Pathogenesis of SARS-CoV-2 induced cardiac injury from the perspective of the virus

Introduction: Cardiac involvement in the setting of thoracic trauma is possible with both blunt and penetrating mechanisms. Overall, structural cardiac injury is rare, but when it occurs, it requires immediate diagnosis. We evaluated our process in decision-taking and further surgical procedures if necessary. The aim of this retrospective study is (1) the analysis of cardiac injury patterns and their therapeutic approaches, (2) in how many of these cases a cardiothoracic surgeon is needed in trauma room care and (3) in how many patients cardiothoracic surgery was indicated. Patients and Methods: We analyzed all blunt and penetrating trauma patients with suspected cardiac injury at the time of admission between 7/2016 and 7/2021. Sonography, cardiac enzymes, and electrocardiography were obtained obligatorily. Computed tomography (CT) was carried out in hemodynamically stable patients. Trauma room protocols were analyzed including available Injury Severy Scores (ISS). Data on cardiac injuries, operations, access routes, outcomes and hospitalization were evaluated. Results: In total, 43 patients with cardiac injury at the time of admission could be identified. Contusio cordis was detected in 27 patients (63%), in whom conservative therapy was performed. We indicated surgical intervention in 16 patients (37.2%): nine patients (21%) after blunt chest trauma with cardiac or pericardial injuries, mean ISS 37.3 (9.7). These included tricuspid regurgitation after traumatic rupture of chordae tendineae and rupture of the left atrial appendage. Seven patients (16%) underwent surgery for penetrating chest trauma: six for cardiac knife injury, one patient for iatrogenic drainage dislocation in the left ventricle. Mortality was 22% in surgically treated blunt trauma patients, whereas no mortality was observed in penetrating trauma. Discussion: The most common cardiac injury after blunt thoracic trauma is contusio cordis. In these patients’ surgical treatment is usually not necessary. In contrast, thoracic trauma with structural cardiac injury needs a coordinated and interdisciplinary management in a center with cardiothoracic surgery. In addition to anamnesis and clinical examination, sonography with echocardiography and CT in particular play a decisive role in a rapid diagnosis. In the patients presented in this study, more than every third case required cardiothoracic surgery (16 out of 43 patients, 37.2%). Thus, cardiothoracic expertise should be present for all trauma room patients with suspected cardiac injury.

The development of rapid, automated, and accurate laboratory testing for creatine kinase MB (CK-MB) revolutionized the treatment of patients with acute cardiac events in the 1970s and 1980s.1 To clinicians, CK-MB values augmented a thorough history, physical, and ECG findings, and elevations rapidly became the gold standard for identifying cardiac injury.1 CK-MB allowed earlier diagnosis of acute myocardial infarction (AMI), and detection of reinfarction, and measurements could be used to provide a facile clinical estimate of infarct size. Elevations of CK-MB were never intended to be synonymous with myocardial infarction, only indicative of cardiac injury.1 However, because of the relative insensitivity of measurements, increased concentrations occurred predominantly with larger insults such those associated with acute ischemic heart disease. For that reason, AMI was rarely diagnosed, assuming appropriate timing of the samples, in the absence of a CK-MB elevation.2,3 CK-MB assays initially relied on the measurement of enzyme activity, but over time, improved accuracy and ease of use were established by the use of mass assays. Mass assays allowed earlier detection of abnormal values and improved both clinical sensitivity and specificity. However, mass assays unmasked an increased frequency of CK-MB elevations due primarily to skeletal muscle injury because of their increased sensitivity.4–6 Clinical use of the percent relative index was then initiated. This approach improved the specificity of elevations for cardiac muscle injury but was insensitive when concurrent cardiac injury and skeletal muscle injury were present because elevations from skeletal muscle often are of a large magnitude.7–10 A large number of analytical confounds such as macrokinases and interfering substances also were substantial problems with these assays.10,11 Attempts to standardize assays12 have been partially successful, but differences still exist between manufacturers and even between the same testing antibodies used on different analytical platforms (ie, …

Laparoscopic Transdiaphragmatic Pericardial Window: Getting to the Heart of the Matter

