Digoxin Combined with Aerobic Interval Training Improved Cardiomyocyte Contractility

Author(s):  
Gabriel Vasconcelos Abreu ◽  
Erick Roberto Gonçalves Claudio ◽  
Andreo Fernando Aguiar ◽  
Morenna Alana Giordani ◽  
Eveline Aparecida Isquierdo Fonseca de Queiroz ◽  
...  

AbstractDigoxin is a cardiotonic that increases the cardiac output without causing deleterious effects on heart, as well as improves the left ventricular performance during physical exercise. We tested whether the association between chronic digoxin administration and aerobic interval training (AIT) promotes beneficial cardiovascular adaptations by improving the myocardial contractility and calcium (Ca2+) handling. Male Wistar rats were randomly assigned to sedentary control (C), interval training (T), sedentary digoxin (DIGO) and T associated to digoxin (TDIGO). AIT was performed on a treadmill (1h/day, 5 days/week) for 60 days, consisting of successive 8-min periods at 80% and 20% of VO2máx for 2 min. Digoxin was administered by orogastric gavage for 60 days. Left ventricle samples were collected to analysis of Ca2+ handling proteins; contractility and Ca2+ handling were performed on isolated cardiomyocytes. TDIGO group had a greater elevation in fractional shortening (44%) than DIGO, suggesting a cardiomyocyte contractile improvement. In addition, T or TDIGO groups showed no change in cardiomyocytes properties after Fura2-acetoxymethyl ester, as well as in sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), phospholamban and calcineurin expressions. The main findings indicate that association of digoxin and aerobic interval training improved the cardiomyocyte contractile function, but these effects seem to be unrelated to Ca2+ handling.

2007 ◽  
Vol 293 (4) ◽  
pp. H2367-H2376 ◽  
Author(s):  
Jon Arne Kro Birkeland ◽  
Fredrik Swift ◽  
Nils Tovsrud ◽  
Ulla Enger ◽  
Per Kristian Lunde ◽  
...  

Rats with congestive heart failure (CHF) develop ventricular inotropic responsiveness to serotonin (5-HT), mediated through 5-HT2A and 5-HT4 receptors. Human ventricle is similarly responsive to 5-HT through 5-HT4 receptors. We studied isolated ventricular cardiomyocytes to clarify the effects of 5-HT on intracellular Ca2+ handling. Left-ventricular cardiomyocytes were isolated from male Wistar rats 6 wk after induction of postinfarction CHF. Contractile function and Ca2+ transients were measured in field-stimulated cardiomyocytes, and L-type Ca2+ current ( ICa,L) and sarcoplasmic reticulum (SR) Ca2+ content were measured in voltage-clamped cells. Protein phosphorylation was measured by Western blotting or phosphoprotein gel staining. 5-HT4- and 5-HT2A-receptor stimulation induced a positive inotropic response of 33 and 18% (both P < 0.05) and also increased the Ca2+ transient (44 and 6%, respectively; both P < 0.05). ICa,L and SR Ca2+ content increased only after 5-HT4-receptor stimulation (57 and 65%; both P < 0.05). Phospholamban serine16 (PLB-Ser16) and troponin I phosphorylation increased by 26 and 13% after 5-HT4-receptor stimulation ( P < 0.05). 5-HT2A-receptor stimulation increased the action potential duration and did not significantly change the phosphorylation of PLB-Ser16 or troponin I, but it increased myosin light chain 2 (MLC2) phosphorylation. In conclusion, the positive inotropic response to 5-HT4 stimulation results from increased ICa,L and increased phosphorylation of PLB-Ser16, which increases the SR Ca2+ content. 5-HT4 stimulation is thus, like β-adrenoceptor stimulation, possibly energetically unfavorable in CHF. 5-HT2A-receptor stimulation, previously studied in acute CHF, induces a positive inotropic response also in chronic CHF, probably mediated by MLC2 phosphorylation.


Heart ◽  
2018 ◽  
Vol 104 (24) ◽  
pp. 2026-2034 ◽  
Author(s):  
Gianluigi Pironti ◽  
Alex Bersellini-Farinotti ◽  
Nilesh M Agalave ◽  
Katalin Sandor ◽  
Teresa Fernandez-Zafra ◽  
...  

ObjectivesPatients with rheumatoid arthritis (RA) display an increased risk of heart failure independent of traditional cardiovascular risk factors. To elucidate myocardial disease in RA, we have investigated molecular and cellular remodelling of the heart in an established mouse model of RA.MethodsThe collagen antibody-induced arthritis (CAIA) RA mouse model is characterised by joint inflammation and increased inflammatory markers in the serum. We used CAIA mice in the postinflammatory phase that resembles medically controlled RA or RA in remission. Hearts were collected for cardiomyocyte isolation, biochemistry and histology analysis.ResultsHearts from mice subjected to CAIA displayed hypertrophy (heart/body weight, mean±SD: 5.9±0.8vs 5.1±0.7 mg/g, p<0.05), fibrosis and reduced left ventricular fractional shortening compared with control. Cardiomyocytes from CAIA mice showed reduced cytosolic [Ca2+]i transient amplitudes (F/F0, mean±SD: 3.0±1.2vs 3.6±1.5, p<0.05) that was linked to reductions in sarcoplasmic reticulum (SR) Ca2+ store (F/F0, mean±SD: 3.5±1.3vs 4.4±1.3, p<0.01) measured with Ca2+ imaging. This was associated to lower fractional shortening in the cardiomyocytes from the CAIA mice (%FS, mean±SD: 3.4±2.2 vs 4.6%±2.3%, p<0.05). Ca2+ handling proteins displayed oxidation-dependent posttranslational modifications that together with an increase in superoxide dismutase expression indicate a cell environment with oxidative stress.ConclusionsThis study shows that inflammation during active RA has long-term consequences on molecular remodelling and contractile function of the heart, which further supports that rheumatology patients should be followed for development of heart failure.


