Three indexes developed originally to assess left ventricular contractile performance were applied instead to the right ventricle (RV) in 11 conscious dogs: the relation between stroke work and end-diastolic volume (EDV), termed the preload recruitable stroke work (PRSW) relation; the end-systolic pressure-volume (ESPV) relation; and the maximum dP/dt (dP/dtmax)-EDV relation. The reproducibility, inotropic sensitivity, chronotropic sensitivity, and afterload sensitivity of these RV relations were compared. RV volume was determined with an ellipsoidal shell subtraction model from orthogonal dimensions measured by sonomicrometry. RV transmural pressure was measured with micromanometers. After autonomic blockade, preload was varied by repeated, transient vena caval occlusions before and during partial occlusion of the main pulmonary artery, after release of the pulmonary arterial occlusion, after calcium infusion, and over a range of heart rates induced by atrial pacing. The slope and volume-axis ...
TY - JOUR. T1 - Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C during Increased Pacing Frequency or β1-Adrenergic Stimulation. AU - Tong, Carl W.. AU - Wu, Xin. AU - Liu, Yang. AU - Rosas, Paola C.. AU - Sadayappan, Sakthivel. AU - Hudmon, Andy. AU - Muthuchamy, Mariappan. AU - Powers, Patricia A.. AU - Valdivia, Héctor H.. AU - Moss, Richard L.. PY - 2015/5/4. Y1 - 2015/5/4. N2 - Background-Mammalian hearts exhibit positive inotropic responses to β-adrenergic stimulation as a consequence of protein kinase A-mediated phosphorylation or as a result of increased beat frequency (the Bowditch effect). Several membrane and myofibrillar proteins are phosphorylated under these conditions, but the relative contributions of these to increased contractility are not known. Phosphorylation of cardiac myosin-binding protein-C (cMyBP-C) by protein kinase A accelerates the kinetics of force development in permeabilized heart muscle, but its role in vivo is unknown. Such understanding is ...
The end-systolic elastance (Ees), the slope of the end-systolic pressure-volume relationship (ESPVR), has been used as an index of cardiac contractility. Although recent studies challenged the initial concept1 2 of linear and load-insensitive ESPVR by demonstrating contractility-dependent curvilinearity3 4 and load-dependence,5 6 Ees is still a powerful index to assess the inotropic state in experimental as well as clinical settings.7 8 9 10 The technical difficulties in measuring this index, however, prevent its widespread clinical acceptance. Difficulties include the need for a precise high-fidelity left ventricular (LV) volume curve as well as the need for multiple pressure-volume (P-V) loops under various loading conditions. Introduction of the conductance catheter9 11 12 and of the concept of a hydromotive pressure source13 14 for single-beat Ees estimation has partly solved these difficulties. Mirsky et al15 16 developed a single-beat method to assess myocardial contractility by fitting a ...
TY - JOUR. T1 - Myocardial contraction and relaxation. Role of anesthesia in depression and recovery during controlled regional ischemia. AU - Behrenbeck, T.. AU - Quasha, A. L.. AU - Tinker, J. H.. AU - Ritman, E. L.. PY - 1979/1/1. Y1 - 1979/1/1. UR - http://www.scopus.com/inward/record.url?scp=17544402207&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=17544402207&partnerID=8YFLogxK. M3 - Article. AN - SCOPUS:17544402207. VL - 27. SP - 671A. JO - Journal of Investigative Medicine. JF - Journal of Investigative Medicine. SN - 1081-5589. IS - 4. ER - ...
Journal of Diabetes Research is a peer-reviewed, Open Access journal that publishes research articles, review articles, and clinical studies related to type 1 and type 2 diabetes. The journal welcomes submissions focusing on the epidemiology, etiology, pathogenesis, management, and prevention of diabetes, as well as associated complications, such as diabetic retinopathy, neuropathy and nephropathy.
The present study provides strong evidence for a dual coupling of β2-AR to Gs and Gi protein at skeletal muscle, with a significant impact on muscle inotropic state. Of more importance, the secondary coupling of β2-AR to Gi protein seems to be indirect and dependent on extracellular degradation of cAMP into adenosine, which in turn activates muscle A1 adenosine receptors.. By studying the time course of clenbuterol and fenoterol effects on diaphragm twitch contraction, here we show that the well established β2-AR positive inotropism (Bowman and Nott, 1969) is attenuated after prolonged exposure (,30 min) to agonists (Figs. 1 and 2). At high concentrations of β2-AR agonists, the decline phase of inotropic effect was so intense that it abolished the positive inotropism.. The ability of PTX to attenuate the descending phase of β2-AR positive inotropism (Fig. 3) supports the idea of dual coupling of β-AR to Gs and Gi proteins, which seems to depend on the concentration and/or exposure time to ...
