Left Ventricular Diastolic Pressure Research Articles

Enhancing Heart Transplantation: Utilizing Gas-Loaded Nanocarriers to Mitigate Cold/Hypoxia Stress

Gas-loaded nanocarriers (G-LN) show promise in improving heart transplantation (HTx) outcomes. Given their success in reducing cell death during normothermic hypoxia/reoxygenation (H/R) in vitro, we tested their integration into cardioplegic solutions and static cold storage (SCS) during simulated HTx. Wistar rat hearts underwent four hours of SCS with four G-LN variants: O2- or N2-cyclic-nigerosyl-nigerose-nanomonomers (CNN), and O2- or N2-cyclic-nigerosyl-nigerose-nanosponges (CNN-NS). We monitored physiological-hemodynamic parameters and molecular markers during reperfusion to assess cell damage/protection. Hearts treated with nanomonomers (N2-CNN or O2-CNN) showed improvements in left ventricular developed pressure (LVDP) and a trend towards faster recovery of the rate pressure product (RPP) compared to controls. However, nanosponges (N2-CNN-NS or O2-CNN-NS) did not show similar improvements. None of the groups exhibited an increase in diastolic left ventricular pressure (contracture index) during reperfusion. Redox markers and apoptosis/autophagy pathways indicated an increase in Beclin 1 for O2-CNN and in p22phox for N2-CNN, suggesting alterations in autophagy and the redox environment during late reperfusion, which might explain the gradual decline in heart performance. The study highlights the potential of nanomonomers to improve early cardiac performance and mitigate cold/H/R-induced stunning in HTx. These early improvements suggest a promising avenue for increasing HTx success. Nevertheless, further research and optimization are needed before clinical application.

Association between Aquaporin 7 Expression and Myocardial Protection with Nicorandil or Del Nido Cardioplegia: An Experimental Study

Background: Aquaporin 7 (AQP7), a member the aquaglyceroporin subgroup of the AQP family, is a water channel that controls transport of glycerol and water in heart tissues. It facilitates the uptake of glycerol, a substrate for cardiac energy production, in cardiomyocytes. St. Thomas' Hospital cardioplegic solution No. 2 has cardio-protective effect even in AQP7-deficient hearts. Here, we aimed to determine whether nicorandil or del Nido cardioplegia (DNC) solution can protect AQP7-deficient hearts. Methods: The hearts of male AQP7 knockout (KO) and wild-type (WT) C57/B6N mice (age >15 weeks) were aerobically perfused using the Langendorff technique, and cardiac function was measured as left ventricular diastolic pressure (LVDP) throughout the study. Troponin T was measured as an indicator of myocardial damage after reperfusion for 60 min. We compared WT and KO controls subjected to 25 min of global ischemia as well as WT and KO groups infused with nicorandil (100 µM) for 10 min followed by 25 min of global ischemia. We also compared WT-DNC and KO-DNC hearts administered with DNC for 2 min followed by 23 min of global ischemia (Study 2). Results: The final recovery rates of LVDP were 20.8 ± 7.0%, 28.1 ± 7.6%, 40.0 ± 8.4%, and 38.7 ± 4.7% in the WT control, KO control, WT nicorandil, and KO nicorandil groups, respectively. The LVDP recovered faster in the hearts treated with DNC and reached a significantly higher plateau in the KO than in the WT hearts. Troponin T values were 2144 ± 493 and 1313 ± 717 in the WT and KO groups, respectively (p = 0.041). Conclusion: The Langendorff perfusion model revealed similar myocardial protective effects of nicorandil in AQP7-deficient mice as in WT mice. AQP7 deficiency did not impair the cardioprotective effects of DNC solution.

Conduit Flow Compensates for Impaired Left Atrial Passive and Booster Functions in Advanced Diastolic Dysfunction.

