Index Of Cardiac Contractility Research Articles

The relationship between diabetes, obesity and cardiovascular disease phenotypes: a UK Biobank cohort study

Abstract Background Obesity and diabetes mellitus (DM) frequently co-exist, yet their individual contributions to cardiovascular risk remain debated. Purpose We explored cardiovascular disease biomarkers, events and mortality in a large cohort stratified by body mass index (BMI) and DM. We hypothesised that DM with normal BMI is associated with a cardiovascular phenotype and event rate comparable to obesity without DM. Methods 451,355 UK Biobank participants were stratified by ethnicity-specific BMI categories (normal, overweight, obese) and DM status. We examined cardiovascular biomarkers including: carotid intima-media thickness (CIMT); arterial stiffness; left ventricular ejection fraction (LVEF) and cardiac contractility index (CCI). Poisson regression models estimated adjusted incidence rate ratios (IRR) for myocardial infarction, ischaemic stroke and cardiovascular death, with normal weight non-DM as comparator. Correlation matrices of Poisson model’s coefficients were used to assess correlations between covariates. Results 5% of participants had DM (10% normal weight, 34% overweight and 55% obese; versus 34%, 43% and 23%, respectively, in non-DM). In the non-DM group, overweight/obesity was associated with higher CIMT, arterial stiffness and CCI, and lower LVEF (p<0.05); these relationships were diminished in the DM group. Within BMI classes, DM was associated with adverse cardiovascular phenotype (p<0.05), particularly in the normal weight group. After 5,323,190 person-years follow-up, incident myocardial infarction, ischaemic stroke and cardiovascular mortality all rose across increasing BMI categories in the DM and non-DM groups (p<0.05). However, normal weight DM had higher cardiovascular mortality than obese non-DM (IRR 2.81 [95% confidence interval: 2.24-3.54] vs IRR 1.84 [1.70-1.98]). Pairwise correlation analysis demonstrated the strongest correlates of cardiovascular parameters were markers of adiposity; this was apparent in the DM and non-DM groups, although these remained modest with Pearson’s correlation coefficients of no more than 0.25. Conclusions Obesity and DM are additively associated with adverse cardiovascular biomarkers and mortality risk. Whilst adiposity metrics are more strongly correlated with cardiovascular biomarkers than diabetes-oriented metrics, both correlate weakly, suggesting other factors underpin the high cardiovascular risk of normal-weight diabetes. Ideal target range for metrics of adiposity may therefore be lower than currently proposed in people with DM.Table 1:Adjusted IRR of CV deathFigure 1:KM Curve for CV death

Circulating Gal-3 and sST2 are associated with acute exercise-induced sustained endothelial activation: Possible relevance for fibrosis development?

Long-term, intense endurance exercise training can occasionally induce endothelial micro-damage and cardiac fibrosis. The underlying mechanisms are incompletely understood. Twenty healthy, well-trained male participants (10runners and 10cyclists) performed a strenuous high-intensity interval training (HIIT) session matched by age, height, weight and maximal oxygen consumption. We assessed the acute exercise response of novel cardiac biomarkers of fibrosis [e.g., galectin-3 (Gal-3) and soluble suppression of tumorigenicity 2 (sST2)] per exercise modality and their relationship with haemodynamic contributors, such as preload, afterload and cardiac contractility index (CTi), in addition to endothelial damage by sustained activation and shedding of endothelial cells (ECs). Serum Gal-3 and sST2 concentrations were investigated by enzyme-linked immunosorbent assays; haemodynamics were analysed via impedance plethysmography and circulating ECs by flow cytometry. The Gal-3 and sST2 concentrations and ECs were elevated after exercise (P<0.001), without interaction between exercise modalities. Circulating Gal-3 and sST2 concentrations both showed a positive relationship with ECs (rrm =0.68, P=0.001 and rrm =0.57, P=0.010, respectively, both n=18). The EC association with Gal-3 was significant only in cyclists, but equally strong for both modalities. Gal-3 was also related to exercise-induced CTi (rrm =0.57, P=0.011, n=18). Cardiac wall stress is increased after an acute HIIT session but does not differ between exercise modalities. Exercise-released Gal-3 from cardiac macrophages could very probably drive systemic endothelial damage, based on an enhanced CTi. The importance of acute exercise-induced vascular resistances and cardiac contractility for the release of fibrotic biomarkers and any long-term pathological endothelial adaptation should be investigated further, also relative to the exercise modality. NEW FINDINGS: What is the central question of this study? Circulating biomarkers of cardiac wall stress and fibrosis are influenced by physical exercise. The underlying mechanisms per exercise modality are still unclear. What is the main finding and its importance? We show that galectin-3 (Gal-3) and soluble suppression of tumorigenicity 2 (sST2) are increased after acute exercise but do not differ between running and cycling. One haemodynamic contributor to the secretion of Gal-3 is an enhanced cardiac contractility. Acute exercise-released Gal-3 and sST2 are linked to sustained endothelial activation and cell shedding. This could be relevant in the context of fibrosis development and could identify athletes at risk for pathological endothelial adaptations.