The twitch force (Ft)-interval relation of cardiac muscle reflects recovery of calcium release from the sarcoplasmic reticulum (SR). The calcium content of the SR is thought to be reflected by force developed during a contracture (Fc), induced by rapid cooling to near 0 degrees C. In right ventricular trabeculae of rat, under control conditions, the Ft-interval relation consisted of recovery of Ft to steady state (early recovery), followed by a secondary increase of Ft up to a maximum at an interval of approximately 100 seconds (rest potentiation) and a decline of Ft at intervals greater than 100 seconds (rest depression). The mechanisms that may underlie recovery of force after the last twitch at short intervals are 1) time-dependent transport of Ca2+ from the uptake compartment of the SR to the release compartment, 2) recovery of slow inward Ca2+ current during the action potential, and 3) recovery of the Ca2+ release channels in the SR. The Fc-interval relation was similar to the Ft-interval ...
Objectives: This study sought to determine significance of S100A1 genetically-targeted therapy in human failing myocardium focusing on the key pathological features emanating from contractile dysfunction and negative force-frequency response (FFR), blunted contractile reserve, susceptibility to arrhythmogenic Ca2+ leakage and impaired energy homeomostasis in failing ventricular cardiomyocytes.. Background: One pillar of heart failure (HF) is the depletion of the calcium (Ca2+) sensor protein S100A1 driving progressive deterioration of cardiac performance and transition to failure. Repairing this molecular defect by genetically-targeted S100A1 replacement in preclinical studies reversed the disease by restoring cardiomyocyte Ca2+ handling.. Methods and Results: S100A1 genetically-targeted therapy of isolated human failing cardiomyocytes (HFCMs) employing the human S100A1 cDNA both reversed contractile dysfunction and negative FFR due to normalized S100A1 protein expression. Therapeutic effects of ...
In this study, we provide two novel findings. First, we demonstrated that ISO is able to reduce force development without affecting the intracellular Ca2+ transient. For the first time, we show that ISO decreased Fmax and increased Ca50 of the steady-state force-Ca2+ relation in individual muscles, both before and after they were chemically skinned. Second, we demonstrated the ability of HNO donors such as NCA to rescue force development in ISO-treated muscles by virtue of their sensitizing action to Ca2+ at the myofilament level. This study extended the results from previous investigations on the effect of ISO on myocardial contractility while deepening our understanding of how ISO may dampen myocardial function.. The myofilament desensitizing effect of ISO (and/or sevoflurane) has been shown by a number of prior studies in intact cardiac muscles and myocytes (Hanley and Loiselle, 1998; Jiang and Julian, 1998; Graham et al., 2005). ISO may decrease myofilament Ca2+ responsiveness by 1) directly ...
Omecamtiv mecarbil (AMG 423, CK-1827452) is a novel small molecule that increases cardiac contractility by selectively and directly activating the enzymatic domain of cardiac myosin heavy chain, the force-generating motor protein of the cardiac sarcomere. This is a randomized, placebo-controlled, multicenter, phase 2 study, consisting of a dose escalation phase to select 1 of 3 omecamtiv mecarbil oral formulations in 2 dose escalation cohorts, followed by an expansion phase to evaluate 20 weeks of administration of the selected omecamtiv mecarbil formulation at 2 target dose levels, compared with placebo ...
