Heart Specimens Research Articles

Morphological Array of Cardiac and Coronary Artery Diseases in Cases of Sudden Death: An Autopsy-Based Histopathological Study in Rural Setup

Cardiovascular diseases are the foremost cause of sudden death in adults. The primary objective of this study is to estimate the prevalence of various cardiac and coronary artery diseases in sudden unexpected death cases in rural setup. Estimation of age and sex-wise frequency of coronary atherosclerotic disease (CAD), and grading of CAD by applying the Modified American Heart Association (AHA) classification are secondary objectives. In this three years prospective cross-sectional study, heart specimens were studied from 136 persons whose death was sudden and unexpected. Gross dissection and histopathological examination of coronary arteries and heart were done. Diagnoses were based on both gross and microscopic findings. CAD with or without other diseases was the most frequent pathology (n-100, 73.5%). Left ventricular hypertrophy in 45 cases (33.09%), myocardial infarction in 30 cases (22.06%), valvular abnormalities in three cases (2.2%), infective endocarditis in two cases (1.47%), aortic dissection in one case (0.74%), right ventricular hypertrophy in one case (0.74%) and cardiac myocyte atrophy in one case (0.74%) were observed. Male-female ratio of CAD was 8.09:1. Advanced CADs (type IV, V, VI) were found in 94 (94%) cases. In males, the maximum number of advanced CAD was observed in the fifth decade (n- 27, 31.76%) and in females in the seventh decade (n- 4, 44.44%). This study reveals the increasing trend of CAD in rural populations. This study adds rare entities like young-age aortic dissection and cardiac myocyte atrophy to the existing literature and emphasises the importance of autopsy in sudden death cases.

Can Intranasal Administration of Adipose-Derived Stem Cells Reach and Affect the Histological Structure of Distant Organs of Aged Wistar Rat?

Stem cell therapy is a highly promising strategy in various degenerative diseases. Intranasal administration of stem cells could be considered as a non-invasive treatment option. However, there is great debate concerning the ability of stem cells to reach distant organs. It is also unclear in such a case if they can alleviate age-related structural changes in these organs. The aim of this study is to evaluate the ability of intranasal administration of adipose-derived stem cells (ADSCs) to reach distant organs of rats at different time intervals and to investigate their effects on age-related structural changes in these organs. Forty-nine female Wistar rats were used in this study, seven of which were adults (6-month-old) and 42 were aged (2-year-old). Rats were divided into three-groups: Group-I (adult control), Group-II (aged), and Group-III (aged ADSCs treated). Rats of Groups I and II were sacrificed after 15 days from the beginning of the experiment. Rats of Group III were treated with intranasal ADSCs and were sacrificed after 2-h, 1-day, 3-day, 5-day, and 15-day. Heart, liver, kidney, and spleen specimens were collected and processed for H and E, CD105 immunohistochemistry, and immunofluorescent techniques. Morphometric study and statistical analysis were performed. ADSCs appeared in all organs examined after 2-h of intranasal administration. Their maximum presence was detected after 3-day of administration, after which their immunofluorescence gradually decreased and nearly disappeared from these organs by the 15th day. Improvement of some age-related deterioration in the structure of the kidney and liver occurred at day 5 after intranasal administration. ADSCs effectively reached the heart, liver, kidney, and spleen after intranasal administration. ADSCs ameliorated some age-related changes in these organs.

Calcified False Tendon Linked to Sudden Cardiac Death in a Young Adult: An Autopsy-based Case Report

Left Ventricular False Tendons (LVFTs) are cord-like structures that traverse the cavity of the left ventricle, connecting the left ventricular free wall or papillary muscle and the ventricular septum without attachment to the mitral valve leaflets. They are incidentally found in autopsy heart specimens. False tendons are generally benign anatomic variants and can be associated with functional murmurs and electrocardiographic abnormalities. False tendons can also be a cause of ventricular arrhythmias. Two-dimensional echocardiography serves as a useful imaging modality in detecting false tendons. They should be differentiated from other entities such as thickened ventricular trabeculations, an accessory anterior mitral leaflet, thrombus, vegetation, and ventricular masses or tumours. Most LVFTs are transverse and are located in the apex. They are found to arise from the inner trabeculated layer of the myocardium. The exact prevalence of LVFTs remains unclear. Present report is a case of postmortem findings in the heart of a 34-year-old male who experienced a sudden collapse while walking after lunch. On gross examination, the left ventricular wall and the lower part of the interventricular septum showed focal grey-white areas. A well-defined, grey-white, hard polypoidal lesion was noted in the left ventricle near the apex, attached to the papillary muscles. The left anterior descending artery showed early atherosclerotic changes. LVFT was diagnosed, which could have been the reason for the arrhythmia. Hence, the evaluation of cardiac murmurs and arrhythmias by two-dimensional echocardiography and cardiac Magnetic Resonance Imaging (MRI) serves as helpful parameters in detecting LVFTs.

