scholarly journals Teratogenic effect of alcohol on the myocardium of laboratory animals at the stages of prenatal ontogenesis (literature review)

Morphologia ◽  
2021 ◽  
Vol 15 (3) ◽  
pp. 30-38
Author(s):  
O.A. Cherkas
Keyword(s):  
Alcohol Consumption ◽  
Adverse Effects ◽  
Retrospective Analysis ◽  
Structural Organization ◽  
Alcohol Intoxication ◽  
Left Ventricular ◽  
Laboratory Animals ◽  
Heart Weight ◽  
Heart Cells ◽  
Time Frequency

Background. To date, close attention is paid to the problems of formation and development of the myocardium in general and in particular its structural components. This phenomenon is associated with an increase in cardiovascular malformations in both adults and infants. These defects can be caused by genetic factors, as well as various teratogenic substances. One such substance is alcohol. Despite the risks, many women still drink alcohol during pregnancy. The main problem is that almost half of pregnancies are unplanned, so a woman may continue to consume alcohol for several weeks before learning about her condition. Especially in young women, fertilization can occur in a state of intoxication. In addition, under the influence of ethanol, cardiac function may be impaired in the absence of structural abnormalities. Chronic alcohol intoxication causes changes in the myocardium at all levels of its structural organization. First of all, teratogenic changes caused by the action of ethanol affect the development of cardiomyocytes in the process of embryogenesis, which contributes to the underdevelopment of the structure or function of heart cells. Although the effect of maternal alcohol consumption on the fetus has been studied for decades, there are still conflicting conclusions about the severity of myocardial morphological changes depending on the time, frequency and duration of alcohol consumption. Objective: to conduct a retrospective analysis of literature sources devoted to the study of adverse effects on the fetus caused by alcohol. Methods. The paper conducted a retrospective analysis of literature references and formed an understanding of the changes in the structure of the myocardium caused by teratogenic effects of alcohol. Results and conclusion. Analysis of literature sources showed a high level of adverse effects observed in offspring born to alcoholic mothers. Detrimental effects of alcohol cause changes in the myocardium at all levels of structural organization, including its ultrastructure. It was studied that prenatal exposure to ethanol induces significant changes in relative heart weight, left ventricular wall thickness and cardiomyocyte size. Exposure to high concentrations of alcohol in experimental animals during gestation can lead to congenital heart defects, such as atrial, ventricular, and septal defects. The main manifestation of the prenatal effect of alcohol after birth is the fetal alcohol syndrome, which combines various degrees of deviation in the development of the child.

The aging-induced hyperexcretion of glucose-dependent insulinotropic peptide is essential for the healthy cardiac remodeling by prevention of cardiac ceramide accumulation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Kureishi Bando ◽  
Y.R Remina ◽  
T.K Kamihara ◽  
K.N Nishimura ◽  
T.M Murohara
Keyword(s):  
Oxidative Stress ◽  
Ketone Bodies ◽  
Left Ventricular ◽  
Heart Weight ◽  
Lv Function ◽  
Cardiac Aging ◽  
Normal Left Ventricular ◽  
Insulinotropic Peptide ◽  
Ceramide Accumulation ◽  
And Oxidative Stress

Abstract Background Glucose-dependent insulinotropic peptide (GIP) is incretin hormone that is emerged as an important regulator of lipid metabolism. Fat intake induces hypersecretion of GIP that is involved in obesity and ectopic fat accumulation. Aging is another stimulant of GIP hypersecretion, which is suggested as a cause of “sarcopenic obesity in elderly”. In heart, aging is the known risk factor of HFpEF, of which typical characteristics is pathological cardiac hypertrophy induced by unknown cause(s). It remained uncertain whether any ectopic fat accumulation, such as cardiac steatosis may cause the aging-induced cardiac hypertrophy. Ceramide is one of the lipid metabolites that involves in apoptosis, inflammation, and stress responses, which are among the pathogenic components of heart failure. However, it remained unclear whether the ceramide may play any pathophysiological role in cardiac aging. Purpose We thus hypothesized whether cardiac aging may alter cardiac lipid metabolism and the GIP may play a regulatory role in the cardiac aging via modulating cardiac steatosis, particularly ceramide. Methods Mouse model of GIPR deficiency (GIPR-KO) was employed and cardiac evaluation of GIPR-KO and the age-matched wild type mice were performed. Results Aging (50w/o) induced GIP hypersecretion in control mice and their body and heart weight were 50% increased as compared to younger counterpart (10w/o). In contrast, the aging-induced increase rate in body and heart weight of GIPR-KO was significantly lower (22%). Aging also increased the circulating ketone bodies with increase in FGF21 expression in heart and, notably, there was no pathological increase in cardiac ceremide and oxidative stress with normal left-ventricular (LV) function (LVEF=82.2±1.8). In contrast, GIPR-KO exhibited pathological increase in cardiac ceramide without the elevation of the circulating ketone bodies. The younger GIPR-KO (10 w/o) exhibited normal left-ventricular (LV) function, however, the older mice (50 w/o) exhibited systolic LV dysfunction (LVEF=55.8±8.5) with increase in cardiac apoptosis and oxidative stress. Cardiac ceramide accumulation was increased in the aged normal mice, which was significantly higher in the aged GIPR-KO. Furthermore, GIPR-KO exhibited increase in cardiac fibrosis and oxidative stress, which were absent in the aged normal counterpart. Conclusion Aging increased circulating GIP level the leads to compensatory rise in the circulating ketone bodies without pathological increase in cardiac ceremide and related oxidative stress in heart. Loss of GIP signaling caused pathological increase in cardiac ceramide, leading to the aging-induced progression of systolic left-ventricular dysfunction. Collectively, we conclude that the aging-induced GIP hyperexcretion is essential for the aging-induced healthy cardiac remodeling by augmenting compensatory ketone body elevation. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): KAKEN-HI

