PEX3 promotes regenerative repair after myocardial injury in mice through facilitating plasma membrane localization of ITGB3.

The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3ß signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury.

Cardiac Perforation Caused By Pectus Excavatum Metal Bar Stabilizer: A Case Report.

This paper reports the case of a female patient who underwent minimally invasive repair of pectus excavatum (MIRPE) in another service that evolved with bar rotation and cardiac perforation caused by the left stabilizer. The unique and frightening aspect of the case is that despite having the stabilizer inside the ventricle, the patient was oligosymptomatic: occasional chest pain and respiratory discomfort. Preoperative imaging showed rotation of the bar with stabilizers within the thoracic cavity. During surgery, intense ossification was observed around the prosthesis and it was noted that the left stabilizer had perforated the patient's left ventricle. Cardiac repair required a Clamshell incision and cardiopulmonary bypass. This case reinforces the validity of late radiological follow-up after MIRPE in an attempt to avoid this type of event, and the need to reevaluate the use of stabilizers perpendicular to the bar since they are not safe to prevent rotation of these implants.

Right ventricle pierced by a traditional sharp hair straightener: a case report.

The case presents a traumatic ventricular perforation of a girl, accidentally felt on a sharp instrument. The uniqueness of the case presented is due to the very high infrequency of injuries with this type of sharp object. The 7-year-old girl was transported to the hospital after accidentally falling on a sharp instrument. The child had no signs of heart failure. On opening the chest, it was found that the metal object was lodged in the right ventricle. Quickly proceeded to remove the object and suture the entry hole. After a short hospitalization, the child was discharged completely cured.

Podophyllotoxin via SIRT1/PPAR /NF-κB axis induced cardiac injury in rats based on the toxicological evidence chain (TEC) concept.

BACKGROUND: The study of cardiotoxicity of drugs has become an important part of clinical safety evaluation of drugs. It is commonly known that podophyllotoxin (PPT) and its many derivatives and congeners are broad-spectrum pharmacologically active substances. Clinical cardiotoxicity of PPT and its derivatives has been raised, basic research on the mechanism of cardiotoxicity remains insufficient. PURPOSE: In present study, our group's innovative concept of toxicological evidence chain (TEC) was applied to reveal the cardiac toxicity mechanism of PPT by targeted metabolomics, TMT-based quantitative proteomics and western blot. METHODS: The injury phenotype evidence (IPE) acquired from the toxicity manifestations, such as weight and behavior observation of Sprague-Dawley rat. The damage to rat hearts were assessed through histopathological examination and myocardial enzymes levels, which were defined as Adverse Outcomes Evidence (AOE). The damage to rat hearts was assessed through histopathological examination and myocardial enzyme levels, which were defined as evidence of adverse outcomes.Overall measurements of targeted metabolomics based on energy metabolism and TMT-based quantitative proteomics were obtained after exposure to PPT to acquire the Toxic Event Evidence (TEE). The mechanism of cardiac toxicity was speculated based on the integrated analysis of targeted metabolomics and TMT-based quantitative proteomics, which was verified by western blot. RESULTS: The results indicated that exposure to PPT could result in significant elevation of myocardial enzymes and pathological alterations in rat hearts. In addition, we found that PPT caused disorders in cardiac energy metabolism, characterized by a decrease in energy metabolism fuels. TMT-based quantitative proteomics revealed that the PPAR (Peroxisome proliferators-activated receptor) signaling pathway needs further study. It is worth noting that PPT may suppress the expression of SIRT1, subsequently inhibiting AMPK, decreasing the expression of PGC-1α, PPARα and PPARγ. This results in disorders of glucose oxidation, glycolysis and ketone body metabolism. Additionally, the increase in the expression of p-IKK and p-IκBα, leads to the nuclear translocation of NF-κB p65 from the cytosol, thus triggering inflammation. CONCLUSION: This study comprehensively evaluated cardiac toxicity of PPT and initially revealed the mechanism of cardiotoxicity,suggesting that PPT induced disorders of energy metabolism and inflammation via SIRT1/PPAR/NF-κB axis, potentially contributing to cardiac injury.

Rare case of multiple self-inflicted gunshot wounds to the chest in Poland.

