Maximum Rate Of Contraction Research Articles

Origami-Inspired Bionic Soft Robot Stomach with Self-Powered Sensing.

The stomach is a vital organ in the human digestive system, and its digestive condition is critical to human health. The physical movement of the stomach during digestion is controlled by the circular and oblique muscles. Existing stomach simulators are unable to realistically reproduce the physical movement of the stomach. Due to the complexity of gastric motility, it is challenging to simulate and sense gastric motility. This study proposes for the first time a bionic soft robotic stomach (BSRS) with an integrated drive and sensing structure inspired by origami and self-powered sensing technology. This soft stomach (SS) can realistically simulate and sense the movements of various parts of the human stomach in real-time. The contraction force and contraction rate of the BSRS are investigated with different viscosity contents, and the experimental values are similar to the physiological range (maximum contraction force is 3.2 N, and maximum contraction rate is 0.8). This paper provides an experimental basis for the study of gastric digestive medicine and food science by simulating the peristaltic motion of the BSRS according to the human stomach and by combining the triboelectric nanogenerator (TENG) sensing technology to monitor the motion of the BSRS in real-time.

Passively stretchable vacuum-powered artificial muscle with variable stiffness skin

A passively stretchable vacuum-powered artificial muscle (VPAM) is proposed in this work that extends the deformation mode of the existing VPAM, allowing it to have passively stretchable properties while maintaining the performance benefits. The passively stretchable VPAM is made possible by a new variable stiffness skin consisting of two composite layers. Each composite layer is divided into two parts: a non-stretchable part and a stretchable part. When vacuum pressure is applied, the composite layers are jammed and the skin becomes non-stretchable. Conversely, in the absence of pressure, the skin becomes stretchable, making the VPAM stretchable. The behaviour of the actuator has been theoretically modelled and the corresponding experiments have been carried out. Since the behaviour of the actuator with the skin in jammed state is consistent with that of the existing VPAM, the effect of passive tensile deformation on the behaviour of this type of VPAM is primarily analyzed. It is shown that the passively stretchable properties not only make the VPAM more similar to the deformation behaviour of biological muscles, but also enable the regulation of the blocked force and maximum contraction rate of the VPAM. We believe that the proposed artificial muscle will contribute to new robotic systems and provide more inspiration to the robotics community.

New biomarkers for 1,1-dimethylhydrazine

Introduction. Despite the large-scale use of asymmetric dimethylhydrazine (UDMH) in the domestic rocket and space industry, its biomarkers of exposure in blood plasma and urine, as well as biomarkers of cardiotoxic effects, have not yet been described. Material and methods. The study of blood and urine samples of rats after a single injection of 10 mg/kg UDMH (1/16 LD50) was carried out by HPLC-MS. The determination of the non-metabolized form of UDMH was also carried out using the method of gas chromatography with mass-selective detection with preliminary derivatization with 4-pyridinecarboxyaldehyde. The cardiotoxic effect of UDMH was assessed on a model of an isolated rat heart with subchronic intragastric administration for 28 days at doses of 0,02; 0,2; 2,0 mg/kg. Results. It has been established that the main metabolites of UDMH are dimethylhydrazones of pyridoxal (vitamin B6) and pyruvic acid (pyruvate). The possibility of determining the non-metabolized form of UDMH in blood and urine by HPLC-MS was shown, concentrations reach 10-60 ng/ml of blood plasma and 200-2000 ng/ml. The use of UDMH leads to an increase in the mass coefficient of the heart at a dose of 2,0 mg/kg. In ex vivo experiments on the rat heart, the cardiotoxic effect of UDMH was shown at subchronic use at a dose of 0,2 mg/kg and above, expressed in significant dilatation of the coronary bloodstream and left ventricle, the development of pronounced negative inotropic and chronotropic effects, and a decrease in the maximum rate of contraction and relaxation of the left ventricle. ventricle, reflecting the inhibition of myocardial energy metabolism. Limitations of the study. In the work, biomarkers were detected after a single intragastric injection of NDMG, the toxicokinetic characteristics of biomarkers and their retrospectivity were not evaluated. Conclusion. The main metabolites of UDMH with intravenous administration of 1/16 DL50 are dimethylhydrazones of pyridoxal (vitamin B6) and pyruvic acid (pyruvate). With subchronic administration, UDMH has cardiotoxicity at a dose of 0,02 mg/kg and above.

