scholarly journals β3-Adrenergic receptor antagonist improves exercise performance in pacing-induced heart failure

2013 ◽  
Vol 305 (6) ◽  
pp. H923-H930 ◽  
Author(s):  
Satoshi Masutani ◽  
Heng-Jie Cheng ◽  
Atsushi Morimoto ◽  
Hiroshi Hasegawa ◽  
Qing-Hua Han ◽  
...  
Keyword(s):  
Heart Failure ◽  
Receptor Antagonist ◽  
Exercise Performance ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Systolic Pressure ◽  
Mechanical Efficiency ◽  
Left Ventricular ◽  
Diastolic Filling ◽  
Stimulation Of

In heart failure (HF), the impaired left ventricular (LV) arterial coupling and diastolic dysfunction present at rest are exacerbated during exercise. We have previously shown that in HF at rest stimulation of β3-adrenergic receptors by endogenous catecholamine depresses LV contraction and relaxation. β3-Adrenergic receptors are activated at higher concentrations of catecholamine. Thus exercise may cause increased stimulation of cardiac β3-adrenergic receptors and contribute to this abnormal response. We assessed the effect of L-748,337 (50 μg/kg iv), a selective β3-adrenergic receptor antagonist (β3-ANT), on LV dynamics during exercise in 12 chronically instrumented dogs with pacing-induced HF. Compared with HF at rest, exercise increased LV end-systolic pressure (PES), minimum LV pressure (LVPmin), and the time constant of LV relaxation (τ) with an upward shift of early diastolic portion of LV pressure-volume loop. LV contractility decreased and arterial elastance (EA) increased. LV arterial coupling (EES/EA) (0.40 vs. 0.51) was impaired. Compared with exercise in HF preparation, exercise after β3-ANT caused similar increases in heart rate and PES but significantly decreased τ (34.9 vs. 38.3 ms) and LVPmin with a downward shift of the early diastolic portion of LV pressure-volume loop and further augmented dV/d tmax. Both EES and EES/EA (0.68 vs. 0.40) were increased. LV mechanical efficiency improved from 0.39 to 0.53. In conclusion, after HF, β3-ANT improves LV diastolic filling; increases LV contractility, LV arterial coupling, and mechanical efficiency; and improves exercise performance.

Vascular β-adrenergic receptor system is dysfunctional after myocardial infarction

2001 ◽  
Vol 280 (3) ◽  
pp. H1129-H1135 ◽  
Author(s):  
Mohamed A. Gaballa ◽  
Andrea Eckhart ◽  
Walter J. Koch ◽  
Steven Goldman
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Carotid Artery ◽  
Membrane Protein ◽  
Adrenergic Receptor ◽  
Vascular Reactivity ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Receptor System

We identified abnormalities in the vascular β-adrenergic receptor (β-AR) signaling pathway in heart failure after myocardial infarction (MI). To examine these abnormalities, we measured β-AR-mediated hemodynamics, vascular reactivity, and the vascular β-AR molecular signaling components in rats with heart failure after MI. Six weeks after MI, these rats had an increased left ventricular (LV) end-diastolic pressure, decreased LV systolic pressure, and decreased rate of LV pressure change (dP/d t). LV dP/d t responses to isoproterenol were shifted downward, although the responses for systemic vascular resistance were shifted upward in heart failure rats ( P < 0.05). Isoproterenol- and IBMX-induced vasorelaxations were blunted in heart failure rats ( P< 0.05) with no change in the forskolin-mediated vasorelaxation. These changes were associated with the following alterations in β-AR signaling ( P < 0.05): decreases in β-AR density (aorta: 58.7 ± 6.0 vs. 35.7 ± 1.9 fmol/mg membrane protein; carotid: 29.6 ± 5.6 vs. 18.0 ± 3.9 fmol/mg membrane protein, n = 5), increases in G protein-coupled receptor kinase activity levels (relative phosphorimage counts of 191 ± 39 vs. 259 ± 26 in the aorta and 115 ± 30 vs. 202 ± 7 in the carotid artery, n = 5), and decreases in cGMP and cAMP in the carotid artery (0.85 ± 0.10 vs. 0.31 ± 0.06 pmol/mg protein and 2.3 ± 0.3 vs. 1.2 ± 0.1 pmol/mg protein, n = 5) with no change in Gαs or Gαi in the aorta. Thus in heart failure there are abnormalities in the vascular β-AR system that are similar to those seen in the myocardium. This suggests a common neurohormonal mechanism and raises the possibility that treatment in heart failure focused on the myocardium may also affect the vasculature.

scholarly journals Features of structural and geometric remodeling of the heart and changes in heart diastolic filling in patients with chronic heart failure of ischemic genesis with reduced left ventricular ejection fraction