Quantification of left atrial (LA) conduit function and its contribution to left ventricular (LV) filling is challenging because it requires simultaneous measurements of both LA and LV volumes. The functional relationship between LA conduit function and the severity of diastolic dysfunction remains controversial. We studied the role of LA conduit function in maintaining LV filling in advanced diastolic dysfunction. We performed volumetric and flow analyses of LA function across the spectrum of LV diastolic dysfunction, derived from a set of consecutive patients undergoing multiphasic cardiac computed tomography scanning (n=489). From LA and LV time-volume curves, we calculated 3 volumetric components: (1) early passive emptying volume; (2) late active (booster) volume; and (3) conduit volume. Results were prospectively validated on a group of patients with severe aortic stenosis (n=110). The early passive filling progressively decreased with worsening diastolic function (P<0.001). The atrial booster contribution to stroke volume modestly increases with impaired relaxation (P=0.021) and declines with more advanced diastolic function (P<0.001), thus failing to compensate for the reduction in early filling. The conduit volume increased progressively (P<0.001), accounting for 75% of stroke volume (interquartile range, 63-81%) with a restrictive filling pattern, compensating for the reduction in both early and booster functions. Similar results were obtained in patients with severe aortic stenosis. The pulmonary artery systolic pressure increased in a near-linear fashion when the conduit contribution to stroke volume increased above 60%. Maximal conduit flow rate strongly correlated with mitral E-wave velocity (r=0.71; P<0.0001), indicating that the increase in mitral E wave in diastolic dysfunction represents the increased conduit flow. An increase in conduit volume contribution to stroke volume represents a compensatory mechanism to maintain LV filling in advanced diastolic dysfunction. The increase in conduit volume despite increasing LV diastolic pressures is accomplished by an increase in pulmonary venous pressure.

ATP releasing channels and the ameliorative effects of high intensity interval training on diabetic heart: a multifaceted analysis

Type 2 diabetes (T2D) can cause severe cardiac complications at functional, histologic and molecular levels. These pathological complications could be mediated by ATP-releasing channels such as Panx1 and ATP receptors, in particular P2X7. The aim of our study was to investigate the effect of high-intensity interval training (HIIT) on T2D-induced cardiac complications at the functional, histopathological and molecular levels, with a particular focus on ATP-releasing channels. 48 male Wistar rats at the age of 8 weeks were randomly allocated into four groups: control (Con), Diabetes (T2D), Training (TR), and Diabetes + Training (T2D + TR). T2D was induced by a high-fat diet plus a low dose (35 mg/kg) of STZ administration. Rats in the TR and T2D + TR groups underwent an 8-weeks training program involving intervals ranging from 80 to 100% of their maximum running speed (Vmax), with 4–10 intervals per session. Protein expression of Interleukin 1β (IL1β), Interleukin 10 (IL-10), Pannexin 1 (Panx1), P2X7R (purinergic P2X receptor 7), NLRP1 (NLR Family Pyrin Domain Containing 1), BAX, and Bcl2 were measured in the heart tissue. Additionally, we assessed heart function, histopathological changes, as well as insulin resistance using the homeostasis model assessment of insulin resistance (HOMA-IR). In contrast to the T2D group, HIIT led to increased protein expression of Bcl2 and IL-10 in the heart. It also resulted in improvements in systolic and diastolic blood pressures, heart rate, ± dp/dt (maximum and minimum changes in left ventricular pressure), while reducing protein expression of IL-1β, Panx1, P2X7R, NLRP1, and BAX levels in the heart. Furthermore, left ventricular diastolic pressure (LVDP) was reduced (P ≤ 0.05). Moreover, heart lesion scores increased with T2D but decreased with HIIT, along with a reduction in fibrosis percentage (P ≤ 0.05). The results of this study suggest that the cardioprotective effects of HIIT on the diabetic heart may be mediated by the modulation of ATP-releasing channels. This modulation may lead to a reduction in inflammation and apoptosis, improve cardiac function, and attenuate cardiac injury and fibrosis.

Reduction of left ventricular diastolic pressure as a key regulator of infarct coronary flow under mechanical left ventricular support.

Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Acute mechanical left ventricular (LV) support has been suggested to improve infarct tissue perfusion. However, its regulatory mechanism remains unclear. We investigated the physiological mechanisms in six Yorkshire pigs, which were subjected to 90-min balloon occlusion of the left anterior descending artery. During the acute reperfusion phase, LV support using an Impella heart pump was initiated. LV pressure, coronary flow and pressure of the infarct artery were simultaneously recorded to evaluate the impact of LV support on coronary physiology. Coronary wave intensity was calculated to understand the forces regulating coronary flow. Significant increases in coronary flow velocity and its area under the curve were found after mechanical LV support. Among the coronary flow-regulating factors, coronary pressure was increased mainly during the late diastolic phase with less pulsatility. Meanwhile, LV pressure was reduced throughout diastole resulting in significant and consistent elevation of coronary driving pressure. Interestingly, the duration of diastole was prolonged with LV support. In the wave intensity analysis, the duration between backward suction and pushing waves was extended, indicating that earlier myocardial relaxation and delayed contraction contributed to the extension of diastole. In conclusion, mechanical LV support increases infarct coronary flow by extending diastole and augmenting coronary driving pressure. These changes were mainly driven by reduced LV diastolic pressure, indicatingthat the key regulator of coronary flow under mechanical LV support is downstream of the coronary artery, rather than upstream. Our study highlights the importance of LV diastolic pressure in infarct coronary flow regulation. KEY POINTS: Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Although mechanical left ventricular (LV) support has been suggested to improve infarct coronary flow, its specific mechanism remains to be clarified. LV support reduced LV pressure, and elevated coronary pressure during the late diastolic phase, resulting in high coronary driving pressure. This study demonstrated for the first time that mechanical LV support extends diastolic phase, leading to increased infarct coronary flow. Future studies should evaluate the correlation between improved infarct coronary flow and resulting infarct size.