Progressive deterioration of cardiac contractility is a central feature of congestive heart failure (CHF) in humans. In this report we review those studies that have addressed the idea that alterations of intracellular calcium (Ca(2+)) regulation is primarily responsible for the depressed contractility of the failing heart. The review points out that Ca(2+)transients and contraction are similar in non-failing and failing myocytes at very slow frequencies of stimulation (and other low stress environments). Faster pacing rates, high Ca(2+)and beta-adrenergic stimulation reveal large reductions in contractile reserve in failing myocytes. The underlying cellular basis of these defects is then considered. Studies showing changes in the abundance of L-type Ca(2+)channels, Ca(2+)transport proteins [sarcoplasmic reticulum Ca(2+)ATPase (SERCA2), phospholamban (PLB), Na(+)/Ca(2+) exchanger (NCX)] and Ca(2+) release channels (RYR) in excitation-contraction coupling and Ca(2+)release and uptake by the sarcoplasmic
During further development the ability of sarcoplasmic reticulum to accumulate Ca2+ increases and there is a progressive maturation of Ca2+ release from the
Genetically manipulated animals like mice or rabbits play an important role in the exploration of human cardiovascular diseases. It is therefore important to identify animal models that closely mimic physiological and pathological human cardiac function. In-vivo phase contrast cardiovascular magnetic resonance (CMR) was used to measure regional three-directional left ventricular myocardial motion with high temporal resolution in mice (N=18), rabbits (N=8), and humans (N=20). Radial, long-axis, and rotational myocardial velocities were acquired in left ventricular basal, mid-ventricular, and apical short-axis locations. Regional analysis revealed different patterns of motion: 1) In humans and rabbits, the apex showed slower radial velocities compared to the base. 2) Significant differences within species were seen in the pattern of long-axis motion. Long-axis velocities during systole were fairly homogeneously distributed in mice, whereas humans showed a dominant component in the lateral wall and rabbits
Cardiovascular disease generally refers to conditions that involve narrowed or blocked blood vessels that can lead to a heart attack, chest pain (angina) or stroke. Diseases under the cardiovascular disease umbrella include blood vessel diseases, such as coronary artery disease; heart rhythm problems (arrhythmias); and heart defects youre born with (congenital heart defects), among others.. Atrial fibrillation (AF, or A-fib) is a disorder in which the normally regular and coordinated contraction pattern of the hearts two small upper chambers, or the atria, becomes irregular and uncoordinated. The irregular contraction pattern associated with AF causes blood to pool in the atria, predisposing the formation of clots potentially resulting in stroke. In addition, AF increases the risk of stroke and may also contribute to worsening heart failure.. AF is considered an epidemic cardiovascular disease. The estimated number of individuals with AF globally in 2010 was 33.5 million. According to the ...
Taken together, our data suggest that aging and obesity compromise cardiac contractile function possibly via phosphorylation of Akt, eNOS and stress signaling-associated O2(-) release.
TY - JOUR. T1 - The power of metabolism - Linking energy supply and demand with cardiac contractile function. AU - Schwarzer, Michael. AU - Doenst, Torsten. AU - Des Rosiers, Christine. AU - Glatz, Jan F. C.. PY - 2019/4/1. Y1 - 2019/4/1. U2 - 10.1016/j.bbadis.2019.02.006. DO - 10.1016/j.bbadis.2019.02.006. M3 - Editorial. VL - 1865. SP - 725. EP - 727. JO - Biochimica et Biophysica Acta-Molecular Basis of Disease. JF - Biochimica et Biophysica Acta-Molecular Basis of Disease. SN - 0925-4439. IS - 4. ER - ...
in Computer Methods & Programs in Biomedicine (2013), 109(2), Estimation of ventricular contractility and ventricular arterial coupling is clinically important in diagnosing and treating cardiac dysfunction in the critically ill. However, experimental assessment of ... [more ▼]. Estimation of ventricular contractility and ventricular arterial coupling is clinically important in diagnosing and treating cardiac dysfunction in the critically ill. However, experimental assessment of indexes of ventricular contractility, such as the end-systolic pressure-volume relationship, requires a highly invasive maneuver and measurements that are not typical in an intensive care unit (ICU). This research describes the use of a previously validated cardiovascular system model and parameter identification process to evaluate the right ventricular arterial coupling in septic shock. Model-based ventricular arterial coupling is defined by the ratio of the end systolic right ventricular elastance (E(esrvf)) over ...
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Mechanistic studies will provide insight into how CCM improves LV function. We observed that CCM did not just augment contractility at the septal and adjacent walls where the 2 electrodes were placed; rather, systolic function was enhanced in the entire LV including the free-wall segments. Therefore, in the long run, the concerted force in all 6 regions of the LV would contribute to the improvement of LV global systolic function, resulting in LV reverse remodeling and reduction of mitral regurgitation. These findings are completely consistent with a recent report concerning CCM-induced reverse molecular remodeling (8). When HF was experimentally induced in animals, there was a switch in expression of a host of genes from a normal adult genotype to a fetal genotype indicative of myocardial pathology. In such animals, Imai et al. (8) showed that within hours of initiating CCM signal delivery, there was a reversion back towards a normal genotype only in the region of the heart where signals were ...