Myocardial Bridging in Cases of Sudden Death and its Association with Clinicopathologic Characteristics.

Myocardial bridging (MB) is the course of the epicardial segment of a coronary artery within the myocardium. The systolic compression of this segment called the tunneled segment may lead to alterations in blood flow to the heart. We have studied the gross and microscopic features of MB in cases of sudden cardiac death and analyzed its characteristics and whether there is any association with other clinicopathological characteristics which may help us to understand the pathogenesis and risk stratification. This is a retrospective descriptive study of 132 postmortem heart specimens of sudden cardiac death. The coronary arteries were dissected, and MB and its characteristics were studied. Statistical analysis was performed using the Chi-square and Fisher's exact tests (P < 0.05 significant). MB was present in 28 cases (21.2%), with a mean age of 49.5 years and male:female ratio of 27:1. MB was seen in the left anterior descending artery in 86.2% of cases, the right coronary artery in 10%, and left circumflex artery in 3.5% of cases. Atherosclerosis was seen in the segment proximal to the tunneling in 89.2% of cases leading to infarction in four cases. Left ventricular hypertrophy (LVH) was significantly associated with MB cases (19/68%) (P < 0.05). MB causes turbulence of blood in the proximal segment leading to coronary atherosclerosis, thereby predisposing the heart to ischemic changes and LVH and may lead to infarction in a few cases.

216 ARRHYTHMOGENIC CARDIOMYOPATHY: IS THERE EVIDENCE OF AN INFLAMMATORY MYOCARDIAL DISEASE?

Abstract Background and aim Arrhythmogenic cardiomyopathy (ACM) is a heredo-familiar primary heart muscle disease, mainly due to mutations of desmosomal genes and characterized by progressive myocardial atrophy with fibro-fatty replacement, causing electrical instability at risk of sudden cardiac death (SCD). Since the first anatomopathological descriptions, the hypothesis that myocardial inflammation could have an important role in the onset and evolution of ACM has been advanced. With this work we aim to describe the prevalence of inflammatory cells in ACM and their characterization through histological and immunohistochemical (IHC) analysis in endomyocardial biopsy (EMB) and heart specimens coming from either SCD or heart transplantation (HTx). Material and methods We analysed EMB and whole heart specimens (from juvenile SCD registry – below 40 years of age at the time of death – and HTx) with a diagnosis of ACM, focusing on the presence of inflammatory infiltrates. For the whole hearts, in a subgroup of cases the inflammatory infiltrate was evaluated on 9 myocardial sections by applying a semi-quantitative score according to the number of sections involved (0 = none; 1 = 1 section involved; 2 = 2-5 sections; 3 = &amp;gt;5 sections) and an IHC panel for myocarditis on 1 right ventricular and 1 left ventricular section (CD45, CD3, CD8, CD4, CD68, CD20, CD138 and vimentin- as a control for fibroblast). Results Among the 63 analysed EMB (41 M, mean age 45 years, range 18-71 years), 26 cases (41%) showed foci of inflammation with CD3+ &amp;gt; 7/mm2. In all cases viral genome (DNA and RNA virus) was absent. A total of 106 heart specimens with a diagnosis of ACM were enrolled, including 73 juvenile SCD (49 M, mean age 26 years) and 33 HTx (18 M, mean age 45 years). Inflammation was reported in 95% of SCD an d 67% of HTx. The inflammatory infiltrate was focal or multifocal in all, except one case of juvenile SCD with diffuse myocarditis in the postero-lateral wall of the left ventricle. In the 24 reviewed cases, the inflammation was focal with a mean inflammatory score of 1.75 ±0.9 in the HTx group and 1.5±0.9 in the SD group (p = NS). By IHC we showed that: a) there is no significant difference in the inflammatory score between SD and HTx; b) the inflammation is mostly near-scarring (13 cases); c) inflammatory cells consist prevalently of cytotoxic T lymphocytes CD3+CD8+ (with CD4+&amp;lt;CD8+ both in SD and HTx, p &amp;lt; 0.05). Conclusions Our pathological data confirm that ACM is an inflammatory cardiomyopathy with a higher prevalence of inflammation in SCD cases. The inflammatory infiltrate is mainly composed of cytotoxic T lymphocytes with a variable presence of macrophages. These data, combined with the recent experimental studies demonstrating the role of immune mediators in the evolution of the disease, support the potential application of immunosuppressive therapy in ACM.

