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Abstract Background Heart diseases are among the leading causes of death worldwide, many of which lead to pathological cardiomyocyte hypertrophy and capillary rarefaction in both patients and animal models, the quantification of which is both technically challenging and highly time-consuming. Here we developed a semiautomated pipeline for quantification of the size of cardiomyocytes and capillary density in cardiac histology, termed HeartJ, by generating macros in ImageJ, a broadly used, open-source, Java-based software. Methods We have used modified Gomori silver staining, which is easy to perform and digitize in high throughput, or Fluorescein-labeled lectin staining. The latter can be easily combined with other stainings, allowing additional quantitative analysis on the same section, e.g., the size of cardiomyocyte nuclei, capillary density, or single-cardiomyocyte protein expression. We validated the pipeline in a mouse model of cardiac hypertrophy induced by transverse aortic constriction, and in autopsy samples of patients with and without aortic stenosis. Results In both animals and humans, HeartJ-based histology quantification revealed significant hypertrophy of cardiomyocytes reflecting other parameters of hypertrophy and rarefaction of microvasculature and enabling the analysis of protein expression in individual cardiomyocytes. The analysis also revealed that murine and human cardiomyocytes had similar diameters in health and extent of hypertrophy in disease confirming the translatability of our murine cardiac hypertrophy model. HeartJ enables a rapid analysis that would not be feasible by manual methods. The pipeline has little hardware requirements and is freely available. Conclusions In summary, our analysis pipeline can facilitate effective and objective quantitative histological analyses in preclinical and clinical heart samples.

Background: Heart diseases are among the leading causes of death worldwide, many of which lead to pathological cardiomyocyte hypertrophy and capillary rarefaction in both patients and animal models, the quantification of which is both technically challenging and highly time-consuming. Here we developed a semiautomated pipeline for quantification of the size of cardiomyocytes and capillary density in cardiac histology, termed HeartJ, by generating macros in ImageJ, a broadly used, open-source, Java-based software. Methods: We have used modified Gomori silver staining, which is easy to perform and digitize in high throughput, or Fluorescein-labeled lectin staining. The latter can be easily combined with other stainings, allowing additional quantitative analysis on the same section, e.g., the size of cardiomyocyte nuclei, capillary density, or single-cardiomyocyte protein expression. We validated the pipeline in a mouse model of cardiac hypertrophy induced by transverse aortic constriction, and in autopsy samples of patients with and without aortic stenosis. Results: In both animals and humans, HeartJ-based histology quantification revealed significant hypertrophy of cardiomyocytes reflecting other parameters of hypertrophy and rarefaction of microvasculature and enabling the analysis of protein expression in individual cardiomyocytes. The analysis also revealed that murine and human cardiomyocytes had similar diameters in health and extent of hypertrophy in disease confirming the translatability of our murine cardiac hypertrophy model. HeartJ enables a rapid analysis that would not be feasible by manual methods. The pipeline has little hardware requirements and is freely available. Conclusions: In summary, our analysis pipeline can facilitate effective and objective quantitative histological analyses in preclinical and clinical heart samples. [ABSTRACT FROM AUTHOR]

Policosanol, a mixture of long-chain alcohols found in animal and plant waxes, has several biological effects including lipid-lowering that have been extensively studied. However, its bioavailability is low. To investigate the effect of nanoemulsified rice bran wax policosanol (NPOL) on plasma homocysteine, heart and liver histology in hyperlipidemic rats, high-fat diet containing 2.5% cholesterol was used to induce hyperlipidemia in Sprague Dawley rats. The hyperlipidemic rats were treated with NPOL and rice bran wax policosanol (POL) in comparison with normal diet (ND), high-cholesterol diet (HCD) and simvastatin-treated rats. Plasma homocysteine, heart and liver histology, and hepatic mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG) were evaluated. The NPOL group, similar to the simvastatin group, showed reduced plasma homocysteine, preserved heart and liver histology, and down-regulated hepatic PPARG mRNA in comparison to the control group, and was better than the POL group. The results suggest that the modest effect of NPOL on homocysteine and preservation of heart and liver histology could be through the regulation of PPARG expression on a background of increased assimilation of rice bran wax policosanol. [ABSTRACT FROM AUTHOR]