In this study we will investigate a method combining transoesophageal echocardiography and non-invasive finger arterial blood pressure waveforms to non-invasively construct pressure-volume (P-V) loops to describe the end-systolic pressure-volume relations in the heart. This may provide a method to obtain more insight on cardiac contractile function and the interaction of the heart with the vasculature during surgery ...
Experiments with selective agonists and antagonists of purinoceptors allowed us to evaluate the subtype of P2X receptors. We showed that the myocardium of 14-100-day-old rats contains functionally active P2X1 receptors. These receptors are involved in the realization of the positive inotropic effect of the atria and ventricles. Selective P2X1 receptor agonist β,γ-methylene-ATP induced a dose-dependent increase in the strength of atrial and ventricular contractions. P2X1 receptor antagonist TNP-ATP abolished the effect of the agonist in rats of all age groups.
High performance computing in multiscale modeling cardiac contraction: Bridging proteins to cells to whole heart . J. Jeremy Rice. Computational Biology Center Thomas J. Watson Research Center [email protected] Motivation. Slideshow 88620 by HarrisCezar
Quantification of cardiovascular flow and motion is essential in the diagnosis, treatment and follow-up of cardiovascular disease. The accuracy and quantification of many imaging methods used in this field have important shortfalls, however, that result from limitations in spatial and temporal dimensions. Improvement in application of these methods requires an in-depth understanding of the technical and perceptual aspects that contribute to errors in their use.. Visual assessment of echocardiographic images for asynchrony in regional myocardial motion during systolic contraction is an example of the need for better definition of limitations. The discernible delay in wall motion improved from 89 ms to 71 ms by allowing side-by-side comparison to normal motion. Clinically important delays are almost certainly missed with current "eyeballing" methods. Different and more quantitative approaches to this problem have been developed. Anatomic M-mode (AMM) assesses motion along an arbitrary line within ...
Contraction and Unwinding of Cardiac Fibres. Work group of Physiology and Pharmacology, School of Agriculture, Faisalabad. The mammalian core pumping systems the our blood all over the frame by speedily maintaining the pumping move throughout fast adjustment in system metabolic expectations. A persons heart and soul performs its action without the need of sophistication. Many different experiments have most certainly been undertaken about the activities of heart and soul in strong and unhealthy regions that can be required to figure out some creative treatment plans so that you can enhance and extend activities of affected individuals. Puppy models are employed commonly in cardiac exploration to analyze and examine many types of core operations and restorative label (Nima and Paul, 2014).. http://bestessaysforsale.net/term-paper-writing-service/ Cardiac contraction and relaxations are governed by Calcium. The position of calcium for myocardial contraction slowly became obvious because of the ...
BioAssay record AID 218832 submitted by ChEMBL: Tested for beta-1-adrenergic blocking effect by measuring the ability to inhibit the positive inotropic effect of isoproterenol on the isolated right atrium of guinea pigs.
The MMC has been likened to a housekeeper. A housekeeper comes in after the feast and cleans up the place, restoring the environment. It has been suggested that the MMC may exist "to clean the digestive tract of residual food, secretions, and cellular debris."2 An increase in secretions from the stomach, gall bladder, and pancreas is also seen in conjunction with the motor activity. These secretions probably aid in the cleansing activity of the MMC and assist in preventing a buildup of bacterial populations in the small intestine. It is during the fasting state that the MMC is put into action. For many, the term fasting implies skipping meals and enduring long periods of abstinence from food. In this case the specific periodic migrating contraction pattern we are referring to takes place when significant time occurs between meals. The MMC is interrupted by eating. For example, you ate a lovely breakfast. The food spent its time in the stomach and intestine and is making its way down the canal. ...
