Morphological Changes In Myocardium Research Articles

BRUGADA SYNDROME: FROM PRIMARY ELECTRIC HEART DISEASE TO MORPHOLOGICAL SUBSTRATE

Nowadays interest in channelopathies is growing, and developing diagnostic capabilities make Brugada syndrome much more actual problem than ever. Conception of «primary electric heart disease», which earlier was so popular, now couldn’t explain the absence of single genetic syndromes’ substrate, its’ common combinations with another arrhythmias and the presence of Brugada phenocopy. Conjunction of Brugada syndrome with morphological changes in myocardium , especially myocarditis, is an area of special interest. Infl ammation associates with clinical manifestation of the syndrome, and this situation forces to think about channelopathies’ primacy and to look for another possible mechanisms of Brugada syndrome.

The mechanism of irbesartan against diabetes induced myocardial fibrosis in rat model

To observe the protective effect of irbesartan on myocardial fibrosis in diabetic rats, and analyze the role of extracellular signal-regulated kinase (ERK) pathway in this protection. Thirty two male SD rats were randomly divided into two groups:normal control group (CON, n=10), experimental group (n=22). Twenty diabetic rats which had modelled successfully were randomly divided into two groups:diabetic group (DM, n=10), irbesartan + DM group (Ir+DM, n=10). After 8 weeks, fasting blood glucose (FBG) level, body weight (BW), the ratio of heart weight/body weight (H/B) and left ventricular weight index (LVWI) were measured. The myocardial morphological and fibrotic changes were observed by Masson staining. Col I and col Ⅲ contents were evaluated using ELISA method, and the protein expressions of ERK1/2, p-ERK1/2 in heart tissue were tested by Western blot. Compared with CON group, in diabetic rats, the levels of FBG, H/B and LVWI were increased while BW was decreased. The contents of col I and col Ⅲ were increased as well as the protein expression of p-ERK1/2 and the ratio of p-ERK1/2/ERK1/2(P<0.05,P<0.01), which had the statistic differences, while ERK1/2 protein expression was not changed. Masson staining showed myocardial collagen was increased, arranged in disorder and uneven distribution. However, in Ir+ DM group, BW was increased obviously, H/B, LVWI, the contents of col I and col Ⅲ were decreased significantly (P<0.05,P<0.01), p-ERK1/2 protein expression and the ratio of p-ERK1/2/ERK1/2 were decreased (P<0.01), which had the statistic differences. Meanwhile myocardial morphology was improved significantly. Diabetes can induce the happening of myocardial fibrosis, and irbesartan can induce the damage of myocardial fibrosis through inhibitting the activation of ERK.

STRUCTURE OF MORPHOLOGICAL CHANGES OF MYOCARDIUM IN NON-CORONARY ORIGIN SYSTOLIC DYSFUNCTION OF THE LEFT VENTRICLE

Aim. To assess morphological changes of myocardium in patients with noncoronarogenic systolic dysfunction of the left ventricle (LV). Material and methods. Totally, 96 patients studied. Among the 80 males, 16 females at the age 14-66 y. o. Follow-up duration: April, 2010 — August, 2014. In 81 patient coronary arteriography was done to rule out atherosclerotic lesion of arteries. Nine patients were excluded due to hemodynamically significant stenoses. Others underwent endomyocardial biopsy of the right ventricle. Results. All patients suffered from various degree CHF (by NYHA): FC I — 2,83%, FC II — 16,9%, FC III — 56,33%, FC IV — 23,94%. By EchoCG the ejection fraction of LV was 20,67±8,10%, by left ventriculography — 21,75±8,94%. The intervention group underwent biopsy of the right ventricle with further qualitative and quantitative study of myocardial infiltrate and its histomorphological assessment. We got following results: definite myocarditis — 1,39%, possible myocarditis — 9,71%, myocarditis cardiosclerosis — 6,94%, non-inflammatory cardiomyopathy — 38,9%, amyloidosis — 1,39%. In 37,5% cases myocardial specimens were of common histological structure, without signs of current inflammation and myocyte necrosis; 4,17% of specimens were non-informative due to lack of amount for assessment. Conclusion. The data obtained in the study makes it possible to define nosological structure of severe systolic dysfunction of the LV of non-coronary origin in Krasnodarsky Region. Taken the absence in Russian Federation of any large scale epidemiological studies of the problem, it is necessary to elaborate database and to implement it into routine practice of cardiologists. Such data might improve diagnostics, etiotropic and pathogenetic therapy, and improve outcomes of the diseases group.

