ptx3a+ fibroblast/epicardial cells provide a transient macrophage niche to promote heart regeneration.

Macrophages conduct critical roles in heart repair, but the niche required to nurture and anchor them is poorly studied. Here, we investigated the macrophage niche in the regenerating heart. We analyzed cell-cell interactions through published single-cell RNA sequencing datasets and identified a strong interaction between fibroblast/epicardial (Fb/Epi) cells and macrophages. We further visualized the association of macrophages with Fb/Epi cells and the blockage of macrophage response without Fb/Epi cells in the regenerating zebrafish heart. Moreover, we found that ptx3a+ epicardial cells associate with reparative macrophages, and their depletion resulted in fewer reparative macrophages. Further, we identified csf1a expression in ptx3a+ cells and determined that pharmacological inhibition of the csf1a pathway or csf1a knockout blocked the reparative macrophage response. Moreover, we found that genetic overexpression of csf1a enhanced the reparative macrophage response with or without heart injury. Altogether, our studies illuminate a cardiac Fb/Epi niche, which mediates a beneficial macrophage response after heart injury.

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.

Sophocarpine alleviates doxorubicin-induced heart injury by suppressing oxidative stress and apoptosis.

Doxorubicin (DOX) is an effective anti-tumor drug accompanied with many side effects, especially heart injury. To explore what effects of sophocarpine (SOP) on DOX-induced heart injury, this study conducted in vivo experiment and in vitro experiment, and the C57BL/6J mice and the H9C2 cells were used. The experimental methods used included echocardiography, enzyme-linked immunosorbent assay (ELISA), dihydroethidium (DHE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, western blotting and so on. Echocardiography showed that SOP alleviated DOX-induced cardiac dysfunction, as evidenced by the improvements of left ventricle ejection fraction and left ventricle fractional shortening. DOX caused upregulations of creatine kinase (CK), creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH), while SOP reduced these indices. The relevant stainings showed that SOP reversed the increases of total superoxide level induced by DOX. DOX also contribute to a higher level of MDA and lower levels of SOD and GSH, but these changes were suppressed by SOP. DOX increased the pro-oxidative protein level of NOX-4 while decreased the anti-oxidative protein level of SOD-2, but SOP reversed these effects. In addition, this study further discovered that SOP inhibited the decreases of Nrf2 and HO-1 levels induced by DOX. The TUNEL staining revealed that SOP reduced the high degree of apoptosis induced by DOX. Besides, pro-apoptosis proteins like Bax, cleaved-caspase-3 and cytochrome-c upregulated while anti-apoptosis protein like Bcl-2 downregulated when challenged by DOX, but them were suppressed by SOP. These findings suggested that SOP could alleviate DOX-induced heart injury by suppressing oxidative stress and apoptosis, with molecular mechanism activating of the Nrf2/HO-1 signaling pathway.

Sulfide-modified nanoscale zero-valent iron as a novel therapeutic remedy for septic myocardial injury.

INTRODUCTION: Myocardial injury is a serious complication in sepsis with high mortality. Zero-valent iron nanoparticles (nanoFe) displayed novel roles in cecal ligation and puncture (CLP)-induced septic mouse model. Nonetheless, its high reactivity makes it difficult for long-term storage. OBJECTIVES: To overcome the obstacle and improve therapeutic efficiency, a surface passivation of nanoFe was designed using sodium sulfide. METHODS: We prepared iron sulfide nanoclusters and constructed CLP mouse models. Then the effect of sulfide-modified nanoscale zero-valent iron (S-nanoFe) on the survival rate, blood routine parameters, blood biochemical parameters, cardiac function, and pathological indicators of myocardium was observed. RNA-seq was used to further explore the comprehensive protective mechanisms of S-nanoFe. Finally, the stability of S-nanoFe-1d and S-nanoFe-30 d, together with the therapeutic efficacy of sepsis between S-nanoFe and nanoFe was compared. RESULTS: The results revealed that S-nanoFe significantly inhibited the growth of bacteria and exerted a protective role against septic myocardial injury. S-nanoFe treatment activated AMPK signaling and ameliorated several CLP-induced pathological processes including myocardial inflammation, oxidative stress, mitochondrial dysfunction. RNA-seq analysis further clarified the comprehensive myocardial protective mechanisms of S-nanoFe against septic injury. Importantly, S-nanoFe had a good stability and a comparable protective efficacy to nanoFe. CONCLUSIONS: The surface vulcanization strategy for nanoFe has a significant protective role against sepsis and septic myocardial injury. This study provides an alternative strategy for overcoming sepsis and septic myocardial injury and opens up possibilities for the development of nanoparticle in infectious diseases.

