scholarly journals Ajwa Nanopreparation Prevents Doxorubicin-Associated Cardiac Dysfunction: Effect on Cardiac Ischemia and Antioxidant Capacity

2019 ◽  
Vol 18 ◽  
pp. 153473541986235
Author(s):  
Soad Al-Jaouni ◽  
Seham Abdul-Hady ◽  
Hany El-Bassossy ◽  
Numan Salah ◽  
Magda Hagras
Keyword(s):  
Antioxidant Capacity ◽  
Cardiac Tissue ◽  
Reduced Glutathione ◽  
Cardiac Contractility ◽  
Left Ventricular Pressure ◽  
Heart Tissue ◽  
Left Ventricular ◽  
Cardiac Ischemia ◽  
Tissue Samples ◽  
Before And After

Background: This study evaluated the cardioprotective effect of Ajwa nano-preparation against doxorubicin-associated cardiotoxicity. Methods: Twenty-four male Wistar rats (200-250 g) were divided into 3 groups. One group was given the nanopreparation containing both Ajwa fruit and pit in a dose of 1.4 g/kg orally 1 hour before doxorubicin infusion (Dates-DOX group). Another group was given the vehicle for 1 hour before doxorubicin infusion (DOX group). The third group received the vehicle but no DOX infusion (time control). Cardiac hemodynamics, blood pressure, cardiac contractility, and conductivity were recorded before and after 45 minutes of infusion of doxorubicin (15 mg/kg, slow intravenous over 45 minutes). Blood samples were collected before and after doxorubicin infusion. Heart tissue samples were collected and snap frozen until assay of reduced glutathione. Results: Rats pre-administered Ajwa nanopreparation were protected from doxorubicin-associated systolic and diastolic dysfunction based on the significant elevation in the rate of rise in left ventricular pressure (d p/d tmax) and (d p/d tmin) compared with the DOX group. In addition, it prevented the doxorubicin-associated ischemia based on the significant shortening in QT interval, JT interval, and Tpeak- Tend interval versus the DOX group. There was no effect on atrial conductivity (PR interval and P duration). Ajwa pretreatment increased the antioxidant capacity of cardiac tissue, as evidenced by increasing the cardiac content of reduced glutathione compared with the untreated doxorubicin group. Conclusion: Ajwa nanopreparation protects from doxorubicin-associated cardiotoxicity through alleviating cardiac ischemia and increasing cardiac antioxidant capacity.

Abstract MP216: Identification Of Novel Phosphoprotein Signaling Pathways In Human Dilated Cardiomyopathy By Integrative Proteomic And Phosphoproteomic Analysis

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Cristine J Reitz ◽  
Marjan Tavassoli ◽  
Da Hye Kim ◽  
Sina Hadipour-Lakmehsari ◽  
Saumya Shah ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Cardiac Tissue ◽  
Regulatory Element ◽  
Critical Role ◽  
Left Ventricular ◽  
Confocal Imaging ◽  
Intercalated Disc ◽  
Bioinformatics Analyses ◽  
Tissue Samples ◽  
And Function

Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure, yet the majority of the underlying signaling mechanisms remain poorly characterized. Protein phosphorylation is a key regulatory element with profound effects on the activity and function of signaling networks; however, there is a lack of comprehensive phosphoproteomic studies in human DCM patients. We assessed the hypothesis that an integrative phosphoproteomics analysis of human DCM would reveal novel phosphoprotein candidates involved in disease pathophysiology. Combined proteomic and phosphoproteomic analysis of explanted left ventricular tissue samples from DCM patients ( n =4) and non-failing controls ( n =4) identified 5,570 unique proteins with 13,624 corresponding phosphorylation sites. From these analyses, we identified αT-catenin as a unique candidate protein with a cluster of 4 significantly hyperphosphorylated sites in DCM hearts ( P <0.0001), with no change in total αT-catenin expression at the protein level. Bioinformatics analyses of human datasets and confocal imaging of human and mouse cardiac tissue show highly cardiac-enriched expression of αT-catenin, localized to the cardiomyocyte intercalated disc. High resolution 3-dimensional reconstruction shows elongated intercalated disc morphology in DCM hearts (10.07±0.76 μm in controls vs. 17.20±1.87 μm in DCM, P <0.05, n =3/group), with significantly increased colocalization of αT-catenin with the intercalated disc membrane protein N-cadherin (Pearson’s coefficient 0.55±0.04 in controls vs. 0.71±0.02 in DCM, P <0.05, n =3/group). To investigate the functional role of cardiac αT-catenin phosphorylation, we overexpressed WT protein vs. non-phosphorylatable forms based on the loci identified in DCM hearts, in adult mouse cardiomyocytes using lentiviral transduction. Confocal imaging revealed significant internalization of the phospho-null form, as compared to the prominent intercalated disc staining of the WT protein (17.78±0.79% of WT vs. 9.25±0.49% of 4A mutant, P <0.0001, n =50 cells/group). Together, these findings suggest a critical role for αT-catenin phosphorylation in maintaining cardiac intercalated disc organization in human DCM.