Effects of circulating microvesicles derived from myocardial ischemic preconditioning on myocardial ischemia/reperfusion injury in rats

To investigate the effects of circulating microvesicles (MVs) derived from ischemic preconditioning (IPC) on myocardial ischemia/reperfusion (I/R) injury in rats and explore the underlying mechanism. To establish the IPC model, the rats were subjected to brief cycles of left anterior descending (LAD) coronary occlusion and reperfusion. The blood was drawn from abdominal aorta once the operation was finished. IPC-MVs were isolated by ultracentrifugation from the peripheral blood and characterized by flow cytometry. The myocardial I/R model of rats was established in vivo. Rats were injected via the femoral vein with IPC-MVs at 7 mg/kg. Morphological changes of myocardium were observed microscopically after HE staining. Apoptosis of myocardial cells was detected with TUNEL assay. Myocardial infarct size was detected by TTC staining. Moreover, activity of plasma lactate dehydrogenase (LDH) was tested by colorimetry. The activity of caspase 3 in myocardium was assayed with spectrophotometry. Expression levels of Bcl-2 and Bax protein were examined with Western blot. The concentration of IPC-MVs, which was detected by flow cytometry, was 4380±745 cells/μl. Compared with I/R group, IPC-MVs alleviated the damage of tissues in I/R injured rats significantly. The myocardial infarct size and the cardiomyocyte apoptotic index were obviously decreased after IPC-MVs treatment (P<0.01, respectively). The activity of plasma LDH was significantly decreased in IPC-MVs treated rats (P<0.01). Moreover, the activity of caspase 3 was markedly decreased after IPC-MVs treatment (P<0.01). In addition, the expression of Bcl-2 was increased (P<0.01), the expression of Bax was decreased (P<0.01), the ratio of Bcl-2/Bax was significantly increased after IPC-MVs treatment (P<0.01). IPC-MVs protected myocardial against I/R injury by up-regulating the expression of Bcl-2 protein, down-regulating the expression of Bax protein, increasing the ratio of Bcl-2/Bax and decreasing cleavage of caspase 3.

The effects of N-acetylcysteine on cisplatin-induced changes of cardiodynamic parameters within coronary autoregulation range in isolated rat hearts.

The aim of this study was to evaluate the effects of chronic NAC administration along with cisplatin on cisplatin-induced cardiotoxicity by means of coronary flow (CF), cardiodynamic parameters, oxidative stress markers and morphological changes in isolated rat heart. Isolated hearts of Wistar albino rats (divided into four groups: control, cisplatin, NAC and cisplatin+NAC group) were perfused according to Langendorff technique at constant coronary perfusion pressure starting at 50 and gradually increased to 65, 80, 95 and 110 cm H2O to evaluate cardiodynamic parameters within autoregulation range. Samples of coronary venous effluent (CVE) were collected for determination of CF and biochemical assays, and heart tissue samples for biochemical assays and histopathological examination. Cisplatin treatment decreased CF and heart rate, and increased left ventricular systolic pressure and maximum left ventricular pressure development rate. Cisplatin increased H2O2 and TBARS, but decreased NO2(-) levels in CVE. In tissue samples, cisplatin reduced pathological alterations in myocardium and coronary vessels, with no changes in the amount of total glutathione, as well as in activity of glutathione peroxidase and glutathione reductase. NAC coadministration, by reducing oxidative damage, attenuated cisplatin-induced changes of cardiodynamic and oxidative stress parameters, as well as morphological changes in myocardium and coronary vasculature.

Value of cardiac magnetic resonance imaging in the setting of familiar cardiomyopathy: A step toward pre-clinical diagnosis