Aging presents profound structural and physiological changes in the cardiovascular system. Oxidative stress, a major contributing factor during the aging process, has been involved in various age-related cardiovascular pathologies. Nevertheless, the underlying mechanism of oxidative stress in the aging heart is still unclear. This study was designed to determine whether changes in cardiac structure and function in aged rats were associated with decreases in the antioxidative defense mechanism. Young (3-month-old) and aged (24-month-old) rats were used in this study, and the differences in function, structure, antioxidative capacity and the expression of antioxidative-related proteins between the two groups were compared. By using echocardiography, we observed that compared to young rats, the left ventricular internal end-diastolic diameter (LVID; d) and left ventricular volume at diastole (LV Vol; d) were significantly increased in aged rats, while the MV E/A (E wave and A wave ratio, the ratio of peak velocity of early to late filling of mitral inflow), which represents heart diastolic function, was significantly decreased in aged rats. In addition, we observed degenerative histological modifications and an increased number of apoptotic cells in aged rats. We further detected the protein expression of catalase (CAT), glutathione synthetase (GSS), superoxide dismutase-1 (SOD-1), heme oxygenase-1 (HO-1) and NADPH: quinone oxidoreductase 1 (NQO1) in cardiac tissue. Western blot results showed that the expression of GSS was significantly decreased and that the expressions of CAT, SOD-1, and HO-1 were slightly decreased in aged rats. Immunohistochemistry results further confirmed the decreased expression of GSS, SOD-1 and NQO1 in cardiomyocytes in aged rats. Taken together, our data suggest that aging may affect the morphology and function of the heart by oxidative stress and the antioxidative defense mechanism. • The heart morphology and the diastolic function was changed in natural aged rats. • The level of oxidative stress was increased and the activities of antioxidant enzymes was declined in aged rats. • The variation of heart morphology and function was associated with the decreased antioxidant ability in aged rats. [ABSTRACT FROM AUTHOR]

Aims With the maturation of placenta, ventricular chamber maturation enhances cardiac contractile performance to adapt to the metabolic demand of growing embryo. The organization of cardiomyocytes is required for the morphological remodelling in ventricular chamber maturation. However, the mechanism governing the establishment of cardiac cytoarchitecture during ventricular chamber maturation is still poorly studied. Methods and results Here, we found that the expression of geranylgeranyl pyrophosphate synthase (Ggpps), which mediates protein geranylgeranylation, increased in the mouse heart after the onset of placental function. By using different Cre lines, we found that the cardiac inactivation of Ggpps by the Nkx2.5Cre/+ line disrupted protein geranylgeranylation as early as E9.5, which affected ventricular chamber maturation and resulted in mid-gestational embryonic lethality. In contrast, a-SMA-Cre line mediated the disruption of protein geranylgeranylation from E13.5 did not affect embryonic heart development. Further analysis of Nkx2.5Cre/+; Ggppsfl/fl mutants showed that the loss of Ggpps caused disorganized cardiac cytoarchitecture as early as E11.5 by disturbing cell-cell junctions. Ggpps inactivation decreased Rho GTPase geranylgeranylation and their activity, which might account for the disruption of cell-cell junctions. Moreover, elevating the protein geranylgeranylation by supplement of geranylgeranyl pyrophosphate (GGPP) could recover the Ggpps deficient induced defects of cytoarchitecture and cell-cell junctions in vitro and in vivo. Conclusion Our present study demonstrates that GGPPS-mediated protein geranylgeranylation plays an indispensable role in the ventricular chamber maturation and acts as a stage-specific signal to regulate the establishment of cardiac cytoarchitecture during mid-gestation. [ABSTRACT FROM AUTHOR]

Background The occurrence of medulloblastoma in the absence of hereditary syndromes is rare. Dextrocardia with situs inversus is also called mirror-image dextrocardia. A combination of mirror-image dextrocardia with medulloblastoma has not been reported previously. To the best of our knowledge, this is the first report of this rare combination in a family with medulloblastoma. Methods The clinical manifestation, radiographic characteristics, treatment, and outcomes of 3 medulloblastoma cases in 2 cousins and their maternal uncle was described. Tumor samples of the 2 cousins were first examined for histologic subtypes. Total RNA of their tumors was extracted from formalin-fixed and paraffin-embedded samples. Then, expression of 22 subgroup-specific genes and 3 housekeeping genes was analyzed by the NanoString nCounter Analysis System. The posttest data were normalized by NanoStringNorm package for molecular subgroup prediction. Results The proband remains tumor free and alive up to the latest follow-up. His cousin, who had combined mirror-image dextrocardia with situs inversus, died of anoxia after surgery and his uncle died of tumor 2.5 years after surgery. Medulloblastoma of the 2 cousins was classified as classic and molecular group 4 subtype. Conclusions The same classic and molecular group 4 subtype of the 2 cousins may suggest a similar genetic predisposition. Involvement of the Otx2 gene dysfunction in both group 4 subtype medulloblastoma and mirror-image dextrocardia with situs inversus points to a possible mechanism that dysfunction of a shared signaling pathway such as Otx2 might be the underlying cause of these 2 conditions in this family. [ABSTRACT FROM AUTHOR]