Inverse ESPVR Estimation with Singularity Avoidance via Constrained EDPVR Parameter Optimization.

Left ventricular end-systolic elastance Ees, as an index of cardiac contractility, can play a key role in continuous patient monitoring during cardiac treatment scenarios such as drug therapies. The clinical feasibility of Ees estimation remains challenging because most techniques have been built on left ventricular pressure and volume, which are difficult to measure or estimate in the regular ICU/CCU setting. The purpose of this paper is to propose and validate a novel approach to estimate Ees, which is independent of left ventricular pressure and volume. Our methods first derive an analytical representation of Ees as the inverse function of the gradient of the Frank-Starling Curve based on cardiac mechanics. Second, elucidating the mechanism of singularities in the inverse function, we derive multiple conditions in both end-systolic pressure-volume relationship (ESPVR) and end-diastolic pressure-volume relationship (EDPVR) parameters to avoid these singularities analytically. Third, we formulate a constrained nonlinear least squares problem to optimize both ESPVR and EDPVR parameters simultaneously to avoid singularities. The effectiveness of the proposed method in avoiding singularities was evaluated in an animal experiment. Compared to the conventional Ees estimation by linear regression, our proposed method reproduced in-vivo hemodynamics more accurately when simulating the estimated Ees variation during drug administration. Our method can be applied using the available data in the regular ICU/CCU setting. The improved clinical feasibility can support not only physicians' decision-making, including adjusting drug dosages in current clinical treatment, but also a closed-loop hemodynamic control system requiring accurate continuous Ees estimation.

Systolic Indices of Cardiac Contractility: Modeling and Analysis using Pressure-Volume Loop

Modeling cardiac contractility in pre-clinical catheterization laboratory settings remains an important task to collect results under controlled hemodynamic conditions, while providing an assessment of systolic and diastolic indices. Diligent hemodynamic monitoring with acute-based pressure-volume modeling uncovers early indicators of heart failure (HF). In this article, basic procedural assessments are outlined, while deeper dive into systolic index of contractility, the end systolic elastance is provided with references to older, while comparing it to novel approaches. Transient preload reduction using inferior vena cava occlusion (IVCO) is the current standardized maneuver used in hemodynamic protocols to provide an assessment of contractile responsiveness. In this article an example of standard measures from a single catheterization lab were depicted using tables and figures, giving background to transient preload reduction to assess the values of systolic cardiac contractility. Additionally, novel twists on other possible index(ices) coming from capturing ES point may well present future opportunities to collect systolic cardiac contractility. In this instance, both single beat systolic PPESPVR and IVCO using ES points present unique opportunities in this niche area of research. Final two sections of this article are dedicated to procedural steps and how to standardize execution of IVCO. Final section is reserved for analytical steps of how to visually compare systolic indices post-IVCO in case of linear and quadratic relationship.

A cross-species validation of single-beat metrics of cardiac contractility.

The assessment of left ventricular (LV) contractility in animal models is useful in various experimental paradigms, yet obtaining such measures is inherently challenging and surgically invasive. In a cross-species study using small and large animals, we comprehensively tested the agreement and validity of multiple single-beat surrogate metrics of LV contractility against the field-standard metrics derived from inferior vena cava occlusion (IVCO). Fifty-six rats, 27 minipigs and 11 conscious dogs underwent LV and arterial catheterization and were assessed for a range of single-beat metrics of LV contractility. All single-beat metrics were tested for the various underlying assumptions required to be considered a valid metric of cardiac contractility, including load-independency, sensitivity to inotropic stimulation, and ability to diagnose contractile dysfunction in cardiac disease. Of all examined single-beat metrics, only LV maximal pressure normalized to end-diastolic volume (EDV), end-systolic pressure normalized to EDV, and the maximal rate of rise of the LV pressure normalized to EDV showed a moderate-to-excellent agreement with their IVCO-derived reference measure and met all the underlying assumptions required to be considered as a valid cardiac contractile metric in both rodents and large-animal models. Our findings demonstrate that single-beat metrics can be used as a valid, reliable method to quantify cardiac contractile function in basic/preclinical experiments utilizing small- and large-animal models KEY POINTS: Validating and comparing indices of cardiac contractility that avoid caval occlusion would offer considerable advantages for the field of cardiovascular physiology. We comprehensively test the underlying assumptions of multiple single-beat indices of cardiac contractility in rodents and translate these findings to pigs and conscious dogs. We show that when performing caval occlusion is unfeasible, single-beat metrics can be utilized to accurately quantify cardiac inotropic function in basic and preclinical research employing various small and large animal species. We report that maximal left-ventricular(LV)-pressure normalized to end-diastolic volume (EDV), LV end-systolic pressure normalized to EDV and the maximal rate of rise of the LV pressure waveform normalized to EDV are the best three single-beat metrics to measure cardiac inotropic function in both small- and large-animal models.