Long-term outcomes and reverse remodelling in recently diagnosed unexplained left ventricular systolic dysfunction.

In patients with recently diagnosed non-ischaemic LV systolic dysfunction, left ventricular reverse remodelling (LVRR) and favourable prognosis has been documented in studies with short-term follow-up. The aim of our study was to assess the long-term clinical course and stability of LVRR in these patients. We prospectively studied 133 patients (37 women; 55 [interquartile range 46, 61] years) with recently diagnosed unexplained LV systolic dysfunction, with heart failure symptoms lasting <6months and LV ejection fraction <40% persisting after at least 1week of therapy. All patients underwent endomyocardial biopsy (EMB) at the time of diagnosis and serial echocardiographic and clinical follow-up over 5years. LVRR was defined as the combined presence of (1) LVEF≥50% or increase in LVEF≥10% points and (2) decrease in LV end-diastolic diameter index (LVEDDi)≥10% or (3) LVEDDi≤33mm/m2. LVRR was observed in 46% patients at 1year, in 60% at 2years and 50% at 5years. Additionally, 2% of patients underwent heart transplantation and 12% experienced heart failure hospitalization. During 5-year follow-up, 23 (17%) of the study cohort died. In multivariate analysis, independent predictors of mortality were baseline right atrial size (OR 1.097, CI 1.007-1.196), logBNP level (OR 2.02, CI 1.14-3.56), and PR interval (OR 1.02, CI 1.006-1.035) (P<0.05 for all). The number of macrophages on EMB was associated with overall survival in univariate analysis only. LVRR at 1year of follow-up was associated with a lower rate of mortality and heart failure hospitalization (P=0.025). In multivariate analysis, independent predictors of LVRR were left ventricular end-diastolic volume index (OR 0.97, CI 0.946-0.988), LVEF (OR 0.89, CI 0.83-0.96), and diastolic blood pressure (OR 1.04, CI 1.01-1.08) (P<0.05 for all). LVRR occurs in over half of patients with recent onset unexplained LV systolic dysfunction during first 2years of optimally guided heart failure therapy and then remains relatively stable during 5-year follow-up. Normalization of adverse LV remodelling corresponds to a low rate of mortality and heart failure hospitalizations during long-term follow-up.

The Role of Arterial Elasticity in Determining the Degree of Chronic Heart Failure in Myocardial Infarction.

Aim To study the left ventricular (LV) contractile and pumping function during the recovery phase following ligation of the anterior descending coronary artery (CA).Material and methods Cardiodynamic parameters were studied in Wistar rats 2-4 weeks after experimental myocardial infarction (MI). MI was induced by ligation of the anterior descending CA under zoletil anesthesia. LV catheterization was performed with a standard FTH-1912B-8018 PV catheter inserted into the LV through the right carotid artery.Results After the induction of MI, the mortality rate of animals was 50%. Survived animals developed significant LV dilatation and a decrease in ejection fraction (EF) by an average of 31%. However, major indexes of the pumping function, including minute volume, heart work, and maximum ejection velocity, were within a normal range whereas the maximum filling velocity was almost doubled. Approximately 50% of hearts with dilated LV had normal EF, delayed relaxation, and increased LV diastolic pressure, which qualified this group as a diastolic dysfunction group. The systolic dysfunction group with EF less than 50% of normal had similar values of myocardial contractility and relaxation but differed from the diastolic dysfunction group in more than 50% reduced maximum LV ejection velocity and 1.7 times increased elasticity of the arterial wall. A close inverse correlation was found between these values (r= -0.91).Conclusion The study results showed that, with a similar myocardial contractile function, the cardiac pumping function is determined by the elasticity of the aortic wall. Therefore, restriction of reactive fibrosis during MI is an important task of modern cardiology.

