scholarly journals Short-term exercise affects cardiac function ex vivo partially via changes in calcium channel levels, without influencing hypoxia sensitivity

2021 ◽  
Author(s):  
Tytti-Maria Uurasmaa ◽  
Tomi Streng ◽  
Milla Alkio ◽  
Ilkka Heinonen ◽  
Katja Anttila
Keyword(s):  
Calcium Channels ◽  
Cardiac Function ◽  
Wheel Running ◽  
Ex Vivo ◽  
Heart Function ◽  
Hypoxia Tolerance ◽  
Generation Rate ◽  
Sodium Calcium Exchanger ◽  
Short Term ◽  
Generation Capacity

AbstractExercise is known to improve cardiac recovery following coronary occlusion. However, whether short-term exercise can improve cardiac function and hypoxia tolerance ex vivo independent of reperfusion injury and the possible role of calcium channels in improved hypoxia tolerance remains unknown. Therefore, in the current study, heart function was measured ex vivo using the Langendorff method at different oxygen levels after a 4-week voluntary wheel-running regimen in trained and untrained male mice (C57Bl/6NCrl). The levels of cardiac Ca2+-channels: L-type Ca2+-channel (CACNA1C), ryanodine receptor (RyR-2), sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2), and sodium-calcium exchanger were measured using western blot. Trained mice displayed lower cardiac afterload pressure generation capacity (rate and amplitude), but unaltered hypoxia tolerance when compared to untrained mice with similar heart rates. The level of CACNA1C positively correlated with the pressure generation rate and amplitude. Furthermore, the CACNA1C-RYR-2 ratio also positively correlated with the pressure generation rate. While the 4-week training period was not enough to alter the intrinsic cardiac hypoxia tolerance, interestingly it decreased pressure generation capacity and slowed pressure decreasing capacity in the mouse hearts ex vivo. This reduction in pressure generation rate could be linked to the level of channel proteins in sarcolemmal Ca2+-cycling in trained mice. However, the Ca2+-channel levels did not differ significantly between the groups, and thus, the level of calcium channels cannot fully explain all the functional alterations, despite the detected correlations. Therefore, additional studies are warranted to reveal further mechanisms that contribute to the reduced intrinsic capacity for pressure production in trained mouse hearts.

Prediction of Poststorage Cardiac Function From Cardioplegic Effluent in an Ex Vivo Porcine Heart Model

2019 ◽  
Vol 2 (4) ◽  
Author(s):  
Benjamin Kappler ◽  
Sjoerd van Tuijl ◽  
Teus J. van Laar ◽  
Dara R. Pabittei ◽  
Marc P. Buijsrogge ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Ex Vivo ◽  
Heart Function ◽  
Laboratory Animals ◽  
Organ Protection ◽  
Isolated Hearts ◽  
Cardiac Functions ◽  
Proactive Measures

Abstract The use of slaughterhouse-based hearts has advantages over hearts obtained from laboratory animals for preclinical testing. However, slaughterhouse hearts have greater variability in cardiac function; this has resulted in a dispute over their actual reproducibility. This study explores the feasibility of examining the cardioplegic effluent during hypothermic cardiac arrest for the presence of biomarkers to predict poststorage heart function of slaughterhouse hearts. This may enable proactive measures to optimize preservation strategies and improve the initial cardiac performance of slaughterhouse heart experiments. Slaughterhouse pig hearts (n = 9; 420 ± 30 g) were arrested and flushed with an additional liter cardioplegia after 1 h. Effluent samples were examined for ammonia, lactate, troponin, and inorganic phosphate. After 2 h, hearts were hemoreperfused in the ex vivo heart platform PhysioHeart™ to restore physiological cardiac functions and to identify correlations between biomarkers and cardiac output. There was a negative correlation between cardiac output of revived hearts and levels of ammonia (r = −0.865; p = 0.002) and lactate (r = −0.763; p = 0.01). No correlation was found between cardiac output and levels of phosphate (r = −0.553; p = 0.12) and troponin (r = −0.367; p = 0.331). The analysis approach to assess cardioplegic biomarkers was feasible and enabled the estimation of the effectiveness of organ protection and cardiac function before reperfusion. Ammonia is a predictor for cardiac dysfunction. Effluent analysis prior to heart revival can uncover poststorage cardiac dysfunction in isolated hearts and may prevent failed experiments while improving reproducibility and standardization.