Background The objective of this study was to assess the efficacy of a computed tomography (CT) scan of the chestin detecting structural cardiac and pericardial injuries. Methods We retrospectively analyzed data from a data registry at a trauma center between January 2015 and June 2022. This study included individuals with severe chest trauma (defined as an Abbreviated Injury Scale score of ≥3 for the chest). The assessment of cardiac injury from chest CT scans relied on the information provided in the official radiological reports. Definitive diagnoses of structural cardiac injury were confirmed on the basis of surgical findings or the diagnosis upon discharge. Results The chest CT scans revealed 11 cases of pericardial abnormalities: 10 (90.9%) cases of pericardial effusion in patients with blunt trauma and one (9.1%) case of pneumopericardium in a patient with a stab wound. Among these 11 cases, surgical exploration identified four structural cardiac and pericardial injuries, and three died during hospitalization. The remaining seven cases underwent nonsurgical intervention, and none exhibited any cardiac and pericardial abnormalities. The chest CT for traumatic structural cardiac and pericardial injuries had a sensitivity of 4/4 (100.0%), a specificity of 402/411 (97.8%), a positive predictive value of 4/11 (36.4%), and a negative predictive value of 404/404 (100.0%). Conclusion This study highlighted a high mortality rateamong patients diagnosed with structural cardiac injuries, underscoring the critical importance of accurate and timely diagnostic investigations in such cases. Our findings confirmed that chest CT is a reliable screening tool for detecting structural cardiac injuries in patients with both blunt and penetrating chest trauma. However, given the relatively low positive predictive value of chest CT for structural cardiac injuries, additional diagnostic imaging or prompt surgical intervention may be necessary in cases where pericardial abnormalities are identified on chest CT to address potential occult cardiac injuries.

Cardiac injury following penetrating chest trauma: Delayed diagnosis and successful repair

Background Immune checkpoint inhibitors (ICI), specifically directed against CTLA-4 and PD-1, have revolutionized cancer therapy but are associated with immune-related adverse events, including fulminant myocarditis. The mechanisms are unknown, but one possibility is that CTLA-4 and PD-1 play a critical role in cardiovascular homeostasis. Purpose The purpose of this study is to investigate the role of these immune checkpoints in cardiac injury. We hypothesize that cardiomyocytes can express immune checkpoint ligands in response to stress and that CTLA-4 and/or PD-1 play a key role in cardiac response to injury. Methods We measured expression levels of CTLA-4 ligands (Cd80, Cd86) and PD-1 ligands (Pdcdl1, Pdcdl2) in in vitro and in vivo models of cardiac injury, including iPSC-derived cardiomyocytes (iPSC-CM) and diseased human cardiac samples. Immunofluorescent staining and multiplex immunohistochemistry were used to derive more granular data on cell type expressing specific immune checkpoint associated proteins. To determine the functional role of CTLA-4 and PD-1 in cardiac injury, myocardial infarction (MI) was induced in C57Bl/6 mice treated with anti-CTLA-4 or in mice with a genetic knock-out of CTLA-4 and PD-1 (Pdcd1−/−Ctla4+/+ and Pdcd1−/−Ctla4+/−). Flow cytometry was performed 2-days post-MI to determine immune cell infiltration, echocardiography was performed 7-days and 28-days post-MI and plasma samples were analyzed for ANP and Troponin I. Results Doxorubicin or hypoxia increased expression of Cd80, Cd86, Pdcdl1 and Pdcdl2 in iPSC-CM. After MI, isolated cardiomyocytes from the ischemic/border zone area yielded significant increased expression of both Cd80 and Cd86, which was confirmed at the protein level. However, pharmacologic inhibition of CTLA-4 during MI resulted in better survival compared to no treatment (p<0.007). No differences were seen in immune cell infiltration, troponin I and ANP levels and echocardiography. Pdcd1−/-Ctla4+/+ and Pdcd1−/−Ctla4+/− mice showed a decrease in immune cell infiltration. Conclusions Whole hearts, isolated cardiomyocytes and iPSC-CM from both mice and humans express immune checkpoint ligands in response to cardiac injury. Pharmacologic or genetic inhibition of CTLA-4 and PD-1 in MI did not result in adverse effects regarding survival, cardiac function, immune cell infiltration and heart enzyme levels in mice. These data support the hypothesis that immune checkpoint pathways play a role in cardiac injury and in these preliminary studies immune checkpoint inhibition during cardiac ischemic injury did not result in adverse effects. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health grants R56 HL141466 and R01 HL141466