Rats with Postinfarction Heart Failure: Effects of Propranolol Therapy on Intracellular Calcium Regulation and Left Ventricular Function

Patients with heart failure may live longer if they receive chronic treatment with beta-adrenergic blocking medications. Unresolved are the mechanisms underlying the beneficial effects and if they may be applied to ischemic heart failure. Rats (n = 28) underwent echocardiographic-Doppler exams one and six weeks following a simulated operation or myocardial infarction (MI). After the first echocardiography, rats were randomized to either no therapy or 500 mg/l of propranolol in their drinking water. The noninfected left ventricular (LV) papillary muscles were used to record isometric contractions and intracellular Ca transients simultaneously. Untreated MI rats had a restrictive LV diastolic filling pattern, decreased systolic function (13% ± 2%), and significant LV dilatation (10.6 ± 0.4 mm vs. 8.9 ± 0.3 mm, MI vs. control). The LV chamber diameters of the propranolol-treated MI rats were 10.6 ± 0.5 mm, and systolic performance (13% ± 2%). Higher LV end-diastolic pressures (27 ± 2 mmHg vs. 20 ± 3 mmHg) and a more constrained LV diastolic filling pattern (increased ratio of early to late filling velocities and faster E wave deceleration rate) were seen in the propranolol-treated animals. Papillary muscle contractility in untreated MI rats was lower (1.6 ± 0.3 g mm²). Furthermore, the inotropic response to isoproterenol was attenuated, and Ca transients were extended. During isoproterenol stimulation, beta-adrenergic blocking administration had no effect on force development (1.6 ± 0.3 g mm²) or the length of Ca transients. Rats with postinfarction heart failure receiving chronic propranolol treatment did not have improvements in systolic function or LV remodeling. Propranolol exacerbated LV diastolic pressures and filling patterns. Additionally, there was no discernible improvement in intracellular contractility following treatment, Calcium control, or beta-adrenergic sensitivity in the myocardium that is not infarcted).

Mechanical LV support lowers diastolic LV pressure and prolongs diastolic coronary flow in the infarcted artery

Abstract Background Percutaneous left ventricular (LV) assist device provides not only circulatory support but also LV unloading. However, impact of LV unloading on coronary flow and mechanisms by which it is regulated remain unclear. We aimed to elucidate potential effects of LV unloading on coronary physiology in a pig model of myocardial infarction (MI). Methods First, six Yorkshire pigs underwent mechanical LV unloading using Impella two weeks after percutaneous MI induction. Regional blood flow (RBF) in infarct, border and remote myocardium were measured by fluorescent microsphere injections before and 120 min after LV unloading (Study 1). Next, we investigated coronary flow patterns with detailed temporal information. Six Yorkshire pigs were subjected to 90-minute balloon occlusion of the middle left anterior descending artery followed by reperfusion. At 60 minutes after reperfusion, LV unloading was initiated and maintained at maximal support. LV pressure, coronary flow and pressure in the infarcted artery were simultaneously recorded. Measurements were repeated with and without LV mechanical support. Coronary wave intensity was calculated from the flow/pressure data (Study 2). Results In Study 1, RBF calculated using microsphere was significantly increased only in the infarct area, but not in the border or remote areas. In Study 2, LV unloading resulted in lower LV pressure during the whole diastolic phase and higher coronary pressure during the late diastolic phase in all animals. Coronary flow velocity was higher throughout the diastole under LV unloading. In addition, the proportion of diastole to the whole cardiac cycle was significantly prolonged with LV unloading. Accordingly, area under the curve of coronary flow was increased during diastole and also for the whole cardiac cycle. In the wave intensity analysis, the magnitude of forward wave intensity was reduced by LV unloading, suggesting that the impact of forces from the aortic side was less significant under continuous device support. The duration between backward suction and pushing waves was extended, implicating earlier relaxation and delayed contraction, further supporting prolonged diastole from the myocardial force perspective. Conclusions Mechanical LV unloading increases coronary flow by prolonging diastolic phase in the infarcted artery.

Acute Hemodynamic Effect of a NovelDual-Vein, Multisite Biventricular Pacing Configuration.

Biventricular pacing (BVP) from multiple left ventricular (LV) sites could enhance the efficacy of cardiac resynchronization therapy (CRT) by engaging a greater myocardial mass. The goal of this study was to evaluate the acute hemodynamic effect of various multisite pacing (MSP) configurations against conventional BVP. Twenty patients with nonischemic dilated cardiomyopathy and left bundle branch block (mean age: 59 ± 14 years; LV ejection fraction: 27% ± 6%; native QRS: 171 ± 16 milliseconds) were investigated during a routine CRT implant procedure. In addition to conventional right atrial and right ventricular leads, 2 quadripolar leads were placed in the distant coronary venous branches. LV hemodynamics was evaluated by using a micromanometer-tipped catheter during atrioventricular BVP with 4 LV lead configurations: single-lead conventional BVP; single-lead multipoint pacing; triventricular pacing from distal dipoles of 2 LV leads; and maximum MSP (MSP-Max) from 4 dipoles of 2 LV leads. Compared with right atrial pacing, any BVP configuration produced a significant increase in the maximal LV diastolic pressure rise (LVdP/dTMax) (amedian relative increase of 28% [IQR: 8%-45%], 25% [IQR: 18%-46%], 36% [IQR: 18%-54%], and 38% [IQR: 28%-58%], respectively; all, P< 0.001). MSP-Max but no other multisite BVP generated a significant increase of the maximal LVdP/dTMax than conventional BVP (P=0.041). Increased LVdP/dTMax during MSP-Max was associated with greater LV diameter and lower LV ejection fraction, independently of the QRS width. The study shows the hemodynamic advantage of a novel dual-vein MSP-Max configuration that could be useful for CRT in patients with advanced LV remodeling.

