Right Ventricle Contractility Research Articles

Progressive right ventricular functional and structural changes in a mouse model of pulmonary arterial hypertension.

Right ventricle (RV) dysfunction occurs with progression of pulmonary arterial hypertension (PAH) due to persistently elevated ventricular afterload. A critical knowledge gap is the molecular mechanisms that govern the transition from RV adaptation to RV maladaptation, which leads to failure. Here, we hypothesize that the recently established mouse model of PAH, via hypoxia and SU5416 treatment (HySu), captures that transition from adaptive to maladaptive RV remodeling including impairments in RV function and decreases in the efficiency of RV interactions with the pulmonary vasculature. To test this hypothesis, we exposed C57BL6 male mice to 0 (control), 14, 21, and 28 days of HySu and then obtained synchronized RV pressure and volume measurements in vivo. With increasing HySu exposure duration, arterial afterload increased monotonically, leading to a continuous increase in RV stroke work, RV fibrosis, and RV wall stiffening (P < 0.05). RV contractility increased at 14 days of HySu exposure and then plateaued (P < 0.05). As a result, ventricular–vascular coupling efficiency tended to increase at 14 days and then decrease. Our results suggest that RV remodeling may begin to shift from adaptive to maladaptive with increasing duration of HySu exposure, which would mimic changes in RV function with PAH progression found clinically. However, for the duration of HySu exposure used here, no drop in cardiac output was found. We conclude that the establishment of a mouse model for overt RV failure due to PAH remains an important task.

Impact of continuous-flow left ventricular assist device support on right ventricular function

Continuous-flow (CF) pumps have yielded improvements in short- and long-term survival and quality of life, and have reduced the number of left ventricular assist device (LVAD)-related complications. However, their ability to unload the right ventricle (RV) and improve RV function has not been as clearly defined. We evaluated the short- and mid-term effects of CF-LVADs on central venous pressure (CVP), pulmonary artery pressures (PAP), pulmonary capillary wedge pressure (PCWP), cardiac index (CI), RV ejection fraction (RVEF), RV end-diastolic dimension (RVEDD), RV stroke work index (RVSWI), tricuspid annular plane systolic excursion (TAPSE) and severity of tricuspid regurgitation (TR). From March 2006 through June 2012, 130 patients with chronic heart failure underwent implantation of a CF-LVAD (122 HeartMate II and 8 HeartWare devices) as a bridge to transplant (n = 76) or as destination therapy (n = 54). Patients with pre-operative long-term LVADs (n = 4) and patients who underwent concomitant tricuspid valve repairs during their LVAD implant (n = 21) were excluded from the analysis. Echocardiograms and right heart catheterizations of the remaining 105 patients were reviewed pre-operatively and at 1 and 6 months post-LVAD implantation. At 1 month post-LVAD implantation, CVP decreased from 12.4 ± 5.9 mm Hg to 8.7 ± 4.5 mm Hg (p < 0.001), systolic PAP decreased from 52.3 ± 14.1 mm Hg to 36.8 ± 11.3 mm Hg (p < 0.001), PCWP decreased from 23.0 ± 9.4 mm Hg to 12.9 ± 8.0 mm Hg (p < 0.001), CI index increased from 1.8 ± 0.5 liters/min m2 to 2.4 ± 0.5 liters/min m2 (p < 0.001), RVEF increased from 33.1 ± 4.9% to 40.4 ± 6.2% (p < 0.001), RVEDD decreased from 36 mm to 31 mm (p = 0.020), RVSWI improved from 408.6 ± 144.6 mm Hg ml m2 to 614.4 ± 196.2 mm Hg ml m2 (p < 0.001), and mean TAPSE increased from 1.1 ± 0.4 cm to 1.9 ± 0.4 cm (p = 0.004). Similarly, qualitative RV function on echocardiography improved from 57.1% moderately or severely reduced pre-operatively to 38.1% at 1 month (p = 0.008). Severity of TR decreased from 11.4% moderate or severe pre-operatively to 4.8% at 1 month (p < 0.001). These improvements were maintained at 6 months post-LVAD. CF-LVAD support significantly decreased CVP and RVEDD, with concomitant improvement in RV function, as measured by increases in RVEF, RVSWI and TAPSE, as well as improvements in the qualitative echocardiographic appearance of RV contractility and a reduction in TR.