Abstract 11983: Associations Between Circulating Proteins and Intracardiac Immune Populations in Immune Checkpoint Inhibitor-Associated Myocarditis

Introduction: Myocarditis due to immune checkpoint inhibitors (ICIs), a type of cancer immunotherapy, is associated with high morbidity and mortality. The cellular and molecular pathogenesis of ICI myocarditis remains largely unknown. Identification of circulating factors associated with intracardiac pathology may aid new clinical approaches. Hypothesis: We hypothesized that ICI myocarditis is associated with increased abundance of intracardiac immune cells and upregulated inflammatory genes in the heart and serum. Methods: Heart tissue from 13 patients with ICI myocarditis was acquired by endomyocardial biopsy or autopsy; peripheral blood mononuclear cells (PBMCs) were also collected from ten of these patients and eight additional ICI myocarditis patients. Control heart tissue was derived from six hearts declined for transplantation (non-ICI-exposed) and from the biopsy and autopsy of one ICI-treated patient without myocarditis. The 10x Genomics Chromium system was used to generate single-cell RNA sequencing (scRNAseq) data from heart and PBMC specimens. Serum proteins were measured by core lab assay (for troponin T) or by multiplexed Luminex immunoassay. Results: Unbiased clustering of scRNAseq data from 77,071 cells recovered from heart samples revealed 37 cell subsets across 10 cell lineages. Myocarditis heart tissue demonstrated enrichment of T/NK cells (odds ratio 8.3, p=0.0006), B/plasma cells (OR 5.1, p=0.01), and dendritic cells (DCs) (OR 9.2, p=0.006) relative to controls. Circulating DC abundance was decreased in fatal (n=3) versus nonfatal (n=15) myocarditis cases (p=0.008), while intracardiac DC abundance was directly associated with serum troponin T values (p=0.02). The levels of five immunomodulatory factors - IL-15, CXCL9, CCL3, TNFα, and CCL21 - were found to be significantly upregulated transcriptionally in at least one intracardiac cell subset and at the protein level in the serum of myocarditis cases. Conclusions: Fatality status and troponin level associated with intracardiac DC abundance and multiple immunomodulatory genes were upregulated in both the heart and serum in ICI myocarditis. These observations may guide novel diagnostic and therapeutic strategies.

Novel Automated Suturing Technology for Minimally Invasive Mitral Chord Implantation: A Preclinical Evaluation Study.

This study evaluated the ergonomics and time requirements of using a novel automated suturing and titanium fastener deployment technology for chordal replacement in human heart specimens in open and minimally invasive cardiac surgery (MICS) simulators. Five cardiac surgeons used novel, manually powered expanded polytetrafluoroethylene (ePTFE) suturing devices to automate suture placement between mitral leaflets and papillary muscles in explanted cadaver hearts, along with customized titanium fastener delivery devices to secure suture and trim suture tails. This mitral chordal replacement test was conducted using surgical models simulating open and MICS mitral repair access. The study was approved by the institutional ethical board. After a brief introduction to this technique using plastic models, study surgeons performed 48 chordal replacements in human mitral valves, placing 18 in an open model and 30 in a right minithoracotomy model. The time range to complete a single chordal replacement was between 55 s and 8 min, with an overall mean duration of 3.6 ± 1.5 min. No difference in duration of implantation was recorded for the MICS and open sternotomy simulators used. Good control of suture delivery was reported in 95.8% (n = 46) of leaflet aspect of the sutures and in 100% (N = 48) of papillary muscle sutures. Automated mitral chordal ePTFE suturing simulated through open and MICS access demonstrated quality handling and accurate placement of sutures in human heart specimens. A clinical trial using this technology is currently ongoing. This innovation may present an important advance facilitating enhanced minimally invasive mitral valve repair.

Development of Digital Fetal Heart Models with Virtual Ultrasound Function Based on Cardiovascular Casting and Computed Tomography Scan.

