Changes In Cardiac Contractility Research Articles

Airborne polystyrene nanoplastics exposure leads to heart failure via ECM-receptor interaction and PI3K/AKT/BCL-2 pathways

Environmental contamination has been recognized as a significant threat to human well-being, and recent findings of microplastic presence in human cardiac tissues have raised concerns. However, research on the effects of airborne nanoplastics (NPs) on cardiac physiology remains limited. We utilized a comprehensive body exposure apparatus to simulate the impact of airborne polystyrene NPs pollution, focusing on understanding how airborne NPs affect cardiac morphology and function. Following two weeks of NPs exposure, mice exhibited a 23.89 ± 8.30 % reduction in heart mass, a 20.05 ± 2.97 % decrease in heart rate as detected, and a myocardial electrical conduction block. Echocardiography showed significant changes in cardiac contractility, with increases in cardiac ejection fraction and stroke volume of 13.00 ± 3.00 % and 43.00 ± 17.00 %, respectively. In addition, histologic assessments revealed signs of ventricular hypertrophy, ventricular myocardial hypertrophy, and myocardial necrotic fibrosis. Of particular interest, our mechanistic investigations highlighted the harmful effects of NPs on cardiac structure and function, mediated through extracellular matrix (ECM) receptor interactions and the PI3K/AKT/BCL-2 signaling pathway. The insights gained provide a foundation for understanding the risks posed by airborne NPs to human cardiac health, emphasizing the need for increased vigilance and implementation of mitigation strategies in environmental management.

Detection of contractility changes in the heart from arterial blood pressure data using symmetric Projection Attractor Reconstruction

The potential for unintended drug induced changes in cardiac contractility is a major concern in medicines development. Whilst direct left ventricular pressure (LVP) measurement is the gold standard for measuring cardiac contractility in vivo, it is resource intensive and poses a welfare burden on research animals. In contrast, arterial blood pressure (BP) measurement has fewer challenges. Symmetric Projection Attractor Reconstruction (SPAR) is a signal processing technique which transforms physiological time-series signals into a corresponding visual image (‘attractor’), amplifying morphology changes within physiological waveforms. It was hypothesized that SPAR analysis of BP signals would provide a surrogate measure of cardiac contractility by specifically amplifying the maximum slope of the systolic upstroke. BP (abdominal aorta) signals obtained from beagle dogs, treated with positive and negative inotropes, were retrospectively analysed to identify signal features that correlated with the maximum upslope of the LVP signal from simultaneously acquired LVP recordings. SPAR transformation of BP signals quantified drug induced changes in the maximum slope of the systolic upstroke. We identified key SPAR metrics that provided >0.8 correlation with the LVP maximum upslope, outperforming the BP systolic upstroke alone. This was observed for all 4 different drugs, doses and time points evaluated across studies. Thus, we conclude that the SPAR measures derived from the BP signal could be used as a first pass in vivo screen to flag any risk of drug induced changes in cardiac contractility during the conduct of non-clinical medicines development, potentially reducing or replacing the need to perform direct left ventricular measurements.

Bias-Free Cardiac Monitoring Capsule.

Cardiovascular disease (CVD) remains the leading cause of death worldwide. Patients often fail to recognize the early signs of CVDs, which display irregularities in cardiac contractility and may ultimately lead to heart failure. Therefore, continuously monitoring the abnormal changes in cardiac contractility may represent a novel approach to long-term CVD surveillance. Here, a zero-power consumption and implantable bias-free cardiac monitoring capsule (BCMC) is introduced based on the triboelectric effect for cardiac contractility monitoring in situ. The output performance of BCMC is improved over 10 times with nanoparticle self-adsorption method. This device can be implanted into the right ventricle of swine using catheter intervention to detect the change of cardiac contractility and the corresponding CVDs. The physiological signals can be wirelessly transmitted to a mobile terminal for analysis through the acquisition and transmission module. This work contributes to a new option for precise monitoring and early diagnosis of CVDs.

