplasia of the palate: a case report.

Osseous metaplasia is defined as the formation of lamellar bone inside soft tissue structures where bone normally does not exist. It results from the transformation of non-osseous connective tissue into mature bone. This condition is rare in the oral and maxillofacial region. We report a case of osseous metaplasia of the maxilla, a rare benign tumor in an uncommon region. A 60-year-old male patient visited our clinic complaining of foreign body sensation and asymptomatic swelling on the right palatal side. However, he did not experience pain and reported no local trauma that he could remember. Intra-oral examination revealed an exophytic lesion on the right palatal portion. On computed tomography, there was a round hard-tissue mass approximately 2 cm in diameter on the right palate area. The mass was biopsied and diagnosed as an osseous metaplasia. We review the clinical, radiographic, and histologic features and common causes of osseous metaplasia and report a rare case of osseous metaplasia of the palate.

Clinical presentation and cardiac imaging findings in patient cases of perimyocarditis and pericarditis with a temporal association to SARS-CoV-2 vaccination.

Aims: We aimed to investigate and present cases of perimyocarditis and pericarditis verified by cardiovascular resonance (CMR) imaging in patients with a strong temporal association to SARS-CoV-2 vaccination. We sought to describe the clinical presentation including coronary artery angiography, CMR, transthoracic echocardiography, blood samples, electrocardiography, and symptoms. Methods: We included 10 patients admitted with chest pain shortly after vaccination for SARS-CoV-2, who were diagnosed with pericarditis or perimyocarditis by CMR. We reviewed the CMR, echocardiography, electrocardiography, blood samples, coronary artery angiography, vital signs and medical history. The updated Lake Louise Criteria were used to determine the diagnosis by CMR. Results: Eight patients had perimyocarditis and two patients had pericarditis. The mean age was 22 ± 5 years (range 16 to 31 years), 90% were male. The median time from vaccination to hospital admission was 4 days (range 2 to 28 days). Admissions were seen after vaccination with three different SARS-CoV-2 vaccine manufacturers. Nine Patients had ST-elevation on the initial electrocardiography. Peak troponins varied from 357 to 23,547 ng/l, with a median of 4,304 ng/l. Two patients had an LVEF <50% on echocardiography and four patients had left ventricular global longitudinal strain values <18%. CMR revealed preserved left ventricular ejection fraction (LVEF), although one patient had decreased LVEF on CMR. The T1 and T2 mapping values were increased in all patients. Of the 8 patients with perimyocarditis, all patients had signs of myocardial injury in the lateral segments of the left ventricle. Conclusions: This case series of 10 patients supports the emerging evidence of an association between vaccination for SARS-CoV-2 and perimyocarditis and pericarditis, especially in young males. The temporal association was seen after vaccines from three different manufacturers. Imaging data from echocardiography and CMR displayed normal to mildly impaired cardiac function, usually with a mild disease course.

Changes in a facial recognition algorithm following different types of orthognathic surgery: a comparative study.

Objectives: Contemporary biometric technologies have been gaining traction in both public and private security sectors. Facial recognition is the most commonly used biometric technology for this purpose. We aimed to evaluate the ability of a publicly available facial recognition application program interface to calculate similarity scores of presurgical and postsurgical photographs of patients who had orthognathic surgery. Materials and Methods: Presurgical and postsurgical photographs of 75 patients who had orthognathic surgery between January 2018 and November 2020 in our department were used. Frontal photographs of patients in relaxed and smiling states were taken. The patients were classified into three groups: Group 2 had one-jaw surgery, Group 3 had two-jaw surgery to correct mandibular prognathism, and Group 4 had two-jaw surgery to correct facial asymmetry. For comparison, photographs of 10 participants were used as controls (Group 1). Two facial recognition application programs (Face X and Azure) were used to assess similarity scores. Results: The similarity scores in the two programs showed significant results. The similarity score of the control group, which did not undergo orthognathic surgery, was the highest. The results for Group 2, Group 3, and Group 4 were higher in the order of Group 2, Group 3, and Group 4. Conclusion: In this study, all orthodontic patients were recognized as the same person using the face recognition program before and after surgery. A significant difference in similarity results was obtained between the groups with both Face X and Azure and in both relaxed and smiling states.

Cardiac Performance and Cardiopulmonary Fitness After Infection With SARS-CoV-2.