Predicting donor heart function in a heartbeat

2020 ◽  
Vol 12 (538) ◽  
pp. eabb5667
Author(s):  
Steven P. Keller
Keyword(s):  
Machine Learning ◽  
Cardiac Function ◽  
Ex Vivo ◽  
Heart Function ◽  
Donor Heart ◽  
Learning Methods ◽  
Ex Vivo Perfusion ◽  
Machine Learning Methods

Machine learning methods can assess contractility of donor hearts maintained via ex vivo perfusion to predict posttransplant cardiac function.

scholarly journals Mixture of MMP-2, MLC, and NOS Inhibitors Affects NO Metabolism and Protects Heart from Cardiac I/R Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Anna Krzywonos-Zawadzka ◽  
Aleksandra Franczak ◽  
Grzegorz Sawicki ◽  
Iwona Bil-Lula
Keyword(s):  
Oxidative Stress ◽  
Cardiac Function ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Tissue Expression ◽  
Matrix Metalloproteinase 2 ◽  
No Production ◽  
Nos Inhibitors

Objectives. Coronary reperfusion procedure leads to ischemia/reperfusion injury of the heart (IRI). IRI arises from increased degradation of myosin light chains and increased activity of matrix metalloproteinase 2 (MMP-2). Increased production of toxic peroxynitrite (ONOO−) during oxidative stress is a source of increased nitration/nitrosylation of contractile proteins, which enhance their degradation through MMP-2. Hence, an imbalance in nitric oxide (NO) metabolism along with oxidative stress is an important factor contributing to pathophysiology of cardiovascular disorders, including myocardial infarction. The aim of the current study was to provide an important insight into understanding the interaction of iNOS, eNOS, and ADMA during oxidative stress and to propose the beneficial therapy to modulate this interaction. Material and Methods. Pathogen-free Wistar rats were used in this study as a surrogate heart model ex vivo. Rat hearts perfused using the Langendorff method were subjected to global no-flow ischemia with or without administration of DOXY (1 µM), ML-7 (0.5 µM), and L-NAME (2 µM) mixture. Haemodynamic parameters of heart function, markers of I/R injury, tissue expression of iNOS, eNOS, and phospho-eNOS, asymmetric dimethylarginine, and NO production as well as MMP-2 activity were measured. Results. Mechanical heart function and coronary flow (CF) were decreased in the hearts subjected to I/R. Treatment of the hearts with the tested mixture resulted in a recovery of mechanical function due to decreased activity of MMP‐2. An infusion of Doxy, ML-7, and L-NAME mixture into I/R hearts decreased the expression of iNOS, eNOS, and phospho-eNOS and in consequence reduced ADMA expression. Decreased ADMA production led to enhanced NO synthesis and improvement of cardiac function at 85% of aerobic control. Conclusions. Synergistic effect of the multidrug therapy with the subthreshold doses allows addressing a few pathways of I/R injury simultaneously to achieve protection of cardiac function during I/R.

Co-expression of skeletal and cardiac troponin T decreases mouse cardiac function

2008 ◽  
Vol 294 (1) ◽  
pp. C213-C222 ◽  
Author(s):  
Q.-Q. Huang ◽  
H. Z. Feng ◽  
J. Liu ◽  
J. Du ◽  
L. B. Stull ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Contractile Function ◽  
Troponin T ◽  
Ex Vivo ◽  
Heart Function ◽  
Left Ventricular Pressure ◽  
Experimental System ◽  
Left Ventricular ◽  
Negative Effects

In contrast to skeletal muscles that simultaneously express multiple troponin T (TnT) isoforms, normal adult human cardiac muscle contains a single isoform of cardiac TnT. To understand the significance of myocardial TnT homogeneity, we examined the effect of TnT heterogeneity on heart function. Transgenic mouse hearts overexpressing a fast skeletal muscle TnT together with the endogenous cardiac TnT was investigated in vivo and ex vivo as an experimental system of concurrent presence of two classes of TnT in the adult cardiac muscle.This model of myocardial TnT heterogeneity produced pathogenic phenotypes: echocardiograph imaging detected age-progressive reductions of cardiac function; in vivo left ventricular pressure analysis showed decreased myocardial contractility; ex vivo analysis of isolated working heart preparations confirmed an intrinsic decrease of cardiac function in the absence of neurohumoral influence. The transgenic mice also showed chronic myocardial hypertrophy and degeneration. The dominantly negative effects of introducing a fast TnT into the cardiac thin filaments to produce two classes of Ca2+ regulatory units in the adult myocardium suggest that TnT heterogeneity decreases contractile function by disrupting the synchronized action during ventricular contraction that is normally activated as an electrophysiological syncytium.