Shockwave cardiac injury in thoracoabdominal gunshot wound

Hemorrhagic shock (HS) is a critical condition with high mortality caused by acute blood loss. Cardiac injury and dysfunction induced by HS is a major factor associated with the poor prognosis of affected patients. Schisandrin A (Sch A), a dibenzocyclooctadiene lignan extracted from Fructus schisandrae, exhibits multiple biological activities, including anti-inflammatory, and antioxidant effects. However, the effect of Sch A on HS-caused cardiac injury and its underlying mechanism still lack research. In this study, we established an HS rat model through blood loss from the femoral artery and monitoring mean arterial pressure (MAP) followed by fluid resuscitation. Our findings suggested that cardiac dysfunction and pathological injury were induced by HS and attenuated by Sch A treatment in a dose-dependent manner. Apoptosis in cardiac tissue was promoted by HS, but suppressed after administration of Sch A by decreasing the protein expressions of cleaved-caspase-3 and -9. Moreover, excessive ROS production induced by HS was mitigated by Sch A, and the levels of oxidative stress indicators were improved by Sch A. Additionally, HS triggered the reduction of mitochondrial membrane potential (MMP), and led to mitochondrial dysfunction. Sch A reversed this effect of HS on mitochondria. The transformation of cytochrome c (Cyto c) induced by HS was also restored by Sch A. Importantly, the activation of the Nrf2 signaling pathway mediated the protective effects of Sch A against cardiac injury induced by HS. In conclusion, it was found that Sch A ameliorated HS-induced cardiac injury and dysfunction through suppressing apoptosis and oxidative stress, as well as alleviating mitochondrial dysfunction via the Nrf2 signaling pathway.

Inflammation plays an important role in hypertensive cardiac injury. The endoplasmic reticulum (ER) stress pathway is involved in the inflammatory response. However, the role of ER stress in elevated angiotensin II (Ang II)-induced cardiac injury remains unclear. In this study, we investigated the role of ER stress in Ang II-induced hypertensive cardiac injury. Transcriptome analysis and quantitative real-time PCR showed that Ang II infusion in mice increased ER stress-related genes expression in the heart. C/EBP homologous protein (CHOP) deficiency, a key mediator of ER stress, increased infiltration of inflammatory cells, especially neutrophils, the production of inflammatory cytokines, chemokines in Ang II-infused mouse hearts. CHOP deficiency increased Ang II-induced cardiac fibrotic injury: (1) Masson trichrome staining showed increased fibrotic areas, (2) immunohistochemistry staining showed increased expression of α-smooth muscle actin, transforming growth factor β1 and (3) quantitative real-time PCR showed increased expression of collagen in CHOP-deficient mouse heart. Bone marrow transplantation experiments indicated that CHOP deficiency in bone marrow cells was responsible for Ang II-induced cardiac fibrotic injury. Moreover, TUNEL staining and flow cytometry revealed that CHOP deficiency decreased neutrophil apoptosis in response to Ang II. Taken together, our study demonstrated that hypertension induced ER stress after Ang II infusion. ER stress in bone marrow-derived cells protected acute cardiac inflammation and injury in response to Ang II.

Pediatric cardiac and great vessel injuries: Recent experience at two pediatric trauma centers

The development and progression of heart failure (HF) involves many processes that occur after cardiac stress and/or injury. Compensatory neuro-hormonal activation and chronic stimulation of the sympathetic nervous system (SNS) is accompanied by the pathological increase in G protein-coupled receptor kinase (GRK) 2 expression. Data indicates that elevated GRK2 activity participates in the progression of HF after cardiac injury such as a myocardial infarction (MI) and this includes chronic β 1 -adrenergic receptor (β 1 AR) desensitization. The molecular transcriptional or translational mechanism of GRK2 upregulation in the heart is largely unknown. MicroRNAs (miRNAs) have been discovered as critical regulatory molecules in the heart as their expression profiles become dysregulated after cardiac injury. Further, miRNAs can play key roles in orchestrating many phenotypic changes observed in HF. Previous studies have shown that components of the βAR pathway, including the β 1 AR, are targeted by miRNAs whose levels are aberrant during cardiac injury. This study was started to determine if GRK2 may also be targeted by a miRNA that goes down after injury, participating in the up-regulation of this pathological kinase. MiRNA profiles of 2 week post-MI C57BL/6 mice were examined through miRNA microarray analysis. MiRNAs that were down-regulated after MI and had seed sequence complementarity to GRK2’s 3’UTR were selected as candidates for further testing. MiR-378a-5p (miR-378a) was chosen as a suitable candidate and transfection of a miR-378a mimic into neonatal rat ventricular myocytes was able to significantly reduce GRK2 protein levels compared to a negative control, while mRNA levels seem to be unaffected. This suggests miR-378a may work primarily through translational inhibition rather than transcriptional inhibition. Using a 3’UTR reporter system, we found that miR-378a was able to directly bind to the 3’UTR of GRK2 and inhibit reporter activity. These data support the hypothesis that GRK2 is regulated by a miRNA in the heart and provides a possible mechanism for GRK2 post-transcriptional regulation . In vivo studies are currently in progress to determine if miR-378a may be a novel therapeutic strategy to decrease GRK2 levels in the failing heart.