A 24-years-old asymptomatic man was referred to our Institution for screening of familiar idiopathic dilated cardiomyopathy (CMP) due to the important family history of dilated CMP with associated severe burden of ventricular arrhythmias (Fig. 1). His father and a first-degree father's cousin were indeed both affected by idiopathic dilated CMP, which was diagnosed in their third decade after an episode of sustained ventricular tachycardia (VT); both underwent implantable cardioverter defibrillator (ICD) implantation for secondary prevention of sudden cardiac death (SCD) and subsequently experienced multiple appropriate ICD interventions. Due to further dilatation and dysfunction of the left ventricle (LV) and worsening of the arrhythmic burden as well as heart failure symptoms despite optimal medical therapy, they were finally referred to heart transplantation at the age of 40 and 45 years, respectively. In addition, two more first-degree father's cousins died suddenly at the age of 14 and 47 years. The histologic examination of the explanted heart of proband's father showed multiple areas of dense fibrosis with intra-myocardial and sub-epicardial patchy distribution (Fig. 2A –B, Mallory trichromic stain: blue areas); myocyte apoptotic and degenerative phenomena were also observed (Fig. 2C–D, arrows). Of note, a strong family history of breast cancer was also present in the family (Fig. 1). Fig. 2Cardiomyopathy-related myocardial morphological changes are shown in histological sections of the explanted heart of the proband's father. They consist of a spectrum of changes beginning with focal degeneration and necrosis of cardiomyocytes with no or minimal cellular response, followed by myofiber loss and replacement of the cardiomyocytes with varying degrees of fibrosis. Low magnification shows intra-myocardial (A) and sub-epicardial (B) areas of dense fibrotic scar with patchy distribution (blue with Mallory trichromic stain). Higher magnification reveals foci of myocardial degeneration with vacuolization of cardiomyocytes (panel C–D, arrows, Hematoxylin and Eosin stain). Necrotic cardiomyocytes exhibit homogeneously brightly eosinophilic sarcoplasm with pyknotic or karyorrhectic nuclei (panels C–D, arrows). View Large Image Figure Viewer Download Hi-res image

Myocardial protective effects of Munziq in myocardial ischemia-reperfusion injury rats with abnormal savda syndrome.

This study evaluated the influence and mechanism of different Munziq doses on myocardial ischemia reperfusion injury (MIRI) rats with abnormal savda. Wistar rats (N = 96) were divided into the following 8 groups (12 rats each): ischemia-reperfusion (I/R) model group, high-dose, medium-dose, and low-dose Munziq groups, normal I/R group, sham model group, normal sham group, and Atorvastatin group. Changes in heart physiology and myocardial morphology after injury with MIRI were monitored in each group. Heat shock protein 70 (HSP70) and calcitonin gene-related peptide (CGRP) protein expression and serum concentrations of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin (IL)-6, and IL-8 were detected by using western blot and ELISA methods, respectively. The large-dose Munziq group showed the most significant changes. The VPC incurring time was not delayed in the small-dose group, but the accumulative time was significantly reduced (P < 0.01). The ventricular tachycardia incurring time did not differ significantly between groups. Compared with the normal sham surgical group, the I/R groups showed significant increases in HSP70 and CGRP expression (P < 0.01) and MDA, IL-6, and IL-8 concentrations (P < 0.05) and a significant decrease in the SOD concentration (P < 0.05). Compared with the I/R groups, Munziq intervention significantly enhanced HSP70 and CGRP expression (P < 0.01), significantly decreased MDA, IL-6, and IL-8 concentrations (P < 0.05), and significantly increased the SOD concentration (P < 0.05). In conclusion, Munziq intervention improves cardiac physiological function, increases the expression of HSP70 and CGRP, and decreases the inflammatory reaction in MIRI model rats.

Nucleolus expression in diabetic cardiomyopathy

To investigate the nucleolus expression in the diabetic cardiomyopathy. The rats were divided into a control group and a type II diabetic cardiomyopathy group (model group). In the model group, rats were fed with high-fat and high-sugar food (rats were intravenously injected with 60 mg/kg chain urea with cephalosporins in the 5th and 6th weeks in mice). The level of blood glucose was determined at the end of 8th week and the level of fasting blood glucose was examined at the end of 20th week. The ratio of the heart mass and body mass was calculated, and the pathological changes in myocardial morphology were observed. The immunohistochemical method and Western blot were used to detect the expression level of myocardial nucleolin. The level of fasting blood glucose was significantly increased in the diabetic model group than that in the control group (P<0.05). Rats in the model group were found hypertrophic cardic cells, with fracture, dissolusion, and disordered arrangement. Immunohistochemical staining and Western blot showed the protein levels of myocardial nucleolin in the model group were obviously higher than those in the control group (P<0.05). Nucleolin may play a role in the pathogenesis and development of the diabetic cardiomyopathy.

Cardiac hypertrophy-related pathways in obesity.

