Bladder compliance dynamics of pelvic organ prolapse in women undergoing robotic-assisted sacrocolpopexy.

STUDY OBJECTIVE: Although mean/static compliance of bladder filling can be readily assayed via cystometry, a protocol measuring compliance dynamics at a specific stage of bladder filling has not been established in human patients. For patients with pelvic organ prolapse (POP), the objective benefits of robotic-assisted sacrocolpopexy (RSCP) surgical intervention for restoring bladder functions, primarily urine storage, have yet to be established. Also, bladder compliance is a viscoelastic parameter crucially defines the storage function. Therefore, we aimed to investigate the impact of RSCP on bladder compliance of POP patients using a pressure-volume analysis (PVA), which graphically illustrate bladder compliance. DESIGN: A retrospective pre- and post-operative study. SETTING: Multiple hospitals in Taiwan. PATIENTS: 27 female POP patients (stage ≥ II). INTERVENTION: RSCP for POP repair. MEASUREMENTS AND MAIN RESULTS: We retrospectively reviewed the pre- and post-operative PVAs for women with POP, who underwent RSCP. The mean compliance of the entire (Cm), the early half (C1/2), and the late half (C2/2) of bladder filling were analyzed as primary outcomes. Changes in intra-vesical volume (ΔVive) and detrusor pressure (ΔPdet) of bladder filling, ΔPdet in the early (ΔPdet1/2) and late (ΔPdet2/2) filling, and post-voiding residual volume (Vres) were analyzed as secondary outcomes. Compared with the pre-operative control, RSCP increased Cm (p=0.010, N=27) and C2/2 (p<0.001, N=27) but negligibly affected C1/2 (p=0.457, N=27). Mechanistically, RSCP decreased ΔPdet (p=0.001, N=27) without significantly affecting ΔVive (p=0.863, N=27). Furthermore, RSCP decreased the ΔPdet2/2 (p<0.001, N=27) but not ΔPdet1/2 (p=0.295, N=27). CONCLUSIONS: This is the first report of applying PVA in assaying dynamics of bladder compliance in patients with POP. Our results suggest that RSCP improved bladder storage in women with POP since it increased bladder compliance, particularly in the late filling possibly by restoring the anatomical location and geometric conformation for bladder expansion. CLINICAL TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov (https://clinicaltrials.gov/study/NCT05682989); registration number: NCT05682989 submitted on 12/28, 2022.

Hemodynamic characterization of a transgenic rat strain stably expressing the calcium sensor protein GCaMP2.

A novel transgenic rat strain has recently been generated that stably expresses the genetically engineered calcium sensor protein GCaMP2 in different cell types, including cardiomyocytes, to investigate calcium homeostasis. To investigate whether the expression of the GCaMP2 protein itself affects cardiac function, in the present work we aimed at characterizing in vivo hemodynamics in the GCaMP2 transgenic rat strain. GCaMP2 transgenic rats and age-matched Sprague-Dawley control animals were investigated. In vivo hemodynamic characterization was performed by left ventricular (LV) pressure-volume analysis. Postmortem heart weight data showed cardiac hypertrophy in the GCaMP2 group (heart-weight-to-tibial-length ratio: 0.26 ± 0.01 GCaMP2 vs. 0.23 ± 0.01 g/cm Co, P < 0.05). We detected elevated mean arterial pressure and increased total peripheral resistance in transgenic rats. GCaMP2 transgenesis was associated with prolonged contraction and relaxation. LV systolic function was not altered in transgenic rats, as indicated by conventional parameters and load-independent, sensitive indices. We found a marked deterioration of LV active relaxation in GCaMP2 animals (τ: 16.8 ± 0.7 GCaMP2 vs. 12.2 ± 0.3 ms Co, P < 0.001). Our data indicated myocardial hypertrophy, arterial hypertension, and impaired LV active relaxation along with unchanged systolic performance in the heart of transgenic rats expressing the GCaMP2 fluorescent calcium sensor protein. Special caution should be taken when using transgenic models in cardiovascular studies. NEW & NOTEWORTHY Genetically encoded Ca2+-sensors, like GCaMP2, are important tools to reveal molecular mechanisms for Ca2+-sensing. We provided left ventricular hemodynamic characterization of GCaMP2 transgenic rats and found increased afterload, cardiac hypertrophy, and prolonged left ventricular relaxation, along with unaltered systolic function and contractility. Special caution should be taken when using this rodent model in cardiovascular pharmacological and toxicological studies.

Acute stimulation of the soluble guanylate cyclase does not impact on left ventricular capacitance in normal and hypertrophied porcine hearts in vivo.