Background: We investigated the influence of geographical predisposition on the spatial distribution and composition of coronary plaques. Methods: Thirty coronary arteries were evaluated. A total of 1441 cross-sections were collected from intravascular ultrasound (IVUS) and radio-frequency signal-based virtual histology (VH-IVUS) imaging. To exclude complex geographical effects of side branches and to localise the plaque distribution, we analysed only eccentric plaques in non-branching regions. The spatial distribution of eccentric plaques in the coronary artery was classified into myocardial, lateral, and epicardial regions. The composition of eccentric plaques was analysed using VH-IVUS. Results: The plaque was concentric in 723 sections (50.2%) and eccentric in 718 (49.9%). Eccentric plaques were more frequently distributed towards the myocardial side than towards the epicardial side (46.7 ± 7.5% vs. 12.5 ± 4. 2%, p = 0.003). No significant difference was observed between the myocardial and lateral sides (46.7 ± 7.5% vs. 20.8 ± 5. 0%) or between the lateral and epicardial sides. Eccentric thin-capped fibroatheromas were more frequently distributed towards the myocardial side than towards the lateral side (p = 0.024) or epicardial side (p = 0.005). Conclusion: Geographical predisposition is associated with distribution, tissue characterisation, and vulnerability of plaques in non-branching coronary arteries. [ABSTRACT FROM AUTHOR]

Background and aims Recent development of high resolution MRI techniques have enabled imaging of intracranial atherosclerotic plaque in vivo . However, identifying plaque composition remains challenging given the small size and the lack of histological validation. This study aims to quantify the relaxation times of intracranial plaque components ex vivo at 3 T and to determine whether multi-contrast MRI could classify intracranial plaque according to the American Heart Association classification with histological validation. Methods A total of 53 intracranial arteries with atherosclerotic plaques from 20 cadavers (11 male, age 73.8 ± 10.9) were excised. Quantitative T 1 /T 2 /T 2 * mapping sequences and multi-contrast fast-spin echo sequences (T 1 , T 2 , proton-density weighted and short time inversion recovery) were acquired. Plaque components including: fibrous cap, lipid core, fibrous tissue, calcification, and healthy wall were segmented on histology, and their relaxation times were derived from quantitative images. Two radiologists independently classified plaque type blinded to the histology results. Results Relaxation times of plaque components are distinct and different. T 2 and T 2 * values of lipid core are lower than fibrous cap (p = 0.026 & p < 0.0001), but are comparable with fibrous tissue and healthy wall (p = 0.76 & p = 0.42). MRI reliably classified plaque type compared with histology (κ = 0.69) with an overall accuracy of 80.7%. The sensitivity and specificity using MRI to identify fibro-lipid atheroma (type IV-V) was 94.8% and 77.1%, respectively. Inter-observer agreement was excellent (κ = 0.77). Conclusion Intracranial plaque components have distinct and different relaxation times at 3 T. High-resolution MRI is able to characterize intracranial plaque composition and classify plaque types ex vivo at 3 T. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the antitumor activity of doxorubicine (DOX)-loaded nanoemulsion (NE) on Ehrlich ascites carcinoma (EAC)-bearing Swiss albino mice. Methods: The mice were divided into five groups (n = 20) according to the administered drug. Groups I - V were labeled as negative control (normal), positive control of the untreated EAC bearing mice (EAC control), blank nanoemulsion (BI-NE), DOX-loaded-NE (DOX/LNE) and free DOX (DOX-Sol), respectively. Cardiotoxicity was assessed by measuring changes in body and organ weight, analyzing serum enzymes and lipids, and examining histological changes in heart tissues by light microscopy. In addition, mean survival time (MST), increase in life span (ILS) and survival (S) of the mice were determined. Results: DOX/LNE group reduced levels of serum enzymes and lowered damage to heart tissues relative to DOX-Sol group. The MST of the DOX/LNE group (80 ± 0.0 days) was significantly greater than that for DOX-Sol group (34.6 ± 8.9 days), while ILS of DOX/LNE (265.30 days) was higher than that of DOX-Sol (57.99 days) by 4.6-fold. Conclusion: Administration of DOX/LNE to EAC-bearing mice improves the efficacy of DOX and reduce its side effects on the heart. [ABSTRACT FROM AUTHOR]