The aim of the present study was to characterize the mechanoenergetic alterations in a rat model of LVH undergoing pressure unloading therapy using LV P-V analysis method. According to our best knowledge, this is the first study demonstrating that the regression of LVH by pressure unloading leads not only to reversed myocardial contractility augmentation and restored diastolic function, but also to maintained cardiac mechanoenergetics.. According to Laplaces law, when the pathological stimulus of sustained pressure overload emerges, the myocardial wall thickness increases to normalize wall tension (18). This maladaptive response reaction, also known LVH, is characterized by increased expression of sarcomeric proteins with subsequent enlargement of the cardiomyocytes, ECM remodeling (10), and decreased capillary density (39). The reversibility of these alterations has been already proven by numerous previous works, since they demonstrated that the regression of preestablished pathological ...
You must be wondering how all of this applies to your fat loss program. Well, let me break it down for you - with enhanced signaling strength & motor pathways, your body is going to be able to perform movement with less effort, thereby allowing the Premotor Area of your brain to start working harder. The Premotor Area is your movement planning center. By properly learning to activate your movement planning center, you can increase contractile strength by up to 30%. Pretty crazy, huh ...
Chain P. (DC)(DG)(DA)(DA)(DA)(DA)(DC)(DG)(DA)(DC)(DG)(DG)(DC)(DC)(DA)(DG)(DT)(DG)(DC)(DC) (DT)(2DA). Chain T. (DC)(DC)(DC)(TTD)(DA)(DG)(DG)(DC)(DA)(DC)(DT)(DG)(DG)(DC)(DC)(DG)(DT)(DC)(DG) (DT)(DT)(DT ...
The cardiac muscle possesses automaticity and contract spontaneously. A myogenic heart is capable of generating a cardiac contraction independent of nervous input. ...
Trabeculae are supportive tissue structures in the body. They vary in function and size based on their location in the body, but...
TY - CHAP. T1 - Negative inotropic influence of hyperosmotic solutions on cardiac muscle. AU - Wildenthal, K.. AU - Adcock, R. C.. AU - Crie, J. S.. AU - Templeton, G. H.. AU - Willerson, J. T.. PY - 1975. Y1 - 1975. N2 - In cardiac muscle, moderate degrees of hyperosmolality of the type encountered physiologically or clinically (i.e., less than 200 mosM above control) characteristically exert a positive inotropic effect, which presumably is mediated by increased Ca 2+ availability for binding to troponin. In contrast, skeletal muscle displays significant contractile depression on exposure to hyperosmotic solutions, even at mild degrees of hypertonicity. To determine whether a similar potential for hyperosmolarity induced depression also exists in cardiac muscle, right ventricular papillary muscles from cats were exposed to hypertonic solutions of mannitol or sucrose under circumstances in which positive inotropic effects were precluded by prior exposure to a bathing solution of 4.0 mM Ca 2+ and ...
Many of cTnT mutations linked to cardiomyopathies fall the TNT1 domain/N terminal tail region of unresolved high definition structure. This region (∼94-170) of cTnT is critical to Tm binding and contraction regulation. Here, the impact of the E163R mutation in cTnT-TNT1 on contractile function and tension cost was investigated using intact and skinned preparations from WT and transgenic mouse hearts. Methods: Left and right ventricular trabeculae were dissected from non-transgenic wild type (WT) and heterozygous (E163R or R92Q) mouse hearts and mounted isometrically to record twitch tension or, when skinned, Ca2+ activated force. Myofibrillar ATPase activity was measured by fluorimetric enzyme coupled assay (de Tombe and Stienen, 1995). In this thesis we aimed to assess the primary alterations of the contractile function and of tension cost caused by E163R cTnT-TNT1domain mutation, using skinned preparations or single myofibrils from WT and transgenic mouse hearts. Than we aimed to ...
The present work addressed the determination and visualization of the direction and extent of polymerization shrinkage in the light-initiated composite. Hypotheses about the light-cured composite contraction patterns are controversial. With high resolution µCT images, the displacement vector fields are examined and calculated two-dimensionally via an elastic registration algorithm using vector-spline regularization and three-dimensionally with a local rigid registration (block matching) following images segmentation (corresponding traceable fillers in composite). It appears that the light-initiated resin composites do not always shrink toward the light source. Two major contraction patterns were observed: either shrink toward the top-surface (free surface), or toward one side of the cavity wall, in which the bonding was stronger or remained intact. With the proposed methods, it is possible to describe the contraction patterns in great detail. We could demonstrate that the bonding quality to the ...