scholarly journals Diet-induced obese mice are resistant to improvements in cardiac function resulting from short-term adropin treatment

2021 ◽  
Author(s):  
Dharendra Thapa ◽  
Bingxian Xie ◽  
Bellina AS Mushala ◽  
Manling Zhang ◽  
Janet R Manning ◽  
...  
Keyword(s):  
Cardiac Function ◽  
High Fat Diet ◽  
Contractile Function ◽  
Ex Vivo ◽  
Obese Mice ◽  
High Fat ◽  
Short Term ◽  
Neonatal Cardiomyocytes ◽  
Low Fat Diet ◽  
Short Term Exposure

Previous studies have shown that treatment with recombinant adropin, a circulating peptide secreted by the liver and brain, restores glucose utilization in the hearts of diet-induced obese mice. This restoration of fuel substrate flexibility, which is lost in obese and diabetic animals, has the potential to improve contractile function in the diabetic heart. Using an ex vivo approach, we examined whether short-term adropin treatment could enhance cardiac function in a mouse model of diet-induced obesity. Our study showed that acute adropin treatment reduces inhibitory phosphorylation of pyruvate dehydrogenase in primary neonatal cardiomyocytes, and leads to moderate improvements in ex vivo cardiac function in mice fed a low fat diet. Conversely, short-term exposure to adropin led to a small decrease in cardiac function in mice fed a long-term high fat diet. Insulin treatment did not significantly alter cardiac function in adropin treated hearts from either low or high fat diet mice, however acute adropin treatment did moderately restore downstream insulin signaling in high fat diet fed mice. Overall, these data suggest that in an ex vivo setting, acute adropin treatment alone is not sufficient to promote improved cardiac function in obese animals.

scholarly journals PO-131 Impact of short-term inhibition of PKA in Nucleus Accumbens on voluntary wheel running

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Xuansong Mao ◽  
Kolter Grigsby ◽  
Frank Booth
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Wheel Running ◽  
Ex Vivo ◽  
Skf 38393 ◽  
Short Term ◽  
Voluntary Running ◽  
Kinase A ◽  
Stimulation Of ◽  
Voluntary Wheel

Objective Based upon a Booth lab goal of establishing molecular regulators of physical activity motivation, my current study focuses on the effects of short-term inhibition of protein kinase A (PKA) activity in the nucleus accumbens (NAc). The NAc is a brain region integral to motivated behaviors. Downstream immediate-early gene (IEG) expression from PKA has been shown to exhibit rapid responses to acute stimuli, such as voluntary wheel-running behavior. According to previous work in our lab, long-term NAc overexpression of the endogenous PKA inhibitor, Protein Kinase Inhibitor Alpha (PKIα), increased nightly running distance in rats selectively bred for low voluntary running (LVR) behavior (Mol Neurobiol 2018 Jun 21). However, paradoxically, the same PKIα overexpression failed to increase running distance in wild-type (WT) rats. It is known that chronic manipulation of the NAc PKA pathway produces different molecular (gene expression profiles) and behavioral outcomes from that of acute manipulations. Given the above, the goal of the current work is to determine how short-term inhibition of PKA in the NAc influences its downstream gene networks and the nightly voluntary running behavior in WT rats. Methods An ex vivo preparation of the NAc was utilized to determine the effects of Rp-cAMPS, a selective protein kinase A inhibitor, upon its stimulation of dopamine D1-like receptor agonist SKF 38393 on downstream gene expression level in sedentary WT female rats. Further, real-time PCR was implemented to analyze the transcriptional expression of IEGs (Homer-1, Arc, Zif268) following Rp-cAMPS administration.   Results Data showed that there were no significant difference of mRNA level for Homer-1, Arc or Zif268 among the vehicle, 50uM, 100uM and 200uM Rp-cAMPS treatment groups upon the stimulation of 10uM SKF 38393. Conclusions In addition to the PKA, other protein kinases such as Ca++ activated and growth factor activated kinases have both been shown to phosphorylate CREB at Ser133, and thus, lead to activation of gene transcription. Given the above results of the ex vivo experiment, in which NAc slices were treated with multiple dosages of Rp-cAMPS concurrent with the stimulation of SKF 38393, it is possible that other protein kinase pathways could be compensating the effects of short-term inhibition of PKA and, in turn, lead to no difference of IEG expression. Further experiments will need to be performed  in order to testify this hypothesis.