Experimental data indicate that stimulation of the nitric oxide-soluble guanylate cyclase(sGC)-cGMP-PKG pathway can increase left ventricular (LV) capacitance via phosphorylation of the myofilamental protein titin. We aimed to test whether acute pharmacological sGC stimulation with BAY 41-8543 would increase LV capacitance via titin phosphorylation in healthy and deoxycorticosteroneacetate (DOCA)-induced hypertensive pigs. Nine healthy Landrace pigs and 7 pigs with DOCA-induced hypertension and LV concentric hypertrophy were acutely instrumented to measure LV end-diastolic pressure-volume relationships (EDPVRs) at baseline and during intravenous infusion of BAY 41-8543 (1 and 3 µg·kg-1·min-1 for 30 min, respectively). Separately, in seven healthy and six DOCA pigs, transmural LV biopsies were harvested from the beating heart to measure titin phosphorylation during BAY 41-8543 infusion. LV EDPVRs before and during BAY 41-8543 infusion were superimposable in both healthy and DOCA-treated pigs, whereas mean aortic pressure decreased by 20-30 mmHg in both groups. Myocardial titin phosphorylation was unchanged in healthy pigs, but total and site-specific (Pro-Glu-Val-Lys and N2-Bus domains) titin phosphorylation was increased in DOCA-treated pigs. Bicoronary nitroglycerin infusion in healthy pigs ( n = 5) induced a rightward shift of the LV EDPVR, demonstrating the responsiveness of the pathway in this model. Acute systemic sGC stimulation with the sGC stimulator BAY 41-8543 did not recruit an LV preload reserve in both healthy and hypertrophied LV porcine myocardium, although it increased titin phosphorylation in the latter group. Thus, increased titin phosphorylation is not indicative of increased in vivo LV capacitance. NEW & NOTEWORTHY We demonstrate that acute pharmacological stimulation of soluble guanylate cyclase does not increase left ventricular compliance in normal and hypertrophied porcine hearts. Effects of long-term soluble guanylate cyclase stimulation with oral compounds in disease conditions associated with lowered myocardial cGMP levels, i.e., heart failure with preserved ejection fraction, remain to be investigated.

Pressure-volume analysis reveals characteristic sex-related differences in cardiac function in a rat model of aortic banding-induced myocardial hypertrophy.

Sex differences in pressure overload (PO)-induced left ventricular (LV) myocardial hypertrophy (LVH) have been intensely investigated. Nevertheless, sex-related disparities of LV hemodynamics in LVH were not examined in detail. Therefore, we aimed to provide a detailed characterization of distinct aspects of LV function in male and female rats during different stages of LVH. Banding of the abdominal aorta (AB) was performed to induce PO for 6 or 12 wk in male and female rats. Control animals underwent sham operation. The development of LVH was followed by serial echocardiography. Cardiac function was assessed by pressure-volume analysis. Cardiomyocyte hypertrophy and fibrosis were evaluated by histology. At week 6, increased LV mass index, heart weight-to-tibial length, cardiomyocyte diameter, concentric LV geometry, and moderate interstitial fibrosis were detected in both male and female AB rats, indicating the development of an early stage of LVH. Functionally, at this time, impaired active relaxation, increased contractility, and preserved ventricular-arterial coupling were observed in the AB groups in both sexes. In contrast, at week 12, progressive deterioration of LVH-associated structural and functional alterations occurred in male but not female animals with sustained PO. Accordingly, at this later stage, LVH was associated with eccentric remodeling, exacerbated fibrosis, and increased chamber stiffness in male AB rats. Furthermore, augmented contractility declined in male but not female AB animals, resulting in contractility-afterload mismatch. Maintained contractility augmentation, preserved ventricular-arterial coupling, and better myocardial compliance in female rats contribute to sex differences in LV function during the progression of PO-induced LVH. NEW & NOTEWORTHY We investigated sex differences in pressure overload-induced left ventricular myocardial hypertrophy for the first time on the functional level by pressure-volume analysis. We found that left ventricular hypertrophy was initially characterized by prolonged active relaxation, increased contractility, and maintained ventricular-arterial coupling in both sexes. However, at a later stage, augmented contractility declined in mate but not female rats, resulting in contractility-afterload mismatch. Furthermore, in male rats, increased myocardial stiffness also contributed to hypertrophy-associated diastolic dysfunction.

Myocardial reverse remodeling after pressure unloading is associated with maintained cardiac mechanoenergetics in a rat model of left ventricular hypertrophy.