Microsurgical Transplantation of Pedicled Muscles in an Isolation Chamber—A Novel Approach to Engineering Muscle Constructs via Perfusion-Decellularization

Decellularized whole muscle constructs represent an ideal scaffold for muscle tissue engineering means as they retain the network and proteins of the extracellular matrix of skeletal muscle tissue. The presence of a vascular pedicle enables a more efficient perfusion-based decellularization protocol and allows for subsequent recellularization and transplantation of the muscle construct in vivo. The goal of this study was to create a baseline for transplantation of decellularized whole muscle constructs by establishing an animal model for investigating a complete native muscle isolated on its pedicle in terms of vascularization and functionality. The left medial gastrocnemius muscles of 5 male Lewis rats were prepared and raised from their beds for in situ muscle stimulation. The stimulation protocol included twitches, tetanic stimulation, fatigue testing, and stretching of the muscles. Peak force, maximum rate of contraction and relaxation, time to maximum contraction and relaxation, and maximum contraction and relaxation rate were determined. Afterwards, muscles were explanted and transplanted heterotopically in syngeneic rats in an isolation chamber by microvascular anastomosis. After 2 weeks, transplanted gastrocnemius muscles were exposed and stimulated again followed by intravascular perfusion with a contrast agent for µCT analysis. Muscle constructs were then paraffin embedded for immunohistological staining. Peak twitch and tetanic force values all decreased significantly after muscle transplantation while fatigue index and passive stretch properties did not differ between the two groups. Vascular analysis revealed retained perfused vessels most of which were in a smaller radius range of up to 20 µm and 45 µm. In this study, a novel rat model of heterotopic microvascular muscle transplantation in an isolation chamber was established. With the assessment of in situ muscle contraction properties as well as vessel distribution after 2 weeks of transplantation, this model serves as a base for future studies including the transplantation of perfusion-decellularized muscle constructs.

Inotropic and lusitropic, but not arrhythmogenic, effects of adipocytokine resistin on human atrial myocardium

The adipocytokine resistin is released from epicardial adipose tissue (EAT). Plasma resistin and EAT deposition are independently associated with atrial fibrillation. The EAT secretome enhances arrhythmia susceptibility and inotropy of human myocardium. Therefore, we aimed to determine the effect of resistin on the function of human myocardium and how resistin contributes to the proarrhythmic effect of EAT. EAT biopsies were obtained from 25 cardiac surgery patients. Resistin levels were measured by ELISA in 24-h EAT culture media (n = 8). The secretome resistin concentrations increased over the culture period to a maximal level of 5.9 ± 1.2 ng/mL. Coculture with β-adrenergic agonists isoproterenol (n = 4) and BRL37344 (n = 13) had no effect on EAT resistin release. Addition of resistin (7, 12, 20 ng/mL) did not significantly increase the spontaneous contraction propensity of human atrial trabeculae (n = 10) when given alone or in combination with isoproterenol. Resistin dose-dependently increased trabecula-developed force (maximal 2.9-fold increase, P < 0.0001), as well as the maximal rates of contraction (2.6-fold increase, P = 0.002) and relaxation (1.8-fold increase, P = 0.007). Additionally, the postrest potentiation capacity of human trabeculae was reduced at all resistin doses, suggesting that the inotropic effect induced by resistin might be due to altered sarcoplasmic reticulum Ca2+ handling. EAT resistin release is not modulated by common arrhythmia triggers. Furthermore, exogenous resistin does not promote arrhythmic behavior in human atrial trabeculae. Resistin does, however, induce an acute dose-dependent positive inotropic and lusitropic effect.

Growth differentiation factor 15 (GDF-15) inhibition to increase muscle mass and function in cancer cachexia.