Dexmedetomidine Preconditioning Attenuates Myocardial Ischemia/Reperfusion Injury in Rats by Suppressing Mitophagy Via Activating Α2-Adrenergic Receptor.

Dexmedetomidine (DEX), a specific α2-adrenergic receptor agonist, is protective against myocardial ischemia/reperfusion injury (MIRI). However, the association between DEX preconditioning-induced cardioprotection and mitophagy suppression remains unclear. Hence, we aimed to investigate whether DEX preconditioning alleviates MIRI by suppressing mitophagy via α2-adrenergic receptor activation. Sixty isolated rat hearts were treated with or without DEX before inducing ischemia and reperfusion; an α2-adrenergic receptor antagonist, yohimbine (YOH), was also administered before ischemia, alone or with DEX. The heart rate (HR), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP), maximal and minimal rate of left ventricular pressure development (±dp/dtmax), and myocardial infarction size were measured. The mitochondrial ultrastructure and autophagosomes were assessed using transmission electron microscopy. Mitochondrial membrane potential and reactive oxygen species (ROS) levels were measured using JC-1 and dichloride hydrofluorescein diacetate assays, respectively. The expression levels of the mitophagy-associated proteins Beclin1, LC3II/I ratio, p62, PINK1, and Parkin were detected by western blotting. Compared with the control group, in the ischemia/reperfusion group, the HR, LVDP, and ±dp/dtmax were remarkably decreased (p< 0.05), whereas LVEDP and infarct sizes were significantly increased (p< 0.05). DEX preconditioning significantly improved cardiac dysfunction reduced myocardial infarction size, maintained mitochondrial structural integrity, increased mitochondrial membrane potential, inhibited autophagosomes formation, and decreased ROS production and Beclin1, LC3II/I ratio, PINK1, Parkin, and p62 expression(p< 0.05). When DEX and YOH were combined, YOH canceled the effect of DEX, whereas the use of YOH alone had no effect. Therefore, DEX preconditioning was cardioprotective against MIRI in rats by suppressing mitophagy via α2-adrenergic receptor activation.

Impact of bimonthly repeated total sleep deprivation and recovery sleep on cardiovascular indices.

Since short sleep duration adversely affects cardiovascular (CV) health, we investigated the effects of exposures to total sleep deprivation (TSD), and baseline (BL) and recovery (REC) sleep on CV measures. We conducted a 5-day experiment at months 2 and 4 in two separate studies (N = 11 healthy adults; 5 females). During these repeated experiments, CV measures [stroke volume (SV), cardiac index (CI), systemic vascular resistance index (SVRI), left ventricular ejection time, heart rate (HR), systolic and diastolic blood pressure (SBP and DBP) and mean arterial pressure (MAP)] were collected at three assessment time points after: (1) two BL 8 h time-in-bed (TIB) sleep opportunity nights; (2) a TSD night; and (3) two REC 8-10 h TIB nights. CV measures were also collected pre-study. TSD significantly increased SV and CI, and decreased SVRI, with large effect sizes, which importantly were reversed with recovery, indicating these measures are possible novel biomarkers for assessing the adverse consequences of TSD. Pre-study SV, CI, SVRI, HR, SBP, and MAP measures also significantly associated with TSD CV responses at months 2 and 4 [Pearson's r: 0.615-0.862; r2 : 0.378-0.743], indicating they are robust correlates of future TSD CV responses. Our novel findings highlight the critical impact of sleep on CV health across time.

Analysis of Relaxation Phase in the Rat Heart

The rate and depth of myocardial relaxation determine left ventricular (LV) filling in early diastole. To analyze the relaxation phase, the method of logarithm of LV pressure fall in rats was used. A gradual acceleration of relaxation was found during the transition from the isovolumic phase to the auxovolumic phase, immediately before the opening of the atrioventricular valves. The relaxation rate constant in this phase has been inversely correlated with the values of the minimum LV diastolic pressure and LV endsystolic volume. The results suggest that the gradual acceleration of relaxation is due to the straightening of the spring-like structure of connectin (titin), which is compressed during contraction.