Pressure unloading represents the only effective therapy in increased afterload-induced left ventricular hypertrophy (LVH) as it leads to myocardial reverse remodeling (reduction of increased left ventricular mass, attenuated myocardial fibrosis) and preserved cardiac function. However, the effect of myocardial reverse remodeling on cardiac mechanoenergetics has not been elucidated. Therefore, we aimed to provide a detailed hemodynamic characterization in a rat model of LVH undergoing pressure unloading. Pressure overload was induced in Sprague-Dawley rats by abdominal aortic banding for 6 (AB 6th wk) or 12 wk (AB 12th wk). Sham-operated animals served as controls. Aortic debanding procedure was performed after the 6th experimental week (debanded 12th wk) to investigate the regression of LVH. Pressure unloading resulted in significant reduction of LVH (heart weight-to-tibial length ratio: 0.38 ± 0.01 vs. 0.58 ± 0.02 g/mm, cardiomyocyte diameter: 18.3 ± 0.1 vs. 24.1 ± 0.8 µm debanded 12th wk vs. AB 12th wk, P < 0.05), attenuated the extracellular matrix remodeling (Masson's score: 1.37 ± 0.13 vs. 1.73 ± 0.10, debanded 12th wk vs. AB 12th wk, P < 0.05), provided protection against the diastolic dysfunction, and reversed the maladaptive contractility augmentation (slope of end-systolic pressure-volume relationship: 1.39 ± 0.24 vs. 2.04 ± 0.09 mmHg/µl, P < 0.05 debanded 12th wk vs. AB 6th wk, P < 0.05). In addition, myocardial reverse remodeling was also associated with preserved ventriculoarterial coupling and increased mechanical efficiency (50.6 ± 2.8 vs. 38.9 ± 2.5%, debanded 12th wk vs. AB 12th wk, P < 0.05), indicating a complete functional and mechanoenergetic recovery. According to our best knowledge, this is the first study demonstrating that the regression of LVH is accompanied by maintained cardiac mechanoenergetics.

Strain and strain rate by speckle-tracking echocardiography correlate with pressure-volume loop-derived contractility indices in a rat model of athlete's heart.

Contractile function is considered to be precisely measurable only by invasive hemodynamics. We aimed to correlate strain values measured by speckle-tracking echocardiography (STE) with sensitive contractility parameters of pressure-volume (P-V) analysis in a rat model of exercise-induced left ventricular (LV) hypertrophy. LV hypertrophy was induced in rats by swim training and was compared with untrained controls. Echocardiography was performed using a 13-MHz linear transducer to obtain LV long- and short-axis recordings for STE analysis (GE EchoPAC). Global longitudinal (GLS) and circumferential strain (GCS) and longitudinal (LSr) and circumferential systolic strain rate (CSr) were measured. LV P-V analysis was performed using a pressure-conductance microcatheter, and load-independent contractility indices [slope of the end-systolic P-V relationship (ESPVR), preload recruitable stroke work (PRSW), and maximal dP/dt-end-diastolic volume relationship (dP/dtmax-EDV)] were calculated. Trained rats had increased LV mass index (trained vs. control; 2.76 ± 0.07 vs. 2.14 ± 0.05 g/kg, P < 0.001). P-V loop-derived contractility parameters were significantly improved in the trained group (ESPVR: 3.58 ± 0.22 vs. 2.51 ± 0.11 mmHg/µl; PRSW: 131 ± 4 vs. 104 ± 2 mmHg, P < 0.01). Strain and strain rate parameters were also supernormal in trained rats (GLS: -18.8 ± 0.3 vs. -15.8 ± 0.4%; LSr: -5.0 ± 0.2 vs. -4.1 ± 0.1 Hz; GCS: -18.9 ± 0.8 vs. -14.9 ± 0.6%; CSr: -4.9 ± 0.2 vs. -3.8 ± 0.2 Hz, P < 0.01). ESPVR correlated with GLS (r = -0.71) and LSr (r = -0.53) and robustly with GCS (r = -0.83) and CSr (r = -0.75, all P < 0.05). PRSW was strongly related to GLS (r = -0.64) and LSr (r = -0.71, both P < 0.01). STE can be a feasible and useful method for animal experiments. In our rat model, strain and strain rate parameters closely reflected the improvement in intrinsic contractile function induced by exercise training.