World Health Organization Pulmonary Hypertension Group 2: Pulmonary hypertension due to left heart disease in the adult—a summary statement from the Pulmonary Hypertension Council of the International Society for Heart and Lung Transplantation

Pulmonary hypertension associated with left heart disease is the most common form of pulmonary hypertension encountered in clinical practice today. Although frequently a target of therapy, its pathophysiology remains poorly understood and its treatment remains undefined. Pulmonary hypertension in the context of left heart disease is a marker of worse prognosis and disease severity, but whether its primary treatment is beneficial or harmful is unknown. An important step to the future study of this important clinical problem will be to standardize definitions across disciplines to facilitate an evidence base that is interpretable and applicable to clinical practice. In this current statement, we provide an extensive review and interpretation of the current available literature to guide current practice and future investigation. At the request of the Pulmonary Hypertension (PH) Council of the International Society for Heart and Lung Transplantation (ISHLT), a writing group was assembled and tasked to put forth this document as described above. The review process was facilitated through the peer review process of the Journal of Heart and Lung Transplantation and ultimately endorsed by the leadership of the ISHLT PH Council.

Right ventricle dysfunction in heart failure rats following myocardial infarction involves the increment of phospholamban to phosphorilated‐phospholamban ratio

The aim of this study was to assess right ventricle (RV) contractility and proteins involving in calcium transient early (1 week) and late phase (8 weeks) in rats with or without heart failure (HF) after myocardial infarction (MI). The Increment of left ventricle end diastolic pressure, lung weight and body weight ratio and right ventricle to body weight ratio was used to divide MI rats with (HF) and without HF (Inf). The scar size was not different between groups neither was correlated to signals of HF. Strips from RV were superfused with Krebs in an isometric apparatus. The inotropic response to Ca2+ and Isoproterenol were preserved early and reduced late after MI. Inversely, in the Inf group, the positive intropic response was reduced only in the early phase. The SERCA‐2a, phospholamban (PLB total), PLB phosphorylated and Na+/Ca2+ exchange proteins were not different among groups in the early phase. In the late phase there was a SERCA‐2a overexpression only in the Inf group (Sham=0.79±0.05; Inf=1.81±0.06*; HF=0,88±0.1; *P&lt;0.05). There was an increment on SERCA/PLB ratio also in Inf group (Sham=0.8±0.08; Inf=1.33±0.12*; HF=0.87±0.09; *P&lt;0.05). The PLB/PLBPratio was increased only in the HF animals at 8 weeks (Sham=1.19±0.19; Inf=1.72±0.24; HF=3.51±1.04* P&lt;0.05). These results suggest that increased SERCA‐2a expression contribute to maintain RV contractility in Inf group. The reduced RV contractility in the HF group at 8 weeks could be related to the increment on PLB/PLBP ratio.

Hypertonic Saline Hydroxyethylstarch Restores Right Ventricular-Arterial Coupling after Normovolemic Hemodilution in Piglets

Normovolemic hemodilution is known to inhibit hypoxic pulmonary vasoconstriction. How the coupling between the pulmonary arterial (PA) circulation and the right ventricle (RV) is affected by normovolemic hemodilution and by the composition of replacement solutions remains unknown. Therefore, the effects of isotonic and hypertonic saline hydroxyethylstarch solutions on the pulmonary circulation and RV, in control and hypoxic conditions, were compared. Anesthetized piglets (n = 14) were equipped with manometer-tipped catheters in the RV and main PA and an ultrasonic flow probe around the main PA. The pulmonary circulation was assessed by pressure-flow relations and vascular impedance, RV afterload by effective arterial elastance (Ea), RV contractility by end-systolic elastance (Ees), and RV-PA coupling by the Ees/Ea ratio. Measurements were done in control (Fio2 0.40) and hypoxic (Fio2 0.12) conditions before and after acute normovolemic hemodilution with either 20 ml/kg isotonic saline hydroxyethylstarch (hydroxyethylstarch 130/0.4 6% in NaCl 0.9%, Voluven, Fresenius-Kabi, Sevres, France) or 5 ml/kg hypertonic saline hydroxyethylstarch (hydroxyethylstarch 200/0.5 6% in NaCl 7.2%, HyperHES, Fresenius-Kabi) solutions. Hypoxic pulmonary vasoconstriction was associated with proportional increases in Ea and Ees and did not affect RV-PA coupling. Hemodilution attenuated the hypoxic response. Hemodilution with isotonic saline hydroxyethylstarch did not affect the RV-PA coupling, whereas hemodilution with hypertonic saline hydroxyethylstarch increased Ees and the Ees/Ea ratio. In experimental normovolemic hemodilution, both in control and in hypoxic conditions, RV-PA coupling is unaffected by isotonic saline hydroxyethylstarch but improved by hypertonic saline hydroxyethylstarch, mainly because of an increase in RV contractility.