The Left Ventricular End-Systolic Pressure Correlation with Aortic Valve Timing; a Novel Inotropic Index Description Using a Dual Pressure Catheter

Myocardial contraction is generated by ventricular pressure in early systole by the isometric force against closed valves, as ventricle is contracting without changing volume. This initial contractile phase of cardiac cycle (early systole) is followed by rapid shortening, isotonic contraction, allowing ejection of the blood against changing LV afterload. LV is coupled to the systemic arterial pressure; hence LV ejection is closely linked to the properties of the aortic valve, aorta, and its distributing arteries. Isometric relationship in the LV was characterized using the load-dependent example (naïve vs. post-dobutamine), observed mostly in case of rate of rise of LVP, LV ESP and decrease of pulse wave velocity, characteristics of LV baroinometry. Furthermore, by performing load-independent maneuver, afterload (LV ESP) was adjusting at every cardiac cycle, while an assessment of LV ESP and aortic valve timing was able to be established. By plotting decaying LV ESP against aortic valve timing, highly linear correlation of load-independent isotonic, but also an isometric contractility was captured. Steeper linear slope and time-axis intercept (IC) were identified in case of post-inotropic challenge, recapitulating changes otherwise measured during pressure-volume exam. This relationship, measured by dual-pressure catheter, could serve as novel inotropic index of functional cardiac contractility. Keywords: Left Ventricle (LV); Contractility; Inotropy; Load-Dependent and Independent; Stressed Volume; Dual Pressure Catheter. 1. Assessment of cardiac contractility using dual pressure catheter. 2. IVCO inferior vena cava occlusion, ECC excitation-contraction coupling, EF ejection fraction, TTE transthoracic echocardiography, Ea end arterial elastance, PRSW preload recruitable stroke work, IC intercept, PWV pulse wave velocity.

Acromegaly: The Research and Practical Value of Noninvasive Hemodynamic Assessments via Impedance Cardiography.

BackgroundArterial hypertension (AH) that accompanies acromegaly (AC) may lead to cardiovascular dysfunction. Such consequences may be detected with impedance cardiography (ICG), which is a noninvasive method of hemodynamic assessment. Early detection of subclinical hemodynamic alterations in AC patients may be crucial for optimizing treatment and preventing cardiovascular remodeling. The purpose of this study was to identify the hemodynamic parameters of the cardiovascular system that differentiate patients with AC from those in the control group (CG), with a particular emphasis on potential targets for medical therapy.MethodsThis observational, prospective, clinical study involved a comparative analysis of 33 AC patients with no significant comorbidities and the controls selected via propensity score matching based on a set of baseline characteristics (age, sex, body mass index, mean blood pressure [MBP]), with comparable proportions of AH patients. The assessed hemodynamic parameters included the stroke volume index (SI), cardiac index, systemic vascular resistance index, velocity index (VI), acceleration index, Heather index (HI), and thoracic fluid content (TFC).ResultsBoth the AC group and the CG had well-controlled AH (mean blood pressure of 121/77 mmHg and 119/76 mmHg, respectively). In terms of baseline characteristics, the AC group was characterized by a higher hear rate and lower creatinine levels than the CG (76.2 bpm vs. 66.8 bpm [p = 0.001] and 0.755 mg/dL vs. 0.850 mg/dL [p = 0.035], respectively). ICG assessment of AC patients and CG patients showed the former to have higher heart rates (73.5 bpm vs. 65.2 bpm; p = 0.003), lower SI (43.8 mL/m2 vs. 53.4 mL/m2; p = 0.0001), lower VI (42.1 1/1000/s vs. 49.3 1/1000/s; p = 0.037), lower HI (8.49 Ohm/s2 vs. 13.4 Ohm/s2, p ≤ 0.0001), and higher thoracic fluid content (TFC) (38.4 1/kOhm vs. 28.1 1/kOhm; p ≤ 0.0001), respectively.ConclusionsEven with well-controlled hypertension, AC is associated with a high TFC, increased heart rate, and decreased indices of cardiac contractility. Hemodynamic changes in AC patients may be detected with the modern, noninvasive diagnostic tool, ICG.

The effect of intravenous ferric carboxymaltose on cardiac reverse remodelling following cardiac resynchronization therapy-the IRON-CRT trial.