Obesity is often associated with the development of cardiac hypertrophy but the hypertrophy-related pathways in obesity remain unknown. The purpose of this study was to evaluate cardiac hypertrophy-related markers, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), tumor necrosis factor-alpha (TNFα) and hypertrophy-related pathways, interleukin (IL)-6-STAT3, IL-6-MEK5-ERK5 and calcineurin-nuclear factor of activated T-cells (NFAT)3 in the excised hearts from obese rats. Twelve obese Zucker rats were studied at 5-6 months of age and twelve age-matched lean Zucker rats served as the control group. The cardiac characteristics, myocardial architecture, ANP, BNP, TNFα levels, IL-6, STAT3, p-STAT3, MEK5, ERK-5, p-ERK-5, calcineurin and NFAT3 in the left ventricle from the rats were measured by heart weight index, echocardiography, vertical cross section, histological analysis, reverse transcription polymerase chain reaction and western blotting. Compared with the lean control, the whole heart weight, the left ventricule weight, the ratio of the whole heart weight to tibia length, echocardiographic interventricular septum, left ventricular posterior wall thickness, myocardial morphological changes and systolic blood pressure were found to increase in the obese rats. The protein levels of ANP, BNP, TNFα, IL-6, STAT3, p-STAT3, MEK-5, ERK-5, p-ERK 5, calcineurin and NFAT3 were also significantly increased in the hearts of the obese rats. The results showed that the hypertrophy-related markers, ANP, BNP and TNFα, the hypertrophy-related pathways IL-6-STAT3 and IL-6-MEK5-ERK5, and the calcineurin-NFAT3 hypertrophy-related pathways were more active in obese Zucker rats, which may provide possible hypertrophic mechanisms for developing cardiac hypertrophy and pathological changes in obesity.

CLINICAL SIGNIFICANCE OF HEMOCIRCULATORY ANGIOARCHITECTONY OF THE HEART FOR THE ISSUES OF TREATMENT STRATEGY IN CORONARY HEART DISEASE

Coronary heart disease is higly prevalent in many world countries including Russia, and for several decades cardiovascular disease are being the main reason for death and are regarded as serious medico-social problem. Rapid development of cardiosurgery, invention and enhancement of diagnostic and endovascular interventions require not only a perfect knowledge of surgical heart vessels anatomy, but knowledge of antropometric parameters of hemocirculatory angioarchitectonic and morphological changes of myocardium. In the literature we could not find the data on principles of morphometric parameters of coronary vessels and structurally-functional condition of myocardial cells. So to say, the complex scientific studies required in this area to improve the diagnostic value and objectivity of indication to treatment methods, optimization and correction of surgical methods to improve quality of cardiovascular patients' care.

Effects of praeruptorin C on blood pressure and expression of phospholamban in spontaneously hypertensive rats

BackgroundThe traditional Chinese medicine Praeruptorin c (Pra-c) has many physiological and pharmacological effects, including antagonistic effects on blood pressure and calcium levels, maintenance of cellular calcium homeostasis, and improved cardiac systolic and diastolic function. It is potentially a novel and versatile drug for the treatment and prevention of cardiovascular diseases. ObjectiveTo explore the possible impact of Pra-c on blood pressure in SHR and its mechanism of action. Materials and methodsTwenty SHR were randomly divided into a Pra-c group [Pra-c was administered intragastrically, 20mgkg−1d−1, n=10] or an untreated control group (n=10), containing 10 age-matched SD rats. Each group of rats was followed for 8 weeks. Before and during the treatment, tail artery systolic blood pressure was measured using a tail-cuff every 2 weeks. After 8 weeks, the rats were sacrificed and RNA was extracted from homogenates of cardiac tissue. Tissue from the left ventricle was fixed, sectioned and H&E stained to assess possible changes in myocardial cell structure and morphology. Semi-quantitative RT-PCR was used to assess changes in phospholamban gene expression in treated and untreated rats. ResultsSHR treated with Pra-c for 8 weeks had a lower systolic pressure than untreated SHR (p<0.05), two measures of cardiac damage, the heart mass index and left ventricle mass index (HMI and LVMI, respectively) were improved, and the level of PLB mRNA expression was lower in the untreated SHR group (p<0.05). Discussion and conclusionWith continuous hypertension, SHR gradually formed or developed cardiac hypertrophy and fibrosis. Pra-c had a clear effect on blood pressure in SHR, and reversed SHR ventricular remodeling by upregulating the gene expression of sarcoplasmic reticulum PLB.