Despite recent breakthroughs in diagnosis and treatment, congenital heart defects (CHDs) continue to be the leading cause of death among newborns. Fetal echocardiography is the most effective and non-invasive method for the prenatal diagnosis of CHDs. However, the challenge of obtaining standard views can lead to a low diagnostic accuracy. To explore new methods for training, the combined use of cardiovascular casting, computed tomography (CT) scanning, and virtual ultrasound generation methods was studied to preserve the cardiac structures of a fetus in digital form. The feasibility of the proposed workflow was verified by testing three fetal heart specimens collected after the termination of pregnancy. As a result, the anatomical structures were imaged clearly by a CT scan after cardiovascular casting, and the virtually generated ultrasound images based on the use of the Public software Library for UltraSound imaging research (PLUS) toolkit successfully demonstrated both the standard views and the views with diagnostic values for the visualization of the cardiovascular structures. This solution provides great data extensibility while being simple and cost-effective for end users. Therefore, the proposed method could provide a promising educational system for trainees to understand standard views of fetal echocardiography and the corresponding anatomical correlations.

Anthropo-morphometric patterns of design and proportionality of the aortic valve leaflets in light of reconstructive surgery

Background. As long as the design of leaflets is crucial for aortic valve replacement, inaccurate reconstruction can result in failure or stenosis postoperatively.Aim. To analyze average parameters of normal valve leaflets and to assess the correlation between various parameters of a normal aortic valve and personal morphometrics. Methods. The morphometrics of the aortic root were assessed on 54 specimens of the adult heart without any valvular abnormality. We measured following parameters: circumference of the ventriculo-aortic junction and the sino-tubular junction; inter-commissural distance, length of free margin, length of cusp attachment, and height for right coronary, non-coronary, and left coronary aortic leaflets. Results. Based on the average values, the left coronary leaflet is distinguished by the smallest dimensions of the length of free margin and length of cusp attachment. The height of the left coronary leaflet is maximum as compared to the right coronary and non-coronary leaflets, but these differences are minimal (up to 0.2 mm), where the left coronary leaflet is the smallest. Statistically, no significant intergroup difference was found. For all valve sizes, p &gt; 0.05 (inter-commissural distance p = 0.083, length of free margin p = 0.331, length of cusp attachment p = 0.056, height of leaflet p = 0.518). Significant correlations were found between all aortic valve leaflet sizes and the ventriculo-aortic junction and the sino-tubular junction. A weaker correlation was found between all leaflets sizes and the body height.Conclusion. The findings can be used to optimize the leaflet reconstruction and improve the aortic valve function. Received 9 September 2020. Revised 10 September 2021. Accepted 29 June 2022. Funding: The study did not have sponsorship. Conflict of interest: Authors declare no conflict of interest. Contribution of the authorsConception and study design: R.N. Komarov, V.N. Nikolenko, S.N. OdinokovaData collection and analysis: S.N. Odinokova, V.V. Studennikova, L.O. SeverginaStatistical analysis: S.N. OdinokovaDrafting the article: S.N. Odinokova, R.Kh. BelkharoevaCritical revision of the article: R.N. Komarov, V.N. NikolenkoFinal approval of the version to be published: S.N. Odinokova, R.N. Komarov, V.N. Nikolenko, L.O. Severgina, V.V. Studennikova, R.Kh. Belkharoeva

Study of necrotic apoptosis by pulsed electric field ablation in rabbit left ventricular myocardium.