Multiple gunshot suicides are relatively rare and present significant challenges for investigators and forensic pathologists. In such cases, assessing the possibility of more than one shot being fired can be crucial in distinguishing homicide from suicide. We present a rare case of multiple self-inflicted gunshot wounds to the chest with severe injury to the heart and left lung. Both the sudden, unexpected death of the man, the unknown source of the firearm, and the number and nature of the injuries sustained seemed quite unusual. The investigation revealed that the wounds were self-inflicted at close range, and the interval between successive shots (estimated by witnesses at up to 2 min) suggests that even multiple gunshot wounds perforating the heart and lungs may not necessarily cause immediate incapacitation. Forensic investigations in such cases should be multi-faceted and include full autopsy and ballistics expertise, as well as witness testimony and medical history.

Impact of neuromuscular block on myocardial injury after non-cardiac surgery (MINS) incidence in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection: a randomized controlled study.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) is a common and serious complication in older patients. This study investigates the impact of neuromuscular block on the MINS incidence and other cardiovascular complications in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection. METHODS: 70 older patients who underwent laparoscopic colorectal cancer resection were separated into the deep neuromuscular block group and moderate neuromuscular block group for 35 cases in each group (n = 1:1). The deep neuromuscular block group maintained train of four (TOF) = 0, post-tetanic count (PTC) 1-2, and the moderate neuromuscular block group maintained TOF = 1-2 during the operation. Sugammadex sodium was used at 2 mg/kg or 4 mg/kg for muscle relaxation antagonism at the end of surgery. The MINS incidence was the primary outcome and compared with Fisher's exact test. About the secondary outcomes, the postoperative pain was analyzed with Man-Whitney U test, the postoperative nausea and vomiting (PONV) and the incidence of cardiovascular complications were analyzed with Chi-square test, intraoperative mean artery pressure (MAP) and cardiac output (CO) ratio to baseline, length of stay and dosage of anesthetics were compared by two independent samples t-test. RESULTS: MINS was not observed in both groups. The highest incidence of postoperative cardiovascular complications was lower limbs deep vein thrombosis (14.3% in deep neuromuscular block group and 8.6% in moderate neuromuscular group). The numeric rating scale (NRS) score in the deep neuromuscular block group was lower than the moderate neuromuscular block group 72 h after surgery (0(1,2) vs 0(1,2), P = 0.018). The operation time in the deep neuromuscular block group was longer (356.7(107.6) vs 294.8 (80.0), min, P = 0.008), the dosage of propofol and remifentanil was less (3.4 (0.7) vs 3.8 (1.0), mg·kg-1·h-1, P = 0.043; 0.2 (0.06) vs 0.3 (0.07), µg·kg-1·min-1, P < 0.001), and the length of hospital stay was shorter than the moderate neuromuscular block group (18.4 (4.9) vs 22.0 (8.3), day, P = 0.028). The differences of other outcomes were not statistically significant. CONCLUSIONS: Maintaining different degrees of the neuromuscular block under TOF guidance did not change the MINS incidence within 7 days after surgery in older patients who underwent laparoscopic colorectal cancer resection. TRIAL REGISTRATION: The present study was registered in the Chinese Clinical Trial Registry (10/02/2021, ChiCTR2100043323).

Septal venous channel perforation during left bundle branch area pacing: a prospective study.

AIMS: To characterize the diagnosis, frequency, and procedural implications of septal venous channel perforation during left bundle branch area pacing (LBBAP). METHODS AND RESULTS: All consecutive patients undergoing LBBAP over an 8-month period were prospectively studied. During lead placement, obligatory septal contrast injection was performed twice, at initiation (implant entry zone) and at completion (fixation zone). An intuitive fluoroscopic schema using orthogonal views (left anterior oblique/right anterior oblique) and familiar landmarks is described. Using this, we resolved zonal distribution (I-VI) of lead position on the ventricular septum and its angulation (post-fixation angle θ). Subjects with and without septal venous channel perforation were compared. Sixty-one patients {male 57.3%, median age [interquartile range (IQR)] 69.5 [62.5-74.5] years} were enrolled. Septal venous channel perforation was observed in eight (13.1%) patients [male 28.5%, median age (IQR) 64 (50-75) years]. They had higher frequency of (i) right-sided implant (25% vs. 1.9%, P = 0.04), (ii) fixation in zone III at the mid-superior septum (75% vs. 28.3%, P = 0.04), (iii) steeper angle of fixation-median θ (IQR) [19 (10-30)° vs. 5 (4-19)°, P = 0.01], and (iv) longer median penetrated-lead length (IQR) [13 (10-14.8) vs. 10 (8.5-12.5) mm, P = 0.03]. Coronary sinus drainage of contrast was noted in five (62.5%) patients. Abnormal impedance drops during implantation (12.5% vs. 5.7%, P = NS) were not significantly different. CONCLUSION: When evaluated systematically, septal venous channel perforation may be encountered commonly after LBBAP. The fiducial reference framework described using fluoroscopic imaging identified salient associated findings. This may be addressed with lead repositioning to a more inferior location and is not associated with adverse consequence acutely or in early follow-up.