CHAPTER II: CARDIAC MECHANICS Asst. Prof. Dr. Emre Hamurtekin EMU Faculty of Pharmacy 1. 2. 3. 4. CARDIAC CYCLE CARDIAC OUTPUT DETERMINANTS of CARDIAC OUTPUT CARDIAC WORK encyclopedia.lubopitko-bg.com medical-dictionary.thefreedictionary.com • Cardiac cycle can be divided into seven phases: 1. Atrial systole 2. Isovolumic ventricular contraction 3. Rapid ventricular ejection 4. Reduced ventricular ejection 5. Isovolumic ventricular relaxation 6. Rapid ventricular filling 7. Reduced ventricular filling • Atrial systole is initiated by …………………... atrial excitation • Atrial systole follows the crest of P wave on the ECG. • Atrial contraction forces a small additional blood into the venticular chamber (atrial kick). • Ventricular systole begins with isovolumic ventricular contraction. • In isovolumic ventricular contraction, when intraventricular pressure rises, mitral valve closes. • In isovolumic ventricular contraction, aortic valve is still held closed by higher ...
Advancements in cardiovascular magnetic resonance (CMR) have made it possible to accurately assess not only standard clinical metrics such as ejection fraction (EF) and ventricular volumes, but also advanced measures of cardiac mechanics such as strain and torsion [1]-[3]. These measures of cardiac mechanics demonstrate a higher prognostic value when combined with both clinical risk factors and more traditional metrics such as ejection fraction [4]. Cine displacement encoding with stimulated echoes (DENSE) is an advanced CMR technique for measuring cardiac mechanics which encodes the displacement of the myocardium into the phase of the MR signal [5]. DENSE data can be used to reproducibly quantify cardiac mechanics, ventricular volumes, and ejection fraction [6]-[8]. Recent work has demonstrated the clinical utility of DENSE, specifically for predicting response to cardiac resynchronization therapy [9]. Despite its apparent clinical utility, DENSE has yet to see widespread adoption in clinical ...
The Frank-Starling law of the heart (also known as Starling's law and the Frank-Starling mechanism) represents the relationship between stroke volume and end diastolic volume . The law states that the stroke volume of the heart increases in response to an increase in the volume of blood in the ventricles , before contraction (the end diastolic volume), when all other factors remain constant. As a larger volume of blood flows into the ventricle, the blood stretches the cardiac muscle fibers, leading to an increase in the force of contraction. The Frank-Starling mechanism allows the cardiac output to be synchronized with the venous return, arterial blood supply and humoral length, without depending upon external regulation to make alterations. The physiological importance of the mechanism lies mainly in maintaining left and right ventricular output equality. Physiology The Frank-Starling mechanism occurs as the result of the length-tension relationship observed in skeletal muscles . As a muscle
Results: CHU significantly increased body mass (P , 0.001) compared with age-matched control rats but was without effect on relative cardiac mass. For incremental increases in left ventricular balloon volume, diastolic pressure was preserved. However, systolic pressure was significantly greater following CHU for balloon volume = 50 μl (P , 0.01) and up to 200 μl (P , 0.05). For higher balloon volumes systolic pressure was not significantly different from control. Developed pressures were correspondingly increased relative to controls for balloon volumes up to 250 μl (P , 0.05).Left ventricular free wall capillary density was significantly decreased in both epicardium (18%; P ,0.05) and endocardium (11%; P , 0.05) despite preserved coronary flow. Western blot analysis revealed no change to the expression of SERCA2a or nNOS but immuno-detectable eNOS protein was significantly decreased (P , 0.001) in cardiac tissue following chronic hypoxia in utero ...
How Digoxin (lanoxin) works: INCREASES CONTRACTILITY OF THE HEART: TECH Term, it creates a POSITIVE INOTROPIC EFFECT. The Positive INOTROPIC Effect occur secondary to the inhibition of of the sodium potassium adenosine triphosphate pump. When the actions Read More …. ...
BACKGROUND: Estimating contractility of the left ventricle with noninvasive techniques is an important yet elusive goal. Positive inotropic interventions are mirrored by smaller end-systolic volumes and higher end-systolic pressures. An increased heart rate progressively increases the force of ventricular contraction (Bowditch treppe or staircase phenomenon). AIM: To assess the feasibility of a noninvasive estimation of force-frequency relation (FFR) during pacing stress in the echo lab in patients with permanent pacemaker (PM). METHODS: Transthoracic stress pacing echocardiography was performed in 26 patients with a permanent pacemaker (age 69+/-11 years; 21 men, 5 women). Seven patients had normal function at baseline and during stress ("normals"); eight had angiographically assessed coronary artery disease (three with and five without induced ischemia with stress echo); eleven patients had dilated cardiomyopathy (DC). To build the FFR, the force was determined at different steps as the ratio ...