ObjectiveWe investigate the characteristics of histological damage to myocardial cells in the ablation region and surrounding areas of the left ventricular epicardium in rabbits using our self-developed cardiac pulsed electric field (PEF) ablation instrument and ablation catheter.MethodsForty eight New Zealand rabbits underwent ablation on the left ventricular myocardium after open-heart exposure with a cardiac arrhythmia PEF ablation device and ablation catheter developed by the Medical Translation Laboratory of Pulsed Electric Field Technology in Zhejiang Province. The ablation parameters were set as biphasic electrical pulses; voltage, ±800 V; pulse width, 10 μs; interphase delay, 500 us. Six rabbits were included in the sham group and 42 other rabbits were randomly divided into immediately, 6-h, 1-, 3-day, 1-, 2-, and 4-week post-ablation groups, with six rabbits in each group. Creatine kinase- (CK)-MB isoenzyme (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels were measured before and at different time points after PEF ablation to analyze their dynamic evolution. Masson staining of tissue block sections of left ventricular myocardial ablation and adjacent tissue heart specimens was performed, and the occurrence of TUNEL apoptosis in myocardium tissue was analyzed.ResultsAll rabbits completed the PEF ablation procedure and the follow-up process. After PEF ablation, the levels of cardiac enzymes, including CK-MB, CK, and AST, increased significantly, peaking 1–3 days after the procedure. In particular, those of CK and CK-MB increased by 15–20 times but returned to the preoperative level after 2 weeks. Based on general observation, it was found that the myocardium in the ablation area was swollen immediately after PEF ablation. Masson staining analysis revealed that cardiomyocytes were broken and infiltrated by erythrocytes after 6 h. After 1 day, the cells started to experience atrophy and necrosis; after 3 days, fibrotic replacement of the necrotic area became obvious. Then, by 4 weeks, the myocardial cells were completely replaced by hyperplasia. Apoptosis occurred significantly at 6 h and peaked at 24 h post-ablation, demonstrating a 37.7-fold increase; apoptotic cell counts decreased significantly at 3 days post-ablation, and no significant apoptotic cardiomyocytes were seen after 1 week.ConclusionAfter PEF ablation, cardiomyocytes showed apoptotic process and dyed, at least partially, through a secondary necrosis, the ablation boundary was clear, the ablation area was replaced by structurally intact fibroblasts, no island myocardium tissue were seen, and the ablation area vessels and nerves were not affected.

Use of potassium ion channel and spliceosome proteins as diagnostic biomarkers for sudden unexplained death in schizophrenia

Sudden unexplained death in schizophrenia (SUD-SCZ) is not uncommon and its incidence is approximately three times higher than that in the general population. However, diagnosis of SUD-SCZ remains a great challenge in forensic pathology. This study designed a two-phase study to investigate whether three proteins, namely two potassium ion channel proteins (KCNJ3 and KCNAB1) and one spliceosome protein (SF3B3) that were identified in our previous work, could be applied in the postmortem diagnosis of SUD-SCZ. Immunohistochemical staining of the three biomarkers, followed by a rigorous quantitative analysis, was performed on heart specimens from both SUD-SCZ and control groups. A diagnostic software based on the logistic regression formula derived from the test phase data was then constructed. In the test phase, we found that the staining intensities of KCNJ3, KCNAB1, and SF3B3 were all significantly lower in the SUD-SCZ group (n = 20) as compared with the control group that died from non-natural causes (n = 25), with fold-changes being 14.85 (p < 0.001), 4.13 (p = 0.028) and 2.12 (p = 0.048), respectively. Receiver operating characteristic analysis further illustrated that combination of the three biomarkers achieved the optimal diagnostic specificity (92%) and area under the curve (0.886). In the validation phase, the diagnostic software was confirmed to be a promising tool for predicting the risk of SUD-SCZ in authentic cases. Our study provided a valid strategy towards the practical diagnosis of SUD-SCZ by using KCNJ3, KCNAB1, and SF3B3 proteins as diagnostic biomarkers.

Theileriosis in naturally infected roan antelope (Hippotragus equinus).

Cases of Theileria-associated mortality are rarely reported in African wild artiodactyls. Descriptions of lesions are limited, particularly in endangered hippotraginids. Here, we analyzed retrospectively the gross and histologic findings in 55 roan antelope (Hippotragus equinus) with fatal natural theileriosis. The most frequently recorded gross findings in 40 cases were widespread petechiae and ecchymoses (72.5%), probable anemia (67.5%), icterus (60%), splenomegaly (60%), hepatomegaly (52.5%), and pulmonary edema (50%). Histologic lesions in 34 cases were characterized by multi-organ infiltrates of parasitized and nonparasitized mononuclear leukocytes (MLs), and fewer multinucleate giant cells (MNGCs). Liver, lung, kidney, adrenal gland, and heart were most consistently infiltrated, followed by spleen and lymph nodes. Leukocytes were phenotyped in lung, liver, kidney, and heart specimens from 16 cases, using immunohistochemistry to detect CD20, CD3, myeloid/histiocyte antigen (MAC387), IBA-1, and CD204 surface receptors. A roan polyclonal anti-Theileria sp. (sable) antibody was applied to the same tissues to identify intraleukocytic parasite antigens. Similar proportions of intravascular and extravascular IBA-1-, CD204-, and MAC387-reactive putative monocyte-macrophages and fewer CD3-positive putative T-lymphocytes were identified in all organs, especially the lungs in infected roan. CD20-positive putative B-lymphocytes were significantly scarcer than in uninfected controls. Intraleukocytic Theileria parasites labeled consistently in affected tissues. Some parasitized and nonparasitized MLs and the MNGCs failed to label with selected leukocyte markers. Fatal theileriosis in roans may largely be the result of multi-organ monocyte-macrophage activation with associated tissue injury and overwhelming systemic inflammation. The identity of the parasitized leukocytes and characteristics of the lymphohistiocytic response require further clarification in roans.