Knockdown of LncRNA Lcn2-204 alleviates sepsis-induced myocardial injury by regulation of iron overload and ferroptosis.

Ferroptosis is an iron-dependent programmed cell death form resulting from lipid peroxidation damage, it plays a key role in organ damage and tumor development from various causes. Sepsis leads to severe host response after infection with high mortality. The long non-coding RNAs (LncRNAs) are involved in different pathophysiological mechanisms of multiple diseases. Here, we used cecal ligation and puncture (CLP) operation to mimic sepsis induced myocardial injury (SIMI) in mouse model, and LncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Based on the microarray results, 552 LncRNAs and 520 mRNAs were differentially expressed in the sham and CLP groups, among them, LncRNA Lcn2-204 was the highest differentially expressed up-regulated LncRNA. Iron metabolism disorder was involved in SIMI by bioinformatics analysis, meanwhile, myocardial iron content and lipocalin-2 (Lcn2) protein expressions were increased. The CNC network comprised 137 positive interactions and 138 negative interactions. Bioinformatics analysis showed several iron-related terms were enriched and six genes (Scara5, Tfrc, Lcn2, Cp, Clic5, Ank1) were closely associated with iron metabolism. Then, we constructed knockdown LncRNA Lcn2-204 targeting myocardium and found that it ameliorated cardiac injury in mouse sepsis model through modulating iron overload and ferroptosis. In addition, we found that LncRNA Lcn2-204 was involved in the regulation of Lcn2 expression in septic myocardial injury. Based on these findings, we conclude that iron overload and ferroptosis are the key mechanisms leading to myocardial injury in sepsis, knockdown of LncRNA Lcn2-204 plays the cardioprotective effect through inhibition of iron overload, ferroptosis and Lcn2 expression. It may provide a novel therapeutic approach to ameliorate sepsis-induced myocardial injury.

Needle Decompression Complicated by Cardiac Injury in a Prehospital Environment.

Needle decompression is a mainstay intervention for tension pneumothorax in trauma medicine. It is used in combat and prehospital medicine when definitive measures are often not available or ideal. It can temporarily relieve increased intrathoracic pressure and treat a collapsed lung or great vessel obstruction. However, when done incorrectly, it can result in underlying visceral organ and vessel trauma. This is a case of an adult male who presented to the emergency department after sustaining multiple stab wounds during an altercation. On arrival, the patient had a 14-gauge angiocatheter inserted at the 4th intercostal space (ICS), left of the parasternal line traversing the right ventricle and interventricular septum and terminating in the left ventricle. The case emphasizes the importance of understanding the landmarks of performing needle decompression in increasing the procedure's efficacy and reducing iatrogenic complications.

Melatonin improves nitric oxide bioavailability in isoproterenol induced myocardial injury.

Isoproterenol administration is associated with cardiac inflammation and decreased NO availability. Melatonin has been reported to have cardioprotective effect. The aim of this study was to investigate the effect of melatonin on NO bioavailability and inflammation in myocardial injury induced by isoproterenol. Isoproterenol was administrated in male Wistar rats for 7 days to induce cardiac injury. The animals were divided into 3 groups: Control, Isoproterenol, Isoproterenol + Melatonin. Animals received melatonin for 7 days. Echocardiographic analysis was performed and the hearts were collected for molecular analysis. Animals that received isoproterenol demonstrated a reduction in left ventricle systolic and diastolic diameter, indicating the presence of concentric hypertrophy. Melatonin was able to attenuate this alteration. Melatonin also improved NO bioavailability and decreased NF-κß, TNFα and IL-1ß expression. In conclusion, melatonin exhibited a cardioprotective effect which was associated with improving NO bioavailability and decreasing the pro-inflammatory proteins.