e15633 Background: Almost half of cancer deaths are attributed to cancers most frequently associated with cachexia. Cachexia is a complex metabolic disease characterized by anorexia and unintentional weight loss. Skeletal muscle depletion has been recognized as a key feature of the disease, however muscle anabolic therapies have not been successful, suggesting that treatments that target multiple aspects of the disease will be most effective. Growth differentiation factor 15 (GDF-15) is a cytokine that induces anorexia and weight loss and is associated with cachexia in cancer patients. In preclinical cancer cachexia models, GDF-15 inhibition is sufficient to normalize food intake and body weight, including skeletal muscle mass. However, it remains to be determined whether the increased skeletal muscle mass also results in restoration of muscle function. Therefore, we examined the effect of GDF-15 inhibition on muscle mass and function in mouse models of cancer cachexia in comparison with myostatin inhibition, an established muscle anabolic pathway. Methods: Cachectic mouse tumor models were established with subcutaneous implantation of tumor cell lines reported to be GDF-15-dependent; mouse renal cell carcinoma (RENCA) and human ovarian cancer (TOV-21G) cell lines. Mice were treated with anti-GDF-15 (mAB2) or anti-myostatin (RK35) monoclonal antibodies and skeletal muscle function was assessed in vivo via maximum force, maximum rate of contraction and half relax time. In the RENCA tumor model, GDF-15 inhibition fully restored body weight and skeletal muscle mass whereas myostatin inhibition showed only a modest effect. Results: Consistent with the muscle mass improvement, GDF-15 inhibition dramatically increased functional muscle endpoints compared to the partial effect of myostatin inhibition. Interestingly, in the TOV-21G tumor model GDF-15 inhibition only partially restored body weight, however skeletal muscle mass and muscle function were completely normalized. Consistent with the functional assessment, GDF-15 inhibition in the RENCA tumor model decreased the expression of several catabolic genes (i.e. Trim63, Fbxo32, Myh7 and Myh2). The GDF-15 effect is likely to be secondary to the reversal of anorexia since wildtype mice pair-fed to Fc-GDF-15-treated mice demonstrated equivalent muscle mass loss. Conclusions: Taken together these data suggest that GDF-15 inhibition holds potential as an effective therapeutic approach to alleviate multiple aspects of cachexia.

Resistance training promotes reduction in Visceral Adiposity without improvements in Cardiomyocyte Contractility and Calcium handling in Obese Rats.

Resistance training (RT) improves the cardiomyocyte calcium (Ca2+) cycling during excitation-contraction coupling. However, the role of RT in cardiomyocyte contractile function associated with Ca2+ handling in obesity is unclear. Wistar rats were distributed into four groups: control, sedentary obese, control plus RT, and obesity plus RT. The 10-wk RT protocol was used (4-5 vertical ladder climbs, 60-second interval, 3× a week, 50-100% of maximum load). Metabolic, hormonal, cardiovascular and biochemical parameters were determined. Reduced leptin levels, epididymal, retroperitoneal and visceral fat pads, lower body fat, and adiposity index were observed in RT. Obesity promoted elevation of collagen, but RT did not promote modifications of LV collagen in ObRT. RT induced elevation in maximum rates of contraction and relaxation, and reduction of time to 50% relaxation. ObRT group did not present improvement in the cardiomyocyte contractile function in comparison to Ob group. Reduced cardiac PLB serine16 phosphorylation (pPLB Ser16) and pPLB Ser16/PLB ratio with no alterations in sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) and phospholamban (PLB) expression were observed in Ob groups. Resistance training improved body composition reduced fat pads and plasma leptin levels but did not promote positive alterations in cardiomyocyte contractile function, Ca2+ handling and phospholamban phosphorylation.

Adult human cardiac stem cell supplementation effectively increases contractile function and maturation in human engineered cardiac tissues

BackgroundDelivery of stem cells to the failing heart is a promising therapeutic strategy. However, the improvement in cardiac function in animal studies has not fully translated to humans. To help bridge the gap between species, we investigated the effects of adult human cardiac stem cells (hCSCs) on contractile function of human engineered cardiac tissues (hECTs) as a species-specific model of the human myocardium.MethodsHuman induced pluripotent stem cell-derived cardiomyoctes (hCMs) were mixed with Collagen/Matrigel to fabricate control hECTs, with an experimental group of hCSC-supplemented hECT fabricated using a 9:1 ratio of hCM to hCSC. Functional testing was performed starting on culture day 6, under spontaneous conditions and also during electrical pacing from 0.25 to 1.0 Hz, measurements repeated at days 8 and 10. hECTs were then frozen and processed for gene analysis using a Nanostring assay with a cardiac targeted custom panel.ResultsThe hCSC-supplemented hECTs displayed a twofold higher developed force vs. hCM-only controls by day 6, with approximately threefold higher developed stress and maximum rates of contraction and relaxation during pacing at 0.75 Hz. The spontaneous beat rate characteristics were similar between groups, and hCSC supplementation did not adversely impact beat rate variability. The increased contractility persisted through days 8 and 10, albeit with some decrease in the magnitude of the difference of the force by day 10, but with developed stress still significantly higher in hCSC-supplemented hECT; these findings were confirmed with multiple hCSC and hCM cell lines. The force-frequency relationship, while negative for both, control (− 0.687 Hz− 1; p = 0.013 vs. zero) and hCSC-supplemented (− 0.233 Hz− 1;p = 0.067 vs. zero) hECTs, showed a significant rectification in the regression slope in hCSC-supplemented hECT (p = 0.011 vs. control). Targeted gene exploration (59 genes) identified a total of 14 differentially expressed genes, with increases in the ratios of MYH7/MHY6, MYL2/MYL7, and TNNI3/TNNI1 in hCSC-supplemented hECT versus controls.ConclusionsFor the first time, hCSC supplementation was shown to significantly improve human cardiac tissue contractility in vitro, without evidence of proarrhythmic effects, and was associated with increased expression of markers of cardiac maturation. These findings provide new insights about adult cardiac stem cells as contributors to functional improvement of human myocardium.