A STUDY OF FOSSA OVALIS : HOW THE MORPHOMETRY AND LOCATION AFFECTS TRANSSEPTAL APPROACH TO LEFT ATRIUM.

Background- Fossa Ovalis (FO) surrounded by limbus are embryological remnants in inter atrial septum of heart. By Trans-septal approach, towards the left heart chambers, floor of FO is punctured to perform various types of diagnostic and therapeutic procedures. Variable position and morphometry of FO remains main challenge. Materials and Methods– 30 heart specimens were procured from properly embalmed cadavers. FO was Inspected in interior of the right atrium. Shapes, diameters, position of FO were determined by Vernier callipers. Probe patency test was performed in cases of Patent Foramen Ovale (PFO). occurrence of PFO is 23.3% (7 out of 30 hearts). The average Result- transverse diameter of FO was 11.68 mm and average vertical diameter was 13.70 mm. Most of the FOs ware oval with longer vertical diameter. In 26 cases (86.6%) limbus is raised and in 4 it is totally flat with the surface of IAS. In 22 hearts, wall of FO were thinner than rest of inter atrial septum (IAS). In one case Chiari strands are found in the floor of FO. Conclusion– Raised limbus of FO prevents slipping of needle while puncturing. Small FO, Chiari strands or multiple cardiac anomalies are unfavourable for TS puncture. To perform Left atrial pressure measurement, and in different cardiac surgeries proper visualization and knowledge of FO is very important.

Aortic Arch Phenotypes in Double Outlet Right Ventricle (DORV)-Implications for Surgery and Multi-Modal Imaging.

Abnormal aortic arches (AAAs) cover a spectrum of malformations, including abnormal laterality, branching patterns, and flow-limiting narrowing, which themselves vary from tubular hypoplasia, through discrete coarctation, to complete interruption of the arch. Neonatal surgery within the first days of life is necessary for most of these morphologies. Patch aortoplasty is widely used as it can offer a good haemodynamic result, being tailored to each combination of presenting pathologies. Our study hypothesis was that arch malformations are frequent in DORV and exhibit a plethora of phenotypes. We reviewed 54 post-mortem heart specimens from the UCL Cardiac Archive, analysing morphological features that would potentially influence the surgical repair, and taking relevant measurements of surgical importance. AAAs were found in half of the specimens, including 22.2% with aortic arch narrowing. In total, 70% and 30% of narrow arches had a subpulmonary and subaortic interventricular defect, respectively. Z-scores were significantly negative for all cases with tubular hypoplasia. We concluded that arch malformations are a common finding among hearts with DORV. Surgery on the neonatal aortic arch in DORV, performed in conjunction with other interventions that aim to balance pulmonary to systemic flow (Qp/Qs), should be anticipated and form an important part of multi-modal imaging.

Exercise Augments the Effect of SGLT2 Inhibitor Dapagliflozin on Experimentally Induced Diabetic Cardiomyopathy, Possible Underlying Mechanisms.