A porcine model of hypertensive cardiomyopathy: implications for heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFPEF) evolves with the accumulation of risk factors. Relevant animal models to identify potential therapeutic targets and to test novel therapies for HFPEF are missing. We induced hypertension and hyperlipidemia in landrace pigs (n = 8) by deoxycorticosteroneacetate (DOCA, 100 mg/kg, 90-day-release subcutaneous depot) and a Western diet (WD) containing high amounts of salt, fat, cholesterol, and sugar for 12 wk. Compared with weight-matched controls (n = 8), DOCA/WD-treated pigs showed left ventricular (LV) concentric hypertrophy and left atrial dilatation in the absence of significant changes in LV ejection fraction or symptoms of heart failure at rest. The LV end-diastolic pressure-volume relationship was markedly shifted leftward. During simultaneous right atrial pacing and dobutamine infusion, cardiac output reserve and LV peak inflow velocities were lower in DOCA/WD-treated pigs at higher LV end-diastolic pressures. In LV biopsies, we observed myocyte hypertrophy, a shift toward the stiffer titin isoform N2B, and reduced total titin phosphorylation. LV superoxide production was increased, in part attributable to nitric oxide synthase (NOS) uncoupling, whereas AKT and NOS isoform expression and phosphorylation were unchanged. In conclusion, we developed a large-animal model in which loss of LV capacitance was associated with a titin isoform shift and dysfunctional NOS, in the presence of preserved LV ejection fraction. Our findings identify potential targets for the treatment of HFPEF in a relevant large-animal model.

Impact of Interventricular Interaction on Ventricular Function: Insights From Right Ventricular Pressure-Volume Analysis.

BACKGROUND: Interventricular interactions may be responsible for the decline in ventricular performance observed in various disease states that primarily affect the contralateral ventricle. OBJECTIVES: This study sought to quantify the impact of such interactions on right ventricular (RV) size and function using clinically stable individuals with left ventricular assist devices (LVADs) as a model for assessing RV hemodynamics while LV loading conditions were acutely manipulated by changing device speed during hemodynamic optimization studies (ie, ramp tests). METHODS: The investigators recorded RV pressure-volume loops with a conductance catheter at various speeds during ramp tests in 20 clinically stable HeartMate3 recipients. RESULTS: With faster LVAD speeds and greater LV unloading, indexed RV end-diastolic volume increased (72.28 ± 15.07 mL at low speed vs 75.95 ± 16.90 at high speed; P = 0.04) whereas indexed end-systolic volumes remained neutral. This resulted in larger RV stroke volumes and shallower end-diastolic pressure-volume relationships. Concurrently, RV end-systolic pressure decreased (31.58 ± 9.75 mL at low speed vs 29.58 ± 9.41 mL at high speed; P = 0.02), but contractility, as measured by end-systolic elastance, did not change significantly. The reduction in RV end-systolic pressure was associated with a reduction in effective arterial elastance from 0.65 ± 0.43 mm Hg/mL at low speed to 0.54 ± 0.33 mm Hg/mL at high speed (P = 0.02). CONCLUSIONS: Interventricular interactions resulted in improved RV compliance, diminished afterload, and did not reduce RV contractility. These data challenge the prevailing view that interventricular interactions compromise RV function, which has important implications for the understanding of RV-LV interactions in various disease states, including post-LVAD RV dysfunction.

Distinct loading conditions reveal various patterns of right ventricular adaptation.

Right ventricular (RV) failure due to chronically abnormal loading is a main determinant of outcome in pulmonary hypertension (PH) and congenital heart disease. However, distinct types of RV loading have been associated with different outcomes. To determine whether the adaptive RV response depends on loading type, we compared hemodynamics, exercise, and hypertrophy in models of pressure overload due to pulmonary artery banding (PAB), pressure overload due to PH, combined pressure and volume overload, and isolated volume load. Ninety-four rats were subjected to either PAB, monocrotaline-induced PH (PH), aortocaval shunt (shunt), or combined monocrotaline and aortocaval shunt (PH + shunt). We performed pressure-volume analysis and voluntary exercise measurements at 4 wk. We compared PAB to PH (part I) and PH + shunt to either isolated PH or shunt (part II). In part I, enhanced contractility (end-systolic elastance and preload recruitable stroke work) was present in PH and PAB, but strongest in PAB. Frank-Starling mechanism was active in both PAB and PH. In PAB this was accompanied by diastolic dysfunction (increased end-diastolic elastance, relaxation constant), clinical signs of RV failure, and reduced exercise. These distinct responses were not attributable to differences in hypertrophy. In part II, in PH + shunt the contractility response was blunted compared with PH, which caused pseudonormalization of parameters. Additional volume overload strongly enhanced hypertrophy in PH. We conclude that different types of loading result in distinct patterns of RV adaptation. This is of importance for the approach to patients with chronically increased RV load and for experimental studies in various types of RV failure.

Rat model of exercise-induced cardiac hypertrophy: hemodynamic characterization using left ventricular pressure-volume analysis.