Background: Myocardial fibrosis is a common hallmark of many diseases of the heart. Late gadolinium enhanced MRI is a powerful tool to image replacement fibrosis after myocardial infarction (MI). Interstitial fibrosis can be assessed indirectly from an extracellular volume fraction measurement using contrast-enhanced T1 mapping. Detection of short T2* species resulting from fibrotic tissue may provide an attractive non-contrast-enhanced alternative to directly visualize the presence of both replacement and interstitial fibrosis. Objective: To goal of this paper was to explore the use of a T2*-weighted radial sequence for the visualization of fibrosis in mouse heart. Methods: C57BL/6 mice were studied with MI (n = 20, replacement fibrosis), transverse aortic constriction (TAC) (n = 18, diffuse fibrosis), and as control (n = 10). 3D center-out radial T2*-weighted images with varying TE were acquired in vivo and ex vivo (TE = 21 μs-4 ms). Ex vivo T2*-weighted signal decay with TE was analyzed using a 3-component model. Subtraction of short- and long-TE images was used to highlight fibrotic tissue with short T2*. The presence of fibrosis was validated using histology and correlated to MRI findings. Results: Detailed ex vivo T2*-weighted signal analysis revealed a fast (T2*fast), slow (T2*slow) and lipid (T2*lipid) pool. T2*fast remained essentially constant. Infarct T2*slow decreased significantly, while a moderate decrease was observed in remote tissue in post-MI hearts and in TAC hearts. T2*slow correlated with the presence of diffuse fibrosis in TAC hearts (r = 0.82, P = 0.01). Ex vivo and in vivo subtraction images depicted a positive contrast in the infarct co-localizing with the scar. Infarct volumes from histology and subtraction images linearly correlated (r = 0.94, P<0.001). Region-of-interest analysis in the in vivo post-MI and TAC hearts revealed significant T2* shortening due to fibrosis, in agreement with the ex vivo results. However, in vivo contrast on subtraction images was rather poor, hampering a straightforward visual assessment of the spatial distribution of the fibrotic tissue. [ABSTRACT FROM AUTHOR]

Bifid cardiac apex is a very rare finding in human and its presence is generally associated with other heart defects. We present the case of an 11-year old boy, with a positive family history for sudden cardiac death, who died while he was playing with his friends. An autopsy was performed, and on gross examination, bifid cardiac apex and high take off of right coronary artery were found. Furthermore, on histological examination, signs of myo-pericarditis were observed. This is, at our knowledge, the first case in literature in which bifid cardiac apex is associated with a high take off of right coronary artery. [ABSTRACT FROM AUTHOR]

Cardiac valve lipomatous hamartomas are very rare lesions with preferential localization on the pericardium, followed by the endocardial surfaces. We report a quite unique case of a lipomatous hamartoma-like lesion involving a bicuspid aortic valve. The lesion was incidentally found in a young patient undergoing cardiac surgery for aortic regurgitation, and the diagnosis was done by histology. It cannot be excluded that the lipomatous hamartoma-like lesion might have contributed to aortic valve regurgitation. [ABSTRACT FROM AUTHOR]

The main function of the sinus node is to provide the electrical impulse responsible for normal cardiac rhythm. The rhythmic coordination depends on the passage of the excitation wave by the heart through its conductive system of impulse. There is considerable variability in the size and exact location of the sinus node of individual hearts even within the same species. Histological features of the sinus node including the cells, the nodal artery, the collagen framework, and the innervation, and also some physiological characteristics of the node, will be discussed. [ABSTRACT FROM AUTHOR]