Non-Invasive Assessment of the Intraventricular Pressure Using Novel Color M-Mode Echocardiography in Animal Studies: Current Status and Future Perspectives in Veterinary Medicine.

The assessment of diastolic function has received great interest in order to comprehend its crucial role in the pathophysiology of heart failure and for the early identification of cardiac events. Silent changes in the intraventricular flow (IVF) dynamics occur before the deterioration of the cardiac wall, although they cannot be detected using conventional echocardiography. Collective information on left ventricular (LV) pressures throughout the cardiac cycle has great value when dealing with patients with altered hemodynamics. Accurate pressure measurement inside the ventricle can be obtained by invasive methods to determine the LV diastolic pressures, which reflect the myocardial relaxation and compliance. However, catheterization is only feasible in the laboratory setting and is not suitable for clinical use due to its disadvantages. In contrast, echocardiography is simple, safe, and accessible. Color M-mode echocardiography (CMME) is an advanced cardiac evaluation technique that can measure the intraventricular pressure differences (IVPDs) and intraventricular pressure gradients (IVPGs) based on the Doppler shift of the IVF. Recently, the assessment of IVPD and IVPG has gained growing interest in the cardiovascular literature in both animal and human studies as a non-invasive method for the early diagnosis of cardiac dysfunctions, especially diastolic ones. The usability of IVPD and IVPG has been reported in various surgically induced heart failure or pharmacologically altered cardiac functions in rats, dogs, cats, and goats. This report aims to give an overview of the current studies of CMME-derived IVPD and IVPG in animal studies and its feasibility for clinical application in veterinary practice and to provide the prospects of the technique's ability to improve our understanding.

Characterization of a robust mouse model of heart failure with preserved ejection fraction.

Heart failure (HF) is a leading cause of morbidity and mortality particularly in older adults and patients with multiple metabolic comorbidities. Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome with multisystem organ dysfunction in which patients develop symptoms of HF as a result of high left ventricular (LV) diastolic pressure in the context of normal or near normal LV ejection fraction (LVEF; ≥50%). Challenges to create and reproduce a robust rodent phenotype that recapitulates the multiple comorbidities that exist in this syndrome explain the presence of various animal models that fail to satisfy all the criteria of HFpEF. Using a continuous infusion of angiotensin II and phenylephrine (ANG II/PE), we demonstrate a strong HFpEF phenotype satisfying major clinically relevant manifestations and criteria of this pathology, including exercise intolerance, pulmonary edema, concentric myocardial hypertrophy, diastolic dysfunction, histological signs of microvascular impairment, and fibrosis. Conventional echocardiographic analysis of diastolic dysfunction identified early stages of HFpEF development and speckle tracking echocardiography analysis including the left atrium (LA) identified strain abnormalities indicative of contraction-relaxation cycle impairment. Diastolic dysfunction was validated by retrograde cardiac catheterization and analysis of LV end-diastolic pressure (LVEDP). Among mice that developed HFpEF, two major subgroups were identified with predominantly perivascular fibrosis and interstitial myocardial fibrosis. In addition to major phenotypic criteria of HFpEF that were evident at early stages of this model (3 and 10 days), accompanying RNAseq data demonstrate activation of pathways associated with myocardial metabolic changes, inflammation, activation of extracellular matrix (ECM) deposition, microvascular rarefaction, and pressure- and volume-related myocardial stress.NEW & NOTEWORTHY Heart failure with preserved ejection fraction (HFpEF) is an emerging epidemic affecting up to half of patients with heart failure. Here we used a chronic angiotensin II/phenylephrine (ANG II/PE) infusion model and instituted an updated algorithm for HFpEF assessment. Given the simplicity in generating this model, it may become a useful tool for investigating pathogenic mechanisms, identification of diagnostic markers, and for drug discovery aimed at both prevention and treatment of HFpEF.