Identification of the exact cause and time of death are important questions that have to be answered by the forensic pathologist. Traumatic cardiac injuries is a leading cause of death. This work aimed at using cardiac troponin C (cTnC) expression to differentiate between different types of cardiac injuries at different postmortem intervals (PMI). This study was performed on 90 forensic autopsies selected in the Medicolegal Department of Ministry of Justice. The cases were divided equally into 5 groups of different causes of death i.e. non-cardiac causes of death (control group), blunt cardiac injury (BCI), civilian cardiac firearm injury, civilian stab injury and sudden cardiac death (SCD). Brown Immunohistochemical expression of TnC was observed in all groups, where the non-cardiac death, blunt injury and firearm injury groups showed less immunohistochemical staining than stab injury and SCD. The density of the cTnC immunohistochemical staining increased by the increase in the PMI. Quantitative morphometric measurement of cTnC immunohistochemical expression was measured. Significant increases in the mean surface area of cTnC immunohistochemical expression were detected in the groups of only stab injury and SCD compared to the other studied groups (p<0.001), while non-significant differences were detected between non-cardiac, BCI and civilian cardiac firearm injury groups. Besides, the mean surface area of cTnC immunohistochemical expression increased significantly by the increase in the postmortem interval. These findings suggest that the mean surface area of cTnC immunohistochemical expression can differentiate between cardiac and non-cardiac deaths, and between the different types of cardiac deaths.

In recent years, the incidence of cardiovascular disease has been increasing year by year, has gradually developed into a global health problem, in the world wide concern. Non - cardiac injury is one of the most common cardiovascular diseases. The rehabilitation of patients with non-cardiac myocardial injury is related to their life and quality of life. Rehabilitation exercise is helpful to improve the therapeutic effect of patients. The purpose of this paper is to explore the specific effects of rehabilitation exercise on non-cardiac myocardial injury and to promote the full play of the role of rehabilitation exercise in the treatment of noncardiac myocardial injury. First to illustrate the application of optical microscope, and then from the specific reflection of non cardiac myocardial damage and formation mechanism are introduced, based on the cases were retrospectively analyzed experiment, to explore the rehabilitation exercise in the cardiac effects of myocardial injury treatment, and on the basis of this puts forward the corresponding scientific rehabilitation exercise plan. Experimental results show that compared with the rehabilitation exercise intervention before and after rehabilitation exercise intervention, non cardiac myocardial injury in the therapeutic effect of 17% or so, in the treatment of speed increased by about 21%, in the recurrence rate was reduced by 17% or so, so sports in promoting the cardiac myocardial injury treatment has good effect.

Squash injury countermeasures: A review of the literature

Blunt thoracic trauma comprises approximately 8% of all traumatic admissions in the United States. While chest wall injuries comprise much of this burden, mediastinal injuries, including cardiac and great vessel injuries, are being recognized more frequently given the diagnostic capabilities of modern CT imaging. In penetrating trauma, close proximity of structures in the mediastinal space, comes with a higher incidence of injury to multiple structures. Further, cardiac injury is estimated to comprise 10% of the mortality of gunshot wound victims, while more than 90% of great vessel injury is associated with penetrating injury, representing a significant burden of disease. Management and care of these injuries requires consideration of multiple details and exposure techniques. This article will address diagnosis, management and repair of esophageal, thoracic duct, cardiac, and great vessel injuries. This review contains 4 figures, 2 tables, and 49 references. Keywords: Mediastinal structures, esophageal injury, esophageal repair, thoracic duct injury, thoracic duct ligation, blunt cardiac injury, penetrating cardiac injury, blunt aortic injury, great vessel injury, endovascular stenting