Aims: Persistent cardiac symptoms are an increasingly reported phenomenon following COVID-19. However, the underlying cause of cardiac symptoms is unknown. This study aimed to identify the underlying causes, if any, of these symptoms 1 year following acute COVID-19 infection. Methods and Results: 22 individuals with persistent cardiac symptoms were prospectively investigated using echocardiography, cardiovascular magnetic resonance (CMR), 6-min walking test, cardio-pulmonary exercise testing and electrocardiography. A median of 382 days (IQR 368, 442) passed between diagnosis of COVID-19 and investigation. As a cohort their echocardiography, CMR, 6-min walking test and exercise testing results were within the normal ranges. There were no differences in left ventricular ejection fraction (61.45 ± 6.59 %), global longitudinal strain (19.80 ± 3.12 %) or tricuspid annular plane systolic excursion (24.96 ± 5.55 mm) as measured by echocardiography compared to a healthy control group. VO2 max (2045.00 ± 658.40 ml/min), % expected VO2 max (114.80 ± 23.08 %) and 6-minute distance walked (608.90 ± 54.51 m) exceeded that expected for the patient cohort, whilst Troponin I (5.59 ± 6.59 ng/l) and Nt-proBNP (88.18 ± 54.27 ng/l) were normal. Conclusion: Among a cohort of 22 patients with self-reported persistent cardiac symptoms, we identified no underlying cardiac disease or reduced cardiopulmonary fitness 1 year following COVID-19.

Effect of remote ischaemic conditioning on left ventricular function in ST-segment elevation myocardial infarction patients: The CONDI-2 echocardiographic sub-study.

Background: Remote ischaemic conditioning (RIC) applied to the arm by inflation and deflation of a pneumatic cuff has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PPCI). However, the effect of RIC on left ventricular ejection fraction (LVEF) following infarct healing remains unknown. Objective: To investigate whether RIC applied in the ambulance before PPCI can improve left ventricular (LV) function in STEMI patients 3 months following infarction. Methods: Echocardiography was performed in a total of 694 patients from the CONDI-2 study a median of 112 days (IQR 63) after the initial admission. LVEF and LV end-diastolic and end-systolic volumes were calculated using the modified Simpsons biplane method of disks. LV global longitudinal strain (GLS) was estimated using 2-dimensional cine-loops with a frame rate > 55 frames/second, measured in the three standard apical views. Results: There was no difference in the measured echocardiographic parameters in the RIC group as compared to the control group, including LV EF, LV GLS, tricuspid annular plane systolic excursion or left ventricular volumes. In the control group, 32% had an ejection fraction < 50% compared to 37% in the RIC group (p = 0.129). Conclusion: In this largest to date randomized imaging study of RIC, RIC as an adjunct to PPCI was not associated with a change in echocardiographic measures of cardiac function compared to standard PPCI alone.

Remodeling after myocardial infarction and effects of heart failure treatment investigated by hyperpolarized [1-13 C]pyruvate magnetic resonance spectroscopy.

PURPOSE: Hyperpolarized [1-13 C]pyruvate MRS can measure cardiac metabolism in vivo. We investigated whether [1-13 C]pyruvate MRS could predict left ventricular remodeling following myocardial infarction (MI), long-term left ventricular effects of heart failure medication, and could identify responders to treatment. METHODS: Thirty-five rats were scanned with hyperpolarized [1-13 C]pyruvate MRS 3 days after MI or sham surgery. The animals were re-examined after 30 days of therapy with ß-blockers and ACE-inhibitors (active group, n = 12), placebo treatment (placebo group, n = 13) or no treatment (sham group, n = 10). Furthermore, heart tissue mitochondrial respiratory capacity was assessed by high-resolution respirometry. Metabolic results were compared between groups, over time and correlated to functional MR data at each time point. RESULTS: At 30 ± 0.5 days post MI, left ventricular ejection fraction (LVEF) differed between groups (sham, 77% ± 1%; placebo, 52% ± 3%; active, 63% ± 2%, P < .001). Cardiac metabolism, measured by both hyperpolarized [1-13 C]pyruvate MRS and respirometry, neither differed between groups nor between baseline and follow-up. Three days post MI, low bicarbonate + CO2 /pyruvate ratio was associated with low LVEF. At follow-up, in the active group, a poor recovery of LVEF was associated with high bicarbonate + CO2 /pyruvate ratio, as measured by hyperpolarized MRS. CONCLUSION: In a rat model of moderate heart failure, medical treatment improved function, but did not on average influence [1-13 C]pyruvate flux as measured by MRS; however, responders to heart failure medication had reduced capacity for carbohydrate metabolism.