2019 ◽  
Vol 51 (7) ◽  
pp. 1420-1428 ◽  
Author(s):  
YU-CHIEH HUANG ◽  
HSING-HUA TSAI ◽  
TIEH-CHENG FU ◽  
CHIH-CHIN HSU ◽  
JONG-SHYAN WANG

2011 ◽  
Vol 89 (4) ◽  
pp. 305-310 ◽  
Author(s):  
Wellington Lunz ◽  
Antônio José Natali ◽  
Miguel Araújo Carneiro ◽  
Luciano dos Santos Aggum Capettini ◽  
Marcelo Perim Baldo ◽  
...  

The main purpose of this study was to investigate the effects of short-term L-NAME treatment on the contractile function of left ventricle (LV) myocytes and the expression of proteins related to Ca2+ homeostasis. Data from Wistar rats treated with L-NAME (L group, n = 20; 0.7 g/L in drinking water; 7 days) were compared with results from untreated controls (C group, n = 20). Cardiomyocytes from the L group showed increased (p < 0.05) fractional shortening (23%) and maximum rate of shortening (20%) compared with the C group. LV from the L group also showed increased (p < 0.05) expression of the ryanodine receptor 2 and Na+/Ca2+ exchanger proteins (76% and 83%, respectively; p < 0.05). However, the L and C groups showed similar in vivo hemodynamic parameters of cardiac function. In conclusion, short-term NOS inhibition determines an increased expression of Ca2+ regulatory proteins, which contributes to improving cardiomyocyte contractile function, preserving left ventricular function.


2014 ◽  
Vol 116 (10) ◽  
pp. 1259-1262 ◽  
Author(s):  
Meliza Goi Roscani ◽  
Bertha Fulan Polegato ◽  
Suzana Erico Tanni Minamoto ◽  
Ana Paula Mena Lousada ◽  
Marcos Minicucci ◽  
...  

Although an increased left ventricular (LV) diastolic diameter (DD) and a decreased ejection fraction have been used as markers for the surgical replacement of an insufficient aortic valve, these signals may be observed when irreversible myocardium damage has already occurred. The aim of this study was to determine whether change in LV geometry predicts systolic dysfunction in experimental aortic regurgitation. Male Wistar rats underwent surgical acute aorta regurgitation (aorta regurgitation group; n = 23) or a sham operation (sham group; n = 12). After the procedure, serial transthoracic echocardiograms were performed at 1, 4, 8, and 16 wk. At the end of protocol, the LV, lungs, and liver were dissected and weighed. During the follow-up, no animal developed overt heart failure. There was a correlation between the LV sphericity index and reduced fractional shortening ( P < 0.001) over time. A multiple regression model showed that the LVDD-sphericity index association at 8 wk was a better predictor of decreased fractional shortening at week 16 ( R2 = 0.50; P < 0.001) than was the LVDD alone ( R2 = 0.39; P = 0.001). LV geometry associated with increased LVDD improved the prediction of systolic dysfunction in experimental aortic regurgitation.


2007 ◽  
Vol 43 (3) ◽  
pp. 354-361 ◽  
Author(s):  
Ole J. Kemi ◽  
Øyvind Ellingsen ◽  
Marcello Ceci ◽  
Serena Grimaldi ◽  
Godfrey L. Smith ◽  
...  

2018 ◽  
Vol 257 ◽  
pp. 193-198 ◽  
Author(s):  
Caroline M. Van De Heyning ◽  
Catherine De Maeyer ◽  
Nele Pattyn ◽  
Paul J. Beckers ◽  
Véronique A. Cornelissen ◽  
...  

2012 ◽  
pp. 419-423 ◽  
Author(s):  
H. ŘÍHA ◽  
F. PAPOUŠEK ◽  
J. NECKÁŘ ◽  
J. PIRK ◽  
B. OŠŤÁDAL

Transthoracic echocardiography (TTE) has become an important modality for the assessment of cardiac structure and function in animal experiments. The acquisition of echocardiographic images in rats requires sedation/anesthesia to keep the rats immobile. Commonly used anesthetic regimens include intraperitoneal or inhalational application of various anesthetics. Several studies have compared the effects of anesthetic agents on echocardiographic parameters in rats; however, none of them examined the effects of different concentrations of inhalational anesthetics on echocardiographic parameters. Accordingly, the aim of this study was to examine the effects of different concentrations of isoflurane used for anesthesia during TTE examination in rats on basic echocardiographic parameters of left ventricular (LV) anatomy and systolic function. TTE examinations were performed in adult male Wistar rats (n=10) anesthetized with isoflurane at concentrations of 1.5-3 %. Standard echocardiograms were recorded for off-line analysis. An absence of changes in basic echocardiographic parameters of LV anatomy and systolic function was found under isoflurane anesthesia using concentrations between 1.5-2.5 %. An isoflurane concentration of 3 % caused a small, but statistically significant, increase in LV chamber dimensions without a concomitant change in heart rate or fractional shortening. For the purpose of TTE examination in the rat, our results suggest that isoflurane concentrations ≤ 2.5 % can be safely recommended.


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