Long-term exercise training is associated with characteristic structural and functional changes of the myocardium, termed athlete's heart. Several research groups investigated exercise training-induced left ventricular (LV) hypertrophy in animal models; however, only sporadic data exist about detailed hemodynamics. We aimed to provide functional characterization of exercise-induced cardiac hypertrophy in a rat model using the in vivo method of LV pressure-volume (P-V) analysis. After inducing LV hypertrophy by swim training, we assessed LV morphometry by echocardiography and performed LV P-V analysis using a pressure-conductance microcatheter to investigate in vivo cardiac function. Echocardiography showed LV hypertrophy (LV mass index: 2.41 ± 0.09 vs. 2.03 ± 0.08 g/kg, P < 0.01), which was confirmed by heart weight data and histomorphometry. Invasive hemodynamic measurements showed unaltered heart rate, arterial pressure, and LV end-diastolic volume along with decreased LV end-systolic volume, thus increased stroke volume and ejection fraction (73.7 ± 0.8 vs. 64.1 ± 1.5%, P < 0.01) in trained versus untrained control rats. The P-V loop-derived sensitive, load-independent contractility indexes, such as slope of end-systolic P-V relationship or preload recruitable stroke work (77.0 ± 6.8 vs. 54.3 ± 4.8 mmHg, P = 0.01) were found to be significantly increased. The observed improvement of ventriculoarterial coupling (0.37 ± 0.02 vs. 0.65 ± 0.08, P < 0.01), along with increased LV stroke work and mechanical efficiency, reflects improved mechanoenergetics of exercise-induced cardiac hypertrophy. Despite the significant hypertrophy, we observed unaltered LV stiffness (slope of end-diastolic P-V relationship: 0.043 ± 0.007 vs. 0.040 ± 0.006 mmHg/µl) and improved LV active relaxation (τ: 10.1 ± 0.6 vs. 11.9 ± 0.2 ms, P < 0.01). According to our knowledge, this is the first study that provides characterization of functional changes and hemodynamic relations in exercise-induced cardiac hypertrophy.

Quantification of cardiac pumping mechanics in TAVI patients: A pilot study utilizing minimally invasive method for pressure-volume analysis.

The ventriculo-arterial coupling (VAC) and left ventricle (LV) mechanics are crucial and play an important role in the pathophysiology of aortic stenosis (AS). The pressure-volume (PV) analysis is a powerful tool to study VAC and LV mechanics. We proposed a novel minimally-invasive method for PV analysis in patients with severe AS receiving transcatheter aortic valve implantation (TAVI). Patients with severe AS were prospectively enrolled in a single center. LV pressure and cardiac output were recorded before and after TAVI. We constructed the PV loop for analysis by analyzing LV pressure and the assumed flow. 26 patients were included for final analysis. The effective arterial elastance (Ea) decreased after TAVI (3.7 ± 1.3 vs. 2.9 ± 1.1 mmHg/mL, p < 0.0001). The LV end-systolic elastance (Ees) did not change immediately after TAVI (2.4 ± 1.3 vs. 2.6 ± 1.1 mmHg/mL, p = 0.3670). The Ea/Ees improved after TAVI (1.8 ± 0.8 vs. 1.2 ± 0.4, p < 0.0001), demonstrating an immediate improvement of VAC. The stroke work (SW) did not change (7669.6 ± 1913.8 vs. 7626.2 ± 2546.9, p = 0.9330), but the pressure-volume area (PVA) decreased (14469.0 ± 4974.1 vs. 12177.4 ± 4499.9, p = 0.0374) after TAVI. The SW/PVA increased after TAVI (0.55 ± 0.12 vs. 0.63 ± 0.08, p < 0.0001) representing an improvement of LV efficiency. We proposed a novel minimally invasive method for PV analysis in patients with severe AS receiving TAVI. The VAC and LV efficiency improved immediately after TAVI.

Lung Mechanics: A Review of Solid Mechanical Elasticity in Lung Parenchyma.

The lung is the main organ of the respiratory system. Its purpose is to facilitate gas exchange (breathing). Mechanically, breathing may be described as the cyclic application of stresses acting upon the lung surface. These forces are offset by prominent stress-bearing components of lung tissue. These components result from the mechanical elastic properties of lung parenchyma. Various studies have been dedicated to understanding the macroscopic behaviour of parenchyma. This has been achieved through pressure-volume analysis, numerical methods, the development of constitutive equations or strain-energy functions, finite element methods, image processing and elastography. Constitutive equations can describe the elastic behaviour exhibited by lung parenchyma through the relationship between the macroscopic stress and strain. The research conducted within lung mechanics around the elastic and resistive properties of the lung has allowed scientists to develop new methods and equipment for evaluating and treating pulmonary pathogens. This paper establishes a review of mathematical studies conducted within lung mechanics, centering on the development and implementation of solid mechanics to the understanding of the mechanical properties of the lung. Under the classical theory of elasticity, the lung is said to behave as an isotropic elastic continuum undergoing small deformations. However, the lung has also been known to display heterogeneous anisotropic behaviour associated with large deformations. Therefore, focus is placed on the assumptions and development of the various models, their mechanical influence on lung physiology, and the development of constitutive equations through the classical and non-classical theory of elasticity. Lastly, we also look at lung blast mechanics. No explicit emphasis is placed on lung pathology.