Contractility assessment using aligned human iPSC-derived cardiomyocytes

IntroductionCardiac safety assessment, such as lethal arrhythmias and contractility dysfunction, is critical during drug development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been shown to be useful in predicting drug-induced proarrhythmic risk through international validation studies. Although cardiac contractility is another key function, fit-for-purpose hiPSC-CMs in evaluating drug-induced contractile dysfunction remain poorly understood. In this study, we investigated whether alignment of hiPSC-CMs on nanopatterned culture plates can assess drug-induced contractile changes more efficiently than non-aligned monolayer culture. MethodsAligned hiPSC-CMs were obtained by culturing on 96-well culture plates with a ridge-groove-ridge nanopattern on the bottom surface, while non-aligned hiPSC-CMs were cultured on regular 96-well plates. Next-generation sequencing and qPCR experiments were performed for gene expression analysis. Contractility of the hiPSC-CMs was assessed using an imaging-based motion analysis system. ResultsWhen cultured on nanopatterned plates, hiPSC-CMs exhibited an aligned morphology and enhanced expression of genes encoding proteins that regulate contractility, including myosin heavy chain, calcium channel, and ryanodine receptor. Compared to cultures on regular plates, the aligned hiPSC-CMs also showed both enhanced contraction and relaxation velocity. In addition, the aligned hiPSC-CMs showed a more physiological response to positive and negative inotropic agents, such as isoproterenol and verapamil. DiscussionTaken together, the aligned hiPSC-CMs exhibited enhanced structural and functional properties, leading to an improved capacity for contractility assessment compared to the non-aligned cells. These findings suggest that the aligned hiPSC-CMs can be used to evaluate drug-induced cardiac contractile changes.

Aging Reduces Cardiac Contractility by Altering Cardiac Regulatory and Contractile Proteins

Aging is associated with an increased incidence of cardiac dysfunction. We hypothesized that aging associated changes in cardiac regulatory and contractile proteins produce contractile dysfunction. We assessed regulatory and contractile protein expression as well as contractility in left ventricular cardiac muscle from Fischer F-344 rats at 6-, 18-, and 24-month of age. Age-related changes in the expression of β-MHC as well as the expression and phosphorylation of troponin I (TnI) and cardiac myosin binding C protein (MyBP-C) were assessed by Western blot. Aging was associated with an increase in the expression of β-MHC and the phosphorylation of both TnI at Ser23/24 and MyBP-C. Mechanical properties were assessed in Triton-X permeabilized anterior papillary muscle from the left ventricle from both 6- and 24-month old rats. In papillary muscle of 24-month old rats, there was a decrease in maximum Ca2+ activated force, Ca2+ sensitivity of force and the rate constant for force recovery after quick release (ktr). Additionally, cardiomyocytes were isolated from the left ventricle at 6-, 18-, and 24-month of age using a modified Langendorff system. Cardiomyocytes were then loaded with fura-2 AM to measure cytosolic calcium ([Ca2+]cyt) responses to electrical field stimulation (0.5 Hz). [Ca2+]cyt and contractile (sarcomere length shortening) responses to stimulation were simultaneously measured using an IonOptix system. In older cardiomyocytes, the amplitude of evoked [Ca2+]cyt responses was reduced while there was no difference in the kinetics of the [Ca2+]cyt transient. The extent of sarcomere length shortening as well as the rates of both shortening and relaxation were reduced. These results demonstrate that aging is associated with changes in the expression and phosphorylation of contractile and regulatory proteins, which produce changes in cardiac contractility. Supported by a Mayo CV Prospective Grant (FVB). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Correlations between heart sound components and hemodynamic variables

Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous hemodynamic index. In this study, we aimed to induce hemodynamic variations and clarify the relationship between the heart sounds and hemodynamic variables through an experimental animal study. Changes in the cardiac contractility and vascular resistance were induced in anesthetized pigs by administering dobutamine, esmolol, phenylephrine, and nicardipine. In addition, a decrease in cardiac output was induced by restricting the venous return by clamping the inferior vena cava (IVC). The relationship between the hemodynamic changes and changes in the heart sound indices was analyzed. Experimental data from eight pigs were analyzed. The mean values of the correlation coefficients of changes in S1 amplitude (ΔS1amp) with systolic blood pressure (ΔSBP), pulse pressure (ΔPP), and ΔdP/dt during dobutamine administration were 0.94, 0.96, and 0.96, respectively. The mean values of the correlation coefficients of ΔS1amp with ΔSBP, ΔPP, and ΔdP/dt during esmolol administration were 0.80, 0.82, and 0.86, respectively. The hemodynamic changes caused by the administration of phenylephrine and nicardipine did not correlate significantly with changes in the heart rate. The S1 amplitude of the heart sound was significantly correlated with the hemodynamic changes caused by the changes in cardiac contractility but not with the variations in the vascular resistance. Heart sounds can potentially provide a non-invasive monitoring method to differentiate the cause of hemodynamic variations.

Age-related changes in cardiac contractility in a mouse model of Down syndrome

Over the last couple of decades, the median survival of individuals with Down syndrome (Ds) increased from 30 to 60 years. The Ts65Dn mouse model recapitulates most of the cognitive and neural phenotypes described in Ds individuals and its use continues to expand into other fields. The Ds population is at risk for cardiovascular comorbidities. We hypothesized that contractility in Ts65Dn mice will be lower compared to controls, and differences between strains will become exacerbated with age. The aim of this study was to comprehensively access the cardiac function in the Ts65Dn model across the lifespan. Ts65Dn and C57BL/6J mice (n = 3-5) were tested at 3, 6, and 12 months of age. Left ventricular function was assessed in closed-chest mice using a microtip pressure-volume catheter (PVR-1030, Millar) which was introduced via the right carotid artery and coupled to a digital converter (ADInstruments). By transiently compressing the inferior abdominal vena cava, different preloads were induced, accessing hemodynamic assessment of the left ventricle. Finally, the heart was excised, trimmed, & weighed to assess the Fulton index. The end-diastolic pressure-volume relationship (ESPVR) increased at 12 months in Ts65Dn mice compared to controls. Comparison of the maximal velocity of pressure rise (+ dP/dt) did not differ between ages and genotypes. The maximal velocity of pressure fall (− dP/dt), however, was significantly lower in 12 months Ts65Dn compared to the 6-month group. Cardiac output (Q̇) decreased with aging in Ts65Dn mice compared to controls, therefore decreasing stroke volume (SV) and stroke work (SW). The index of arterial elastance (Ea) increased with aging in Ts65Dn mice compared to the control. Together, Ts65Dn mice have decreased systolic performance accompanied by increased contractility of the heart and increased aortic elastance, and these parameters are revealed as mice age. NIH R21HD099573 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Heart rate changes in swimming exercised 12-13-week-old white experimental rats

The aim of the study was to determine the heart rate in 12-13-week-old rats under conditions of a 6-week dosed swimming load. In general, rat swimming is considered one of the best methods for studying cardiological parameters and the adaptive capabilities of the heart. As part of our study, we ensured 12-13-weeks-old male rats to undergo dosed swimming exercises for 4 and 6 weeks, at the end of each week we studied the electrocardiographic data of rats in order to assess the dynamics of changes in the frequency of contractions in experimental groups. The rats were divided into 3 groups: 1) a control group that did not receive any load (n=6); 2) The frst study group was subjected to a daily 30-minute swimming load for 4 weeks with a weight in the amount of 3% of the body weight of the rat (n=6) attached to the tail, 3) The second study group, which was subjected to a daily 60-minute swimming exercise for 6 weeks, the weight of the load attached to the tail amounted to 4% of the weight of the rat (n=6).  Significant changes in cardiac contractility were observed only in experimental rats (30-minute exercise with a load of 3% of body weight or a 60-minute load with a load of 4% of body weight). In most rats, initial tachycardia was followed by prolonged bradycardia. The mentioned study can be considered as another step forward in the study of the pathogenetic mechanisms of pathological changes in rhythm and frequency that occur during exercise.