Right Ventricular Failure: A Novel Era of Targeted Therapy

There now is strong evidence to recognize the pivotal role of the right ventricle (RV) in heart disease and to establish it as a unique and separate entity than the left ventricle (LV). Here, we summarize the differences between the two ventricles, the diagnosis of RV failure, and the management of acute and chronic RV failure. We review the indices derived by echocardiography used to measure RV function, and novel biomarkers that may play a role diagnosing and prognosticating in RV-specific disease. There are new novel therapies that specifically target the RV in disease. For example, phosphodiesterase type 5 inhibitors improve contractility of the hypertrophied RV while sparing the normal LV in pulmonary arterial hypertension. The metabolism of the hypertrophied RV is another area for therapeutic exploitation by metabolic modulation. We also suggest future potential molecular targets that may be unique to the RV because they are upregulated in RV hypertrophy greater than in LV hypertrophy.

Influence of metabolism modifiers of cyclic nucleotides on contractility of right ventricle of rat heart with intact and removed endocardial endothelium

Endocardial endothelium, a natural biological barrier between circulating blood in heart ventricle and cells, creates a complex yet finely tuned balance of interactions with the immediate environment. We investigated the roles of theophylline, nonspecific phosphodiesterase inhibitor, and imidazole, an activator of phosphodiesterase on contractility of the right ventricle of rat heart, with intact and removed endocardial endothelium. Adult rats, of both sexes, type Wistar albino, were used in this experiment. All experiments were conducted on the preparations of the right ventricle using two experimental models. In the first experimental model, an endocardial endothelium (EE) was preserved, and in the second model, an endocardial endothelium (-EE) was removed using 1% solution Triton X-100. Theophylline (1 x 10(-2) mol/l) expressed the positive inotropic effect on the heart, regardless of the presence of the endocardial endothelium. Inotropic response as multiple process can be induced by inhibition of phosphodiesterase, accumulation of cyclic nucleotides and activation of Ca2+ channels. Imidazole (2 x 10(-3) mol/l) increased the contractility of the right ventricle of the heart with EE. The modulator effect of endocardial endothelium on contractility of imidazole proved to be significant. As imidazole influenced the contractility of the right ventricle only in the presence of the endocardial endothelium, it is assumed that its effect is mediated via deliverance of endothelial mediators with positive inotropic effect. An intact endocardial endothelium is necessary for completion of contractile performance of the heart.

Impact of right ventricular contractility on left ventricular dyssynchrony in patients with chronic systolic heart failure

Background Cardiac resynchronization therapy (CRT) is an important therapeutic approach for patients with symptomatic heart failure. The assessment of mechanical dyssynchrony, however, remains an issue. Little data are available regarding the influence of the right ventricle (RV) on left ventricle (LV) mechanical dyssynchrony as assessed by echocardiography. Aims We sought to assess the impact of RV contractility on LV function and dyssynchrony. Methods A total of 40 patients with congestive heart failure were analyzed. Twenty had RV dysfunction, as defined by a tricuspid annular systolic peak of tissue Doppler (SaRV) < 11.5 cm/s, while the remaining 20 had SaRV>11.5 cm/s. All patients underwent echocardiography in order to determine RV function, LV function, and dyssynchrony. Results The two populations were similar regarding diastolic function, atrio-ventricular conduction and interventricular dyssynchrony. Patients with RV dysfunction showed significantly more severe LV longitudinal dyssynchrony (130 ± 103 ms vs. 62 ± 59 ms; p = 0.01). In addition, SaRV (systolic peak recorded at the tricuspid annulus) was correlated with LV longitudinal dyssynchrony ( r = 0.47; p = 0.001). In contrast, LV radial contractility and dyssynchrony (103 ± 110 ms vs. 100 ± 78 ms; p = 0.5) were not affected by RV function. Conclusion Quantitative analysis of RV function is important when assessing LV function and dyssynchrony in patients with systolic heart failure. RV function is associated with intra-LV dyssynchrony, particularly when considering longitudinal function.

Can we use the end systolic volume index to monitor intrinsic right ventricular function after repair of tetralogy of Fallot?