Effect of experimental periodontitis on cardiac functions: a comprehensive study using echocardiography, hemodynamic analysis, and histopathological evaluation in a rat model.

Introduction: Periodontitis is a prevalent and severe dental condition characterized by the gradual degradation of the bone surrounding the teeth. Over the past two decades, numerous epidemiological investigations have suggested a potential link between periodontitis and cardiovascular disease. However, the complex mechanistic relationship between oral health issues and cardiovascular disorders remains unclear. Aim: This study aimed to explore comprehensively the cardiac function through various methods, including conventional echocardiography, intraventricular pressure gradient (IVPG) analysis, speckle tracking echocardiography (STE), and hemodynamics analysis. Methods: Ligature-induced periodontitis was established in a group of rats while the second group served as sham. The successful establishment of the periodontitis model was confirmed through staining and radiographic examination of the affected mandibles. Results: X-ray films and methylene blue staining revealed alveolar bone resorption in the affected first molar in the model rats, confirming the successful induction of periodontitis. The rats with periodontitis displayed a decrease in ejection fraction compared to the sham group, accompanied by a decrease in mid-to-apical IVPG and mid IVPG. Lower values of strain rate were recorded in the apical segment of the septum, the middle segment of the septum, and the basal segment of the lateral free wall in the periodontitis group, which was associated with histopathological examination showing some degree of myocardial tissue damage. Conversely, rats with periodontitis showed an increase in heart rate, end-systolic volume, and arterial elastance when compared to the sham rats. However, they also exhibited a decrease in stroke work, stroke volume, cardiac output, and end-systolic pressure. Conclusion: This study suggests that experimental periodontitis may lead to cardiac dysfunction especially compromised systolic function and myocardial relaxation, potentially indicating an increased risk of cardiovascular events in clinical periodontitis cases. The comprehensive assessment of cardiac function, hemodynamics, and histopathological evaluation underscores the profound impact of periodontitis on heart functions within this specific experimental model.

Pressure-Volume Loop Analysis of Voiding Workload: An Application in Trans-Vaginal Mesh-Repaired Pelvic Organ Prolapse Patients.

Although trans-vaginal mesh (TVM) offers a successful anatomical reconstruction and can subjectively relieve symptoms/signs in pelvic organ prolapse (POP) patients, its objective benefits to the voiding function of the bladder have not been well established. In this study, we investigated the therapeutic advantage of TVM on bladder function by focusing on the thermodynamic workload of voiding. The histories of 31 POP patients who underwent TVM repair were retrospectively reviewed. Cystometry and pressure volume analysis (PVA) of the patients performed before and after the operation were analyzed. TVM postoperatively decreased the mean voiding resistance (mRv, p < 0.05, N = 31), reduced the mean and peak voiding pressure (mPv, p < 0.05 and pPv, p < 0.01, both N = 31), and elevated the mean flow rate (mFv, p < 0.05, N = 31) of voiding. While displaying an insignificant effect on the voided volume (Vv, p < 0.05, N = 31), TVM significantly shortened the voiding time (Tv, p < 0.05, N = 31). TVM postoperatively decreased the loop-enclosed area (Apv, p < 0.05, N = 31) in the PVA, indicating that TVM lessened the workload of voiding. Moreover, in 21 patients who displayed postvoiding urine retention before the operation, TVM decreased the residual volume (Vr, p < 0.01, N = 21). Collectively, our results reveal that TVM postoperatively lessened the workload of bladder voiding by diminishing voiding resistance, which reduced the pressure gradient required for driving urine flow.

Pathophysiology and Advanced Hemodynamic Assessment of Cardiogenic Shock.

Cardiogenic shock (CGS) is common and highly morbid. According to the National Inpatient Sample, there are more than 100,000 cases per year, and 30-day mortality approaches 50% despite improvements in critical care practices and novel mechanical therapies targeted at restoring normal hemodynamics. This issue aims to enhance clinicians' understanding of CGS, and this review specifically focuses on the underlying pathophysiology. We examine the definition and etiologies of CGS, approaches to risk assessment, and the pressure-volume loop framework that is the foundation for conceptualizing ventricular mechanics, ventricular-vascular interactions, and the derangements observed in CGS. This overview will also contextualize subsequent chapters that discuss nuances of CGS encountered in particular scenarios (ie, post-myocardial infraction, acutely decompensated chronic heart failure, post-cardiac surgery), address pharmacological and mechanical treatments for CGS, and review CGS in a case-based format.

Longitudinal Strain Reflects Ventriculoarterial Coupling Rather Than Mere Contractility in Rat Models of Hemodynamic Overload-Induced Heart Failure.