Muscle metabolism and cardiac function of the myopathic hamster following training

1977 ◽  
Vol 43 (6) ◽  
pp. 936-941 ◽  
Author(s):  
W. L. Sembrowich ◽  
M. B. Knudson ◽  
P. D. Gollnick
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Function ◽  
Myocardial Function ◽  
Cardiac Contractility ◽  
Muscle Metabolism ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Succinate Dehydrogenase Activity ◽  
Positive Effect

The effect of 18 wk of treadmill running on skeletal muscle metabolism and myocardial function of normal and myopathic hamsters was examined. BIO 14.6 hamsters could tolerate an exercise intensity of about 18 m/min for 40 min, 5 days/wk. Further increases in speed or number of bouts per day resulted in a falloff in performance. Normal hamsters could tolerate higher speeds and longer exercise bouts. Exercise did not change the severity of lesions of either the heart or skeletal muscle of the myopathic hamsters. A training effect was evidenced by increased succinate dehydrogenase activity in the soleus muscle. Cardiac function was evaluated as contractility measured from left ventricular pressure curves and expressed as (dP/dt)/kP. The results suggested that cardiac contractility was not as severely depressed in the trained BIO 14.6 strain of hamsters as in nontrained controls. However, (dP/dt)/kP was lower in the trained myopathic animals than in normal hamsters. ATP, CP, and glycogen levels were lower in myopathic hamsters with the lowest values occurring in the trained group. These data demonstrate that the BIO 14.6 strain of hamster can tolerate exercise training and that such training may have a positive effect on cardiac function.

Abstract 13291: Left Ventricular Assist Device Support is Associated with Sustained Cardiac CamKII Activation and Increased MEF2

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Estibaliz Castillero ◽  
Ruiping Ji ◽  
Xiaokan Zhang ◽  
Vivian Choi ◽  
Ayesha Mannan ◽  
...  
Keyword(s):  
Left Ventricular Assist Device ◽  
Ventricular Assist Device ◽  
Cardiac Tissue ◽  
Left Ventricular ◽  
Assist Device ◽  
Ventricular Assist ◽  
Left Ventricular Assist ◽  
Before And After ◽  
Dependent Protein ◽  
Lvad Support

Background: Ca2+/calmodulin-dependent protein kinase (CaMK)II has been implicated in impaired myocardial Ca2+ signaling and may play an important role in the development of heart failure (HF). The objective of this study was to characterize CAMKII signaling in patients with HF before and after prolonged left ventricular assist device (LVAD) support. Methods: LV apex tissue pairs were collected in patients with dilated cardiomyopathy (n=10) at LVAD implantation and explantation. Normal cardiac tissue was used as control (n=4). Total protein, as well as cytoplasmic and nuclear fractions, were analyzed by Western Blot analysis. Results: The duration of LVAD support ranged from 48 to 595 days (mean = 271±54) with no patient exhibiting myocardial recovery. Total CamKIIδ levels in failing hearts were significantly higher than normal hearts and increased after LVAD, mainly due to an increase in cytoplasmic CaMKIIδC, which regulates Ca2+ handling (Table 1). Nuclear CaMKIIδB, which regulates Ca2+ gene transcription, did not change. Calmodulin remained increased in the nuclear and cytoplasmic fractions after LVAD. CaMKII autonomous, non-CaM-dependent activity, reflected by phosphorylation in Thr207, was increased pre- and post LVAD in cytoplasmic CaMKIIδC. The CaMKII-dependent myocyte enhancer factor 2 (MEF2) was increased pre- and significantly further post LVAD in the nucleus while decreased in the cytoplasm, suggesting translocation into the nucleus after LVAD support. Class IIa HDACs 4 and 5 interact with MEF2, resulting in repression of MEF2-dependent genes. Phosphorylated levels of HDAC4 and HDAC5 were increased pre- and post LVAD, which would result in activated MEF2. Conclusions: This study shows for the first time an increase of the hypertrophic factor MEF2 associated with persistent activation of CamKIIδC after prolonged LVAD support, which may have implications for cardiac remodeling during mechanical support.

scholarly journals Empagliflozin improves chronic hypercortisolism-induced abnormal myocardial structure and cardiac function in mice

2020 ◽  
Vol 11 ◽  
pp. 204062232097483
Author(s):  
Qing-Qing Zhang ◽  
Guo-Qing Li ◽  
Yi Zhong ◽  
Jie Wang ◽  
An-Ning Wang ◽  
...  
Keyword(s):  
Myocardial Dysfunction ◽  
Sglt2 Inhibitor ◽  
Heart Tissue ◽  
Left Ventricular ◽  
Tissue Samples ◽  
Beneficial Effects ◽  
Reduced Body ◽  
Sodium Glucose Cotransporter ◽  
And Function ◽  
Visceral Adipose