Early and delayed cardioprotective intervention with dexrazoxane each show different potential for prevention of chronic anthracycline cardiotoxicity in rabbits

Despite incomplete understanding to its mechanism of action, dexrazoxane (DEX) is still the only clearly effective cardioprotectant against chronic anthracycline (ANT) cardiotoxicity. However, its clinical use is currently restricted to patients exceeding significant ANT cumulative dose (300mg/m2), although each ANT cycle may induce certain potentially irreversible myocardial damage. Therefore, the aim of this study was to compare early and delayed DEX intervention against chronic ANT cardiotoxicity and study the molecular events involved. The cardiotoxicity was induced in rabbits with daunorubicin (DAU; 3mg/kg/week for 10 weeks); DEX (60mg/kg) was administered either before the 1st or 7th DAU dose (i.e. after ≈300mg/m2 cumulative dose). While both DEX administration schedules prevented DAU-induced premature deaths and severe congestive heart failure, only the early intervention completely prevented the left ventricular dysfunction, myocardial morphological changes and mitochondrial damage. Further molecular analyses did not support the assumption that DEX cardioprotection is based and directly proportional to protection from DAU-induced oxidative damage and/or deletions in mtDNA. Nevertheless, DAU induced significant up-regulation of heme oxygenase 1 pathway while heme synthesis was inversely regulated and both changes were schedule-of-administration preventable by DEX. Early and delayed DEX interventions also differed in ability to prevent DAU-induced down-regulation of expression of mitochondrial proteins encoded by both nuclear and mitochondrial genome. Hence, the present functional, morphological as well as the molecular data highlights the enormous cardioprotective effects of DEX and provides novel insights into the molecular events involved. Furthermore, the data suggests that currently recommended delayed intervention may not be able to take advantage of the full cardioprotective potential of the drug.

Effect of Lingguizhugan decoction on myocardial Nuclear factor kappa B protein expression in rats with chronic heart failure

ObjectiveTo investigate the effect of Lingguizhugan decoction (LGZGD) on changes of cardiac structure and function, and its putative mechanism of action, by investigating mRNA and protein expression of myocardial nuclear factor kappa B (NF-κB), and the plasma content of NF-κB in rats with chronic heart failure. MethodsThe chronic heart failure (CHF) model in rats was induced by coronary artery ligation. Sham operation was performed in control rats. Six weeks after the procedure, rats were randomly classified into the various treatment groups: model CHF, Captopril (4.4 mg/kg), low LGZGD dose (2.1 g/kg), medium LGZGD dose (4.2 g/kg), and high LGZGD dose (8.4 g/kg). Treatments continued for 4 consecutive weeks. Changes of hemodynamic indices were observed by the PowerLab data acquisition and analysis system. Morphological changes of myocardium were observed by hematoxylin and eosin staining, and Masson staining. The mRNA and protein expression of myocardial NF-κB were detected by reverse transcription-polymerase chain reaction and western blotting, respectively. The plasma content of NF-κB was detected by enzyme-linked immuno-sorbent assay. ResultsCHF rats showed significant dysfunction in hemodynamic indices and in cardiac structure. Compared with the sham operation group, mRNA expression of myocardial NF-κB and plasma content of NF-κB of the model group was significantly increased. All three doses of LGZGD, and Captopril, improved the hemodynamic dysfunction, and inhibited the change of cardiac structure while significantly improving the survival rate. Furthermore, compared with the model group, mRNA expression of myocardial NF-κB and plasma content of NF-κB were significantly reduced by all dosage groups of LGZGD as well as the Captopril group. ConclusionIn CHF rats, LGZGD improves changes of cardiac structure and function via its inhibition of NF-κB.

Acute ethanol exposure increases the susceptibility of the donor hearts to ischemia/reperfusion injury after transplantation in rats

Background Many donor organs come from youths involved in alcohol-related accidental death. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion while acute ethanol intoxication is associated with myocardial functional and morphological changes. The aims of this work were 1) to evaluate in rats the time-course cardiac effects of acute ethanol-exposure and 2) to explore how its abuse by donors might affect recipients in cardiac pump function after transplantation.