2021 ◽  
Vol 23 (1) ◽  
pp. 17-23
Author(s):  
V. A. Lysenko
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Left Ventricular Ejection Fraction ◽  
Left Ventricle ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Diastolic Filling ◽  
Ventricular Ejection Fraction ◽  
Lv Mass

Chronic heart failure (CHF) does not lose its leading position among the problems of cardiovascular disease. Pathological cardiac remodeling combines the processes of hypertrophy and dilatation of cavities and is the main cause of heart failure progression, and consequently results in high cardiac mortality, especially in CHF patients with reduced left ventricular ejection fraction (LV EF). Despite a substantial range of studies on the features of structural and geometric remodeling of the heart, changes in systolic and diastolic function of the ventricles in CHF patients, this issue still presents a challenge and needs to be improved. The aim of the work – to examine changes in structural and geometric parameters and diastolic function of the heart in patients with CHF of ischemic genesis with reduced LV EF. Materials and methods. The study included 79 patients (men – n = 49; women – n = 30) with CHF of ischemic origin with reduced LV EF, sinus rhythm, stage II AB, NYHA II-IV FC (the main group), and 90 patients with coronary heart disease without signs of CHF (men – n = 40, 44.5 %; women – n = 50, 55.5 %), (the comparison group). The patient groups were age-, sex-, height-, weight-, body surface area-matched. Doppler echocardiographic examination was performed on the device Esaote MyLab Eight (Italy). Results. In CHF patients with reduced LV EF, the following indicators prevailed: EDD LV by 18 % (P = 0.001), LV EDV by 45.8 % (P = 0.001), LV EDV index by 44.6 % (P = 0.001), LV ESD by 44.9 % (P = 0.001), PW by 17.7 % (P = 0.001), LV mass index by 66.6 % (P = 0.001) according to the Penn Convention, and by 62.1 % (P = 0.001) according to the ASE; 16.1 % (P = 0.010) increased RV cavity without changes in its wall thickness. In patients with CHF of ischemic origin with reduced LV EF, the main types of LV geometry were: eccentric (70 %) and concentric (24 %) LV hypertrophy. More than half of the CHF patients with reduced LV EF had significant disorders of LV diastolic filling (25 % – “restrictive” and 28 % “pseudonormal”), a 2.3 times increase (P = 0.001) in E/e’ ratio, a 35 % (P = 0.014) increase in the left atrial volume index and 32 % (P = 0.0001) – in pulmonary capillary wedge pressure (PCWP), increased mean and systolic pressure in the pulmonary artery by 1.5 times (P = 0.002) and 1.6 times (P = 0.0001), respectively. Conclusions. Structural and geometric remodeling of the left ventricle in patients with CHF of ischemic origin with reduced LV EF occurs due to an increase in LV myocardial mass via thickening of its walls and cavity dilatation (44.6 % (P = 0.001) increase in the LV EDV index), as well as 66.6 % (P = 0.001) increase in LV mass index with the predominance of eccentric (70 %) and concentric hypertrophy (24 %) over other types of LV geometry. Severe disorders of LV diastolic filling (25 % – “restrictive” and 28 % “pseudonormal”) are attributable to the significant increase in end-diastolic pressure in the left ventricle (2.3 times increase (P = 0.001) in E/e´) with the development of postcapillary pulmonary hypertension (1.5 times increase (P = 0.002) in the mean and 1.6 times (P = 0.0001) – in systolic pressure in the pulmonary artery).

Abstract 902: A Beta-2 Adrenergic Receptor Polymorphism Is Associated With Increased Left Ventricular Remodeling Following First ST-Elevation Myocardial Infarction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Rhondalyn C McLean ◽  
Glenn A Hirsch ◽  
Gary Gerstenblith ◽  
Steven P Schulman
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Receptor Antagonist ◽  
Adrenergic Receptor ◽  
Left Ventricular ◽  
Regression Analyses ◽  
Lv Remodeling ◽  
St Elevation ◽  
Lv Volumes ◽  
Receptor Polymorphism