Epicardial placement of human placental membrane protects from heart injury in a swine model of myocardial infarction.

Cardiac ischemic reperfusion injury (IRI) is paradoxically instigated by reestablishing blood-flow to ischemic myocardium typically from a myocardial infarction (MI). Although revascularization following MI remains the standard of care, effective strategies remain limited to prevent or attenuate IRI. We hypothesized that epicardial placement of human placental amnion/chorion (HPAC) grafts will protect against IRI. Using a clinically relevant model of IRI, swine were subjected to 45 min percutaneous ischemia followed with (MI + HPAC, n = 3) or without (MI only, n = 3) HPAC. Cardiac function was assessed by echocardiography, and regional punch biopsies were collected 14 days post-operatively. A deep phenotyping approach was implemented by using histological interrogation and incorporating global proteomics and transcriptomics in nonischemic, ischemic, and border zone biopsies. Our results established HPAC limited the extent of cardiac injury by 50% (11.0 ± 2.0% vs. 22.0 ± 3.0%, p = 0.039) and preserved ejection fraction in HPAC-treated swine (46.8 ± 2.7% vs. 35.8 ± 4.5%, p = 0.014). We present comprehensive transcriptome and proteome profiles of infarct (IZ), border (BZ), and remote (RZ) zone punch biopsies from swine myocardium during the proliferative cardiac repair phase 14 days post-MI. Both HPAC-treated and untreated tissues showed regional dynamic responses, whereas only HPAC-treated IZ revealed active immune and extracellular matrix remodeling. Decreased endoplasmic reticulum (ER)-dependent protein secretion and increased antiapoptotic and anti-inflammatory responses were measured in HPAC-treated biopsies. We provide quantitative evidence HPAC reduced cardiac injury from MI in a preclinical swine model, establishing a potential new therapeutic strategy for IRI. Minimizing the impact of MI remains a central clinical challenge. We present a new strategy to attenuate post-MI cardiac injury using HPAC in a swine model of IRI. Placement of HPAC membrane on the heart following MI minimizes ischemic damage, preserves cardiac function, and promotes anti-inflammatory signaling pathways.

The role of mitochondria in myocardial damage caused by energy metabolism disorders: From mechanisms to therapeutics.

Myocardial damage is the most serious pathological consequence of cardiovascular diseases and an important reason for their high mortality. In recent years, because of the high prevalence of systemic energy metabolism disorders (e.g., obesity, diabetes mellitus, and metabolic syndrome), complications of myocardial damage caused by these disorders have attracted widespread attention. Energy metabolism disorders are independent of traditional injury-related risk factors, such as ischemia, hypoxia, trauma, and infection. An imbalance of myocardial metabolic flexibility and myocardial energy depletion are usually the initial changes of myocardial injury caused by energy metabolism disorders, and abnormal morphology and functional destruction of the mitochondria are their important features. Specifically, mitochondria are the centers of energy metabolism, and recent evidence has shown that decreased mitochondrial function, caused by an imbalance in mitochondrial quality control, may play a key role in myocardial injury caused by energy metabolism disorders. Under chronic energy stress, mitochondria undergo pathological fission, while mitophagy, mitochondrial fusion, and biogenesis are inhibited, and mitochondrial protein balance and transfer are disturbed, resulting in the accumulation of nonfunctional and damaged mitochondria. Consequently, damaged mitochondria lead to myocardial energy depletion and the accumulation of large amounts of reactive oxygen species, further aggravating the imbalance in mitochondrial quality control and forming a vicious cycle. In addition, impaired mitochondria coordinate calcium homeostasis imbalance, and epigenetic alterations participate in the pathogenesis of myocardial damage. These pathological changes induce rapid progression of myocardial damage, eventually leading to heart failure or sudden cardiac death. To intervene more specifically in the myocardial damage caused by metabolic disorders, we need to understand the specific role of mitochondria in this context in detail. Accordingly, promising therapeutic strategies have been proposed. We also summarize the existing therapeutic strategies to provide a reference for clinical treatment and developing new therapies.