1178Unsuspected role of the cardiac PKA type I in excitation-contraction coupling and in heart failure development

Abstract The cAMP-dependent protein kinase (PKA) consists of two regulatory (R) and two catalytic (C) subunits and comprises two subtypes, PKAI and PKAII, defined by the nature of their regulatory subunits, RIα and RIIα respectively. Whereas PKAII is thought to play a key role in β-adrenergic (β-AR) regulation of cardiac contractility, the function of PKAI is unclear. To address this question, we generated mice with cardiomyocyte-specific and conditional invalidation of the RIα subunit of PKA. Tamoxifen injection in 8 weeks-old mice resulted in a &gt;70% decrease in RIα protein without modification of other PKA subunits, which was associated with ∼2-fold increased basal PKA activity in RIα-KO mice (p&lt;0.05, N=6/group). This translated into enhanced cardiac contraction and relaxation, as observed in vivo by increased fractional shortening and E-wave velocity (p&lt;0.05, N=10/group) and ex vivo by increased LV pressure and maximal rate of contraction and relaxation (p&lt;0.05, N=9/group). L-type Ca2+ current density was increased in ventricular myocytes from RIα-KO, and β-AR stimulation was decreased by ∼50% (p&lt;0.05, n=38 cells for WT, and, n=40 for RIα-KO). Consistently, Ca2+ transients amplitude and relaxation kinetics were increased, along with increased occurrence of Ca2+ sparks and waves (p&lt;0.05, n=44 cells for WT, and, n=50 for RIα KO). Phosphorylation of Ca2+ channels (CaV1.2), PLB, RyR2 and cMyBP-C at PKA sites was increased &gt;2-fold (p&lt;0.05, N=6/group) in RIα KO without modification of total protein expression. With age, these mice developed a congestive heart failure (HF) phenotype with massive hypertrophy and fibrosis which eventually led to death in 50% of RIα-KO mice at 50 weeks (versus 0% in WT, p&lt;0.01). These results reveal a previously unsuspected role of PKA type I in cardiac excitation-contraction coupling and HF.

Tyrosine nitration of mitochondrial proteins during myocardial ischemia and reperfusion.

Myocardial ischemia reperfusion is associated with mitochondrial dysfunction and increased formation of reactive oxygen/nitrogen species. The main purpose of this study was to assess the role of tyrosine nitration of mitochondrial proteins in postischemic contractile dysfunction known as myocardial stunning. Isolated Langendorff-perfused rat hearts were subjected to 20-min global ischemia followed by 30-min reperfusion. The reperfused hearts showed marked decline in left ventricular developed pressure, maximal rate of contraction (+dP/dt), and maximal rate of relaxation (-dP/dt). Immunofluorescence and ELISA assays demonstrated enhanced protein tyrosine nitration in reperfused hearts. Using two-dimensional gel electrophoresis and MALDI-TOF/TOF mass spectrometry, eight mitochondrial proteins were identified to be nitrated after ischemia reperfusion. These proteins are crucial in mitochondrial electron transport, fatty acid oxidation, tricarboxylic acid cycle, ATP synthesis, and control of high-energy phosphates. The proteome data also indicated reduced abundance in several of nitrated proteins. The results suggest that these changes may contribute to inhibition of aconitase activity but are unlikely to affect electron transport chain activity. Whether tyrosine nitration of mitochondrial proteins can be considered the contributing factor of postischemic contractile dysfunction remains to be explored.