scholarly journals Losing Regulation of the Extracellular Matrix is Strongly Predictive of Unfavorable Prognostic Outcome after Acute Myocardial Infarction

2020 ◽  
Vol 21 (17) ◽  
pp. 6219
Author(s):  
Pei-Hsun Sung ◽  
Kun-Chen Lin ◽  
Han-Tan Chai ◽  
John Y. Chiang ◽  
Pei-Lin Shao ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Left Ventricular ◽  
Heart Weight ◽  
Lung Injury Score ◽  
Opposite Pattern ◽  
Knock Out ◽  
Group 4 ◽  
Prognostic Outcome ◽  
Group 3

This study tested the hypothesis that MMP-9−/−tPA−/− double knock out (i.e., MTDKO) plays a crucial role in the prognostic outcome after acute myocardial infarction (AMI by ligation of left-coronary-artery) in MTDKO mouse. Animals were categorized into sham-operated controls in MTDKO animals (group 1) and in wild type (B6: group 2), AMI-MTDKO (group 3) and AMI-B6 (group 4) animals. They were euthanized, and the ischemic myocardium was harvested, by day 60 post AMI. The mortality rate was significantly higher in group 3 than in other groups and significantly higher in group 4 than in groups 1/2, but it showed no difference in the latter two groups (all p < 0.01). By day 28, the left-ventricular (LV) ejection fraction displayed an opposite pattern, whereas by day 60, the gross anatomic infarct size displayed an identical pattern of mortality among the four groups (all p < 0.001). The ratio of heart weight to tibial length and the lung injury score exhibited an identical pattern of mortality (p < 0.01). The protein expressions of apoptosis (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP), fibrosis (Smad3/T-GF-ß), oxidative stress (NOX-1/NOX-2/oxidized-protein), inflammation (MMPs2,9/TNF-α/p-NF-κB), heart failure/pressure overload (BNP/ß-MHC) and mitochondrial/DNA damage (cytosolic-cytochrome-C/γ-H2AX) biomarkers displayed identical patterns, whereas the angiogenesis markers (small vessel number/CD31+cells in LV myocardium) displayed opposite patterns of mortality among the groups (all p < 0.0001). The microscopic findings of fibrotic/collagen deposition/infarct areas and inflammatory cell infiltration of LV myocardium were similar to the mortality among the four groups (all p < 0.0001). MTDKO strongly predicted unfavorable prognostic outcome after AMI.

RETROSPECTIVE ANALYSIS OF INFECTION IN A GROUP OF LEFT VENTRICULAR ASSIST SYSTEM (LVAS) PATIENTS

ASAIO Journal ◽  
1996 ◽  
Vol 42 (2) ◽  
pp. 44
Author(s):  
W. Springer ◽  
A. Wasler ◽  
B. Radovancevic ◽  
T. Myers ◽  
M. P. Macris ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Left Ventricular ◽  
Left Ventricular Assist System ◽  
Ventricular Assist ◽  
Left Ventricular Assist

Trastuzumab-Associated Cardiac Adverse Effects in the Herceptin Adjuvant Trial

2007 ◽  
Vol 25 (25) ◽  
pp. 3859-3865 ◽  
Author(s):  
Thomas M. Suter ◽  
Marion Procter ◽  
Dirk J. van Veldhuisen ◽  
Michael Muscholl ◽  
Jonas Bergh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Adverse Effects ◽  
Cancer Patients ◽  
Cardiac Dysfunction ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Ventricular Ejection Fraction ◽  
Neo Adjuvant Chemotherapy