AimsIron deficiency is common in heart failure with reduced ejection fraction (HFrEF) and negatively affects cardiac function and structure. The study the effect of ferric carboxymaltose (FCM) on cardiac reverse remodelling and contractile status in HFrEF.Methods and resultsSymptomatic HFrEF patients with iron deficiency and a persistently reduced left ventricular ejection fraction (LVEF <45%) at least 6 months after cardiac resynchronization therapy (CRT) implant were prospectively randomized to FCM or standard of care (SOC) in a double-blind manner. The primary endpoint was the change in LVEF from baseline to 3-month follow-up assessed by three-dimensional echocardiography. Secondary endpoints included the change in left ventricular end-systolic (LVESV) and end-diastolic volume (LVEDV) from baseline to 3-month follow-up. Cardiac performance was evaluated by the force–frequency relationship as assessed by the slope change of the cardiac contractility index (CCI = systolic blood pressure/LVESV index) at 70, 90, and 110 beats of biventricular pacing. A total of 75 patients were randomized to FCM (n = 37) or SOC (n = 38). At baseline, both treatment groups were well matched including baseline LVEF (34 ± 7 vs. 33 ± 8, P = 0.411). After 3 months, the change in LVEF was significantly higher in the FMC group [+4.22%, 95% confidence interval (CI) +3.05%; +5.38%] than in the SOC group (−0.23%, 95% CI −1.44%; +0.97%; P < 0.001). Similarly, LVESV (−9.72 mL, 95% CI −13.5 mL; −5.93 mL vs. −1.83 mL, 95% CI −5.7 mL; 2.1 mL; P = 0.001), but not LVEDV (P = 0.748), improved in the FCM vs. the SOC group. At baseline, both treatment groups demonstrated a negative force–frequency relationship, as defined by a decrease in CCI at higher heart rates (negative slope). FCM resulted in an improvement in the CCI slope during incremental biventricular pacing, with a positive force–frequency relationship at 3 months. Functional status and exercise capacity, as measured by the Kansas City Cardiomyopathy Questionnaire and peak oxygen consumption, were improved by FCM.ConclusionsTreatment with FCM in HFrEF patients with iron deficiency and persistently reduced LVEF after CRT results in an improvement of cardiac function measured by LVEF, LVESV, and cardiac force–frequency relationship.

Deceleration capacity of heart rate variability as a predictor of sedation related hypotension

High risk and geriatric patients are supposed to suffer higher risks of hypotension underwent painless endoscopic procedures. This study evaluated different biomarkers associated with hypotension in off-site patients and aimed to determine the most relevant risk factors in space and monitoring limited environment. The inclusions of this observational cohort study underwent complex endoscopic procedures were sedated with age-adjusted doses of target-controlled infusion of propofol. The following pre-sedative parameters were analysed: time domain, frequency domain, and Deceleration capacity (DC) of heart rate variability, estimated cardiac output data and the index of cardiac contractility from the cardiometer. Patients were divided into hypotension group (blood pressure < 90 mmHg or a > 35% decrease) and non-hypotension group according to peri-sedative blood pressure, regression analysis is used to examine the association between factors and hypotension. Total data from 178 patients (age range: 33–94 years) were analysed. Age was not significantly different between the hypotension and non-hypotension groups (p = 0.978). Among all the factors, DC was most associated with hypotension (p = 0.05), better than cardiometer, age, and ASA status. In conclusion, DC, which can be interpreted as the indicator of parasympathetic activity and was significantly and negatively correlated with sedation-related hypotension. Pre-sedative measuring DC from routine ECG monitoring is simple and cost-effective and should be added to haemodynamic monitoring in the endoscopic room.

Pursuing the non-invasive assessment of cardiac contractility: the added value of pressure-area-strain loop analysis in volume overload-induced heart failure