2015 The Authors. Victims of chlorine (Cl2) inhalation that die demonstrate significant cardiac pathology. However, a gap exists in the understanding of Cl2-induced cardiac dysfunction. This study was performed to characterize cardiac dysfunction occurring after Cl2 exposure in rats at concentrations mimicking accidental human exposures (in the range of 500 or 600 ppm for 30 min). Inhalation of 500 ppm Cl2 for 30 min resulted in increased lactate in the coronary sinus of the rats suggesting an increase in anaerobic metabolism by the heart. There was also an attenuation of myocardial contractile force in an ex vivo (Langendorff technique) retrograde perfused heart preparation. After 20 h of return to room air, Cl2 exposure at 500 ppm was associated with a reduction in systolic and diastolic blood pressure as well echocardiographic/Doppler evidence of significant left ventricular systolic and diastolic dysfunction. Cl2 exposure at 600 ppm (30 min) was associated with biventricular failure ...
in Journal of Cardiovascular Pharmacology (2005), 45(2), 144-152. This study investigated the effects of dobutamine on left ventriculoarterial (VA) coupling and mechanical efficiency in acutely ischemic pigs. Experiments were performed in 12 pigs in which vascular ... [more ▼]. This study investigated the effects of dobutamine on left ventriculoarterial (VA) coupling and mechanical efficiency in acutely ischemic pigs. Experiments were performed in 12 pigs in which vascular properties, including peripheral resistance (R-2), compliance (C), and arterial elastance (E-a), were estimated with a windkessel model, and left ventricular (LV) function by the slope (E-es) of the end-systolic pressure-volume relationship (ESPVR) and stroke work (SW). VA coupling was defined as E-es/E-a, and mechanical efficiency as SW/pressure-volume area (PVA). In all animals, the left anterior descending coronary artery was ligated after basal measures. The animals were then randomly divided into 2 groups: group CTRL (n ...
ABSTRACT: Ventricular pressure-volume area (PVA) is a specific area in the pressure-volume diagram, which represents the total mechanical energy generated by each contraction, consisting of stroke work and mechanical potential energy at end-systole. Animal experiments have shown that PVA is correlated linearly with the ventricular oxygen consumption (Vo2) per beat under a variety of loading conditions in a stable contractile state. The slope of the Vo2-PVA line has been shown to remain constant in different contractile states, implying a constant stoichiometry between Vo2 and PVA. As a first step to understand the nature of this Vo2-PVA relation, we devised a new crossbridge (CB) model to theoretically relate PVA with the total enthalpy change associated with the ATP hydrolysis for all CB cycles. One of the most important assumptions on which this model analysis depended was that the time-varying elasticity model could simulate the instantaneous pressure-volume relation. The result of this ...
MyoKardia is a clinical stage biopharmaceutical company pioneering a precision medicine approach to discover, develop and commercialize targeted therapies for the treatment of serious and rare cardiovascular diseases. MyoKardias initial focus is on the treatment of heritable cardiomyopathies, a group of rare, genetically-driven forms of heart failure that result from biomechanical defects in cardiac muscle contraction. MyoKardia has used its precision medicine platform to generate a pipeline of therapeutic programs for the chronic treatment of the two most prevalent forms of heritable cardiomyopathy-hypertrophic cardiomyopathy, or HCM, and dilated cardiomyopathy, or DCM. MyoKardias most advanced product candidate, MYK-461, is an oral small molecule designed to reduce excessive cardiac muscle contractility leading to HCM and has been evaluated in three Phase 1 clinical trials. MyoKardia is currently studying MYK-461 in the Phase 2 PIONEER-HCM trial in symptomatic, obstructive HCM (oHCM), a ...