Mesenchymal stem cells improve cardiac function in diabetic rats by reducing cardiac injury biomarkers and downregulating JAK/STAT/iNOS and iNOS/Apoptosis signaling pathways.

Cardiovascular complications are prevalent manifestations of type 2 diabetes mellitus (T2DM) and are usually the main cause of death. This study aims to show the underlying mechanisms of the potential therapeutic effect of mesenchymal stem cells (MSCs) on diabetic cardiac dysfunction. Twenty-four male Wistar rats were randomly assigned to one of three groups The control group received standard laboratory chow, and the groups with T2DM received a single dose of 45 mg/kg body weight of streptozotocin (STZ) after 3 weeks of pretreatment with a high-fat diet (HFD). Eight weeks after the diagnosis of T2DM, rats were divided into two groups: the T2DM model group and the T2DM + MSCs group. BM-MSCs were administered systemically at 2 × 106 cells/rat doses. A Significant amelioration in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and dyslipidemia was noted 2 weeks post-administration of MSCs. Administration of MSCs improved dyslipidemia, the altered cardiac injury biomarkers (p ≤ 0.0001), downregulated Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)/inducible Nitric oxide synthase (iNOS) and iNOS/Apoptosis signaling pathways. This was associated with improved cardiac dysfunction (impaired left ventricular performance and decreased contractility index). Our results show that MSCs ameliorate cardiac dysfunction associated with diabetic cardiomyopathy by lowering dyslipidemia and insulin resistance, inhibiting oxidative stress, and inflammation, downregulating JAK2/STAT3/iNOS and iNOS/Apoptosis signaling pathways.

Re-evaluating the Use of High Sensitivity Troponin to Diagnose Blunt Cardiac Injury.

INTRODUCTION: Blunt cardiac injury (BCI) can be challenging diagnostically, and if misdiagnosed, can lead to life-threatening complications. Our institution previously evaluated BCI screening with troponin and electrocardiogram (EKG) during a transition from troponin I to high sensitivity troponin (hsTnI), a more sensitive troponin I assay. The previous study found an hsTnI of 76 ng/L had the highest capability of accurately diagnosing a clinically significant BCI. The aim of this study was to determine the efficacy of the newly implemented protocol. METHODS: Patients diagnosed with a sternal fracture from March 2022 to April 2023 at our urban level-1 trauma center were retrospectively reviewed for EKG findings, hsTnI trend, echocardiogram changes, and clinical outcomes. The BCI cohort and non-BCI cohort ordinal measures were compared using Wilcoxon's two-tailed rank sum test and categorical measures were compared with Fisher's exact test. Youden indices were used to evaluate hsTnI sensitivity and specificity. RESULTS: Sternal fractures were identified in 206 patients, of which 183 underwent BCI screening. Of those screened, 103 underwent echocardiogram, 28 were diagnosed with clinically significant BCIs, and 15 received intervention. The peak hsTnI threshold of 76 ng/L was found to have a Youden index of 0.31. Rather, the Youden index was highest at 0.50 at 40 ng/L (sensitivity 0.79 and specificity 0.71) for clinically significant BCI. CONCLUSIONS: Screening patients with sternal fractures for BCI using hsTnI and EKG remains effective. To optimize the hsTnI threshold, this study determined the hsTnI threshold should be lowered to 40 ng/L. Further improvements to the institutional protocol may be derived from multicenter analysis.

Rat Model of Isoproterenol-Induced Myocardial Injury.

Isoproterenol (ISO) administration produces significant biochemical and histological changes including oxidative stress, reactive oxygen species (ROS) overproduction, and inflammation that leads to aggravation of myocardial injury. Subcutaneous or intraperitoneal ISO injection into rats can replicate several features of human heart disease, making it a useful tool for comprehending the underlying mechanisms and evaluating potential therapeutic strategies. In the present chapter, we elaborate on how depending on the precise experimental goals and the intended level of severity, different dosages and regimens are employed to induce myocardial injury.