Effects of dandelion root on rat heart function and oxidative status

This study aimed to examine the effects of dandelion root on rat heart function and oxidative status. At the beginning of the experimental protocol, Wistar albino rats were randomly classified into two groups (10 rats per group): 1. control group – animals that drank tap water; 2. experimental group – animals that drank dandelion root for four weeks. Every morning for four weeks, the animals received freshly boiled dandelion root in a volume of 250 ml. At the end of the dandelion administration, animals were sacrificed, and their hearts were isolated and retrogradely perfused according to the Langendorff technique at a gradually increasing perfusion pressure between 40 – 120 cm H2O. The following myocardial function parameters were measured: maximum rate of left ventricular pressure development (dp/dt max), minimum rate of left ventricular pressure development (dp/dt min), systolic left ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), heart rate (HR). In addition, the coronary flow (CF) was measured flowmetrically. Finally, blood samples were collected after sacrificing to determine oxidative stress biomarkers: nitrite (NO2−), superoxide anion radical (O2−), hydrogen peroxide (H2O2), the index of lipid peroxidation (TBARS), reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD). The present pioneer results indicated that dandelion root did not manifest a negative impact on functional aspects of isolated rat heart. In addition, dandelion consumption was not associated with promising results in terms of maintaining systemic redox balance.

Diets Containing Corn Oil, Coconut Oil and Cholesterol Alter Ventricular Hypertrophy, Dilatation and Function in Hearts of Rats Fed Copper-Deficient Diets

Cardiac hypertrophy and function were evaluated in rats fed diets containing deficient, marginal or adequate levels of copper. The fat concentration of the diets was either 10 g/100 g corn oil, 10 g/100 g coconut oil or 10 g/100 g coconut oil + 1 g/100 g added cholesterol. Left ventricular (LV) wall thickening of hearts in rats fed copper-deficient diets was characterized by greater (P < 0.05) LV free wall width, regardless of dietary fat type, and greater intraventricular septum width in the rats fed corn oil. Rats fed the copper-deficient diet with coconut oil + cholesterol had LV chamber volumes that were twofold larger than those of rats fed the copper-deficient diet with coconut oil or corn oil. Copper deficiency reduced LV chamber volume only in rats fed coconut oil + cholesterol. Cardiac LV end diastolic pressure in rats fed copper-deficient diets was twofold larger than in copper-adequate and copper-marginal groups fed corn oil or coconut oil. Hearts from rats fed the copper-deficient diet with corn oil compared with those from rats fed the copper-deficient diet with coconut oil + cholesterol had greater right ventricular (RV) and LV end diastolic pressures, LV pressures and LV and RV maximal rates of positive pressure development. Our data suggest that cardiac adaptations in rats fed copper-deficient diets are influenced by dietary fat type: 1) hearts of rats fed the copper-deficient diet with corn oil were concentrically hypertrophied, whereas cardiac contractility was maintained in the presence of high preload; 2) preload and contractility in hearts of coconut oil-fed rats was greater than cardiac response to cholesterol addition to the coconut oil diet; 3) hearts in copper-deficient rats fed coconut oil + cholesterol exhibited eccentric hypertrophy and ventricular dysfunction.

Time domain adaptation of left ventricular diastolic intraventricular pressure in elite female ice hockey athletes.

Ice hockey is a high-intensity dynamic sport for which competitive athletes train for longer than 20 hours each week for several years. The cumulative time of myocardial exposure to hemodynamic stress affects cardiac remodeling. However, the intracardiac pressure distribution of the elite ice hockey athletes' heart during adaptation to long-term training remains to be explored. This study aimed to compare the diastolic intraventricular pressure difference (IVPD) of the left ventricle (LV) between healthy volunteers and ice hockey athletes with different training times. Fifty-three female ice hockey athletes (27 elite and 26 casual) and 24 healthy controls were included. The diastolic IVPD of the LV during diastole was measured by vector flow mapping. The peak amplitude of the IVPD during isovolumic relaxation (P0), diastolic rapid filling (P1), and atrial systole (P4); the difference in the peak amplitude between adjacent phases (DiffP01, DiffP14); the time interval between the peak amplitude of adjacent phases (P0P1, P1P4); and the maximum decrease rate in diastolic IVPD were calculated. Differences between groups, as well as correlations between hemodynamic parameters and training time, were analyzed. Structural parameters of the LV were significantly higher in elite athletes than in casual players and controls. No significant difference in the peak amplitude of the IVPD during the diastolic phase was found among the three groups. The analysis of covariance with heart rate as a covariate showed that P1P4 in the elite athlete and casual player groups was significantly longer than that in the healthy control group (p < 0.001 for all). An increased P1P4 was significantly associated with an increased training year (β = 4.90, p < 0.001). The diastolic cardiac hemodynamics of the LV in elite female ice hockey athletes could be characterized by a prolonged diastolic IVPD, and P1P4 prolonged with an increase in the training years, reflecting a time-domain adaptation in diastolic hemodynamics after long-term training.

Left Atrial Strain: Crucial Cardiac Navigator in Practice

Left ventricular (LV) diastolic pressure estimation is essential for characterization of heart failure. Despite extensive research and the availability of numerous metrics, the assessment of LV diastolic pressures both at rest and after exertion has been challenging. Left atrial strain assessment by echocardiography has recently shown promise in correlating with LV end-diastolic pressure. This review provides information about this novel technology.