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by the New National Excellence Programme (ÚNKP-19-3-I) of the Ministry for Innovation and Technology in Hungary, and the Artificial Intelligence Research Field Excellence Programme of the National Research, Development and Innovation Office of the Ministry of Innovation and Technology in Hungary. Background Global longitudinal strain (GLS) by speckle-tracking echocardiography (STE) is a sensitive parameter of left ventricular (LV) systolic function. Nevertheless, GLS is dependent on loading conditions. Through the analysis of pressure-strain loops, myocardial work was recently introduced and tested in different clinical scenarios. Myocardial work incorporates afterload, but still, it neglects changes in preload and LV geometry. Purpose Accordingly, our aim was to test our hypothesis that adding instantaneous LV size to myocardial work calculation can further mitigate the load-dependency of GLS, and therefore, a better correlation with intrinsic myocardial contractility can be achieved. Methods Volume overload-induced heart failure was established by an aortocaval fistula (ACF) in male Wistar rats (n = 12). Age-matched sham-operated animals served as controls (n = 12). STE was performed to assess GLS, which was immediately followed by invasive pressure-volume (P-V) analysis to assess LV pressure and to compute a gold-standard index of cardiac contractility (preload recruitable stroke work [PRSW]). Global myocardial work index (GMWI) was calculated from GLS and the invasively measured LV pressure. To compute GMWI indexed to LV area (GMWIA), the instantaneous power (calculated by multiplying the strain rate and the instantaneous LV pressure) was divided by the instantaneous LV area, and then it was integrated from mitral valve closure until mitral valve opening. Results LV ejection fraction did not differ significantly (ACF vs. controls: 59 ± 4 vs. 65 ± 9%, p = NS), whereas GLS (Figure 1A - representative animals) was slightly decreased in the ACF group (-13.2 ± 2.3 vs. -15.4 ± 1.9%, p &amp;lt; 0.05). In contrast, PRSW, GMWI (Figure 1B - representative animals) and GMWIA (Figure 1C - representative animals) were considerably reduced in ACF compared to controls (57 ± 13 vs. 111 ± 38mmHg, 1383 ± 382 vs. 1928 ± 281mmHg%, 11.6 ± 3.7 vs. 47.9 ± 22.8mmHg%/mm2, all p &amp;lt; 0.01). GLS showed moderate correlation with PRSW (r=-0.550, p &amp;lt; 0.01), whereas GMWI correlated more significantly, but still moderately with the invasively measured LV contractility (r = 0.681, p &amp;lt; 0.001). Correlation between the pressure-area-strain loop-derived GMWIA and P-V analysis-derived PRSW (Figure 1D) was found to be very strong (r = 0.924, p &amp;lt; 0.001). Conclusions In the case of LV volume overload-induced heart failure, our pressure-area-strain loop-derived metric reflected LV contractility better than GLS and even GMWI. Therefore, the incorporation of instantaneous LV size into myocardial work calculation represents a promising clinical tool to assess and monitor intrinsic myocardial function independently of loading conditions. Abstract Figure 1

Cardioprotection by triiodothyronine following caloric restriction via long noncoding RNAs

Severe caloric-restriction compromises thyroid hormone (TH) status, apparently to save energy and proteins for enduring stress stimulus. However, a persistent decrease in TH levels may compromise heart function. We hypothesized that supplementation of low dose active TH or targeting hypoxia-inducible factor-1-alpha, HIF-1α (a strong activator of deiodinase enzyme that degrades peripheral active THs) will prevent deterioration of cardiac performance. Adult mice were subjected to acute fasting based on institutional animal protocols with ad libitum access to water. The following groups were studied: Control mice with free access to food; severe caloric restriction fasting only group; Fasting with Triiodo-l-Thyronine (T3); Fasting with HIF-1α inhibitor (BAY). Cardiac hemodynamic and electrophysiological studies were performed and role of long noncoding RNAs were explored. Following severe caloric-restriction, we found that body weights, and heart weights to a partial extent, were decreased. Low-dose T3 treatment attenuated left ventricular hemodynamic impairment in indices of cardiac contractility and relaxation. In electrophysiology studies, fasting mice developed atrial tachyarrhythmias upon induction. This reverted to control levels following T3 treatment. There was a significant increase in atrioventricular conduction time and significant decrease in heart rate following fasting. Both these changes were attenuated following T3 treatment. Furthermore, BAY partially improved hemodynamics. Compared to the severe caloric-restriction group, both T3 and BAY reduced MALAT1 and GAS5 long noncoding RNA expression. These new findings indicate that T3 and BAY protect from cardiac decompensation secondary to acute severe caloric-restriction partly mediated by long noncoding RNAs.

Multiscale Modeling of Cardiovascular Function Predicts That the End-Systolic Pressure Volume Relationship Can Be Targeted via Multiple Therapeutic Strategies.

Most patients who develop heart failure are unable to elevate their cardiac output on demand due to impaired contractility and/or reduced ventricular filling. Despite decades of research, few effective therapies for heart failure have been developed. In part, this may reflect the difficulty of predicting how perturbations to molecular-level mechanisms that are induced by drugs will scale up to modulate system-level properties such as blood pressure. Computer modeling might help with this process and thereby accelerate the development of better therapies for heart failure. This manuscript presents a new multiscale model that uses a single contractile element to drive an idealized ventricle that pumps blood around a closed circulation. The contractile element was formed by linking an existing model of dynamically coupled myofilaments with a well-established model of myocyte electrophysiology. The resulting framework spans from molecular-level events (including opening of ion channels and transitions between different myosin states) to properties such as ejection fraction that can be measured in patients. Initial calculations showed that the model reproduces many aspects of normal cardiovascular physiology including, for example, pressure-volume loops. Subsequent sensitivity tests then quantified how each model parameter influenced a range of system level properties. The first key finding was that the End Systolic Pressure Volume Relationship, a classic index of cardiac contractility, was ∼50% more sensitive to parameter changes than any other system-level property. The second important result was that parameters that primarily affect ventricular filling, such as passive stiffness and Ca2+ reuptake via sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), also have a major impact on systolic properties including stroke work, myosin ATPase, and maximum ventricular pressure. These results reinforce the impact of diastolic function on ventricular performance and identify the End Systolic Pressure Volume Relationship as a particularly sensitive system-level property that can be targeted using multiple therapeutic strategies.