Monitoring Long-term Mangrove Shoreline Changes along the Northern Coasts of the Persian Gulf and the Oman Sea

Generally, investigating changes in mangrove shorelines is an important step to evaluate whether mangrove ecosystems are expanding or contracting. In this study, the rates of change of mangrove boundaries were investigated along the coasts of the Persian Gulf and the Oman Sea, over a 30-year period. Seaward edges of mangrove forests were extracted from Landsat images of the years 1986, 2000 and 2016 and the Digital Shoreline Analysis System (DSAS) Software was used to implement the Linear Regression Rate (LRR) method to quantify the rates of boundary changes. On average, areas that experienced boundary expansion progressed by 2.55 m yr-1 and those that experienced contraction regressed by -0.38 m yr-1. The maximum rate of expansion was 25.91 m yr-1 and the maximum rate of contraction was -22.45 m yr-1. Mangroves located on the coasts of the Persian Gulf exhibited differential rates of progression and regression at their borders, with expansion rates increasing in an eastward direction toward the coasts of the Oman Sea. However, on the eastern coasts of the Oman Sea, mangroves are characterized by contraction and erosion.

The cAMP-dependent protein kinase type I regulates cardiac excitation-contraction coupling

The cAMP-dependent protein kinase (PKA) consists of two regulatory (R) and two catalytic (C) subunits and comprises two subtypes, PKAI and PKAII, defined by the nature of their regulatory subunits, RIα and RIIα respectively. Whereas PKAII is thought to play a key role in β-adrenergic (β-AR) regulation of cardiac contractility, the function of PKAI is unclear. To address this question, we generated mice with cardiomyocyte-specific and conditional invalidation of the RIα subunit of PKA. Tamoxifen injection in 8 weeks-old mice resulted in a > 70% decrease in RIα protein without modification of other PKA subunits, which was associated with ∼2-fold increased basal PKA activity in RIα-KO mice ( P < 0.05, N = 6/group). This translated into enhanced cardiac contraction and relaxation, as observed in vivo by increased fractional shortening and E-wave velocity ( P < 0.05, N = 10/group) and ex vivo by increased LV pressure and maximal rate of contraction and relaxation ( P < 0.05, N = 9/group). L-type Ca 2+ current density was increased in ventricular myocytes from RIα-KO, and β-AR stimulation was decreased by ∼50% ( P < 0.05, N = 38 cells for WT, and, N = 40 for RIα-KO). Consistently, Ca 2+ transients amplitude and relaxation kinetics were increased, along with increased occurrence of Ca 2+ sparks and waves ( P < 0.05, N = 44 cells for WT, and, N = 50 for RIα KO). Phosphorylation of Ca 2+ channels (CaV1.2), PLB, RyR2 and cMyBP-C at PKA sites was increased > 2-fold ( P < 0.05, N = 6/group) in RIα KO without modification of total protein expression. With age, these mice developed a congestive heart failure (HF) phenotype with massive hypertrophy and fibrosis which eventually led to death in 50% of RIα-KO mice at 50 weeks (versus 0% in WT, P < 0.01). These results reveal a previously unsuspected role of PKA type I in cardiac excitation-contraction coupling and HF.

STUDY OF THE PHARMACOLOGICAL ACTIVITY OF LOWMOLECULAR ARGINASE II SELECTIVE INHIBITOR USING A MODEL OF MONOCROTALINE-INDUCED PULMONARY HYPERTENSION