α-Lipoic acid alleviates myocardial injury and induces M2b macrophage polarization after myocardial infarction via HMGB1/NF-kB signaling pathway.

BACKGROUND: Myocardial infarction (MI) is a serious cardiovascular disease with a poor prognosis. Macrophages are the predominant immune cells in patients with MI and macrophage regulation during the different phases of MI has important consequences for cardiac recovery. Alpha-lipoic acid (ALA) plays a critical role in MI by modulating the number of cardiomyocytes and macrophages. METHODS: MI mice were generated by ligating the left anterior descending coronary artery. Macrophages were exposed to hypoxia to establish a hypoxia model and M1 polarization was induced by LPS and IFN-γ. Different groups of macrophages and MI mice were treated with ALA. The cardiomyocytes were treated with various macrophage supernatants and the cardiac function, cytokine levels, and pathology were also analyzed. Factors related to apoptosis, autophagy, reactive oxygen species (ROS), and the mitochondrial membrane potential (MMP) were assessed. Finally, the HMGB1/NF-κB pathway was identified. RESULTS: ALA promoted M2b polarization in normal cells and suppressed inflammatory cytokines during hypoxia. ALA inhibited ROS and MMP production in vitro. Supernatants containing ALA inhibited apoptosis and autophagy in hypoxic cardiomyocytes. Moreover, ALA suppressed the HMGB1/NF-κB pathway in macrophages, which may be a potential mechanism for attenuating MI. CONCLUSION: ALA alleviates MI and induces M2b polarization via the HMGB1/NF-κB pathway, impeding inflammation, oxidation, apoptosis, and autophagy, and might be a potential strategy for MI treatment.

Molecular mechanisms mediate roflumilast protective effect against isoprenaline-induced myocardial injury.

BACKGROUND: Myocardial necrosis is one of the most common cardiac and pathological diseases. Unfortunately, using the available medical treatment is not sufficient to rescue the myocardium. So that, we aimed in our model to study the possible cardioprotective effect of roflumilast (ROF) in an experimental model of induced myocardial injury using a toxic dose of isoprenaline (ISO) and detecting the role of vascular endothelial growth factor/endothelial nitric oxide synthase (VEGF/eNOS) and cyclic guanosine monophosphate/cyclic adenosine monophosphate/ sirtuin1 (cGMP/cAMP/SIRT1) signaling cascade. MATERIALS AND METHODS: Animals were divided into five groups; control, ISO given group (150 mg/kg) i.p. on the 4th and 5th day, 3 ROF co-administered groups in different doses (0.25, 0.5, 1 mg/kg/day) for 5 days. RESULTS: Our data revealed that ISO could induce cardiac toxicity as manifested by significant increases in troponin I, creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), and cleaved caspase-3 with toxic histopathological changes. Meanwhile, there were significant decreases in reduced glutathione (GSH), total antioxidant capacity (TAC), VEGF, eNOS, cGMP, cAMP and SIRT1. However, co-administration of ROF showed significant improvement and normalization of ISO induced cardiac damage. CONCLUSION: We concluded that ROF successfully reduced ISO induced myocardial injury and this could be attributed to modulation of PDE4, VEGF/eNOS and cGMP/cAMP/SIRT1 signaling pathways with antioxidant, anti-inflammatory, and anti-apoptotic properties.

Regeneration of the heart: from molecular mechanisms to clinical therapeutics.

Heart injury such as myocardial infarction leads to cardiomyocyte loss, fibrotic tissue deposition, and scar formation. These changes reduce cardiac contractility, resulting in heart failure, which causes a huge public health burden. Military personnel, compared with civilians, is exposed to more stress, a risk factor for heart diseases, making cardiovascular health management and treatment innovation an important topic for military medicine. So far, medical intervention can slow down cardiovascular disease progression, but not yet induce heart regeneration. In the past decades, studies have focused on mechanisms underlying the regenerative capability of the heart and applicable approaches to reverse heart injury. Insights have emerged from studies in animal models and early clinical trials. Clinical interventions show the potential to reduce scar formation and enhance cardiomyocyte proliferation that counteracts the pathogenesis of heart disease. In this review, we discuss the signaling events controlling the regeneration of heart tissue and summarize current therapeutic approaches to promote heart regeneration after injury.