Purpose The purpose of this analysis was to investigate trastuzumab-associated cardiac adverse effects in breast cancer patients after completion of (neo)adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant (HERA) trial is a three-group, multicenter, open-label randomized trial that compared 1 or 2 years of trastuzumab given once every 3 weeks with observation in patients with HER-2–positive breast cancer. Only patients who after completion of (neo)adjuvant chemotherapy with or without radiotherapy had normal left ventricular ejection fraction (LVEF ≥ 55%) were eligible. A repeat LVEF assessment was performed in case of cardiac dysfunction. Results Data were available for 1,693 patients randomly assigned to 1 year trastuzumab and 1,693 patients randomly assigned to observation. The incidence of trastuzumab discontinuation due to cardiac disorders was low (4.3%). The incidence of cardiac end points was higher in the trastuzumab group compared with observation (severe congestive heart failure [CHF], 0.60% v 0.00%; symptomatic CHF, 2.15% v 0.12%; confirmed significant LVEF drops, 3.04% v 0.53%). Most patients with cardiac dysfunction recovered in fewer than 6 months. Patients with trastuzumab-associated cardiac dysfunction were treated with higher cumulative doses of doxorubicin (287 mg/m2 v 257 mg/m2) or epirubicin (480 mg/m2 v 422 mg/m2) and had a lower screening LVEF and a higher body mass index. Conclusion Given the clear benefit in disease-free survival, the low incidence of cardiac adverse events, and the suggestion that cardiac dysfunction might be reversible, adjuvant trastuzumab should be considered for treatment of breast cancer patients who fulfill the HERA trial eligibility criteria.

scholarly journals Prediction of aortic valve regurgitation after continuous-flow left ventricular assist device implantation using artificial intelligence trained on acoustic spectra

2021 ◽  
Author(s):  
Yusuke Misumi ◽  
Shigeru Miyagawa ◽  
Daisuke Yoshioka ◽  
Satoshi Kainuma ◽  
Takuji Kawamura ◽  
...  
Keyword(s):  
Machine Learning ◽  
Left Ventricular Assist Device ◽  
Continuous Flow ◽  
Left Ventricular ◽  
Assist Device ◽  
Ventricular Assist ◽  
Time Frequency ◽  
Left Ventricular Assist ◽  
Acoustic Spectra

AbstractSignificant aortic regurgitation (AR) is a common complication after continuous-flow left ventricular assist device (LVAD) implantation. Using machine-learning algorithms, this study was designed to examine valuable predictors obtained from LVAD sound and to provide models for identifying AR. During a 2-year follow-up period of 13 patients with Jarvik2000 LVAD, sound signals were serially obtained from the chest wall above the LVAD using an electronic stethoscope for 1 min at 40,000 Hz, and echocardiography was simultaneously performed to confirm the presence of AR. Among the 245 echocardiographic and acoustic data collected, we found 26 episodes of significant AR, which we categorized as “present”; the other 219 episodes were characterized as “none”. Wavelet (time–frequency) analysis was applied to the LVAD sound and 19 feature vectors of instantaneous spectral components were extracted. Important variables for predicting AR were searched using an iterative forward selection method. Seventy-five percent of 245 episodes were randomly assigned as training data and the remaining as test data. Supervised machine learning for predicting concomitant AR involved an ensemble classifier and tenfold stratified cross-validation. Of the 19 features, the most useful variables for predicting concomitant AR were the amplitude of the first harmonic, LVAD rotational speed during intermittent low speed (ILS), and the variation in the amplitude during normal rotation and ILS. The predictive accuracy and area under the curve were 91% and 0.73, respectively. Machine learning, trained on the time–frequency acoustic spectra, provides a novel modality for detecting concomitant AR during follow-up after LVAD.

Abstract 16165: Inorganic Arsenic Induces Sex-Dependent Pathological Cardiac Hypertrophy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Raihan Kabir ◽  
Prithvi Sinha ◽  
Sumita Mishra ◽  
Obialunanma V Ebenebe ◽  
Nicole Taube ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Inorganic Arsenic ◽  
Left Ventricular ◽  
Luciferase Assay ◽  
Heart Weight ◽  
Left Ventricular Geometry ◽  
Wall Thickening ◽  
Pathological Cardiac Hypertrophy ◽  
Relevant Dose