Effect of remote ischaemic conditioning on infarct size and remodelling in ST-segment elevation myocardial infarction patients: the CONDI-2/ERIC-PPCI CMR substudy.

The effect of limb remote ischaemic conditioning (RIC) on myocardial infarct (MI) size and left ventricular ejection fraction (LVEF) was investigated in a pre-planned cardiovascular magnetic resonance (CMR) substudy of the CONDI-2/ERIC-PPCI trial. This single-blind multi-centre trial (7 sites in UK and Denmark) included 169 ST-segment elevation myocardial infarction (STEMI) patients who were already randomised to either control (n = 89) or limb RIC (n = 80) (4 × 5 min cycles of arm cuff inflations/deflations) prior to primary percutaneous coronary intervention. CMR was performed acutely and at 6 months. The primary endpoint was MI size on the 6 month CMR scan, expressed as median and interquartile range. In 110 patients with 6-month CMR data, limb RIC did not reduce MI size [RIC: 13.0 (5.1-17.1)% of LV mass; control: 11.1 (7.0-17.8)% of LV mass, P = 0.39], or LVEF, when compared to control. In 162 patients with acute CMR data, limb RIC had no effect on acute MI size, microvascular obstruction and LVEF when compared to control. In a subgroup of anterior STEMI patients, RIC was associated with lower incidence of microvascular obstruction and higher LVEF on the acute scan when compared with control, but this was not associated with an improvement in LVEF at 6 months. In summary, in this pre-planned CMR substudy of the CONDI-2/ERIC-PPCI trial, there was no evidence that limb RIC reduced MI size or improved LVEF at 6 months by CMR, findings which are consistent with the neutral effects of limb RIC on clinical outcomes reported in the main CONDI-2/ERIC-PPCI trial.

Coronary Magnetic Resonance Angiography in Chronic Coronary Syndromes.

Cardiovascular disease is the leading cause of mortality worldwide, with atherosclerotic coronary artery disease (CAD) accounting for the majority of cases. X-ray coronary angiography and computed tomography coronary angiography (CCTA) are the imaging modalities of choice for the assessment of CAD. However, the use of ionising radiation and iodinated contrast agents remain drawbacks. There is therefore a clinical need for an alternative modality for the early identification and longitudinal monitoring of CAD without these associated drawbacks. Coronary magnetic resonance angiography (CMRA) could be a potential alternative for the detection and monitoring of coronary arterial stenosis, without exposing patients to ionising radiation or iodinated contrast agents. Further advantages include its versatility, excellent soft tissue characterisation and suitability for repeat imaging. Despite the early promise of CMRA, widespread clinical utilisation remains limited due to long and unpredictable scan times, onerous scan planning, lower spatial resolution, as well as motion related image quality degradation. The past decade has brought about a resurgence in CMRA technology, with significant leaps in image acceleration, respiratory and cardiac motion estimation and advanced motion corrected or motion-resolved image reconstruction. With the advent of artificial intelligence, great advances are also seen in deep learning-based motion estimation, undersampled and super-resolution reconstruction promising further improvements of CMRA. This has enabled high spatial resolution (1 mm isotropic), 3D whole heart CMRA in a clinically feasible and reliable acquisition time of under 10 min. Furthermore, latest super-resolution image reconstruction approaches which are currently under evaluation promise acquisitions as short as 1 min. In this review, we will explore the recent technological advances that are designed to bring CMRA closer to clinical reality.

Veno-occlusive unloading of the heart reduces infarct size in experimental ischemia-reperfusion.