The aimof the present work was to study the pharmacological activity of a low-molecular arginase II selective inhibitor (low-molecular compound with laboratory code ZB49) with the chemical formula 2-{1-[3-(3-[chloroisoxazole-5-yl) propyl] piperidin-4-yl}-6-(digibroxyboryl) norleucine dihydrochloride) using a model of monocrotaline-induced pulmonary hypertensionMaterials and methods.The work was performed on 40 adult male Wistar rats weighing 180– 220 g. The simulation of monocrotaline pulmonary hypertension was performed on 20 animals using a subcutaneous injection of an alcohol-aqueous solution of monocrotaline (MCT) at a dose of 60 mg/kg in a volume of 0.5 ml per animal. 7 days after the MCT injection, the administration of the studied pharmaceutical substance (PS) (laboratory code ZB49) was started at a dose of 5 mg/kg. ZB49 was administered intragastrically, once a day with the administration duration of 21 days.Results.Under the intragastric FS ZB49 administration at a dose of 5 mg/kg, a statistically significant decrease in the coefficient of endothelial dysfunction, systolic right ventricle pressure (SRVP), average the right ventricle pressure (ARVP), diastolic right ventricle pressure (DRVP), maximum contraction rate (dP/dt max) and minimum contraction rate (dP/dt min) was established at the background of the simulation of monocrotaline-induced pulmonary hypertension. At the same time, a statistically significant positive effect of ZB49 on the blood gas composition was established.Conclusion.The study has confirmed the possibility of using arginase inhibitors to prevent the development of endothelial dysfunction and the disorders of nitric oxide metabolism in pulmonary arterial hypertension. Among the substances of this group, arginase II selective inhibitors should be considered as the most promising.Conflict of interest: the authors declare no conflict of interest.

Linggui Zhugan Decoction (苓桂术甘汤) Inhibits Ventricular Remodeling after Acute Myocardial Infarction in Rats by Suppressing TGF-β1/Smad Signaling Pathway

To investigate the inhibitory effect of Linggui Zhugan Decoction (LZD, ) on the ventricular remodeling (VR) after acute myocardial infarction (AMI) and related mRNA and proteins expression in transforming growth factor-beta 1 (TGF-β1)/Smad signaling pathway, and explain its putative mechanism. A VR model was generated by ligation of coronary artery in mice. Two weeks after surgery, 60 mice were randomly divided into the model group, the sham-operation group (distilled water), the positive control group (2.4 mg/kg simvastatin), and the low-, medium- and high-dose LZD groups (2.1, 4.2, 8.4 g crude drug/kg, respectively) by a random number table, 10 mice in each group. Mice in each group was treated for 4 weeks. Changes of hemodynamics indices and cardiac weight index were detected by the PowerLab data acquisition and analysis recording instrument. Morphology changes of myocardial tissue were observed by hematoxylin-eosin and Masson staining. The expressions of TGF-β1, Smad2, Smad3, p-Smad2 and p-Smad3 in myocardial tissue were detected by Western blotting. The mRNA expressions of TGF-β1, Smad2 and Smad3 were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expressions of matrix metalloprotein 2 (MMP2), MMP9, collagen I and collagen III were observed by immunohistochemical methods. VR mice showed significant dysfunction in hemodynamic indices and cardiac structure and function. Compared with the shamoperation group, myocardial tissue damage, interstitial fibrosis occurred in the model mice, left ventricular systolic pressure (LVSP), left ventricular pressure maximum contraction rate (+dp/dtmax) and left ventricular pressure maximum relaxation rate (-dp/dtmax) decreased significantly (all P<0.01), while left ventricular end-diastolic pressure (LVEDP), cardiac weight index and left ventricular weight index elevated significantly, meanwhile TGF-β1, p-Smad2, p-Smad3, Smad2, Smad3, MMP2, MMP9, collagen I, collagen III protein expressions in myocardial tissue and TGF-β1, Smad2 and Smad3 mRNA expressions increased significantly (all P<0.01). Compared with the model group, LZD could significantly improve the pathological changes of myocardial tissue, increase LVSP, +dp/dtmax and -dp/dtmax, lower LVEDP, reduce the whole heart weight index and left ventricular weight index and inhibit the over-expressions of TGF-β1, p-Smad2, p-Smad3, Smad2, Smad3, MMP2, MMP9, collagen I and collagen III proteins in myocardial tissue and mRNA expressions of TGF-β1, Smad2 and Smad3 (P<0.05 or P<0.01). LZD can significantly suppress VR induced by AMI, and its underlying mechanism may be associated with its inhibitory effect on the TGF-β1/Smad signaling pathway.