Acute Ethanol Exposure Increases the Susceptibility of the Donor Hearts to Ischemia/Reperfusion Injury after Transplantation in Rats

BackgroundMany donor organs come from youths involved in alcohol-related accidental death. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion while acute ethanol intoxication is associated with myocardial functional and morphological changes. The aims of this work were 1) to evaluate in rats the time-course cardiac effects of acute ethanol-exposure and 2) to explore how its abuse by donors might affect recipients in cardiac pump function after transplantation.MethodsRats received saline or ethanol (3.45 g/kg, ip). We evaluated both the mechanical and electrical aspects of cardiac function 1 h, 6 h or 24 h after injection. Plasma cardiac troponin-T and glucose-levels were measured and histological examination of the myocardium was performed. In addition, heart transplantation was performed, in which donors received ethanol 6 h or 24 h prior to explantation. Graft function was measured 1 h or 24 h after transplantation. Myocardial TBARS-concentration was measured; mRNA and protein expression was assessed by quantitative real-time PCR and Western blot, respectively.ResultsEthanol administration resulted in decreased load-dependent (−34±9%) and load-independent (−33±12%) contractility parameters, LV end-diastolic pressure and elevated blood glucose levels at 1 h, which were reversed to the level of controls after 6 h and 24 h. In contrast to systolic dysfunction, active relaxation and passive stiffness are slowly recovered or sustained during 24 h. Moreover, troponin-T-levels were increased at 1 h, 6 h and 24 h after ethanol injection. ST-segment elevation (+47±10%), elongated QT-interval (+38±4%), enlarged cardiomyocyte, DNA-strand breaks, increased both mRNA and protein levels of superoxide dismutase-1, glutathione peroxydase-4, cytochrome-c-oxidase and metalloproteinase-9 were observed 24 h following ethanol-exposure. After heart transplantation, decreased myocardial contractility and relaxation, oxidative stress and altered protein expression were observed.ConclusionsThese results demonstrate acute alcohol abuse increases the susceptibility of donor hearts to ischemia/reperfusion in a rat heart transplant model even though the global contractile function recovers 6 h after ethanol-administration.

624 Acute Ethanol Exposure Increases the Susceptibility of the Donor Hearts to Ischemia/Reperfusion Injury after Transplantation in Rats

Many donor organs come from youths involved in alcohol-related accidental death. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion while acute ethanol intoxication is associated with myocardial functional and morphological changes. We evaluated in rats the time-course cardiac effects of acute ethanol-exposure and explored how its abuse by donors might affect recipients in cardiac pump function after transplantation.

625 Dual Blockade of the Renin-Angiotensin System (RAS) Prevents Tacrolimus-Induced Nephrotoxicity in Normotensive and Hypertensive Rats

Purpose: Many donor organs come from youths involved in alcoholrelated accidental death. The use of cardiac allografts for transplantation from donors after acute poisoning is still under discussion while acute ethanol intoxication is associated with myocardial functional and morphological changes. We evaluated in rats the time-course cardiac effects of acute ethanol-exposure and explored how its abuse by donors might affect recipients in cardiac pump function after transplantation. Methods and Materials: Rats received saline or ethanol (3.45 g/kg, ip). We evaluated 1h, 6h or 24h after injection ECG patterns and cardiac function. Plasma levels of cardiac troponin-T and glucose were measured, myocardial mRNA expression and histopathological examination were assessed. In addition, heart transplantation was performed and 1h after graft function was measured. Results: Ethanol administration resulted in decreased load-dependent ( 34 9%) and load-independent ( 33 12%) contractility parameters, LV end-diastolic pressure and elevated blood glucose levels at 1h, which were reversed to the level of controls after 6h and 24h. In contrast to systolic dysfunction, active relaxation and passive stiffness are slowly recovered or sustained during 24h. Moreover, cardiac troponin-T levels were increased at 1h, 6h and 24h after ethanol. ST-segment elevation ( 47 10%), elongated QT-interval ( 38 4%), enlarged cardiomyocyte, DNA-strand breaks, increased mRNA expression of superoxide dismutase-1, glutathione peroxydase-4, cytochrome-c-oxidase and metalloproteinase-9 were observed 24h following ethanol. After heart transplantation in which donors received ethanol 6h or 24h prior to explantation, decreased myocardial contractility and relaxation were observed. Conclusions: These results demonstrate acute alcohol abuse increases the susceptibility of donor hearts to ischemia/reperfusion in a rat heart transplant model even though the global contractile function recovers 6h after ethanol-administration.