Mechanical unloading of the left ventricle reduces infarct size after acute myocardial infarction by reducing cardiac work. Left ventricular veno-occlusive unloading reduces cardiac work and may reduce ischemia and reperfusion injury. In a porcine model of myocardial ischemia-reperfusion injury we randomized 18 pigs to either control or veno-occlusive unloading using a balloon engaged from the femoral vein into the inferior caval vein and inflated at onset of ischemia. Evans blue and 2,3,5-triphenyltetrazolium chloride were used to determine the myocardial area at risk and infarct size, respectively. Pressure-volume loops were recorded to calculate cardiac work, left ventricular (LV) volumes and ejection fraction. Veno-occlusive unloading reduced infarct size compared with controls (Unloading 13.9 ± 8.2% versus Control 22.4 ± 6.6%; p = 0.04). Unloading increased myocardial salvage (54.8 ± 23.4% vs 28.5 ± 14.0%; p = 0.02), while the area at risk was similar (28.4 ± 6.7% vs 27.4 ± 5.8%; p = 0.74). LV ejection fraction was preserved in the unloaded group, while the control group showed a reduced LV ejection fraction. Veno-occlusive unloading reduced myocardial infarct size and preserved LV ejection fraction in an experimental acute ischemia-reperfusion model. This proof-of-concept study demonstrated the potential of veno-occlusive unloading as an adjunctive cardioprotective therapy in patients undergoing revascularization for acute myocardial infarction.

Pulmonary vasodilation by sildenafil in acute intermediate-high risk pulmonary embolism: a randomized explorative trial.

BACKGROUND: To investigate if acute pulmonary vasodilation by sildenafil improves right ventricular function in patients with acute intermediate-high risk pulmonary embolism (PE). METHODS: Single center, explorative trial. Patients with PE were randomized to a single oral dose of sildenafil 50 mg (n = 10) or placebo (n = 10) as add-on to conventional therapy. The time from hospital admission to study inclusion was 2.3 ± 0.7 days. Right ventricular function was evaluated immediately before and shortly after (0.5-1.5 h) randomization by right heart catheterization (RHC), trans-thoracic echocardiography (TTE), and cardiac magnetic resonance (CMR). The primary efficacy endpoint was cardiac index measured by CMR. RESULTS: Patients had acute intermediate-high risk PE verified by computed tomography pulmonary angiography, systolic blood pressure of 135 ± 18 (mean ± SD) mmHg, increased right ventricular/left ventricular ratio 1.1 ± 0.09 and increased troponin T 167 ± 144 ng/L. Sildenafil treatment did not improve cardiac index compared to baseline (0.02 ± 0.36 l/min/m2, p = 0.89) and neither did placebo (0.00 ± 0.34 l/min/m2, p = 0.97). Sildenafil lowered mean arterial blood pressure (- 19 ± 10 mmHg, p < 0.001) which was not observed in the placebo group (0 ± 9 mmHg, p = 0.97). CONCLUSION: A single oral dose of sildenafil 50 mg did not improve cardiac index but lowered systemic blood pressure in patients with acute intermediate-high risk PE. The time from PE to intervention, a small patient sample size and low pulmonary vascular resistance are limitations of this study that should be considered when interpreting the results. TRIAL REGISTRATION: The trial was retrospectively registered at www.clinicaltrials.gov (NCT04283240) February 2nd 2020, https://clinicaltrials.gov/ct2/show/NCT04283240?term=NCT04283240&draw=2&rank=1 .

Antioxidant and hepatoprotective effects of Korean ginseng extract GS-KG9 in a D-galactosamine-induced liver damage animal model.

BACKGROUND/OBJECTIVES: This study was designed to investigate the improvement effect of white ginseng extract (GS-KG9) on D-galactosamine (Ga1N)-induced oxidative stress and liver injury. SUBJECTS/METHODS: Sixty Sprague-Dawley rats were divided into 6 groups. Rats were orally administrated with GS-KG9 (300, 500, or 700 mg/kg) or silymarin (25 mg/kg) for 2 weeks. The rats of the GS-KG9- and silymarin-treated groups and a control group were then intraperitoneally injected Ga1N at a concentration of 650 mg/kg for 4 days. To investigate the protective effect of GS-KG9 against GalN-induced liver injury, blood liver function indicators, anti-oxidative stress indicators, and histopathological features were analyzed. RESULTS: Serum biochemical analysis indicated that GS-KG9 ameliorated the elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in GalN-treated rats. The hepatoprotective effects of GS-KG9 involved enhancing components of the hepatic antioxidant defense system, including glutathione, glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT). In addition, GS-KG9 treatment inhibited reactive oxygen species (ROS) production induced by GalN treatment in hepatocytes and significantly increased the expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins, which are antioxidant proteins. In particular, by histological analyses bases on hematoxylin and eosin, Masson's trichrome, α-smooth muscle actin, and transforming growth factor-ß1 staining, we determined that the administration of 500 mg/kg GS-KG9 inhibited hepatic inflammation and fibrosis due to the excessive accumulation of collagen. CONCLUSIONS: These findings demonstrate that GS-KG9 improves GalN-induced liver inflammation, necrosis, and fibrosis by attenuating oxidative stress. Therefore, GS-KG9 may be considered a useful candidate in the development of a natural preventive agent against liver injury.