TNC Accelerates Hypoxia-Induced Cardiac Injury in a METTL3-Dependent Manner.

Cardiac fibrosis and cardiomyocyte apoptosis are reparative processes after myocardial infarction (MI), which results in cardiac remodeling and heart failure at last. Tenascin-C (TNC) consists of four distinct domains, which is a large multimodular glycoprotein of the extracellular matrix. It is also a key regulator of proliferation and apoptosis in cardiomyocytes. As a significant m6A regulator, METTL3 binds m6A sites in mRNA to control its degradation, maturation, stabilization, and translation. Whether METTL3 regulates the occurrence and development of myocardial infarction through the m6A modification of TNC mRNA deserves our study. Here, we have demonstrated that overexpression of METTL3 aggravated cardiac dysfunction and cardiac fibrosis after 4 weeks after MI. Moreover, we also demonstrated that TNC resulted in cardiac fibrosis and cardiomyocyte apoptosis after MI. Mechanistically, METTL3 led to enhanced m6A levels of TNC mRNA and promoted TNC mRNA stability. Then, we mutated one m6A site "A" to "T", and the binding ability of METTL3 was reduced. In conclusion, METTL3 is involved in cardiac fibrosis and cardiomyocyte apoptosis by increasing m6A levels of TNC mRNA and may be a promising target for the therapy of cardiac fibrosis after MI.

Immune Cells in Cardiac Injury Repair and Remodeling.

PURPOSE OF REVIEW: Immune cells are emerging as central cellular components of the heart which communicate with cardiac resident cells during homeostasis, cardiac injury, and remodeling. These findings are contributing to the development and continuous expansion of the new field of cardio-immunology. We review the most recent literature on this topic and discuss ongoing and future efforts to advance this field forward. RECENT FINDINGS: Cell-fate mapping, strategy depleting, and reconstituting immune cells in pre-clinical models of cardiac disease, combined with the investigation of the human heart at the single cell level, are contributing immensely to our understanding of the complex intercellular communication between immune and non-immune cells in the heart. While the acute immune response is necessary to initiate inflammation and tissue repair post injury, it becomes detrimental when sustained over time and contributes to adverse cardiac remodeling and pathology. Understanding the specific functions of immune cells in the context of the cardiac environment will provide new opportunities for immunomodulation to induce or tune down inflammation as needed in heart disease.

Berberine Alleviates Doxorubicin-Induced Myocardial Injury and Fibrosis by Eliminating Oxidative Stress and Mitochondrial Damage via Promoting Nrf-2 Pathway Activation.

Doxorubicin (DOX)-related cardiotoxicity has been recognized as a serious complication of cancer chemotherapy. Effective targeted strategies for myocardial protection in addition to DOX treatment are urgently needed. The purpose of this paper was to determine the therapeutic effect of berberine (Ber) on DOX-triggered cardiomyopathy and explore the underlying mechanism. Our data showed that Ber markedly prevented cardiac diastolic dysfunction and fibrosis, reduced cardiac malondialdehyde (MDA) level and increased antioxidant superoxide dismutase (SOD) activity in DOX-treated rats. Moreover, Ber effectively rescued the DOX-induced production of reactive oxygen species (ROS) and MDA, mitochondrial morphological damage and membrane potential loss in neonatal rat cardiac myocytes and fibroblasts. This effect was mediated by increases in the nuclear accumulation of nuclear erythroid factor 2-related factor 2 (Nrf2) and levels of heme oxygenase-1 (HO-1) and mitochondrial transcription factor A (TFAM). We also found that Ber suppressed the differentiation of cardiac fibroblasts (CFs) into myofibroblasts, as indicated by decreased expression of α-smooth muscle actin (α-SMA), collagen I and collagen III in DOX-treated CFs. Pretreatment with Ber inhibited ROS and MDA production and increased SOD activity and the mitochondrial membrane potential in DOX-challenged CFs. Further investigation indicated that the Nrf2 inhibitor trigonelline reversed the protective effect of Ber on both cardiomyocytes and CFs after DOX stimulation. Taken together, these findings demonstrated that Ber effectively alleviated DOX-induced oxidative stress and mitochondrial damage by activating the Nrf2-mediated pathway, thereby leading to the prevention of myocardial injury and fibrosis. The current study suggests that Ber is a potential therapeutic agent for DOX-induced cardiotoxicity that exerts its effects by activating Nrf2.