One of the most prevalent cardiovascular problems linked with type 2 diabetes mellitus (T2DM) is diabetic cardiomyopathy (DCM). DCM is associated with myocardial oxidative stress, inflammation, apoptosis, suppressed autophagy, extracellular matrix remodeling, and fibrosis. The current study aims to investigate the protective effect of sodium-glucose transport 2 inhibitor (SGLT2i) dapagliflozin and/or exercise on DCM. Thirty adult male Sprague Dawley rats are used. T2DM is induced by a 6-week high-fat diet (HFD) followed by a single intraperitoneal (IP) injection of 35 mg/kg streptozotocin (STZ). Rats are divided into five groups, control, diabetic (DM), DM + swimming, DM + dapagliflozin, and DM + dapagliflozin and swimming. Serum glucose, insulin, insulin resistance (HOMA-IR), and cardiac enzymes (CK-MB and lactate dehydrogenase (LDH) are measured. Heart specimens are used for evaluation of cellular oxidative stress markers malondialdehyde (MDA), antioxidant enzymes, glutathione (GSH), and catalase (CAT), as well as mRNA expression of TGF-β, MMP9, IL-1β, and TNF-α. Stained sections with haematoxylin and eosin (H & E) and Masson trichrome are used for histopathological evaluation and detection of fibrosis, respectively. Immunohistochemical staining for apoptosis (caspase-3), and autophagy (LC3) are also carried out. The combinations of SGLT2i and exercise exhibited the most significant cardioprotective effect. It improved diabetic-induced histopathological alterations in the myocardium and attenuated the elevation of serum blood glucose, CK-MB, LDH, myocardial MDA, and mRNA expression of TNF-α, IL-1β, TGF-β, MMP9, and the immune expression of caspase-3. Moreover, this combination increased the serum insulin, myocardial antioxidants GSH and CAT, and increase the immune expression of the LC-3. In conclusion, a combination of SGLT2i and exercise exerted a better antioxidant, anti-inflammatory, and antifibrotic effect in DCM. Moreover, the combination enhances the autophagic capacity of the heart.

Advanced imaging and digitization of preserved heart specimens using virtual reality - A primer.

Preserved congenital heart specimens are an important component of training professionals working with children and adults with congenital heart disease. They are curated in few institutions worldwide and not freely accessible. This was a proof-of-concept project to explore the use of advanced cardiac imaging modalities (computed tomography [CT] and magnetic resonance imaging [MRI]) and virtual reality (VR) simulation to assess the feasibility and identify the best method of imaging curated cardiac pathology specimens. Seven specimens in glass jars with formalin, with varied anatomic lesions, from a curated collection were imaged using MRI and high-dose CT to compare the fidelity of models created via each modality. Three-dimensional (3D) models were created and loaded into a VR headset and viewed in virtual space. Two independent physicians performed a "virtual dissection" and scored the resultant models. The highest fidelity and tissue characterization of more delicate structures was achieved with T2 spoiled gradient-echo sequences on MRI (median score of 4 out of 5). CT (median score of 3), while excellent for external anatomy, lost some fidelity with delicate internal anatomy, even at high-radiation doses. No specimens were damaged. We believe that in vitro heart specimens can be easily scanned with high fidelity at a relatively low cost, without causing damage, using high-dose CT and MRI. The ability to "walk through" different chambers of the heart makes the understanding of anatomy easy and intuitive. VR and 3D printing are technologies that could be easily adapted to digitize preserved heart specimens, making it globally accessible for teaching and training purposes.

Study on arterial patterns of human heart and their variations by using post-mortem coronary arteriogram in Tirupathi population

Background: The impact of post-mortem angiography increases because of the rapid evaluation of organ-specific vascular patterns, vascular alteration under pathologic and physiologic conditions and tissue changes induced by artificial and unnatural causes. Aim: To study the human heart arterial patterns and their variation by using post-mortem arteriogram. Materials and Methods: Eighty human fresh heart specimens were obtained from the Forensic Department, S.V. Medical College, Tirupati. The hearts were perfused with normal saline followed by injection of barium sulphate suspension and ligated at the proximal end of coronary arteries. Skiagrams were taken in different views and studied. Results: we have observed all the branches of right and left coronary arteries. The right and left dominance pattern, Vieussens annulus, anastomosis between the great blood vessels and posterior interventricular branches, AV nodal, SA nodal branches and variations of branches were noted in our study Conclusion: Our study will be useful in analyzing the arterial system of the heart and gives valuable supplement to conventional autopsy procedures.

Altered composition of the mitochondrial Ca2+uniporter in the failing human heart