Low-Dose Landiolol Reduces Heart Rate and Cardiac Oxygen Consumption Without Compromising Initial Hemodynamic Resuscitation in a Canine Model of Endotoxin Shock.

In septic shock, it is not known whether β-blocker can be used to reduce heart rate (HR) safely during the initial phase of hemodynamic resuscitation. The purpose of this study was to experimentally investigate the effects of low-dose landiolol, a β-blocker, on initial hemodynamic resuscitation in dogs with endotoxin shock. In 13 anesthetized dogs [n = 7 in control (CT) group, n = 6 in β-blockade (BB) group], after endotoxin shock was induced by intravenous infusion of lipopolysaccharide (4 mg kg), we started hemodynamic resuscitation to restore mean arterial pressure (AP) and cardiac output (CO) by infusing noradrenaline (NA) and Ringer acetate solution (RiA). During 4 h of hemodynamic resuscitation, dose of NA and RiA were automatically titrated with use of a computer-controlled drug infusion system that we developed previously. In BB group, landiolol was administered at a low-dose range (1-10 μg kg min) to lower HR to lower than 140 bpm. Hemodynamic resuscitation using the system restored AP to 70 mmHg and CO to greater than 90% of baseline level similarly in both groups. Throughout resuscitation, HR and indices of cardiac contractility were significantly lower in BB group than in CT group. However, there were no significant intergroup differences in the dose of NA and RiA. During First 2 h of resuscitation, cardiac oxygen consumption was significantly lower in BB group than in CT group. In conclusion, low-dose landiolol may reduce HR without compromising initial hemodynamic resuscitation in septic shock. To clearly establish this, large-size randomized study using animal models more relevant to septic shock is needed.

Maternal cardiac function, uterine artery hemodynamics and natriuretic peptides at 22-24weeks of gestation and subsequent development of hypertensive disorders of pregnancy.

Maternal cardiac dysfunction as well as abnormal uterine artery (UtA) Doppler are associated with hypertensive disorders of pregnancy (HDP), but their relation is unclear. We investigated the correlation between maternal cardiac function, UtA hemodynamics and natriuretic peptides, and explored differences between women who subsequently developed HDP and those who did not. This wasa prospective cross-sectional cohort study of 347 pregnant women at 22-24weeks. Maternal cardiac function and systemic hemodynamics were investigated at baseline and after 90seconds of passive leg raising using impedance cardiography. Preload reserve was defined as percent change (Δ%) in stroke volume and cardiac output from baseline to passive leg raising. UtA hemodynamics was studied using Doppler ultrasonography. UtA blood flow, resistance and pulsatility index were calculated. Fasting venous blood samples were analyzed for natriuretic peptides (pro atrial natriuretic peptide [proANP], N-terminal pro brain natriuretic peptide [Nt-proBNP] and C-type natriuretic peptide [CNP]). The course and outcome of pregnancy were recorded. At baseline, ProANP correlated significantly with cardiac output (r=-0.122; P= .023) and left cardiac work index (r=-0.112; P= .037), whereas Nt-ProBNP correlated significantly with acceleration index (r= .127; P= .018) and velocity index (r=-0.111; P= .039. CNP correlated significantly with UtA blood flow (r= .118; P= .028) and resistance (r=-0.112; P= .037) but not with UtA pulsatility index (r= .034; P= .523). None of the natriuretic peptides correlated with preload reserve. At 22-24weeks, women who subsequently developed HDP had lower UtA blood flow (552 vs 692mL/min; P= .028), higher UtA resistance (0.28 vs .17mmHg/mL/min; P= .004) and higher mean UtA pulsatility index (1.12 vs .84; P< .001) compared with those who did not; however, the natriuretic peptide levels were similar in the two groups. Women developing HDP had a significantly higher increase in stroke volume and cardiac output and more reduction in systemic vascular resistance following passive leg raising compared with the reference group. Left cardiac work index, acceleration index and velocity index decreased following passive leg raising in the reference group but increased in women who later developed HDP. ProANP correlated with cardiac output and cardiac work, Nt-proBNP with indices of cardiac contractility, and CNP with UtA blood flow and resistance. None of these natriuretic peptides measured at 22-24weeks of gestation reflected cardiac preload reserve or predicted development of HDP.