Impact of recombinant apolipoprotein A-I on myocardial function in experiment

Background. It was shown earlier that high-density lipoproteins of rat blood plasma increased the frequency and strength of contraction of an isolated rat heart. The main protein component of high-density lipoproteins, apolipoprotein A-I, isolated from human blood plasma, increased the force of cardiac contractions, with little effect on the frequency. A method for obtaining recombinant apolipoprotein A-I developed at the Institute of Biochemistry allows for facilitating the research into cardiotropic properties of this protein.Aim. The purpose of this experiment was to study the effect of recombinant apolipoprotein A-I on the performance of an isolated rat heart and to compare it with the action of native apolipoprotein A-I.Methods. The experiment was performed on Wistar male rats weighing 230–250 g. Isolated hearts of the rats were routinely perfused retrograde, and isovolume pressure in the left ventricle was measured. Recombinant apolipoprotein A-I was obtained in E. coli cells in the form of a chimeric polypeptide followed by the conversion of protein into a mature form of recombinant apolipoprotein A-I.Results. It was shown that recombinant apolipoprotein A-I with a concentration of 20 μg/ml caused a stable increase in pressure in the left ventricle, while the magnitude of the coronary flow and heart rate changed insignificantly. The maximum inotropic effect was registered for 20 min from the beginning of perfusion and amounted to 147.5% relative to the reference values. It was found out that in the presence of recombinant apolipoprotein A-I, the maximum rate of contraction of the left ventricle increased. At the same time, the diastole had a tendency to increase and was larger in comparison with the initial data at 10 and 20 minutes of perfusion.Conclusion. The recombinant apolipoprotein A-I under study has cardiotonic properties similar to its native form. However, the mechanism for implementing the inotropic effect requires further study.Received 3 September 2018. Revised 8 October 2018. Accepted 11 October 2018.Funding: The study did not have sponsorship.Conflict of interest: Authors declare no conflict of interest.Author contributionsConception and study design: A.R. Kolpakov, R.A. KnyazevData collection and analysis: N.V. Trifonova, A.V. Ryabchenko, M.V. KotovaCritical revision of the article: R.A. KnyazevDrafting the article R.A. KnyazevCritical revision of the article: A.R. Kolpakov, L.M. Polyakov Final approval of the version to be published: R.A. Knyazev, N.V. Trifonova, A.V. Ryabchenko, M.V. Kotova, A.R. Kolpakov, L.M. Polyakov

Study on the Thermal Contraction Behaviors of Mg and Al

By using a device which could achieve the 1-Dimensional shrinkage instead of 3D shrinkage of the casting during the solidification and cooling, the cooling curves and the relationship between the shrinkage / temperature and time were investigated. Then, the thermal shrinkage behaviors of pure Mg and Al ingots were obtained. As a result, the characterization of the thermal shrinkage behavior of Mg and Al was systematically investigated. The results indicate that the contraction rate of pure Mg ingot increases with the increase of growth rate of dendrites in quantity during solidification. The maximum contraction rate νl, max will be reached when the formationof primary dendrite ends, and the value of νl, max is 1.12×10-2 mm·s-1. However, the shrinkage will not be present until the solid state cooling starting for the pure Al ingot. The contraction of pure Mg ingot in solid state can be divided into two stages: high temperature solid shrinkage stage and low temperature solid shrinkage stage. And the rate of shrinkage firstly increases then decreases with the temperature dropping at the stage of high temperature solid shrinkage. The rate of solid shrinkage of pure Al ingot is present at the beginning of solid-state cooling. And its value is 9.69×10-3 mm·s-1, which is more than 3 times of that of pure Mg ingot. The shrinkage behaviors of both pure Mg and Al ingots tend to be uniform shrinkage when the temperature is below 400°C.

Phrenic nerve stimulation protects against mechanical ventilation-induced diaphragmatic dysfunction through myogenic regulatory factors

Objective: To explore the protective effect of electrical stimulation of phrenic nerve on diaphragmatic function during mechanical ventilation. Methods: Forty healthy adult SD rats were randomly divided into 5 groups: blank control group (BC), spontaneous breathing group (SB), electrical stimulation group (ES), mechanical ventilation group (MV), and electrical stimulation and mechanical ventilation group (MS). The rats in each group were treated for 18 h except for the BC group. After treatment, the diaphragm muscle tissue was obtained and the diaphragm contractility including peak-to-peak value(Vpp) and maximum rate of contraction(+ dT/dt max) were measured. Expression of MyoD and myogenin were detected. Results: Except for the ES and the MS groups, there was a significant difference for peak-to-peak value (Vpp) between each 2 groups (P<0.05). Expression levels of MyoD in treatment groups were also significantly different (P<0.05). Expressions of MS(Q-PCR 2(-ΔΔCt) value: 11.66±2.80) and MV(Q-PCR 2(-ΔΔCt) value: 40.89±24.71) in the treatment group were significantly different (P<0.05). The expression of myogenin in the MS and the MV groups were significantly different from those of the BC group(P<0.05), however there was no significant difference between the MS(Q-PCR 2(-ΔΔCt) value: 2.58±2.75) and the MV group(Q-PCR 2(-ΔΔCt) value: 1.63±0.71). Conclusions: Electrical stimulation of the phrenic nerve can change the expression level of MyoD and myogenin to offset mechanical ventilation induced diaphragmatic function damage, and therefore plays a protective effect on the diaphragm.