Diagnosis of exercise-induced cardiac fatigue based on deep learning and heart sounds

Exercised-induced cardiac fatigue (EICF) refers to an impermanent decline in systolic and diastolic function caused by high-intensity and multi-frequency exercise. Long-term EICF may lead to heart fatigue, myocardial damage, and even sudden cardiac death. However, common cardiac fatigue diagnoses rely on expensive devices or time. Further, cardiac inotropy as an essential reference has not been applied to measure cardiac fatigue. In this paper, heart sound was proposed to evaluate EICF based on its ability to reflect changes of cardiac contractility, with a specialized deep learning network designed to recognize subjects with EICF. First, heart sounds were collected by a physiological signal collection system, and a heart sound database for 20 subjects was established. Then, discrete wavelet transform and logistic regression hidden semi-Markov model were applied to denoise and segment signals respectively, and 1770 samples in total were obtained. Finally, a network unifying residual mapping and attention modules was designed to recognize heart sounds, and the accuracy, precision, and recall of the model were 98.85%, 98.94%, and 98.9% respectively. This study suggests that heart sounds combined with the deep learning model can achieve accurate and objective diagnosis, which is potential for a reliable alternative to diagnose EICF.

Real-Time Monitoring of Changes in Cardiac Contractility Using Silicon Cantilever Arrays Integrated with Strain Sensors.

This paper proposes the use of sensor-integrated silicon cantilever arrays to measure drug-induced cardiac toxicity in real time. The proposed cantilever sensors, unlike the conventional electrophysiological methods, aim to evaluate cardiac toxicity by measuring the contraction force of the cardiomyocytes corresponding to the target drugs. The surface of the silicon cantilever consists of microgrooves to maximize the alignment and the contraction force of the cardiomyocytes. This type of surface pattern also helps in the maturation of the cardiomyocytes by increasing the sarcomere length. The preliminary characterization of the cantilever sensors was performed on the cantilever surface, with the cardiomyocytes seeded with a density of 1000 cells/mm2, and the cardiac contractility was measured as a function of the culture days. The change in the contraction force of the cardiomyocytes due to the drug concentration was successfully measured through the integrated strain sensor in the culture media. The reliability of the sensor-integrated cantilevers and the feasibility of their mass production ensure that they meet the practical requirements in the medical applications.

Lipidated peptides derived from intracellular loops 2 and 3 of the urotensin II receptor act as biased allosteric ligands

Over the last decade, the urotensinergic system, composed of one G protein-coupled receptor and two endogenous ligands, has garnered significant attention as a promising new target for the treatment of various cardiovascular diseases. Indeed, this system is associated with various biomarkers of cardiovascular dysfunctions and is involved in changes in cardiac contractility, fibrosis, and hypertrophy contributing, like the angiotensinergic system, to the pathogenesis and progression of heart failure. Significant investment has been made toward the development of clinically relevant UT ligands for therapeutic intervention, but with little or no success to date. This system therefore remains to be therapeutically exploited. Pepducins and other lipidated peptides have been used as both mechanistic probes and potential therapeutics; therefore, pepducins derived from the human urotensin II receptor might represent unique tools to generate signaling bias and study hUT signaling networks. Two hUT-derived pepducins, derived from the second and the third intracellular loop of the receptor (hUT-Pep2 and [Trp1, Leu2]hUT-Pep3, respectively), were synthesized and pharmacologically characterized. Our results demonstrated that hUT-Pep2 and [Trp1, Leu2]hUT-Pep3 acted as biased ago-allosteric modulators, triggered ERK1/2 phosphorylation and, to a lesser extent, IP1 production, and stimulated cell proliferation yet were devoid of contractile activity. Interestingly, both hUT-derived pepducins were able to modulate human urotensin II (hUII)- and urotensin II-related peptide (URP)-mediated contraction albeit to different extents. These new derivatives represent unique tools to reveal the intricacies of hUT signaling and also a novel avenue for the design of allosteric ligands selectively targeting hUT signaling potentially.