Background: Chronic exposure to excess glucocorticoids is frequently associated with a specific cardiomyopathy. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has beneficial effects as it aids in the reduction of heart failure and cardiovascular mortality in hospitalized patients. The aim of this study was to investigate the effects of empagliflozin on chronic hypercortisolism-induced myocardial fibrosis and myocardial dysfunction in mice. Methods: Male C57BL/6J mice (6 weeks old) were randomized to control, corticosterone (CORT), and empagliflozin + CORT groups. After 4 weeks of administration, heart structure and function were evaluated by echocardiography, and peripheral blood and tissue samples were collected. Expressions of Ccl2, Itgax, Mrc1, and Adgre1 mRNA in heart tissue were evaluated by RT-PCR, and signal transducer and activator of transcription 3 (STAT3) and Toll-like receptor 4 (TLR4) protein expression were analyzed by Western blotting. Results: Empagliflozin effectively reduced body weight, liver triglyceride, visceral adipose volume, and uric acid in CORT-treated mice. Left ventricular hypertrophy and cardiac dysfunction were improved significantly, phosphorylated STAT3 and TLR4 were alleviated, and macrophage infiltration in the myocardium was inhibited after administration of empagliflozin in CORT-treated mice. Conclusion: Empagliflozin has beneficial effects on specific cardiomyopathy associated with CORT, and the results provide new evidence that empagliflozin might be a potential drug for the prevention of this disease.

Chronic alcohol-induced changes in cardiac contractility are not due to changes in the cytosolic Ca2+ transient

1998 ◽  
Vol 275 (1) ◽  
pp. H122-H130 ◽  
Author(s):  
Vincent M. Figueredo ◽  
Kevin C. Chang ◽  
Anthony J. Baker ◽  
S. Albert Camacho
Keyword(s):  
Cardiac Contractility ◽  
Left Ventricular Pressure ◽  
Alcohol Exposure ◽  
Left Ventricular ◽  
Polyacrylamide Gel ◽  
Chronic Alcohol ◽  
Protein Levels ◽  
Chronic Alcohol Exposure ◽  
Induced Changes ◽  
And Control

Long-standing heavy alcohol consumption acts as a chronic stress on the heart. It is thought that alcohol-induced changes of contractility are due to altered Ca2+ handling, but no measurements of cytosolic Ca2+([Ca2+]c) after chronic alcohol exposure have been made. Therefore experiments were performed to determine whether alcohol-induced changes in contractility are due to altered Ca2+ handling by measuring [Ca2+]c(indo 1) in hearts from rats drinking 36% ethanol for 7 mo and age-matched controls. Peak left ventricular pressure was depressed (−16%), whereas rates of contraction (12%) and relaxation (14–20%) were faster in alcohol-exposed hearts. Systolic [Ca2+]c(808 ± 45 vs. 813 ± 45 nM), diastolic [Ca2+]c(195 ± 11 vs. 193 ± 10 nM), and rates of [Ca2+]crise and decline were the same in alcohol-exposed and control hearts. Protein levels of Ca2+-handling proteins, sarcoplasmic reticulum Ca2+-ATPase and phospholamban, were the same in myocytes isolated from alcohol-exposed and control hearts (SDS-polyacrylamide gel). These data suggest that chronic alcohol-induced contractile changes are not due to altered Ca2+ handling but may be due to changes at the level of the myofilament. As a first step in elucidating the mechanism(s) of alcohol-induced changes at the myofilament, we assessed myosin heavy chain (MHC) isoform content (SDS-polyacrylamide gel). α-MHC was decreased relative to β-MHC ( a/ a+ b = 0.55 ± 0.03 vs. 0.66 ± 0.02; P < 0.02) in alcohol-exposed hearts, which cannot account for the observed alcohol-induced contractile changes. In conclusion, changes of myocardial contractility due to chronic alcohol exposure do not result from altered Ca2+ handling but from changes at the level of the myofilament that do not involve MHC isoform shifts.