Novel valve-in-surgical bioprosthetic transcatheter aortic valve replacement: Undermining iatrogenic coronary obstruction with radiofrequency needle (UNICORN).

An 86-year-old female with history of surgical aortic valve replacement presented with clinical signs of heart failure. Echocardiography revealed a reduction in left ventricular systolic function and severe bioprosthetic aortic valve dysfunction. This is the first reported case of valve-in-valve transcatheter aortic valve replacement with concomitant undermining iatrogenic coronary obstruction with radiofrequency needle procedure in a surgical bioprosthetic valve.

[HTD4010 attenuates myocardial injury in mice with septic cardiomyopathy by promoting autophagy via the AMPK/mTOR signaling pathway].

OBJECTIVE: To investigate the protective effects of HTD4010 against lipopolysaccharide (LPS)-induced septic cardiomyopathy (SCM) in mice and explore the mechanisms mediating its effect. METHODS: Forty-five male ICR mice were randomized equally into control group, LPS (10 mg/kg) group, and LPS+HTD4010 group (in which 2.5 mg/kg HTD4010 was injected subcutaneously at 1 h and 6 h after LPS injection). Cardiac function of the mice was evaluated by ultrasound, and pathological changes in the myocardial tissues were observed with HE staining. The levels of IL-6 and TNF-α in serum and myocardial tissues were detected using ELISA, and apoptosis of the cardiomyocytes was detected with TUNEL staining. The expression levels of the key proteins associated with apoptosis, autophagy and the AMPK/mTOR pathway in the myocardial tissues were detected using Western blotting. The ultrastructural changes of cardiac myocardial mitochondria was observed with transmission electron microscopy. RESULTS: LPS exposure caused severe myocardial damage in mice, characterized by myocardial fiber rupture, structural disorder, inflammatory cell infiltration, and mitochondrial damage. The LPS-treated mice exhibited significantly decreased cardiac LVEF and FS values, elevated IL-6 and TNF-αlevels in serum and myocardial tissue, and an increased myocardial cell apoptosis rate with enhanced expressions of Bax, p-62 and p-mTOR and lowered expressions of Bcl-2, LC3 II/I, Beclin-1 and p-AMPK (P < 0.05 or 0.01). Treatment of the septic mice with HTD4010 significantly alleviated myocardial damage, increased LVEF and FS values, reduced IL-6 and TNF-α levels in serum and myocardial tissue, decreased cardiomyocyte apoptosis, lowered myocardial expressions of Bax, p-62 and p-mTOR, and increased Bcl-2, LC3 II/I, Beclin-1 and p-AMPK expressions (P < 0.05 or 0.01). CONCLUSION: HTD4010 can attenuate myocardial injury in SCM mice possibly by promoting autophagy via modulating the AMPK/mTOR signaling pathway.

Antigen presentation plays positive roles in the regenerative response to cardiac injury in zebrafish.

In contrast to adult mammals, adult zebrafish can fully regenerate injured cardiac tissue, and this regeneration process requires an adequate and tightly controlled immune response. However, which components of the immune response are required during regeneration is unclear. Here, we report positive roles for the antigen presentation-adaptive immunity axis during zebrafish cardiac regeneration. We find that following the initial innate immune response, activated endocardial cells (EdCs), as well as immune cells, start expressing antigen presentation genes. We also observe that T helper cells, a.k.a. Cd4+ T cells, lie in close physical proximity to these antigen-presenting EdCs. We targeted Major Histocompatibility Complex (MHC) class II antigen presentation by generating cd74a; cd74b mutants, which display a defective immune response. In these mutants, Cd4+ T cells and activated EdCs fail to efficiently populate the injured tissue and EdC proliferation is significantly decreased. cd74a; cd74b mutants exhibit additional defects in cardiac regeneration including reduced cardiomyocyte dedifferentiation and proliferation. Notably, Cd74 also becomes activated in neonatal mouse EdCs following cardiac injury. Altogether, these findings point to positive roles for antigen presentation during cardiac regeneration, potentially involving interactions between activated EdCs, classical antigen-presenting cells, and Cd4+ T cells.