Hemodynamic Patterns Identified by Impedance Cardiography Predict Mortality in the General Population: The PREVENCION Study.

BackgroundBlood pressure is determined by the interactions between the heart and arterial properties, and subjects with identical blood pressure may have substantially different hemodynamic determinants. Whether arterial hemodynamic indices quantified by impedance cardiography (ICG), a simple operator‐independent office procedure, independently predict all‐cause mortality in adults from the general population, and specifically among those who do not meet criteria for American College of Cardiology/American Heart Association stage 2 hypertension, is currently unknown.Methods and ResultsWe studied 1639 adults aged 18 to 80 years from the general population. We used ICG to measure hemodynamic parameters and metrics of cardiac function. We assessed the relationship between hemodynamic parameters measured at baseline and all‐cause mortality over a mean follow‐up of 10.9 years. Several ICG parameters predicted death. The strongest predictors were total arterial compliance index (standardized hazard ratio=0.38; 95% confidence interval=0.31–0.46; P<0.0001) and indices of cardiac contractility: velocity index (standardized hazard ratio=0.45; 95% confidence interval=0.37–0.55; P<0.0001) and acceleration index (standardized hazard ratio=0.44; 95% confidence interval=0.35–0.55; P<0.0001). These remained independently predictive of death after adjustment for multiple confounders, as well as systolic and diastolic blood pressure. Among subjects without stage 2 hypertension (n=1563), indices of cardiac contractility were independently predictive of death and identified a subpopulation (25% of non‐stage‐2 hypertensives) that demonstrated a high 10‐year mortality risk, equivalent to that of stage 2 hypertensives.ConclusionsHemodynamic patterns identified by ICG independently predict mortality in the general population. The predictive value of ICG applies even in the absence of American College of Cardiology/American Heart Association stage 2 hypertension and identifies higher‐risk individuals who are in earlier stages of the hypertension continuum.

Inhalation of Simulated Smog Atmospheres Affects Cardiac Function in Mice.

The health effects of individual criteria air pollutants have been well investigated. However, little is known about the health effects of air pollutant mixtures that more realistically represent environmental exposures. The present study was designed to evaluate the cardiac effects of inhaled simulated smog atmospheres (SA) generated from the photochemistry of either gasoline and isoprene (SA-G) or isoprene (SA-Is) in mice. Four-month-old female mice were exposed for 4h to filtered air (FA), SA-G, or SA-Is. Immediately and 20h after exposure, cardiac responses were assessed with a Langendorff preparation using a protocol consisting of 20min of global ischemia followed by 2h of reperfusion. Cardiac function was measured by index of left-ventricular developed pressure (LVDP) and cardiac contractility (dP/dt) before ischemia. Pre-ischemic LVDP was lower in mice immediately after SA-Is exposure (52.2 ± 5.7cm H2O compared to 83.9 ± 7.4cm H2O after FA exposure; p = 0.008) and 20h after SA-G exposure (54.0 ± 12.7cm H2O compared to 79.3 ± 7.4cm H2O after FA exposure; p = 0.047). Pre-ischemic left ventricular contraction dP/dtmax was lower in mice immediately after SA-Is exposure (2025 ± 169cm H2O/sec compared to 3044 ± 219cm H2O/sec after FA exposure; p < 0.05) and 20h after SA-G exposure (1864 ± 328cm H2O/sec compared to 2650 ± 258cm H2O/sec after FA exposure; p = 0.05). In addition, SA-G reduced the coronary artery flow rate 20h after exposure compared to the FA control. This study demonstrates that acute SA-G and SA-Is exposures decrease LVDP and cardiac contractility in mice, indicating that photochemically-altered atmospheres affect the cardiovascular system.

Estimating Left Ventricular Elastance from Aortic Flow Waveform, Ventricular Ejection Fraction, and Brachial Pressure: An In Silico Study.

Although left ventricular end-systolic elastance (Ees) serves as a major index of cardiac contractility, a widely-accepted noninvasive estimation of Ees does not exist. To overcome this limitation, we developed a two-step inverse method that allows for its noninvasive estimation from measurements of aortic flow and brachial pressure using a previously validated one-dimensional model of the cardiovascular system. In a first step, aortic flow is set as the model input and the output brachial pressure is compared with the "real" values. Subsequently, the basic properties of the arterial tree are tuned according to an optimization algorithm. In a second step, the same optimization method is used to estimate the elastance parameters that produce an aortic flow waveform that matches the "real" one. Additional knowledge of the ejection fraction can allow for the accurate estimation of the entire P-V loop, including end-diastolic elastance. The method was tested on a database of 50 different in silico hemodynamic cases generated after varying cardiac and arterial model parameters. Implementation of the method yielded good agreement (r = 0.99) and accuracy (n-RMSE = 4%) between "real" and estimated values of Ees. Furthermore, a sensitivity analysis revealed that errors due to poor arterial adjustment and measurements are small (≤ 8% for Ees).