The effect of left ventricular contractility on arterial hemodynamics: A model-based investigation.

Ventricular-arterial coupling is a major determinant of cardiovascular performance, however, there are still inherent difficulties in distinguishing ventricular from vascular effects on arterial pulse phenotypes. In the present study, we employed an extensive mathematical model of the cardiovascular system to investigate how sole changes in cardiac contractility might affect hemodynamics. We simulated two physiologically relevant cases of high and low contractility by altering the end-systolic elastance, Ees, (3 versus 1 mmHg/mL) under constant cardiac output and afterload, and subsequently performed pulse wave analysis and wave separation. The aortic forward pressure wave component was steeper for high Ees, which led to the change of the total pressure waveform from the characteristic Type A phenotype to Type C, and the decrease in augmentation index, AIx (-2.4% versus +18.1%). Additionally, the increase in Ees caused the pulse pressure amplification from the aorta to the radial artery to rise drastically (1.86 versus 1.39). Our results show that an increase in cardiac contractility alone, with no concomitant change in arterial properties, alters the shape of the forward pressure wave, which, consequently, changes central and peripheral pulse phenotypes. Indices based on the pressure waveform, like AIx, cannot be assumed to reflect only arterial properties.

Amplification of Cardiac Motor Functions by Prestin (Slc26a5)

The human heart is a durable biological motor, beating approximately 3.4 billion times in an 80-year lifespan. Actual cardiac performance originates in the function of cardiac myocytes, which are electromotile, changing in length in response to a change in membrane potentials. Groundbreaking work by Hugh Huxley and Jean Hanson et al. in the 1950s introduced the “sliding filament theory” that during muscle contraction, myosin and the filamentous actin protein form cross-bridges, allowing myosin to slide along actin, leading to length changes and force generation. Some muscle contraction mechanisms remain unexplained, such as how the sarcolemma accommodates ∼0.2-μm-displacement length changes per sarcomere per cardiac cycle without experiencing significant distortion. Here we invoke and test for the presence and function of a canonical non-conventional motor protein, prestin (Slc26a5), in cardiomyocytes as an amplifier of actin-myosin force generation. Prestin has been thought to be expressed exclusively in outer hair cells (OHCs) of the inner ear. It is a direct voltage-to-force convertor and mediates electromotility of OHCs as part of the molecular element of cochlear sound amplification. We hypothesize that prestin is expressed in mouse and human heart tissue and serves as the cardiac mechanical amplifier. We investigated whether the genetic deletion of Slc26a5 (Slc26a5-/-) produces in vivo and in vitro cardiac contractility changes. Multimodal Second Harmonic Generation (SHG) two-photon fluorescence microscopy and Stimulated Emission Depletion (STED) microscopy analyses were used to substantiate findings of the expression and functional roles of prestin in ventricular myocytes. We conclude that prestin serves to amplify actin-myosin force generation in cardiomyocytes, accounting for the non-linear properties of muscle contraction. The functional significance of prestin is underpinned by alterations of cardiac contractility in Slc26a5-/-mice. Our results suggest that prestin may serve as a broader cellular motor amplifier.

Inotropic assessment in engineered 3D cardiac tissues using human induced pluripotent stem cell-derived cardiomyocytes in the BiowireTM II platform