Abstract: Deformation and wall-thickening of ventricular myocardium are essential for cardiac pump function. However, insight into the histo-anatomical basis for cardiac tissue re-arrangement during contraction is limited. In this report, we describe dynamic changes in regionally prevailing cardiomyocyte (fibre) and myolaminar (sheet) orientations, using Diffusion Tensor Imaging (DTI) of ventricles in the same living heart in two different mechanical states. Hearts, isolated from Sprague–Dawley rats, were Langendorff-perfused and imaged, initially in their slack state during cardioplegic arrest, then during lithium-induced contracture. Regional fibre- and sheet-orientations were derived from DTI-data on a voxel-wise basis. Contraction was accompanied with a decrease in left-handed helical fibres (handedness relative to the baso-apical direction) in basal, equatorial, and apical sub-epicardium (by 14.0%, 17.3%, 15.8% respectively; p < 0.001), and an increase in right-handed helical fibres of the sub-endocardium (by 11.0%, 12.1% and 16.1%, respectively; p < 0.001). Two predominant sheet-populations were observed, with sheet-angles of either positive (β+) or negative (β−) polarity relative to a ‘chamber-horizontal plane’ (defined as normal to the left ventricular long-axis). In contracture, mean ‘intersection’-angle (geometrically quantifiable intersection of sheet-angle projections) between β+ and β− sheet-populations increased from 86.2 ± 5.5° (slack) to 108.3 ± 5.4° (p < 0.001). Subsequent high-resolution DTI of fixed myocardium, and histological sectioning, reconfirmed the existence of alternating sheet-plane populations. Our results suggest that myocardial tissue layers in alternating sheet-populations align into a more chamber-horizontal orientation during contraction. This re-arrangement occurs via an accordion-like mechanism that, combined with inter-sheet slippage, can significantly contribute to ventricular deformation, including wall-thickening in a predominantly centripetal direction and baso-apical shortening. [Copyright &y& Elsevier]

Despite mounting pre-clinical and clinical evidence of the beneficial effects of cell-based therapy, optimal cell dosing and delivery approaches have not been identified. Cardiospheres are self-assembling three-dimensional (3 D) microtissues formed by cardiac stem cells and supporting cell types. The ability of cardiospheres to augment cardiac function has been demonstrated in animal models of ischemic cardiomyopathy. In this study, we studied the dose dependence of the benefits of human cardiospheres, delivered via intramyocardial injection, upon cardiac function and ventricular remodelling in SCID mice with acute myocardial infarction. Four doses of cardiospheres were used: 1 × 104, 5 × 104, 1 × 105 and 5 × 105 (expressed as number of plated cardiosphere-forming cells). Acute (24 hr) cell retention rates in all groups were similar. Functional assessment and quantitative heart morphometry indicated benefit from higher cell doses (≥5 × 104) in terms of ejection fraction, infarct size and capillary density. Histological analysis indicated that the dose-dependent benefit was primarily because of indirect effects of transplanted cells. The results provide scalable data on cardiosphere dosing for intramyocardial injection. [ABSTRACT FROM AUTHOR]

Mice carrying a deletion of the adhesive extracellular domain of the desmosomal cadherin desmoglein 2 develop an arrhythmogenic right ventricular cardiomyopathy-like phenotype with ventricular dilation, fibrosis and arrhythmia. To unravel the sequence of myocardial alterations and to identify potential pathomechanisms, histological analyses were performed on mutant hearts from the juvenile to the adult state, i.e., between 2 and 13 weeks. At an age of 2 weeks 30% of mutants presented lesions, which were visible as white plaques on the heart surface or in the septum. From 4 weeks onwards, all mutants displayed a cardiac phenotype. Dying cardiomyocytes with calcification were found in lesions of all ages. But lesions of young mutant animals contained high amounts of CD45+ immune cells and little collagen fibers, whereas lesions of the older animals were collagen-rich and harbored only a small but still significantly increased number of CD45+ cells. Electron microscopy further showed that distinct desmosomes cannot be distinguished in intercalated discs of mutant hearts. Widening of the intercellular cleft and even complete dissociation of intercalated discs were often observed close to lesions. Disturbed sarcomer structure, altered Z-discs, multiple autophagic vacuoles and swollen mitochondria were other prominent pathological features. Taken together, the following scenario is suggested: mutant desmoglein 2 cannot fully support the increased mechanical requirements placed on intercalated disc adhesion during postnatal heart development, resulting in compromised adhesion and cell stress. This induces cardiomyocyte death, aseptic inflammation and fibrotic replacement. The acute stage of scar formation is followed by permanent impairment of the cardiac function. [ABSTRACT FROM AUTHOR]