BACKGROUND: Longitudinal strain (LS) is a sensitive marker of systolic function. Recent findings suggest that both myocardial contractility and loading conditions determine LS. The aim of this study was to investigate whether LS reflects the connection of cardiac contractility to afterload (termed ventriculoarterial coupling [VAC]) rather than mere contractility in rat models of hemodynamic overload-induced heart failure (HF). METHODS: Pressure overload-induced HF was evoked by transverse aortic constriction (TAC; n = 14). Volume overload-induced HF was established by an aortocaval fistula (ACF; n = 12). Age-matched sham-operated animals served as controls for TAC (n = 14) and ACF (n = 12), respectively. Pressure-volume analysis was carried out to compute contractility (slope of end-systolic pressure-volume relationship [ESPVR]), afterload (arterial elastance [Ea]), and VAC (Ea/ESPVR). Preload was evaluated by meridional end-diastolic wall stress. Speckle-tracking echocardiography was performed to assess LS. RESULTS: The TAC group presented with maintained ESPVR, increased Ea, and enhanced meridional end-diastolic wall stress. In contrast, the ACF group was characterized by reduced ESPVR, decreased Ea, and enhanced meridional end-diastolic wall stress. VAC increased in both HF groups. Furthermore, LS was also impaired in both HF models (-5.9 ± 0.6% vs -12.9 ± 0.5%, TAC vs Shamt [P < .001], and -11.7 ± 0.7% vs -13.5 ± 0.4%, ACF vs Shama[P = .048]). Statistical analysis revealed that strain parameters were determined predominantly by afterload in the TAC group and by contractility in the ACF group, while preload had a minor effect. In the entire study population, LS showed a correlation with VAC (R = 0.654, P < .001) but not with ESPVR (R = 0.058, P = .668). CONCLUSIONS: Under pathophysiologic conditions when both contractility and afterload become altered, LS reflects VAC rather than mere contractility.

Sex Differences in Morphological and Functional Aspects of Exercise-Induced Cardiac Hypertrophy in a Rat Model.

Background: Recent evidences suggest that sex hormones may be involved in the regulation of exercise-induced left ventricular (LV) hypertrophy. However, the sex-specific functional consequences of exercise-induced myocardial hypertrophy is still not investigated in detail. We aimed at understanding the sex-specific functional and morphological alterations in the LV and the underlying molecular changes in a rat model of athlete's heart. Methods: We divided our young, adult male and female rats into control and exercised groups. Athlete's heart was induced by a 12-week long swim training. Following the training period, we assessed LV hypertrophy with echocardiography, while pressure-volume analysis was performed to investigate in vivo LV function. After in vivo experiments, molecular biological studies and histological investigations were performed. Results: Echocardiography and post-mortem measured heart weight data indicated LV hypertrophy in both genders, nevertheless it was more pronounced in females. Despite the more significant relative hypertrophy in females, characteristic functional parameters did not show notable differences between the genders. LV pressure-volume analysis showed increased stroke volume, improved contractility and stroke work and unaltered LV stiffness in both male and female exercised rats, while active relaxation was ameliorated solely in male animals. The induction of Akt signaling was more significant in females compared to males. There was also a characteristic difference in the mitogen-activated protein kinase pathway as suppressed phosphorylation of p44/42 MAPK (Erk) and mTOR was observed in female exercised rats, but not in male ones. Myosin heavy chain α (MHC)/ß-MHC ratio did not differ in males, but increased markedly in females. Conclusion: Our results confirm that there is a more pronounced exercise-induced LV hypertrophy in females as compared to the males, however, there are only minor differences regarding LV function. There are characteristic molecular differences between male and female animals, that can explain different degrees of LV hypertrophy.

Disturbed ventricular-arterial coupling and increased left atrial stiffness in a patient with heart failure with preserved ejection fraction and hyperaldosteronism: a case report.

BACKGROUND: Aldosterone is involved in almost all parts of the cardiovascular system. Hyperaldosteronism causes arterial hypertension and might predispose to stroke, atrial fibrillation, and heart failure. CASE SUMMARY: A 60-year-old obese woman with long-standing hypertension, hypokalaemia, and shortness of breath was admitted to our hospital. Hypertension was caused by primary hyperaldosteronism due to an adenoma of the adrenal gland. Detailed transthoracic echocardiography revealed diastolic dysfunction, disturbed ventricular-arterial interaction, and atrial compliance resulting in heart failure with preserved ejection fraction (HFPEF). Three months of aldosterone antagonist treatment improved ventricular-arterial coupling, while left ventricular diastolic and atrial dysfunction remained unchanged. DISCUSSION: Presumably, hyperaldosteronism is the reason for HFPEF in this case. Standard criteria to diagnose HFPEF include clinical symptoms of heart failure and an ejection fraction (EF) >50% as well as echocardiographically or invasively assessed elevated filling pressures. Single beat pressure-volume analysis gives insights on the pathophysiology of increased filling pressures, showing in our case diastolic dysfunction as well as disturbed ventricular-arterial interaction. Three months of aldosterone antagonist treatment reduced blood pressure with concomitant improvement of ventricular-arterial interaction, thereby reducing stroke work while stroke volume remained nearly unchanged. Diastolic dysfunction and increased atrial stiffness were unaltered.