After tetralogy of Fallot (ToF) repair the right ventricle (RV) is commonly exposed to abnormal volume load resulting from pulmonary regurgitation (PR) leading to progressive RV dilatation. The objective of this study was to assess the relationship between RV volumes, especially the end systolic volume index (ESVi), and RV contractility in patients after ToF repair and significant PR and to determine whether RV dilatation reflects intrinsic RV dysfunction in these patients. Twenty-nine ToF patients were studied 11.6 (range: 1.9-30.1) years after repair with the pressure-volume conductance system. The patient cohort was divided into two groups according to the median ESVi (group 1: ESVi<34.7 ml/m(2)(×1.18), n = 14; group 2: ESVi ≥ 34.7 ml/m(2)(×1.18), n = 15). The slope of the end systolic pressure-volume relationship (end systolic elastance, Ees) was higher in group 1 compared to group 2 both at baseline and during dobutamine infusion (0.87 ± 0.36 vs. 0.46 ± 0.28 mm Hg/ml and 1.50 ± 0.77 vs. 0.92 ± 0.37 mm Hg/ml; P<0.005 and P = 0.02, respectively). Overall, Ees at baseline correlated significantly with ESVi and also with the end diastolic volume index (r = -0.64, and P<0.001 for both). Receiver operating characteristic curve analysis revealed that ESVi was superior to RV ejection fraction (EF) in predicting an Ees in the lowest quartile of the study group (area under curve ESVi vs. EF: 0.84 (0.64-0.95) vs. 0.68 (0.47-0.85); P = 0.015). ESVi is a valid estimate of intrinsic RV function in repaired ToF patients with residual PR and in this respect seems superior to EF. These data underscore the importance of serial ventricular volume assessment in the follow-up of these patients.

Abstract 5399: Myocardial Contractile Dysfunction is Associated with Fetal Cardiac Bypass in a Sheep Model

Declining cardiac output and placental dysfunction are the key barriers to successful fetal cardiac bypass for in utero repair of congenital heart defects. Identifying myocardial dysfunction, especially in the RV that is considered the systemic ventricle in fetal life, may be important for success. We hypothesized that fetal cardiac bypass results in myocardial contractile dysfunction that reduces cardiac output and placental perfusion, leading to placental dysfunction and fetal demise. Three fetuses from mid-term pregnant ewes were subjected to 30 min of cardiac bypass and followed for 120 min after bypass. Piezoelectric crystals (Sonometrics, Ontario, CA) were placed on three axes of the fetal heart and pressure catheters (Millar Instruments, Houston, TX) were inserted in the left and right ventricle (RV). Data were analyzed by repeated measures ANOVA with Fisher’s PLSD post hoc analyses. Representative RV pressure-volume loops in the figure showed that preload increased after bypass, indicated by increased end-diastolic volume (mean 4.1±.7 vs. 4.4±1 mL) and pressure (mean 14.3 ±7 vs. 31.3± 3 mmHg, P&lt;.05). RV contractility decreased after bypass: pre-bypass dPdt max (mmHg/sec) - 880±93 vs. 731±102 at 120 min after bypass (P≤.1) and dP/dt min - 798±4 vs. 689±11 (P≤.1). Preload recruitable stroke work (slope of regression line) also decreased from 28.5±7 pre-bypass to 22.1±5 at 120 min post-bypass. Increased RV preload and RV contractile dysfunction are evident after fetal cardiac bypass. Minimizing the associated myocardial dysfunction is important for the success of fetal surgery to repair complex congenital heart defects. This research has received full or partial funding support from the American Heart Association, AHA National Center.

Different LV and RV response to α‐adrenergic stimulation in vivo

Objective: α‐adrenergic agonists (α‐Adr) exert positive cardiac inotropic effects. Recent data suggest that rat left ventricle (LV) and right ventricle (RV) respond differently to α‐Adr in vitro. The purpose of this study is to determine whether α‐Adr exerts different effects on the LV and RV in vivo.Methods: Pigs (n=8) were instrumented with micromanometers and sonomicrometry crystals in the LV and RV. Contractility was determined by preload‐adjusted regional external work, a loading condition‐independent index, and regional blood flow by microspheres. Measurements were obtained at baseline, after CaCl2 15 mg‐kg−1 bolus, and during phenylephrine (PHE) 3–6 μg‐kg−1‐min−1 IV for 60 min.Results: LV and RV contractility both increased similarly after CaCl2 (LV: 143±7% of baseline; RV: 145±10% of baseline); in contrast, PHE increased LV but decreased RV contractility (LV: 147±10% of baseline; RV: 90±19% of baseline; p&lt;0.05 for paired difference) despite increased LV and RV pressure. LV and RV regional blood flow both increased during PHE (LV: 0.8±0.2 and RV 0.6±0.1 ml‐gm−1‐min−1 at baseline; LV: 1.5±0.2 and RV: 1.0±0.2 ml‐gm−1‐min−1 during PHE).Conclusions: The α‐Adr agent phenylephrine exerts positive inotropic effects on the LV but negative inotropic effects on the RV in vivo. This difference is not due to differences in loading conditions or regional myocardial blood flow. Supported by NHLBI.