Doxorubicin-Induced Disturbances of Cardiomyocyte Contractile Activity

The disturbances of contractile activity of rat neonatal cardiomyocytes under the influence of anthracycline antibiotics, in particular, doxorubicin, and the possibility of antioxidant correction of these disorders with curcumin were investigated. Also, the role of changes in the level of mitochondrial membrane potential in the contractile activity of cardiomyocytes was shown. It has been revealed that doxorubicin causes significant changes in all contraction parameters compared with control, namely: an increase in the frequency of spontaneous contractions, rhythm disturbance, a decrease in the amplitude and percentage of cell shortening, and an increase in the maximum rate of contraction and relaxation. Co-incubation with doxorubicin and curcumin caused a significant decrease in the frequency of spontaneous contractions (3 times), the restoration of their rhythm, an increase in amplitude (2-fold), the percentage of the cell shortening relative to the previous value, in the maximum contraction rate (1.8 times) and the rate of relaxation (by 16%), without significant changes in the duration of these processes compared with monoincubation with doxorubicin. In the study of mitochondrial membrane potential of neonatal cardiomyocytes by fluorescence method, a significant decrease in the intensity of doxorubicin-induced mitochondrial staining (1.7 times compared to control) was detected. Co-incubation of cells with curcumin and doxorubicin resulted in a significant rise in the fluorescence intensity of mitochondria (2.2 fold compared with doxorubicin alone).

Effects of epinephrine exposure on contractile performance of compact and spongy myocardium from rainbow trout (Oncorhynchus mykiss) during hypoxia

Hypoxia results in elevated circulating epinephrine for many fish species, and this is likely important for maintaining cardiac function. The aims of this study were to assess how hypoxia impacts contractile responses of ventricular compact and spongy myocardium from rainbow trout (Oncorhynchus mykiss) and to assess how and if epinephrine may protect myocardial performance from a depressive effect of hypoxia. Work output and maximum contraction rate of isolated preparations of spongy and compact ventricular myocardium from rainbow trout were measured. Tissues were exposed to the blood PO2 that they experience in vivo during environmental normoxia and hypoxia and also to low (5nM) and high (500nM) levels of epinephrine in 100% air saturation (PO2 20.2kPa) and during hypoxia (PO2 2kPa, 10% air saturation). It was hypothesized that hypoxia would result in a decrease in work output and maximum contraction rate in both tissue types, but that epinephrine exposure would mitigate the effect. Hypoxia resulted in a decline in net work output of both tissue types, but a decline in maximum contraction rate of only compact myocardium. Epinephrine restored the maximum contraction rate of compact myocardium in hypoxia, appeared to slightly enhance work output of only compact myocardium in air saturation but surprisingly not during hypoxia, and restored net work of hypoxic spongy myocardium toward normoxic levels. These results indicate hypoxia has a similar depressive effect on both layers of ventricular myocardium, but that high epinephrine may be important for maintaining inotropy in spongy myocardium and chronotropy in compact myocardium during hypoxia.

Non-singular and cyclic universe from the modified GUP

In this paper, we investigate the effects of a new version of the generalized uncertainty principle (modified GUP) on the dynamics of the Universe. As the modified GUP will modify the relation between the entropy and area of the apparent horizon, it will also deform the Friedmann equations within Jacobson's approach. We explicitly find these deformed Friedmann equations governing the modified GUP-corrected dynamics of such a Universe. It is shown that the modified GUP-deformed Jacobson's approach implies an upper bound for the density of such a Universe. The Big Bang singularity can therefore also be avoided using the modified GUP-corrections to horizons' thermodynamics. In fact, we are able to analyze the pre Big Bang state of the Universe. Furthermore, the equations imply that the expansion of the Universe will come to a halt and then will immediately be followed by a contracting phase. When the equations are extrapolated beyond the maximum rate of contraction, a cyclic Universe scenario emerges.