Heart failure (HF) is a leading cause of hospitalization and mortality worldwide. Yet, there is still limited knowledge on the underlying molecular mechanisms, because human tissue for research is scarce, and data obtained in animal models is not directly applicable to humans. Thus, studies of human heart specimen are of particular relevance. Mitochondrial Ca2+ handling is an emerging topic in HF progression because its regulation is central to the energy supply of the heart contractions as well as to avoiding mitochondrial Ca2+ overload and the ensuing cell death induction. Notably, animal studies have already linked impaired mitochondrial Ca2+ transport to the initiation/progression of HF. Mitochondrial Ca2+ uptake is mediated by the Ca2+uniporter (mtCU) that consists of the MCU pore under tight control by the Ca2+-sensing MICU1 and MICU2. The MICU1/MCU protein ratio has been validated as a predictor of the mitochondrial Ca2+ uptake phenotype.We here determined for the first time the protein composition of the mtCU in the human heart. The two regulators MICU1 and MICU2, were elevated in the failing human heart versus non-failing controls, while the MCU density was unchanged. Furthermore, the MICU1/MCU ratio was significantly elevated in the failing human hearts, suggesting altered gating of the MCU by MICU1 and MICU2. Based on a small cohort of patients, the decrease in the cardiac contractile function (ejection fraction) seems to correlate with the increase in MICU1/MCU ratio. Our findings therefore indicate a possible role for adaptive/maladaptive changes in the mtCU composition in the initiation/progression of human HF in humans and point to a potential therapeutic target at the level of the MICU1-dependent regulation of the mtCU.

Notopterol Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rat.

IntroductionCurrent targeted pulmonary arterial hypertension (PAH) therapies have improved lung hemodynamics, cardiac function, and quality of life; however, none of these have reversed the ongoing remodeling of blood vessels. Considering notopterol, a linear furocoumarin extracted from the root of traditional Chinese medicine Qiang-Huo (Notopterygium incisum), had shown the antiproliferative and anti-inflammatory properties in previous studies, we hypothesized that it could play a role in ameliorating PAH.MethodsIn vivo, we conducted monocrotaline (MCT) induced PAH rats and treated them with notopterol for 3 weeks. Then, the rats were examined by echocardiography and RV catheterization. The heart and lung specimens were harvested for the detection of gross examination, histological examination and expression of inflammatory molecules. In vitro, human pulmonary arterial smooth muscle cells (HPASMCs) were treated with notopterol after hypoxia; then, cell proliferation was assessed by cell counting kit-8 and Edu assay, and cell migration was detected by wound healing assays.ResultsWe found that notopterol improved mortality rate and RV function while reducing right ventricular systolic pressure in MCT-induced PAH rats. Furthermore, notopterol reduced right ventricular hypertrophy and fibrosis, and it also eased pulmonary vascular remodeling and MCT-induced muscularization. In addition, notopterol attenuated the pro-inflammatory factor (IL-1β, IL-6) and PCNA in the lungs of PAH rats. For the cultured HPASMCs subjected to hypoxia, we found that notopterol can inhibit the proliferation and migration of HPASMCs.ConclusionOur studies show that notopterol exerts anti-inflammatory and anti-proliferative effects in the pulmonary arteries, which may contribute to prevention of PAH.

Could allicin alleviate trastuzumab-induced cardiotoxicity in a rat model through antioxidant, anti-inflammatory, and antihyperlipidemic properties?

AimsAlthough trastuzumab (TZB)-induced cardiotoxicity is well documented and allicin (one of the main active garlic ingredients) has ameliorating effects against numerous causes of toxicities; however, the influence of allicin on TZB-induced cardiotoxicity has not been investigated yet. Therefore, the current work explored the potential cardioprotective structural, biochemical, and molecular mechanisms of allicin against TZB-induced cardiotoxicity in a rat's model. MethodsForty rats were divided into four equal groups and treated for five weeks. The control group (G1) received PBS, the allicin group (G2) received allicin (9 mg/kg/day), the TZB group (G3) received TZB (6 mg/kg/week), and the allicin+TZB group (G4) received 9 mg of allicin/kg/day +6 mg of TZB/kg/week. Heart specimens and blood samples were processed for histopathological, immunohistochemical, biochemical, and molecular investigations to determine the extent of cardiac injury in all groups. Key findingsThe myocardium of G3 revealed significant increases in the numbers of inflammatory and apoptotic cells and the area percentage of collagen fibers and TNF-α immunoexpression compared with G1 and G2. Besides, qRT-PCR analysis exhibited significant reductions of SOD3, GPX1, and CAT expressions with significant increases in TNFα, IL-1β, IL-6, cTnI, cTnT, and LDH expressions. Additionally, flow cytometry analysis demonstrated a significant elevation in the apoptotic and ROS levels. In contrast, allicin+TZB cotherapy in G4 ameliorated all previous changes compared with G3. SignificanceThe current study proves that allicin could be used as a novel supplementary cardioprotective therapy to avoid TZB-induced cardiotoxicity via its anti-inflammatory, antifibrotic, antioxidant, antihyperlipidemic, and antiapoptotic properties.