Chronic intermittent hypoxia-induced BNIP3 expression mitigates contractile dysfunction and myocardial injury in animal and cell model via modulating autophagy.

Obstructive sleep apnea syndrome is generally associated with multiple cardiovascular disorders, such as myocardial hypertrophy. Autophagy is strictly modulated to maintain cardiac homeostasis. Post-injury autophagy is closely associated with pathological cardiac hypertrophy. BCL2 interacting protein 3 (BNIP3) and BNIP3-like protein (BNIP3L) can cause cell death and are important for hypoxia-elicited autophagy. Here, we evaluated whether BNIP3 could mitigate functional remodeling and cardiac hypertrophy through regulation of autophagy. Male WT rats or rats with BNIP3 knockout were subjected to chronic intermittent hypoxia (CIH) for 8 h/day over 5 weeks. Echocardiography and morphology were employed to assess the cardioprotective effects. Autophagy was assessed via transmission electron microscopy and detection of LC3, p62, and Beclin-1. Terminal deoxynucleotidyl transferase dUTP nick end labeling and the Bax/Bcl2 ratio were used to monitor apoptosis. Biochemical evaluations were performed to assess oxidative stress. Additionally, BNIP3-knockdown H9c2 cells that were subjected to CIH were used to examine autophagy and apoptosis to confirm the findings of the animal study. The CIH group showed elevated heart weight/body weight and left ventricle weight/body weight proportions, along with left ventricular remodeling. CIH-exposed rats exhibited dramatically higher fractional shortening and ejection fractions than the controls. In addition, the levels of autophagy markers Beclin-1 and LC3-II/I were increased, whereas the level of p62 was reduced by CIH treatment. The oxidative marker levels and the apoptosis index in the CIH group were markedly increased. Knockout of BNIP3 significantly aggravated the impairment in cardiac function, apoptosis, oxidative stress, and hypertrophy of CIH rats, while significantly reducing autophagy. The autophagy-associated PI3K/Akt/mTOR pathway was also deactivated by BNIP3 knockout. At the cellular level, CIH treatment significantly upregulated autophagy and apoptosis; however, BNIP3 silencing reduced autophagy and promoted apoptosis. CIH treatment-mediated upregulation of BNIP3 expression plays a crucial role in autophagy by targeting the PI3K/Akt/mTOR pathway, alleviating cardiac hypertrophy.

CRISPR/Cas9-mediated inactivation of the phosphatase activity of soluble epoxide hydrolase prevents obesity and cardiac ischemic injury.

INTRODUCTION: Although the physiological role of the C-terminal hydrolase domain of the soluble epoxide hydrolase (sEH-H) is well investigated, the function of its N-terminal phosphatase activity (sEH-P) remains unknown. OBJECTIVES: This study aimed to assess in vivo the physiological role of sEH-P. METHODS: CRISPR/Cas9 was used to generate a novel knock-in (KI) rat line lacking the sEH-P activity. RESULTS: The sEH-P KI rats has a decreased metabolism of lysophosphatidic acids to monoacyglycerols. KI rats grew almost normally but with less weight and fat mass gain while insulin sensitivity was increased compared to wild-type rats. This lean phenotype was more marked in males than in female KI rats and mainly due to decreased food consumption and enhanced energy expenditure. In fact, sEH-P KI rats had an increased lipolysis allowing to supply fatty acids as fuel to potentiate brown adipose thermogenesis under resting condition and upon cold exposure. The potentiation of thermogenesis was abolished when blocking PPARγ, a nuclear receptor activated by intracellular lysophosphatidic acids, but also when inhibiting simultaneously sEH-H, showing a functional interaction between the two domains. Furthermore, sEH-P KI rats fed a high-fat diet did not gain as much weight as the wild-type rats, did not have increased fat mass and did not develop insulin resistance or hepatic steatosis. In addition, sEH-P KI rats exhibited enhanced basal cardiac mitochondrial activity associated with an enhanced left ventricular contractility and were protected against cardiac ischemia-reperfusion injury. CONCLUSION: Our study reveals that sEH-P is a key player in energy and fat metabolism and contributes together with sEH-H to the regulation of cardiometabolic homeostasis. The development of pharmacological inhibitors of sEH-P appears of crucial importance to evaluate the interest of this promising therapeutic strategy in the management of obesity and cardiac ischemic complications.