Exposure to inorganic arsenic (iAS) through drinking water is well-associated with adverse cardiovascular outcomes, yet the mechanisms through which it induces these effects are not fully understood. Recent epidemiological findings highlight an association between iAS exposure and altered left ventricular geometry in both the presence and absence of hypertension. We therefore tested the hypothesis that iAS exposure has a bimodal impact on cardiac-intrinsic and hemodynamic mechanisms that together induce pathological remodeling of the myocardium. Adult male and female mice were exposed to an environmentally relevant dose of 615 μg/L NaAsO 2 for eight weeks. Males (n=9-10 mice/group) exhibited increased systolic blood pressure (115.1±3.0 vs. 106.0±2.3 mmHg, p=0.0350) via tail cuff photoplethysmography, left ventricular wall thickening (0.98±0.01 vs. 0.88±0.01 mm, p<0.0001) via transthoracic echocardiography, increased heart weight to tibia length (8.56±0.21 vs. 7.15±0.24 mg/mm; n=24 mice/group), and increased plasma atrial natriuretic peptide (47.85±12.0 vs. 15.14±3.73 pg/mL, p=0.0379) via enzyme immunoassay. Myocardial mRNA transcript levels (n=10 hearts/group) of Acta1 (1.36±0.18 vs. 0.73±0.11, p=0.0037), Myh7 (1.53±0.15 vs. 1.04±0.10, p=0.0138), and Nppa (2.40±0.29 vs. 1.02±0.07, p=0.0001) were increased, and Myh6 (0.92±0.17 vs. 1.14±0.23, p=0.0001) was decreased, evidencing pathological hypertrophy in the male heart. Female hearts, however, were largely protected at this eight-week timepoint as similar changes were not detected. Further investigation found that Rcan1 was upregulated (1.47±0.19 vs. 0.97±0.04, p=0.0161; n=10 hearts/group) in male hearts, suggesting that calcineurin-NFAT was activated. Interestingly, iAS was sufficient to activate NFAT (0.82±0.11 vs. 0.46±0.05, p=0.0214; n=8 wells/group) independent of blood pressure via luciferase assay. In conclusion, these results demonstrate for the first time that iAS may cause pathological cardiac hypertrophy not only by increasing hemodynamic load, but also by activating calcineurin-NFAT and inducing fetal gene expression in the male heart, thus providing novel mechanistic insight into the threat of iAS exposure to the cardiovascular system.

Abstract 280: Deficiency of FKBP12 in the Heart Leads to Impaired Contractility and Pregnancy Induced Cardiomyopathy

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Joshua Oakes ◽  
Susan Hamilton
Keyword(s):  
Ejection Fraction ◽  
Ryanodine Receptors ◽  
Left Ventricular ◽  
Heart Weight ◽  
Mild Phenotype ◽  
Adult Mice ◽  
Significant Difference ◽  
Fk506 Binding Proteins ◽  
Deficient Mice ◽  
Fractional Shortening

FK506 Binding Proteins (FKBPs) are a family of cis-trans prolyl isomerases that bind rapamycin and FK506. FKBP12 and 12.6 interact with ryanodine receptors (RyR), homotetrameric transmembrane ion channels that regulate Ca2+ release from the sarcoplasmic reticulum (SR). FKBP12 interacts with RyR1 in skeletal muscle and FKBP12.6 interacts with RyR2 in cardiac muscle to regulate the Ca2+ leak properties of these channels. Recently it has been suggested that FKBP12 also plays a role in regulating RyR2 activity. Using mice with a cardiac specific deficiency in FKBP12, we analyzed the role of FKBP12 in cardiac function. We found that both male and female mice with a α-MyHC Cre/Lox mediated deficiency in FKBP12 in the heart (FKBP12 KD) developed a mild dilated cardiomyopathy, with enlarged left ventricular diameter both during systole and diastole, decreased ejection fraction and decreased fractional shortening. To elucidate the mechanism for these effects we assessed Ca2+ sparks in isolated cardiomyocytes. We found an increase in both Ca2+ spark frequency and spark amplitude in FKBP12 cardiac deficient mice without a change in spark duration. Despite a mild phenotype in adult mice, we found that approximately 25% of all pregnancies (26/106) in the FKBP12 deficient mice resulted in the mothers dying following the birth. Autopsies show that these cardiac specific FKBP12 deficient mice had increased heart weight and significantly dilated ventricles compared to female Cre mice. Our data suggest that a cardiac specific deficiency in FKBP12 leads to the development of pregnancy induced cardiomyopathy. Echocardiography on FKBP12 deficient mice one day after giving birth found that there was no significant difference in ejection fraction or fractional shortening compared to α-MyHC Cre control mice. FKBP12 deficient females, however, had larger hearts and 50% (2/4) displayed heart failure and died. In conclusion, we show that FKBP12 does indeed alter Ca2+ handling in the heart and that a loss of FKBP12 leads to the development of pregnancy induced cardiomyopathies in females.

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