Myoglobin function in the isolated fluorocarbon-perfused dog heart

1978 ◽  
Vol 234 (5) ◽  
pp. H567-H572 ◽  
Author(s):  
R. P. Cole ◽  
B. A. Wittenberg ◽  
P. R. Caldwell
Keyword(s):  
Oxygen Consumption ◽  
Left Ventricle ◽  
Mechanical Performance ◽  
Left Ventricular Pressure ◽  
Dry Weight ◽  
Left Ventricular ◽  
Facilitated Diffusion ◽  
Dog Heart ◽  
Before And After ◽  
Ringer’S Lactate

An isolated dog heart preparation perfused with hemoglobin-free fluorocarbon suspension has been developed to study the role of myoglobin in myocardial function. The coronary vasculature was perfused at constant flow, with oxygen consumption determined from arteriovenous PO2 differences. Muscle function was assessed by measurement of pressures generated in a latex balloon placed in the left ventricle. The perfusate consisted of 20% perfluorotributylamine and 80% Ringer's lactate with 16 mM glucose. Steady-state oxygen consumption decreased from 0.30 to 0.11 ml/min per gram dry weight left ventricle, as perfusate PO2 decreased from 690 to 150 mmHg. Left ventricular pressure generation and oxygen consumption were determined before and after addition of 8 mM sodium nitrite, which changed functional ferrous myoglobin to high-spin ferric myoglobin. Over the range of perfusate PO2 studied, nitrite addition did not alter mechanical performance or myocardial oxygen consumption. These data suggest that those conditions necessary for substantial myoglobin-facilitated diffusion of oxygen in the myocardium are not present in the isolated fluorocarbon-perfused dog heart.

Hemodynamic alterations in chronically conscious unrestrained diabetic rats

1987 ◽  
Vol 252 (5) ◽  
pp. H900-H905 ◽  
Author(s):  
L. F. Carbonell ◽  
M. G. Salom ◽  
J. Garcia-Estan ◽  
F. J. Salazar ◽  
M. Ubeda ◽  
...  
Keyword(s):  
Weight Control ◽  
Insulin Treatment ◽  
Cardiac Contractility ◽  
Peripheral Resistance ◽  
Left Ventricular Pressure ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic State ◽  
Hemodynamic State ◽  
Male Wistar Rats

Important cardiovascular dysfunctions have been described in streptozotocin (STZ)-diabetic rats. To determine the influence of these changes on the hemodynamic state and whether insulin treatment can avoid them, different hemodynamic parameters, obtained by the thermodilution method, were studied in STZ-induced (65 mg/kg) diabetic male Wistar rats, as well as in age-control, weight-control, and insulin-treated diabetic ones. All rats were examined in the conscious, unrestrained state 12 wk after induction of diabetes or acidified saline (pH 4.5) injection. At 12 wk of diabetic state most important findings were normotension, high blood volume, bradycardia, increase in stroke volume, cardiac output, and cardiosomatic ratio, and decrease in total peripheral resistance and cardiac contractility and relaxation (dP/dtmax and dP/dtmin of left ventricular pressure curves). The insulin-treated diabetic rats did not show any hemodynamic differences when compared with the control animals. These results suggest that important hemodynamic alterations are present in the chronic diabetic state, possibly conditioning congestive heart failure. These alterations can be prevented by insulin treatment.

Detection of Cardiac Variability in the Isolated Rat Heart

2006 ◽  
Vol 8 (1) ◽  
pp. 55-66 ◽  
Author(s):  
Autumn M. Schumacher ◽  
Joseph P. Zbilut ◽  
Charles L. Webber ◽  
Dorie W. Schwertz ◽  
Mariann R. Piano
Keyword(s):  
Rat Heart ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Rat Hearts ◽  
Before And After ◽  
Quantification Analysis ◽  
Physical Attributes ◽  
Cardiac Variability ◽  
Isolated Rat

Cardiac variability can be assessed from two perspectives: beat-to-beat performance and continuous performance during the cardiac cycle. Linear analysis techniques assess cardiac variability by measuring the physical attributes of a signal, whereas nonlinear techniques evaluate signal dynamics. This study sought to determine if recurrence quantification analysis (RQA), a nonlinear technique, could detect pharmacologically induced autonomic changes in the continuous left ventricular pressure (LVP) and electrographic (EC) signals from an isolated rat heart—a model that theoretically contains no inherent variability. LVP and EC signal data were acquired simultaneously during Langendorff perfusion of isolated rat hearts before and after the addition of acetylcholine (n = 11), norepinephrine (n = 12), or no drug (n = 12). Two-minute segments of the continuous LVP and EC signal data were analyzed by RQA. Findings showed that%recurrence,%determinism, entropy, maxline, and trend from the continuous LVP signal significantly increased in the presence of both acetylcholine and norepinephrine, although systolic LVP significantly increased only with norepinephrine. In the continuous EC signal, the RQA trend variable significantly increased in the presence of norepinephrine. These results suggest that when either the sympathetic or parasympathetic division of the autonomic nervous system overwhelms the other, the dynamics underlying cardiac variability become stationary. This study also shows that information concerning inherent variability in the isolated rat heart can be gained via RQA of the continuous cardiac signal. Although speculative, RQA may be a tool for detecting alterations in cardiac variability and evaluating signal dynamics as a nonlinear indicator of cardiac pathology.

Sign in / Sign up

Export Citation Format

Share Document