To develop therapeutics for cardiovascular disease, especially heart failure, translational models for assessing cardiac contractility are necessary for preclinical target validation and lead optimization. The availability of stem cell-derived cardiomyocytes (SC-CM) has generated a great opportunity in developing new in-vitro models for assessing cardiac contractility. However, the immature phenotype of SC-CM is a well-recognized limitation in inotropic evaluation, especially regarding the lack of or diminished positive inotropic response to β-adrenergic agonists. Recent development of 3D engineered cardiac tissues (ECTs) using human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CM) in the BiowireTM II platform has shown improved maturation. To evaluate their suitability to detect drug-induced changes in cardiac contractility, positive inotropes with diverse mechanisms, including β-adrenergic agonists, PDE3 inhibitors, Ca2+-sensitizers, myosin and troponin activators, and an apelin receptor agonist, were tested blindly. A total of 8 compounds were evaluated, including dobutamine, milrinone, pimobendan, levosimendan, omecamtiv mecarbil, AMG1, AMG2, and pyr-apelin-13. Contractility was evaluated by analyzing the amplitude, velocity and duration of contraction and relaxation. All tested agents, except pyr-apelin-13, increased contractility by increasing the amplitude of contraction and velocity. In addition, myosin and troponin activators increase contraction duration. These results indicate that ECTs generated in the BiowireTM II platform can identify inotropes with different mechanisms and provides a human-based in-vitro model for evaluating potential therapeutics.

Aging Attenuates Cardiac Contractility and Affects Therapeutic Consequences for Myocardial Infarction.

Cardiac function of the human heart changes with age. The age-related change of systolic function is subtle under normal conditions, but abrupt under stress or in a pathogenesis state. Aging decreases the cardiac tolerance to stress and increases susceptibility to ischemia, which caused by aging-induced Ca2+ transient impairment and metabolic dysfunction. The changes of contractility proteins and the relative molecules are in a non-linear fashion. Specifically, the expression and activation of cMLCK increase first then fall during ischemia and reperfusion (I/R). This change is responsible for the nonmonotonic contractility alteration in I/R which the underlying mechanism is still unclear. Contractility recovery in I/R is also attenuated by age. The age-related change in cardiac contractility influences the therapeutic effect and intervention timepoint. For most cardiac ischemia therapies, the therapeutic result in the elderly is not identical to the young. Anti-aging treatment has the potential to prevent the development of ischemic injury and improves cardiac function. In this review we discuss the mechanism underlying the contractility changes in the aged heart and age-induced ischemic injury. The potential mechanism underlying the increased susceptibility to ischemic injury in advanced age is highlighted. Furthermore, we discuss the effect of age and the administration time for intervention in cardiac ischemia therapies.

The cardiac work-loop technique to assess drug-induced changes in cardiac contractility

The cardiac work-loop technique to assess drug-induced changes in cardiac contractility

Abstract 918: Pre-B-cell Leukemia Homeobox Interacting Protein 1 is a Novel Regulator of Growth Signaling in the Heart

The cellular mechanisms that allow for cardiomyocyte growth in different directions may yield important information about the development of hypertrophic and dilated cardiomyopathies, diseases which include the widening and lengthening growth of cardiomyocytes, respectively. We have previously found that genetic manipulations of the mitogen-activated protein kinase kinase 1 (MEK1) and extracellular signal-related kinase 1/2 (ERK1/2) signaling pathway cause cardiac hypertrophy and cardiomyocyte widening when the pathway is activated or dilated cardiomyopathy and cardiomyocyte lengthening when it is inhibited. The downstream effectors of the directional growth response controlled by these kinases have yet to be studied. Therefore, an unbiased phosphoproteomic screen was conducted on cardiomyocytes subjected to activation or inhibition of MEK1-ERK1/2 signaling. After validation of the screening hits with western and Phos-tag blots, Pre-B-cell leukemia homeobox interacting protein 1 (PBXIP1) emerged as an interesting target. Although it is known as a microtubule binding protein and regulator of proliferation in cancer cells, its function has never before been studied in the heart. Inhibition of MEK1-ERK1/2 increases phosphorylation of PBXIP1. However, activation of the pathway increases PBXIP1 protein expression, and as such we sought to determine the effects of PBXIP1 overexpression in the heart via adeno-associated virus 9 (AAV9) treatment. At four months of age, mice overexpressing PBXIP1 have significantly larger hearts than controls without a change in cardiac contractility. Intriguingly, histological analysis showed that cardiomyocytes highly infected with PBXIP1 AAV9 are significantly smaller in size compared to uninfected cells. Current studies are manipulating the PBXIP1 phosphorylation sites identified in the phosphoproteomic screen to determine the exact roles they may play in the cardiac growth response.