Vagus nerve stimulation attenuates septic shock-induced cardiac injury in rats.

This research aimed to evaluate whether vagus nerve stimulation (VNS) could effectively prevent septic shock-induced cardiac injury in rats and investigate the potential mechanisms. Female Sprague-Dawley rats were divided into the Sham group (sham cecal ligation and puncture [CLP] plus vagal nerve trunk separation), the Vehicle group (CLP plus vagal nerve trunk separation), and the VNS groups (CLP plus vagal nerve trunk separation plus VNS). The left ventricular function was analyzed by echocardiography. Histologic examinations of the cardiac tissues were performed through hematoxylin and eosin staining and TUNEL staining. The Vehicle group had worse cardiac function, higher levels of cardiac injury markers, and enhanced myocardial apoptosis than the Sham group. The rats in the VNS groups had enhanced cardiac function, lower levels of cardiac injury markers, and inhibited myocardial apoptosis than those in the Vehicle group. Elevated interleukin-1beta and tumor necrosis factor-alpha-levels and activated nuclear factor kappa B (NF-kappa-B) signal in septic shock rats were inhibited by the performance of VNS. This study suggests that VNS contributes to the reduction of myocardial apoptosis and improvement of left ventricular function to attenuate septic shock-induced cardiac injury in rats. The performance of VNS inhibits the inflammatory responses in heart tissues via the regulation of NF-kappa-B signal.

Exercise preconditioning improves electrocardiographic signs of myocardial ischemic/hypoxic injury and malignant arrhythmias occurring after exhaustive exercise in rats.

Exercise preconditioning (EP) has a good myocardial protective effect. This study explored whether EP improves electrocardiographic (ECG) signs of myocardial ischemic/hypoxic injury and the occurrence of malignant arrhythmia after exhaustive exercise. A total of 120 male SD rats were randomly divided into the control group (group C), early exercise preconditioning group (group EEP), late exercise preconditioning group (group LEP), exhaustive exercise group (group EE), early exercise preconditioning + exhaustive exercise group (group EEP + EE) and late exercise preconditioning + exhaustive exercise group (group LEP + EE). Changes in heart rate (HR), ST segment, T wave and QT corrected (QTc) intervals on ECG; hematoxylin-basic fuchsin-picric acid (HBFP) staining; and cTnI levels were used to study myocardial injury and the protective effect of EP. Compared with those in group C, the levels of plasma markers of myocardial injury, HBFP staining and ECG in group EE were significantly increased (P < 0.05). Compared with those in group EE, the levels of plasma markers of myocardial injury, HBFP staining and ECG in group EEP + EE and group LEP + EE were significantly decreased (P < 0.05). The results suggested that EP improved ECG signs of myocardial ischemic/hypoxic injury and malignant arrhythmias that occur after exhaustive exercise. The ST segment and T wave could also serve as indexes for evaluating exhaustive exercise-induced myocardial ischemia/hypoxia.

Cardiac Rupture Due to a Fall from Height: The 'Water Hammer' Effect.