Abstract: Background: Radiotherapy of thoracic and chest wall tumors increases the long-term risk of cardiotoxicity, but the underlying mechanisms are unclear. Methods: Single doses of 2, 8, or 16Gy were delivered to the hearts of mice and damage was evaluated at 20, 40, and 60weeks, relative to age matched controls. Single photon emission computed tomography (SPECT/CT) and ultrasound were used to measure cardiac geometry and function, which was related to histo-morphology and microvascular damage. Results: Gated SPECT/CT and ultrasound demonstrated decreases in end diastolic and systolic volumes, while the ejection fraction was increased at 20 and 40weeks after 2, 8, and 16Gy. Cardiac blood volume was decreased at 20 and 60weeks after irradiation. Histological examination revealed inflammatory changes at 20 and 40weeks after 8 and 16Gy. Microvascular density in the left ventricle was decreased at 40 and 60weeks after 8 and 16Gy, with functional damage to remaining microvasculature manifest as decreased alkaline phosphatase (2, 8, and 16Gy), increased von Willebrand Factor and albumin leakage from vessels (8 and 16Gy), and amyloidosis (16Gy). 16Gy lead to sudden death between 30 and 40weeks in 38% of mice. Conclusions: Irradiation with 2 and 8Gy induced modest changes in murine cardiac function within 20weeks but this did not deteriorate further, despite progressive structural and microvascular damage. This indicates that heart function can compensate for significant structural damage, although higher doses, eventually lead to sudden death. [Copyright &y& Elsevier]

Purpose: To examine the effects of ascorbic acid (AA) administrated during cardiopulmonary resuscitation (CPR) on the myocardial injury in a rat model of ventricular fibrillation (VF) and electrical shock (ES). Methods: VF was induced in male Wistar rats and left untreated for 5 min, followed by 1 min of CPR, and then one ES of 5 J. At the start of CPR, animals received either intravenous administration of AA (100 mg/kg) or Tempol (30 mg/kg), two antioxidants, or 0.9% saline (VF + ES group). After ES, animals were immediately killed. Myocardial lipoxidation was determined by malondialdehyde (MDA) assay. The histology and ultrastructural changes of myocardium were also evaluated. The mitochondrial permeability transition pore (mPTP) opening was measured based on the mitochondrial swelling rate. The complex activities and respiration of mitochondria were assessed, too. Results: Increased myocardial injury and mitochondrial damage in the VF + ES group were noted. AA and Tempol alleviated such damages. Both AA and Tempol improved accelerated mitochondrial swelling; decreased complex activities and respiratory dysfunction occurred in the VF + ES group. The animals receiving AA and Tempol during CPR had better successful resuscitation rates and 72-h survival than the VF + ES group. Conclusions: Intravenous administration of AA and Tempol at the start of CPR may reduce lipid peroxidation and myocardial necrosis, diminish mitochondrial damage, facilitate resuscitation, and improve outcomes after VF + ES. [ABSTRACT FROM AUTHOR]

A number of papers have described high levels of 5-aminolevulinic acid in cases of heart damage due to acute myocardial infarction, acute intermittent porphyria or chronic kidney failure, but it is not known whether the heart damage is directly associated with 5-aminolevulinic acid. The aim of this study was to verify whether such an association exists by injecting rabbits with 5-aminolevulinic acid and searching for the appearance of cardiac necrosis markers and histological heart alterations, and investigate whether the cardiotoxic activity of 5-aminolevulinic acid may involve peroxidation by seeking the presence of the peroxide marker malondialdehyde. The administration of 5-aminolevulinic acid led to the appearance of c-troponin I and creatine kinase, induced histological heart alterations and increased the malondialdehyde levels. The plasma levels of malondialdehyde and cardiac necrosis markers were also measured after the injection of 5-aminolevulinic acid in combination with the daunorubicin agent inducing peroxidation. The combined administration very significantly increased the plasma levels of 5-aminolevulinic acid, malondialdehyde, and the cardiac necrosis markers c-troponin I and creatine kinase. It therefore seems that there is a close relationship between altered 5-aminolevulinic acid levels, malondialdehyde and cardiac necrosis markers, which is attributable to the capacity of 5-aminolevulinic acid to generate toxic oxygen species that damage the heart. High plasma 5-aminolevulinic acid levels should be considered a factor contributing to cardiotoxicity and to the appearance of cardiac necrosis markers. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Bare-metal stents have undergone intense pathological and clinical examination, but histological characterization of drug-eluting stent (DES) restenosis (ISR) remains unknown. We report a series of cases (n =6) with intravascular ultrasound (IVUS) and pathological examinations over 8 months after DES deployment. Tissue samples were obtained using atherectomy devices in 5 cases and a thrombectomy catheter in 1 case. Histology revealed not only smooth muscle cell proliferation, which correlated with homogeneous hypoechoic tissue by IVUS in one case, but also demonstrated delayed healing features such as organized fibrin deposition in 3 cases (one with homogeneous echolucent tissue by IVUS), macrophage and T-lymphocyte infiltration in others. IVUS appearance of ISR components varied from echolucent to echodense images. This report suggests a variable histological and IVUS pattern of ISR after DES implantation. Further investigations are necessary to define the potentially pro-thrombotic histological features of ISR after DES implantation, and the relationship between the molecular mechanisms of thrombosis and DES restenosis. [Copyright &y& Elsevier]