MyoKardia is a clinical stage biopharmaceutical company pioneering a precision medicine approach to discover, develop and commercialize targeted therapies for the treatment of serious and rare cardiovascular diseases. MyoKardias initial focus is on the treatment of heritable cardiomyopathies, a group of rare, genetically-driven forms of heart failure that result from biomechanical defects in cardiac muscle contraction. MyoKardia has used its precision medicine platform to generate a pipeline of therapeutic programs for the chronic treatment of the two most prevalent forms of heritable cardiomyopathy-hypertrophic cardiomyopathy, or HCM, and dilated cardiomyopathy, or DCM. MyoKardias most advanced product candidate, MYK-461, is an oral small molecule designed to reduce excessive cardiac muscle contractility leading to HCM and has been evaluated in three Phase 1 clinical trials. MyoKardia is currently studying MYK-461 in the Phase 2 PIONEER-HCM trial in symptomatic, obstructive HCM (oHCM), a ...
Liguzinediol (LZDO) ester prodrugs 3-5 were synthesized and evaluated in vitro and in vivo for their potential use in prolonging the half-life of the parent drug LZDO (1a) in vivo. Prodrugs 3-5 were found to display a potent positive inotropic effect on the myocardium, without the risk of arrhythmia. Prodrugs 3-5 rapidly underwent enzymatic hydrolysis to release the parent compound LZDO in 1-3 h in rat liver microsomes and rat plasma. The half-life of the parent compound was prolonged after intragastric administration of prodrug 3, which was found to be a superior prodrug candidate for increasing myocardial contractility.
Small heat shock protein which functions as a molecular chaperone probably maintaining denatured proteins in a folding-competent state. Seems to have versatile functions in various biological processes. Plays a role in regulating muscle function such as smooth muscle vasorelaxation and cardiac myocyte contractility. May regulate myocardial angiogenesis implicating KDR. Overexpression mediates cardioprotection and angiogenesis after induced damage. Stabilizes monomeric YWHAZ thereby supporting YWHAZ chaperone-like activity.
In this study, we demonstrate that sodium deprivation in rats causes alterations in cardiac βAR affinity responsiveness assessed by adenylyl cyclase activity. Our data indicate that a primary mechanism is the reduction of the percentage of βARs in the high affinity conformation caused by the increased expression and activity of cardiac βARK1. Interestingly, atenolol treatment prevented the rise in βARK1 levels in the heart and improved βAR signaling.. The pivotal role of βARK1 in cardiac βAR signaling and function was first shown in transgenic mice with cardiac overexpression of this GRK.24 In that study it was shown for the first time that this regulator of βAR signaling was able (in absence of other alterations of the excitation-contractile machinery of the heart) to dampen the cardiac contractile response to βAR stimulation.24 After this initial study, many observational studies have associated increased cardiac βARK1 levels to animal and human models of cardiac dysfunction.5-10 ...
global entire cell i transients in early cardiac cells derived from mouse ESC had been reported to be the result of spontaneous Ca2 release from intracellular Ca2 outlets devoid of the triggering of membrane Checkpoint kinase inhibitor Ca2 currents. The mechanism underlying E C coupling in hESC CMs is somewhat controversial. When some reviews suggested the absence of the functional SR Ca2 retail outlet in hESC CMs and postulated that fundamentally all the i transients in these cells were a consequence of transsarcolemmal Ca2 influx via membranal Ca2 channels, others have argued to get a a lot more mature like CICR mechanism. The latter scientific studies reported the presence of a practical caffeine responsive and ryanodine delicate SR Ca2 keep in not less than a subset if not all, of the cells tested, within a related method to the hiPSCCMs studied in the existing review.. Our outcomes assistance the contribution of both the transsarcolemmal Ca2 Chromoblastomycosis influx and intracellular Ca2 ...
doppler tissue echocardiography (DTE) has been widely used in clinical practice to provide noninvasive information on regional left ventricular (LV) systolic and diastolic function (3, 16, 20, 21, 25, 27) and on filling pressures (8, 12, 14, 15, 17) and to measure mechanical synchronicity (30). By using this imaging modality, regional longitudinal myocardial tissue contraction and relaxation velocities, as well as one-dimensional strain (ε) and strain rate (SR), can be quantified and used as indexes of regional function.. The mitral annulus motion represents changes in longitudinal LV long-axis dimension, which could reflect LV volume changes. In the clinical evaluation of ventricular function, assessment of the rate of change in LV volume, rather than the absolute change, is desirable, since it is assumed that an abnormality reflected in the long-axis dimension could be evident earlier than the clinical manifestation of global LV abnormality. DTE provides this information, as it has the ...