BACKGROUND: Cardiac injury in trauma patients can be secondary to either blunt or penetrating trauma and is a significant cause of death. The commonest etiological factors for blunt cardiac injury include motor vehicle collisions, falls, and crush or blast injuries. The incidence of blunt cardiac injury following falls is reported to be between 5 and 50%.CASE REPORT: A combat pilot lost his life in an aircraft accident. Although he had ejected successfully just before the aircraft caught fire and his parachute had deployed fully, it was engulfed in the ball of fire rising up from the burning aircraft wreckage, causing the parachute to burn up. As a result, the pilot had a free fall from an estimated height of 70-80 ft (21-24 m). Autopsy revealed a ruptured right atrium and endocardial tears at the right atrioventricular junction. The left side of the heart and the coronary arteries were unscathed. The histopathological finding showed evidence that the cardiac injuries sustained were antemortem. The cause of death was ascertained to be due to cardiac rupture, leading to hemorrhagic shock.DISCUSSION: Cardiac rupture in this case appears to be a case of the 'water hammer' effect, the right atrium being the commonest site of blunt cardiac rupture. It is possible that the individual landed on his feet after his parachute got burnt in the ball of fire and the violent compression of the lower limb and abdominal veins, caused by the sudden hyperflexion of the lower limbs over the abdomen, caused the cardiac rupture in this case.CONCLUSION: The possibility of blunt cardiac trauma should always be kept in mind while dealing with survivors of ejection at low levels.Sharma MD, Gupta N, Rajkumar T, Sharma A. Cardiac rupture due to a fall from height: the 'water hammer' effect. Aerosp Med Hum Perform. 2022; 93(10):755-757.

Extracellular Volume Fraction Based on Cardiac Magnetic Resonance T1 Mapping: An Effective Way to Evaluate Cardiac Injury Caused by Cardiac Amyloidosis in Patients with Multiple Myeloma.

Multiple myeloma (MM) is a hematological malignancy of plasma cell origin. Cardiac amyloidosis (CA) is a common form of heart damage caused by MM and is associated with a poor prognosis. This study was a prospective cohort study and was aimed at evaluating the clinical predictive value of extracellular volume fraction (ECV) based on cardiovascular magnetic resonance (CMR) T1 mapping for cardiac amyloidosis and cardiac dysfunction in MM patients. Fifty-one newly diagnosed MM patients in Zhongnan Hospital of Wuhan University were enrolled in the study. A total of 19 patients (19/51; 37.25%) developed CA. The basal ECV of CA group was significantly higher than that of the non-CA group (p < 0.01). Multivariate logistic regression analysis showed that basal ECV (OR = 1.551, 95% CI 1.084-2.219, p < 0.05) and LDH1 level (OR = 1.150, 95% CI 1.010-1.310, p < 0.05) were two independent risk factors for CA. Further study demonstrated that basal ECV in the heart failure group was significantly higher than that of the nonheart failure group (p < 0.01). Notably, ROC curve showed that basal ECV had a good predictive value for CA and heart failure, with AUC of 0.911 and 0.893 (all p < 0.01), and the best cutoff values of 38.35 and 37.45, respectively. Taken together, basal ECV is a good predictor of CA and heart failure for MM patients.

In vivo and in vitro impact of atorvastatin against myocardial ischaemia-reperfusion injury by upregulation of silent information regulator l and attenuation of endoplasmic reticulum stress-induced apoptosis.

We aimed to investigate the effects and mechanism of Atorvastatin on Myocardial Ischaemia-Reperfusion Injury in vitro and in vivo. The effects of Atorvastatin on Silent information regulator l (SIRT1) and endoplasmic reticulum (ER) stress were investigated in Myocardial ischaemia-reperfusion (MI/R) injury rat model and hypoxia/reoxygenation (H/R)-treated H9c2 cells. Pathological changes, inflammatory and heart injury markers, cell apoptosis and cell death, SIRT1 and cleaved Caspase-12 expressions, and ER stress relative proteins were measured through HE, enzyme-linked immunosorbent assay, quantitative TUNEL and flow cytometry, immunofluorescence and Western blotting with the assistance of the SIRT1 specific inhibitor EX527 and ER stress pathway blocker treatment. The results of our study demonstrated that atorvastatin treatment attenuated MI/R and H/R mediated inflammatory and heart injury markers, cell apoptosis and cell death, SIRT1 and cleaved Caspase-12 expressions, and ER stress relative protein levels. Finally, we found that atorvastatin reversed SIRT1 expression and blockade the ER stress pathway and increase the cardiomyocytes survival rate in the presence of MI/R and H/R. Our findings provided a new rationale for subsequent academic and clinical research on MI/R injury.