Background: The purpose of this study was to test the feasibility, effectiveness, and safety of the use of a new laser energy catheter for linear endocardial ablation in an acute sheep model. Methods: Bipolar pacing electrodes were positioned on the left atrial appendage (LAA) and the pulmonary veins (PVs). Laser ablation within the left atrium was performed around the LAA and PVs in six sheep. The temperature in the esophagus was measured continuously during ablation. The animals were weaned from cardiopulmonary bypass (CPB) and were sacrificed two hours after ablation. The heart, lungs, and esophagus were retrieved for histological examination. Results: Aortic cross clamp time was 26.2 ± 6.1 minutes and CPB time was 81 ± 29 minutes. Electrical isolation of the LAA and PVs was confirmed in all sheep. On histological analysis, there was an extensive transmural alteration of the left atrial tissue including vascular lesions, myocardial degeneration, and necrosis, and epi- and endocardial necrosis. In six out of six cases, extensive lesions of the esophagus (muscular layer) were also found. Significant changes in esophageal temperature were observed, reaching up to 70 °C. The epithelial layer of the esophagus was not affected by the laser energy, but mild focal degeneration of the subepithelial connective tissue was observed in all sheep. There were no injuries to the circumflex coronary artery. Conclusions: Laser is an effective tool in endocardial ablation, resulting in electrical isolation and transmurality. Future studies should more completely assess the safety of laser ablation, especially with regards to the nearby esophagus, as well as examine the results of epicardial application. [ABSTRACT FROM AUTHOR]

The present study examines the effects of caloric restriction in cardiac tissue evaluation markers of oxidative stress. High-fat dietary restrictions can have a long-term impact on cardiac health. Dietary restriction of control diet increased myocardial superoxide dismutase (SOD) and catalase activities. Dietary restriction of fatty acid-enriched diets increased myocardial lipoperoxide concentrations, while SOD activity was decreased in cardiac tissue of rats with dietary restriction of fatty acid-enriched diets. Dietary restriction of unsaturated fatty acid-enriched diet induced the highest lipoperoxide concentration and the lowest myocardial SOD activity. Dietary restriction of unsaturated fatty acid decreased myocardial glycogen, and increased the lactate dehydrogenase/citrate synthase ratio. Dietary restriction of fatty acid-enriched diets were more deleterious to cardiac tissue than normal ad lib.-fed diet. In conclusion, the effects of caloric restriction on myocardial oxidative stress is dependent on which nutrient is restricted. Dietary restriction of fatty acid-enriched diets is deleterious relative to ad lib.-fed chow diet. [ABSTRACT FROM AUTHOR]

A non-heart-beating donor model was considered to examine whether pig hearts from the abattoir could be resuscitated by whole blood reperfusion. For preservation, machine perfusion using University of Wisconsin (UW) solution was compared with storage on ice. Nineteen hearts from abattoir pigs, harvested 25 ± 3 min after exsanguination, were harvested and transported to the laboratory. Controls (n = 7) were immediately reperfused with homologous whole pig blood in an isolated heart model for 60 min with monitoring of left ventricular developed pressure (LVDP), contractility, and coronary flow. UW solution hearts (UW, n = 6) were perfused for 4 h with 10°C cold UW solution before blood reperfusion. In the cold storage group (CS, n = 6), the organs were stored for an additional 4 h on ice before blood reperfusion. In all hearts, histology was performed after 60 min of blood reperfusion to evaluate myocardial reperfusion injury. All three groups showed significant increases in LVDP (p < .001), although this functional recovery was earliest in the control group and latest in the UW group. Significant declines were observed for both LVDP and contractility from the peak values in each group to the end of blood reperfusion. Coronary flow increased steadily over the time course for the UW group, whereas in the control and CS groups flow increased during the first 15 min of blood reperfusion and then decreased. In the UW and CS groups, there were significant positive correlations between coronary flow and LVDP (p < .001). Microscopic examination revealed no differences between the three groups. Thus, hearts from an abattoir with 25 min of warm ischemic time can be resuscitated. For storage of these organs, continuous machine perfusion with UW solution is superior to cold storage on ice. [ABSTRACT FROM AUTHOR]