Background: Prior studies demonstrate an association between specific β-adrenergic receptor polymorphisms and clinical outcomes in patients with chronic heart failure and following an acute coronary syndrome. The mechanism may relate to an effect on left ventricular (LV) remodeling. We hypothesized that β-adrenergic receptor polymorphisms predict LV remodeling after acute ST elevation myocardial infarction (STEMI). Methods: We assessed the presence of β-1 and β-2 adrenergic receptor polymorphisms in 122 patients after their first STEMI enrolled in a single-center randomized, double-blind placebo controlled trial of L-arginine vs. placebo, 91% of whom received successful early reperfusion therapy. All patients were treated with a beta-1 receptor antagonist and underwent baseline (mean 5.9 days following STEMI) and 6-month LV volume evaluation using gated blood pool imaging. Univariate and multivariate linear and logistic regressions were used to assess the relationships between the polymorphisms, β1 Arg389Gly, β1 Ser49Gly, β2 Gly16Arg and β2 Gly27Glu and the six-month changes in LV volumes. The top quintiles of LV end-systolic (ESV) and end-diastolic (EDV) 6-month volume increases and LV ejection fraction decrease were compared to the lower quintiles in the logistic regression analyses. Results: The polymorphisms β1 Arg389Gly, β1 Ser49Gly, β2 Gly16Arg were not associated LV remodeling. However, the 25% of patients homozygous for the β2 Glu27 variant were 5.2 times more likely to have an increase in 6-month ESV than those who had the Gln27 variant (OR 5.2, 95%CI 1.4 –19.0). Multiple linear regression analyses demonstrated that absolute ESV at six months was 19 ml greater (p = 0.02) and EDV was 21 ml greater (p = 0.01) in post STEMI patients with the β2 Glu27 polymorphism compared to the wild type or heterozygous patients. Conclusions: Increased LV volumes post-STEMI are associated with an increased risk of heart failure and death. The common β2 receptor polymorphism, Glu27Glu, is associated with increased odds of adverse LV remodeling in patients treated with a beta-one receptor antagonist. Whether treatment with a non-specific β-adrenergic receptor blocker guided by this genetic polymorphism ameliorates the effect requires further study.

scholarly journals Levosimendan improves LV systolic and diastolic performance at rest and during exercise after heart failure

2005 ◽  
Vol 288 (2) ◽  
pp. H914-H922 ◽  
Author(s):  
Hideo Tachibana ◽  
Heng-Jie Cheng ◽  
Tomohiko Ukai ◽  
Akihiko Igawa ◽  
Zhu-Shan Zhang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Mechanical Efficiency ◽  
Left Ventricular ◽  
Diastolic Filling ◽  
Stroke Work ◽  
Arterial Elastance ◽  
Beneficial Effects ◽  
Total P ◽  
Contractile Performance

The new myofilament Ca2+ sensitizer levosimendan (LSM) is a positive inotropic and vasodilatory agent. Its beneficial effects have been demonstrated at rest in congestive heart failure (CHF). However, its effect during exercise (Ex) in CHF is unknown. We assessed the effects of LSM on left ventricular (LV) dynamics at rest and during Ex in eight conscious, instrumented dogs with pacing-induced CHF. After CHF, with dogs at rest, LSM decreased arterial elastance ( Ea) and increased LV contractile performance as assessed by the slope of LV pressure-volume (P-V) relation. LSM caused a >60% increase in the peak rate of mitral flow (dV/d tmax) due to decreases in minimal LV pressure and the time constant of LV relaxation (τ). LV arterial coupling, quantified as the ratio of end-systolic elastance ( Ees) to Ea, was increased from 0.47 to 0.85%. LV mechanical efficiency, determined as the ratio of stroke work to total P-V area, was improved from 0.54 ± 0.09 to 0.61 ± 0.07. These beneficial effects persisted during Ex after CHF. Compared with CHF Ex dogs, treatment with LSM prevented Ex-induced abnormal increases in mean left atrial pressure and end-diastolic pressure and decreased Ees/ Ea. With LSM treatment during CHF Ex, the early diastolic portion of the LV P-V loop was shifted downward with decreased minimal LV pressure and τ values and a further augmented dV/d tmax. Ees/ Ea improved, and mechanical efficiency further increased from 0.61 ± 0.07 to 0.67 ± 0.07, which was close to the value reached during normal Ex. After CHF, LSM produced arterial vasodilatation; improved LV relaxation and diastolic filling; increased contractility, LV arterial coupling, and mechanical efficiency; and normalized the response to Ex.

Abstract 12583: C-Type Natriuretic Peptide Improves Left Ventricular Systolic and Diastolic Functional Performance at Rest and During Exercise After Heart Failure

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Che Ping Cheng ◽  
Hiroshi Hasegawa ◽  
Atsushi Morimoto ◽  
Heng-Jie Cheng ◽  
William C Little
Keyword(s):  
Heart Failure ◽  
Natriuretic Peptide ◽  
Functional Performance ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Diastolic Filling ◽  
Arterial Elastance ◽  
Beneficial Effects ◽  
Mitral Flow