Impact of hypothermia on cardiac performance during targeted temperature management after cardiac arrest

IntroductionTargeted temperature management (TTM) is a well-accepted neuro-protective intervention in the management of comatose survivors of cardiac arrest (CA). However, the impact of TTM on cardiac performance has not been adequately evaluated. MethodsWe reviewed data on consecutive CA survivors undergoing TTM at a quaternary cardiac intensive care unit between January 2015 and June 2017. Enrollment was restricted to cases with invasive hemodynamics (iHDs) at TTM initiation, every 8 h at target temperature (32–34 °C) and at completion of rewarming (>36 °C), unless precluded by mortality. Cardiac index and cardiac index-derived variables were adjusted for a decreased oxygen consumption during hypothermia. We assessed the serial impact of cooling on iHDs and cardiac performance utilizing longitudinal data analysis accounting for the effects of time as surrogate for the expected change from the post arrest syndrome and instituted treatments. A Frank–Starling construct was used to evaluate changes in cardiac contractility. ResultsWe evaluated the effects of cooling on iHDs and cardiac performance in 46 CA survivors. Heart rate decreased with cooling (p < 0.001), to return to baseline after rewarming (p = 0.6). Mean arterial pressure and pulmonary wedge pressure decreased by cooling (p < 0.001 for both), with sustained improvement after rewarming (p < 0.001 for both). Systemic vascular resistance was unaffected by hypothermia (p > 0.05). Left stroke work index increased with cooling (p < 0.001), with return to baseline after rewarming (p = 0.6). Cooling was associated with a left-upward shift in the Frank–Starling curve indicative of increased contractility. ConclusionMild hypothermia in CA survivors appears associated to positive changes in iHDs and cardiac performance, including a potential increase in cardiac contractility. Larger studies are needed to conclusively confirm these findings.

Cardiovascular dynamics during head-up tilt assessed via pulsatile and non-pulsatile models.

This study develops non-pulsatile and pulsatile models for the prediction of blood flow and pressure during head-up tilt. This test is used to diagnose potential pathologies within the autonomic control system, which acts to keep the cardiovascular system at homeostasis. We show that mathematical modeling can be used to predict changes in cardiac contractility, vascular resistance, and arterial compliance, quantities that cannot be measured but are useful to assess the system's state. These quantities are predicted as time-varying parameters modeled using piecewise linear splines. Having models with various levels of complexity formulated with a common set of parameters, allows us to combine long-term non-pulsatile simulations with pulsatile simulations on a shorter time-scale. We illustrate results for a representative subject tilted head-up from a supine position to a [Formula: see text] angle. The tilt is maintained for 5min before the subject is tilted back down. Results show that if volume data is available for all vascular compartments three parameters can be identified, cardiovascular resistance, vascular compliance, and ventricular contractility, whereas if model predictions are made against arterial pressure and cardiac output data alone, only two parameters can be estimated either resistance and contractility or resistance and compliance.

Peningkatan Kadar Troponin-I Paska Resusitasi Cairan pada Sus Scrofa Sebagai Model Hewan Coba Renjatan

Provision large amounts of fluids in a short period is known can cause hypervolemia. Therefore, an examination is needed to find out that the fluid resuscitation being administered does not cause hypervolemia. The purpose of this study is to assess the effect of hypervolemic resuscitation on cardiac contractility. The study was conducted on 10 male Sus Scrofa aged 6-8 weeks, as shocked animal models. There are 3 types of resuscitation treatments : normovolemic, hypervolemic-1, and hypervolemic-2. Cardiac contractility was assessed using DPmax and troponin-i levels. There was an increase in troponin-i levels after hypervolemic fluid resuscitation (p = 0.05). There is a decrease in cardiac contractility after hypervolemic resuscitation. Decreased cardiac contractility is associated with increased troponin-i (r = 0.720; p = 0.020). Based on the results, we conclude hypervolemic resuscitation causes changes in troponin-i levels, which reflect changes in cardiac contractility.