Examines the cellular expression of hyperpolarization-activated cation currents (I[sub h]) in cardiac and neuronal tissues. Identification of I[sub h] in cardiac pacemaker cells and peripheral neurons; Exhibition of distinct activation kinetics; Differential expression of cyclic nucleotide-gated cation channel isoforms.

Reviews data on the role of connexins in mammalian heart function. Topographical heterogeneity of expression of connexins in different cardiac tissues; Conductance properties; Consequences of the multiplicity of connexins in the propagation of action potentials; Functional properties of CX43, CX40 and CX45 channels.

Examines the role of cardiac fibroblasts in mediating the trophic effects of angiotensin II (ANG II) on cardiac myocytes. Endogenous transforming growth factor-beta1 (TGF beta1) as a paracrine trophic factor in response to ANG II; Distribution of ANG II receptors; Inotropic and chronotropic effects of ANG II on the heart.

Rabbit anti-rat thymoglobulin (rATG) administered to donors with brain death (BD) may improve organs quality. We explored the effects of rATG administered to BD donors in the histology of heart, lungs and small bowel in a rat experimental model. Animals were randomly assigned to 3 groups: V (n = 5) no BD, 2 h ventilation; BD (n = 5) BD and 2 h ventilation; BD and rATG: BD, 2 h ventilation, rATG (10 mg/kg) after BD diagnosis. Histopath-ological damage scores were based on neutrophil infiltration, airway epithelial cell damage, interstitial edema, hya-line membrane formation, and pulmonary hemorrhage (lungs); neutrophil infiltration and interstitial edema (heart); Park score (bowel). Lung damage was significantly lower in BD + rATG group: V 5 ± 1.6; BD 11.25 ± 0.5, BD + rATG 6.5 ± 1.9 (p < 0.01). Heart: V 2.0 ± 0.81; BD 4.75 ± 1.25 and BD + rATG 3.5 ± 1.7 (p > 0.05). Small bowel: BD 2.25 ± 0.96 vs. BD + rATG 1.00 ± 1.15 (n.s.). Histological damage amelioration in lung and atten-uation tendency in heart and small bowel encourages research of cytoprotective strategies to improve organ viability. [ABSTRACT FROM AUTHOR]

The identification of new treatments for primary pulmonary arterial hypertension (PAH) is a critical unmet need since there is no a definitive cure for this disease yet. Due to the complexity of PAH, a wide set of methods are necessary to assess the response to a pharmacological intervention. Thus, a rigorous protocol is crucial when experimental studies are designed. In the present experimental protocol, a stepwise approach was followed in a monocrotaline-induced PAH model in the rat, moving from the dose finding study of treatment compounds to the recognition of the onset of disease manifestation, in order to identify when to start a curative treatment. A complete multidimensional evaluation of treatment effects represented the last step. The primary study endpoint was the change in right ventricular systolic pressure after 14 days of treatment; echocardiographic and biohumoral markers together with heart and pulmonary arterial morphometric parameters were considered as secondary efficacy and/or safety endpoints and for the evaluation of the biologic coherence in the different results., Competing Interests: Marco Milioli, Fabrizio Facchinetti, Silvia Cantoni, Marcello Trevisani are employees of Chiesi Farmaceutici S.p.A. The other authors have no conflicts of interest to declare., (© 2019 The Authors.)

Presents information on the first premortem cardiac histologic findings in a patient with severe, acute cardiomyopathy caused by the toxic shock syndrome. Therapeutic application of intravenous diuretics; Findings of a hematoxylin-cosin and Masson-stained section of an endomyocardial biopsy specimen; Effect of cell-mediated myocardial injury.

Reports on a study that produced human heart tissue from embryonic stem cells, conducted by Lior Gepstein and colleagues, published in the 2002 issue of the journal "Circulation Research." Significance of the results of the study; Main application of the research.