The hemodynamic and metabolic effects of spironolactone treatment in acute kidney injury assessed by hyperpolarized MRI.

Renal ischemia-reperfusion injury (IRI) is one of the most common types of acute kidney injury. Spironolactone has shown promising kidney protective effects in renal IRI in rats. We investigated the hemodynamic and metabolic effects of spironolactone (100 mg/kg) administered immediately after 40 min unilateral kidney ischemia in rats. Hyperpolarized MRI using co-polarized [1-13 C]pyruvate and [13 C,15 N2 ]urea as well as 1 H dynamic contrast-enhanced (DCE) MRI was performed 24 h after induction of ischemia. We found a significant decrease in renal blood flow (RBF) in the ischemic kidney compared with the contralateral one measured using DCE and [13 C,15 N2 ]urea. The RBF measured using [1-13 C]pyruvate and [13 C,15 N2 ]urea was significantly altered by spironolactone. The RBFs in the ischemic kidney compared with the contralateral kidney were decreased similarly as measured using both [13 C,15 N2 ]urea and [1-13 C]pyruvate in the spironolactone-treated group. Spironolactone treatment increased the perfusion-corrected pyruvate metabolism by 54% in both the ischemic and contralateral kidney. Furthermore, we showed a correlation between vascular permeability using a histological Evans blue analysis and the ratio of the volumes of distribution (VoDs), ie VoD-[13 C,15 N2 ]urea/VoD-[1-13 C]pyruvate. This suggests that [13 C,15 N2 ]urea/[1-13 C]pyruvate VoD ratio may be a novel indicator of renal vascular permeability associated with renal damage in rodents.

Long-term changes of right ventricular myocardial deformation and remodeling studied by cardiac magnetic resonance imaging in patients with chronic thromboembolic pulmonary hypertension following pulmonary thromboendarterectomy.

BACKGROUND: Right ventricular (RV) afterload in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is associated with reduced myocardial contractility and ventriculoarterial coupling. The impact of increased afterload on RV myocardial deformation was assessed by comparing the characteristics of CTEPH patients to healthy controls at baseline, and by comparing characteristics of CTEPH patients before and 12 months after pulmonary endarterectomy (PEA). METHODS: Cardiac deformation and function of CTEPH patients (n = 20) and healthy controls (n = 20) were assessed by cardiac magnetic resonance (CMR). CTEPH patients were also examined with right heart catheterization before and 12 months after PEA. RESULTS: PEA resulted in significant improvement of invasive hemodynamics and normalization of RV hypertrophy and right atrial, RV and left ventricular dimensions and volumes. RV ejection fraction improved from 30 ±â€¯13% at baseline to 44 ±â€¯10% at 12 months (p < 0.0001) but remained decreased compared with control subjects (54 ±â€¯4%, p < 0.05). RV global circumferential strain (GCS) normalized 12 months after PEA, but RV global longitudinal strain (GLS) remained significantly lower in CTEPH patients than controls (baseline -12.9 ±â€¯3.3% vs. -16.5 ±â€¯3.6% at 12 months p < 0.01, vs. controls -19.3 ±â€¯3.2%, p < 0.05). RV mass changes were significantly correlated with RV-ejection fraction, RV-GLS, and RV-GCS. RV-pulmonary arterial coupling with the volume method improved at 12 months (0.49 ±â€¯0.30 vs. 0.84 ±â€¯0.31, p < 0.0005), but remained significantly reduced compared with healthy controls (1.19 ±â€¯0.20, p < 0.0005). CONCLUSION: RV global longitudinal and circumferential myocardial three-dimensional strain by CMR improved significantly in CTEPH patients 12 months after PEA. Improvements in myocardial deformation were associated with regression of RV hypertrophy and decrease in pulmonary artery pressure.