570 FRAILTY AND DISABILITY IN OLDER PATIENTS AND THE EFFECTS OF APIXABAN ON QUALITY OF LIFE AND DEPRESSIVE SYMPTOMS. THE EXPERIENCE OF THE APULEIO STUDY

Abstract Introduction The APULEIO study was designed to describe the psychological effects of apixaban in Italian elderly patients with non-valvular atrial fibrillation (NVAF), deep vein thrombosis (DVT) or pulmonary embolism (PE). The existence of implications of treatment on health-related quality of life (HRQL) and mood is among the most important knowledge gaps in cardiovascular care of older subjects. Real-world data on these issues, essential to improve therapy adherence, are lacking. Aim of the present analysis was to evaluate the presence of a different response to oral anticoagulation in the disabled, frail and robust subjects enrolled in the study. Methods APULEIO was a multicenter, prospective, observational study including apixaban eligible patients. The 12-Item Short Form Health Survey (SF-12), the Beck Depression Inventory-II (BDI-II) and the Frail non-Disabled (FiND) questionnaire were used to evaluate, respectively, HRQL, depressive symptoms and the presence of disability and frailty. The findings of the baseline and the 6-month evaluation - end of the study - will be presented. Results Overall, 376 patients had complete data. Of these, 163 (43.4%), 111 (29.5%) and 102 (27.1%) subjects were, respectively, defined disabled, frail and robust. No differences for reason to anticoagulate were observed by FiND category (p=0.797; overall, AF: 77.1%; DVT/PE: 22.9%). Patients with disability were older (Disabled – D: 79±11; Frail - F: 72±12; Robust – R: 72±12 years; p&amp;lt;0.0001), more frequently women (D: 66.9; F: 43.2; R: 24.5%; p&amp;lt;0.0001), with a greater clinical complexity, as expressed by the CHA2DS2-VASc score (D: 4.3±1.5; F: 3.2±1.5; R: 2.9±1.6; p&amp;lt;0.0001), and showed a higher heart rate (D: 82±17; F: 77±14; R: 77±15 bpm; p=0.0414). BMI (overall, 27.5±4.7 Kg/m2; p=0.328), left ventricular ejection fraction (overall, 53±10%; p=0.453), and systolic (overall, 129±15 mmHg; p=0.219) and diastolic (overall, 76±10 mmHg; p=0.285) arterial pressure were similar among groups. The incidence of any adverse event was higher in those with disability (D: 14.1; F: 8.1; R: 3.9%; p=0.0190), but the proportion of those with serious adverse events was similar among categories (overall, 6.9%; p=0.105). When studying HRQL, at enrollment, the Physical Health composite score of the SF-12 was significantly different among groups (D: 32.7±7.9; F: 42.4±9.3; R: 45.6±8.0; p&amp;lt;0.0001). At the 6-month evaluation (D: 37.0±10.1; F: 43.9±8.8; R: 47.2±7.3; p&amp;lt;0.0001), only the improvement for disabled subjects was significant (p=0.0020). At Baseline, the Mental Health composite score of the SF-12 was lower in disabled and frail patients, when compared to robust ones (D: 46.8±9.8; F: 47.7±9.2; R: 51.4±8.6; p&amp;lt;0.0001). After 6 months, once again, only the improvement for disabled subjects (D: 37.0±10.1; F: 43.9±8.8; R: 47.2±7.3; p=0.0004) was significant (p&amp;lt;0.0001) and statistically greater than that observed for frail and robust patients. Regarding depressive symptoms, at enrollment, the BDI-II score was worse in the disabled and frail groups (D: 14.7±9.8; F: 9.0±8.1; R: 4.7±4.5; p&amp;lt;0.0001). At the 6-month assessment, it was possible to observe an improvement (D: 10.5±8.5; F: 6.8±7.8; R: 4.2±4.5; p&amp;lt;0.0001) in disabled (p&amp;lt;0.0001) and frail subjects (p=0.0112), but not in robust ones (p=0.1705). Conclusions The APULEIO study demonstrates that disability and frailty are common conditions in older subjects anticoagulated for AF and DVT/PE. Disabled patients present a higher clinical complexity than frail and robust ones. After 6 months of therapy, the use of apixaban is associated with a significant improvement of HRQL in disabled individuals and of depressive symptoms in disabled and frail ones. No changes were found in robust subjects. No differences by group were observed in the incidence of serious adverse events. These findings confirm the efficacy and safety of apixaban also when applying a multidimensional approach to high-risk geriatric populations.