Load-sensitivity of regional tissue deformation in the right ventricle: isovolumic versus ejection-phase indices of contractility

Objective:Doppler myocardial imaging is increasingly being used to evaluate regional and global cardiac function. Quantitative measurements of tissue deformation obtained during ejection as well as isovolumic contraction have been proposed...

Right and left ventricular function after chronic pulmonary artery banding in rats assessed with biventricular pressure-volume loops

In many patients with congenital heart disease, the right ventricle (RV) is subjected to abnormal loading conditions. To better understand the state of compensated RV hypertrophy, which could eventually progress to decompensation, we studied the effects of RV pressure overload in rats. In the present study, we report the biventricular adaptation to 6 wk of pulmonary artery banding (PAB). PAB resulted in an RV pressure overload to approximately 60% of systemic level and a twofold increase in RV mass (P < 0.01). Systemic hemodynamic parameters were not altered, and overt signs of heart failure were absent. Load-independent measures of ventricular function (end-systolic pressure-volume relation, preload recruitable stroke work relation, maximum first time derivative of pressure divided by end-diastolic volume), assessed by means of pressure-volume (PV) loops, demonstrated a two- to threefold increase in RV contractility under baseline conditions in PAB rats. RV contractility increased in response to dobutamine stimulation (2.5 microg.kg(-1).min(-1)) both in PAB and sham-operated rats in a similar fashion, indicating preserved RV contractile reserve in PAB rats. Left ventricular (LV) contractility at baseline was unaffected in PAB rats, although LV volume in PAB rats was slightly decreased. LV contractility increased in response to dobutamine (2.5 microg.kg(-1).min(-1)), both in PAB and sham rats, whereas the response to a higher dose of dobutamine (5 microg.kg(-1).min(-1)) was blunted in PAB rats. RV pressure overload (6 wk) in rats resulted in a state of compensated RV hypertrophy with preserved RV contractile reserve, whereas LV contractile state at baseline was not affected. Furthermore, this study demonstrates the feasibility of performing biventricular PV-loop measurements in rats.

Systemic ventricular function in patients with transposition of the great arteries after atrial repair: a tissue Doppler and conductance catheter study

ObjectivesThe aim of this study was to assess the utility of tissue Doppler echocardiography in the setting of repaired transposition of the great arteries when the right ventricle (RV) functions as the systemic ventricle. BackgroundMyocardial acceleration during isovolumic contraction, “isovolumic myocardial acceleration” (IVA), has been validated as a sensitive non-invasive method of assessing RV contractility. Although traditional indexes may be less valid for the abnormal RV, the relative insensitivity of IVA to an abnormal load makes it a potentially powerful clinical tool for the assessment of RV disease. MethodsWe examined 55 controls and 80 patients (mean age 22 years) with transposition, who had undergone atrial repair at age 8 (0.3 to 72) months. A subgroup of 12 underwent cardiac catheterization. The RV systolic function was derived by analysis of pressure-volume relationships and IVA both at rest and during dobutamine stress. In all 80, myocardial velocities were sampled in the RV free wall. ResultsDuring dobutamine (10 μg/kg/min for 10 min), the increase of IVA mirrored the increase in end-systolic elastance (r = 0.69, p < 0.02). In the group as a whole, IVA was reduced compared with the subpulmonary RV and the systemic left ventricle of controls. There was abnormal wall motion in 44 patients, which was associated with reduced IVA. Diastolic myocardial velocities were also abnormal but unrelated to the presence of wall motion abnormalities. ConclusionsThe IVA can accurately assess changes in RV contractile function in patients with an RV as the systemic ventricle. Global long-axis RV function is reduced in patients with transposition, and this is associated with abnormal regional function.

Management of pulmonary hypertension: physiological and pharmacological considerations for anesthesiologists.

For decades the pulmonary circulation was not considered as important as the systemic (“greater”) circulation. However, pulmonary hypertension can arise because of many diseases of the heart and lung. Therefore, increasing efforts in research have been undertaken leading to a profound increase in un

Right ventricular contractility in myocardial infarctionimplications concerning the measurement of left ventricular filling pressure

Right ventricular contractility in myocardial infarctionimplications concerning the measurement of left ventricular filling pressure