Max dD/Dt: A Novel Parameter to Assess Fetal Cardiac Contractility and a Substitute for Max dP/Dt

Aortic pulse waveforms are composed of a forward wave from the heart and a reflection wave from the periphery. We focused on this forward wave and suggested a new parameter, the maximum slope of aortic pulse waveforms (max dD/dt), for fetal cardiac contractility. Max dD/dt was calculated from fetal aortic pulse waveforms recorded with an echo-tracking system. A normal range of max dD/dt was constructed in 105 healthy fetuses using linear regression analysis. Twenty-two fetuses with suspected fetal cardiac dysfunction were divided into normal and decreased max dD/dt groups, and their clinical parameters were compared. Max dD/dt of aortic pulse waveforms increased linearly with advancing gestational age (r = 0.93). The decreased max dD/dt was associated with abnormal cardiotocography findings and short- and long-term prognosis. In conclusion, max dD/dt calculated from the aortic pulse waveforms in fetuses can substitute for max dP/dt, an index of cardiac contractility in adults.

Influence of Long-Term Salt Diets on Cardiac Ca2+ Handling and Contractility Proteins in Hypertensive Rats.

High sodium intake contributes to the pathogenesis of hypertension and adversely affects cardiac function. Conversely, sodium reduction is associated with a blood pressure decrease and improved cardiovascular function. However, the mechanisms that underlie the cardiac effects induced by salt intake in hypertension have not been fully elucidated. Ca2+ handling is critical for efficient myocardial function; thus, we aimed to investigate the long-term effects of diets with different salt contents on cardiac function and Ca2+ handling proteins in spontaneously hypertensive rats (SHRs). Cardiac function was evaluated by catheterization. Ca2+ handling and contractile proteins were evaluated by immunoblotting in hearts from SHRs fed for 6 months with diets containing high (HS, 3%), low (LS, 0.03%), or normal salt content (NS, 0.3%). Diets were introduced immediately after weaning. Tail cuff pletismography was assessed at the 3rd and 7th months of follow-up. Compared to the NS group, the HS group exhibited worsened hypertension, increased cardiac expression of β-myosin heavy chain (MHC), a decreased α/β-MHC ratio and reduced expression of both phospholamban (PLB) and Na+/Ca2+ exchanger (NCX). LS intake attenuated the blood pressure increase and left ventricle hypertrophy, slightly decreased the cardiac contractility and relaxation index, and increased the α/β-MHC ratio. These effects were accompanied by increased cardiac PLB expression and decreased Ca2+ L-type channel and NCX expression. These findings indicate that the modulation of Ca2+ handling may be one of the molecular mechanisms underlying the effect of salt intake on myocardial function in hypertension.

Улучшение функции сердца у кроликов с хронической сердечной недостаточностью под действием метилина

To study effects of intravenous infusion of a cardioprotective drug metilin, developed at the "National Medical Research Center of Cardiology" on indices of cardiac function in rabbits in vivo after prolonged administration of doxorubicin. Animals of the experimental group were intravenously injected with doxorubicin (2 mg / kg once a week) for 8 weeks, animals of the control group received the same volume of saline. Myocardial damage was characterized by an increase in concentration of malondialdehyde (MDA), troponin (TnI) and MB-fraction of creatine kinase (CK-MB) in venous blood and by disturbances in the left ventricle (LV) structure at morphological examination. Metilin effects on cardiac function were assessed by echocardiography and LV catheterization by the Millar catheter tip pressure transducer. Doxorubicin administration led to a decrease of the body mass of animals, an increase of the plasma concentration of cardiac markers CK-MB and TnI, lipid peroxidation (LPO) product MDA in venous blood, and pronounced disturbances in the structure of LV fibers and microvessels. At the same time, a significant decrease of myocardial contractility indices was observed. Manifestations of this decrease were increase of the end-diastolic and end-systolic dimensions (EDD and ESD, respectively), and decreases in the shortening fraction and ejection fraction (SF and EF, respectively) compared to baseline values. These changes indicated development of chronic heart failure (CHF) in animals of the experimental group. Against this background, intravenous infusion of metilin significantly increased SF and EF, but did not affect the heart rate. Beneficial effects of metilin on the indices of cardiac contractility and relaxation were maintained after the infusion was stopped. Noteworthy, metilin exerted greater influence on cardiac function of rabbits with CHF compared to control animals that did not receive doxorubicin. The obtained results indicate the potential of metilin to reduce LV dysfunction during chemotherapy with doxorubicin.