Attenuated cardiac function degradation in ex vivo pig hearts

2019 ◽  
Vol 43 (3) ◽  
pp. 173-179
Author(s):  
Benjamin Kappler ◽  
Sjoerd van Tuijl ◽  
Bülent Ergin ◽  
Louis Fixsen ◽  
Marco Stijnen ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Ex Vivo ◽  
Heart Function ◽  
Blood Parameters ◽  
Diagnostic Tools ◽  
Control Group ◽  
Isolated Hearts ◽  
Cardiac Hemodynamics ◽  
Cardiac Pump Function

Isolated hearts offer the opportunity to evaluate heart function, treatments, and diagnostic tools without in vivo factor interference. However, the early loss of cardiac function and edema occur over time and do limit the duration of the experiment. This research focuses on delaying these limitations using optimal blood control. This study examines whether blood conditioning by means of the combination of blood predilution and hemodialysis can significantly reduce cardiac function degradation. Slaughterhouse porcine hearts were revived in the PhysioHeart™ platform to restore physiological cardiac performance. Twelve hearts were divided into a control group and a dialysis group; in the latter group, hemodialysis was attached to the blood reservoir. Cardiac hemodynamics and blood parameters were recorded and evaluated. Blood conditioning significantly reduced the loss of cardiac pump function (control group vs dialysis group, −14.9 ± 6.3%/h vs −9.7 ± 2.7%/h) and loss of cardiac output (control group vs dialysis group, −11.8 ± 3.4%/h vs −5.9 ± 2.0%/h). Hemodialysis resulted in physiological and stable blood parameters, whereas in the control group ions reached pathological values, while interstitial edema still occurred. The combination of blood predilution and hemodialysis significantly attenuated ex vivo cardiac function degradation and delayed the loss of cardiac hemodynamics. We hypothesized that besides electrolyte and metabolic control, the hemodialysis-accompanied increase in hematocrit resulted in improved oxygen transport. This could have temporarily compensated the deleterious effect of an increased oxygen-diffusion distance due to edema in the dialysis group and resulted in less progression of cell decay. Clinically validated measures delaying edema might improve the effectiveness of the PhysioHeart™ platform.

scholarly journals Voluntary exercise and cardiac remodeling in a myocardial infarction model

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 545-555
Author(s):  
Hamad Al Shahi ◽  
Tomoyasu Kadoguchi ◽  
Kazunori Shimada ◽  
Kosuke Fukao ◽  
Satoshi Matsushita ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Cardiac Remodeling ◽  
Skeletal Muscles ◽  
Wheel Running ◽  
Voluntary Exercise ◽  
Fibroblast Growth Factor 21 ◽  
Expression Levels ◽  
Factor Α ◽  
Necrosis Factor

AbstractWe investigated the effects of voluntary exercise after myocardial infarction (MI) on cardiac function, remodeling, and inflammation. Male C57BL/6J mice were divided into the following four groups: sedentary + sham (Sed-Sh), sedentary + MI (Sed-MI), exercise + sham (Ex-Sh), and exercise + MI (Ex-MI). MI induction was performed by ligation of the left coronary artery. Exercise consisting of voluntary wheel running started after the operation and continued for 4 weeks. The Ex-MI mice had significantly increased cardiac function compared with the Sed-MI mice. The Ex-MI mice showed significantly reduced expression levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-10 in the infarcted area of the left ventricle compared with the Sed-MI mice. In the Ex-MI mice, the expression levels of fibrosis-related genes including collagen I and III were decreased compared to the Sed-MI mice, and the expression levels of IL-1β, IL-6, follistatin-like 1, fibroblast growth factor 21, and mitochondrial function-related genes were significantly elevated in skeletal muscle compared with the Sed mice. The plasma levels of IL-6 were also significantly elevated in the Ex-MI group compared with the Sed-MI groups. These findings suggest that voluntary exercise after MI may improve in cardiac remodeling associated with anti-inflammatory effects in the myocardium and myokine production in the skeletal muscles.

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