Assessment of PEEP-Ventilation and the Time Point of Parallel-Conductance Determination for Pressure-Volume Analysis Under ß-Adrenergic Stimulation in Mice.

Aim: Cardiac pressure-volume (PV loop) analysis under ß-adrenergic stimulation is a powerful method to simultaneously determine intrinsic cardiac function and ß-adrenergic reserve in mouse models. Despite its wide use, several key approaches of this method, which can affect murine cardiac function tremendously, have not been experimentally investigated until now. In this study, we investigate the impact of three lines of action during the complex procedure of PV loop analysis: (i) the ventilation with positive end-expiratory pressure, (ii) the time point of injecting hypertonic saline to estimate parallel-conductance, and (iii) the implications of end-systolic pressure-spikes that may arise under ß-adrenergic stimulation. Methods and Results: We performed pressure-volume analysis during ß-adrenergic stimulation in an open-chest protocol under Isoflurane/Buprenorphine anesthesia. Our analysis showed that (i) ventilation with 2 cmH2O positive end-expiratory pressure prevented exacerbation of peak inspiratory pressures subsequently protecting mice from macroscopic pulmonary bleedings. (ii) Estimations of parallel-conductance by injecting hypertonic saline prior to pressure-volume recordings induced dilated chamber dimensions as depicted by elevation of end-systolic volume (+113%), end-diastolic volume (+40%), and end-diastolic pressure (+46%). Further, using this experimental approach, the preload-independent contractility (PRSW) was significantly impaired under basal conditions (-17%) and under catecholaminergic stimulation (-14% at 8.25 ng/min Isoprenaline), the ß-adrenergic reserve was alleviated, and the incidence of ectopic beats was increased >5-fold. (iii) End-systolic pressure-spikes were observed in 26% of pressure-volume recordings under stimulation with 2.475 and 8.25 ng/min Isoprenaline, which affected the analysis of maximum pressure (+11.5%), end-diastolic volume (-8%), stroke volume (-10%), and cardiac output (-11%). Conclusions: Our results (i) demonstrate the advantages of positive end-expiratory pressure ventilation in open-chest instrumented mice, (ii) underline the perils of injecting hypertonic saline prior to pressure-volume recordings to calibrate for parallel-conductance and (iii) emphasize the necessity to be aware of the consequences of end-systolic pressure-spikes during ß-adrenergic stimulation.

Pressure-volume analysis in athyroid patients off and on thyroxine supplementation: a pilot study.

Thyroid hormone importantly affects the cardiovascular system. However, evaluation of stroke volume (SV) and its determinants is confounded by variations in volume status that occur along different thyroid states. This study applied the pressure-volume (PV) framework to obtain relatively load-independent estimates of cardiac function in hypothyroidism as compared to euthyroidism. Ten athyroid patients were assessed echocardiographically after 4 weeks in deep hypothyroid state, and again after supplementation with oral Levothyroxine (LT4) for 3 months. Thyroid hormone levels were assessed and noninvasive pressure-volume (PV) analysis based on dedicated repeated echocardiograms was performed. Changes were assessed using paired tests. Results are presented as medians and interquartile ranges. Hypothyroidism was associated with reduced stroke volume (SV: 67.6 ± 17 vs. 75.7 ± 20.6 mL, P = 0.024), preload (end-diastolic volume, EDV: 122.6 ± 32.5 vs. 135.7 ± 33.6 mL, P = 0.004), and contractility (end-systolic elastance, Ees : 1.7 ± 0.33 vs. 2.58 ± 1.33 mmHg/mL, P = 0.01). Afterload was constant (effective arterial elastance, Ea : 1.66 ± 0.32 vs. 1.79 ± 0.52 mmHg/mL, P = 0.43) and the total energy spent was lower (PVA∙HR: 86.7 ± 28 vs. 110.9 ± 32.1 J, P = 0.04). Hemodynamic manifestations of frank hypothyroidism in humans are characterized by reduced preload and contractility, and unchanged total afterload. LT4 therapy increased work efficiency and heart rate, but not the net energy expenditure. Noninvasive PV analysis may be useful to follow-up different thyroid states.