Myocardial Morphological Characteristics and Proarrhythmic Substrate in the Rat Model of Heart Failure Due to Chronic Volume Overload

Chronic volume overload leads to cardiac hypertrophy and later to heart failure (HF), which are both associated with increased risk of cardiac arrhythmias. The goal of this study was to describe changes in myocardial morphology and to characterize arrhythmogenic substrate in rat model of developing HF due to volume overload. An arteriovenous fistula (AVF) was created in male Wistar rats between the inferior vena cava and abdominal aorta using needle technique. Myocardial morphology, tissue fibrosis, and connexin43 distribution, localization and phosphorylation were examined using confocal microscopy and Western blotting in the stage of compensated hypertrophy (11 weeks), and decompensated HF (21 weeks). Heart to body weight (BW) ratio was 89% and 133% higher in AVF rats at 11 and 21 weeks, respectively. At 21 weeks but not 11 weeks, AVF rats had pulmonary congestion (increased lung to BW ratio) indicating presence of decompensated HF. The myocytes in left ventricular midmyocardium were significantly thicker (+8% and +45%) and longer (+88% and +97%). Despite extensive hypertrophy, there was no excessive fibrosis in the AVF ventricles. Distribution and localization of connexin43 were similar between groups, but its phosphorylation was significantly lower in AVF hearts at 21st week, but not 11th week, suggesting that HF, rather than hypertrophy contributes to the connexin43 hypophosphorylation. In conclusion, volume overload leads to extensive eccentric hypertrophy, but not to myocardial fibrosis. Increased vulnerability to arrhythmia in this HF model is possibly related to gap junction remodeling with hypophosphorylation of connexin43.

Fetal myocardial morphological and functional changes associated with well-controlled gestational diabetes

Objective To make a global evaluation of the fetal myocardial changes in a well-controlled gestational diabetic population. Study design Twenty-four pregnant well-controlled diabetic patients were selected. Sixteen normal pregnancies were randomly collected as a control group. Measurements of morphological and functional myocardial parameters were performed. Data from the left ventricular outflow tract and peripheral Doppler data were obtained. Result The thickness of the interventricular septum was increased in diabetic pregnancies ( p < 0.001). Tricuspid E/A index was the only functional parameter showing a significant variation, with lower values in diabetic pregnancies. Doppler parameters from the left ventricular outflow tract and peripheral Doppler waveforms were similar between groups. Conclusion A tendency towards interventricular septum hypertrophy was observed even in well-controlled diabetic pregnancies. Mild hypertrophic cardiac changes were not associated with abnormal cardiac function or signs of left ventricular outflow obstruction, although minor changes in right ventricular diastolic function were recorded.

Opioid δ 1 and δ 2 Receptor Agonist Attenuate Myocardial Injury Via mPTP in Rats With Acute Hemorrhagic Shock

Studies have documented the beneficial roles of δ opioid receptor (OR) agonist for hemorrhagic shock. However, the myocardial protection roles and the mechanisms of hemodynamic stability during resuscitation of δ-OR agonist have not been explored. This study was designed to investigate myocardial protective effects and the mechanisms of high selective δ(1) and δ(2)-OR agonists during resuscitation of acute hemorrhagic shock. Forty-eight adult male SD rats were adopted 60-min hemorrhagic shock through removing 30% (5 mL) of the total blood volume, and followed by 2-h resuscitation with shed blood and L-lactated Ringer's solution. At the end of shock and prior to resuscitation, NS, δ(1)-OR agonist TAN-67 (10 mg/kg) and antagonist BNTX (3 mg/kg), and BNTX+TAN-67, DMSO, δ(2)-OR agonist Deltorphin II (1 mg/kg) and antagonist NTB (2 mg/kg), and NTB+Deltorphin II in 0.5 mL were administrated. Left ventricular function parameters were measured during the whole experimental period. Myocardial mitochondria were isolated to determine opening of mitochondrial permeability transition pore (mPTP). Morphologic changes in myocardium and mitochondria were observed by electron microscope. The hemodynamic indexes in group TAN-67 and group Deltorphin II were higher than control group at each time point during resuscitation, respectively (P<0.05). TAN-67 and Deltorphin II decrease but their antagonists BNTX and NTB increase the opening of mPTP (P<0.05). Myocardial and mitochondrial damage were attenuated in group TAN-67 and group Deltorphin II. δ(1)-OR agonist TAN-67 and δ(2)-OR agonist Deltorphin II protect the heart by targeting the mPTP in rats with acute hemorrhagic shock.