Background: In heart failure (HF), the impaired left ventricular (LV) arterial coupling and diastolic dysfunction present at rest are exacerbated during exercise (Ex). C-type natriuretic peptide (CNP), the third member of the natriuretic peptide family produced by the vascular endothelium and heart is elevated in HF. However, its functional effects are unclear. We tested the hypotheses that CNP with vasodilating, natriuretic, and lusitropic actions may prevent this abnormal Ex response after HF. Methods: We assessed the effects of CNP on LV functional performance at rest and during submaximum Ex (3.5-5.5 mph for 6-8 min) in 10 instrumented dogs with pacing-induced HF. Since CNP mediated its biological actions via cGMP, we also measured plasma cGMP levels in response to CNP infusion at rest before and after HF. Results: CNP (2 μg/kg plus 0.4 μg/kg/min, iv, 20 min) caused a similar increase in cGMP levels before (7.2±3.8 to 24.7±4.9 pmol/ml) and after HF (20.2±4.4 to 71.6±5.0 pmol/ml). After HF, at rest, CNP reduced LV end-systolic pressure (P ES , CNP: 93 vs Baseline: 104 mmHg), arterial elastance (E A , 8.3 vs 11.7 mmHg/ml) and end-diastolic pressure (P ED , 37.2 vs 42.4 mmHg) (p<0.05). The peak mitral flow (dV/dt max , 201±51 vs 160±34ml/sec) was also increased due to decreased minimum LVP (LVP min , 17.1 vs 23.8 mmHg) and the time constant of LV relaxation (t, 40±4 vs 48±6 msec) (p<0.05). In addition, the slope of LV end-systolic pressure-volume relations (E ES ) was increased (5.6±0.7 vs 4.2±0.9 mmHg/ml). The LV-arterial coupling, quantified as E ES /E A , was improved (0.69±0.22 vs 0.48±0.16) (p<0.05). The beneficial effects persisted during Ex. At matched levels of Ex, treatment with CNP, Ex-induced significantly less increases in P ES (ΔP= 3.4±0.5 vs 7.4±0.8 mmHg), mean LAP (ΔP= -3.1±2.2 vs 3.6±2.9 mmHg), and LVP min (ΔP= -3.6±1.4 vs 1.4±1.2 mmHg) (p<0.05). With CNP, t was much shortened (Δ= -0.8±4.0 vs 2.8±3.2 ms), and the peak mitral flow was further augmented (ΔdV/dt max , 75±20 vs 43±12 ml/sec) (p<0.05). Conclusion: After HF, the generation of cGMP in response to CNP is not blunted. CNP produces arterial vasodilatation and augments LV contraction, relaxation, diastolic filling and LV arterial coupling, thus improving LV performance, both at rest and during Ex after HF.

Inhibition of Glutamatergic Synaptic Input to Spinal Lamina IIo Neurons by Presynaptic α2-Adrenergic Receptors

2002 ◽  
Vol 87 (4) ◽  
pp. 1938-1947 ◽  
Author(s):  
Yu-Zhen Pan ◽  
De-Pei Li ◽  
Hui-Lin Pan
Keyword(s):  
Receptor Antagonist ◽  
Synaptic Input ◽  
Adrenergic Receptors ◽  
Adrenergic Receptor ◽  
Dorsal Root ◽  
Primary Afferents ◽  
Noradrenergic System ◽  
Analgesic Action ◽  
Adrenergic Agonists ◽  
Excitatory Synaptic Input

Activation of spinal α2-adrenergic receptors by the descending noradrenergic system and α2-adrenergic agonists produces analgesia. However, the sites and mechanisms of the analgesic action of spinally administered α2-adrenergic receptor agonists such as clonidine are not fully known. The dorsal horn neurons in the outer zone of lamina II (lamina IIo) are important for processing nociceptive information from C-fiber primary afferents. In the present study, we tested a hypothesis that activation of presynaptic α2-adrenergic receptors by clonidine inhibits the excitatory synaptic input to lamina IIo neurons. Whole cell voltage-clamp recordings were performed on visualized lamina IIo neurons in the spinal cord slice of rats. The miniature excitatory postsynaptic currents (mEPSCs) were recorded in the presence of tetrodotoxin, bicuculline, and strychnine. The evoked EPSCs were obtained by electrical stimulation of the dorsal root entry zone or the attached dorsal root. Both mEPSCs and evoked EPSCs were abolished by application of 6-cyano-7-nitroquinoxaline-2,3-dione. Clonidine (10 μM) significantly decreased the frequency of mEPSCs from 5.8 ± 0.9 to 2.7 ± 0.6 Hz (means ± SE) without altering the amplitude and the decay time constant of mEPSCs in 25 of 27 lamina IIo neurons. Yohimbine (2 μM, an α2-adrenergic receptor antagonist), but not prazosin (2 μM, an α1-adrenergic receptor antagonist), blocked the inhibitory effect of clonidine on the mEPSCs. Clonidine (1–20 μM, n = 8) also significantly attenuated the peak amplitude of evoked EPSCs in a concentration-dependent manner. The effect of clonidine on evoked EPSCs was abolished in the presence of yohimbine ( n = 5). These data suggest that clonidine inhibits the excitatory synaptic input to lamina IIo neurons through activation of α2-adrenergic receptors located on the glutamatergic afferent terminals. Presynaptic inhibition of glutamate release from primary afferents onto lamina IIoneurons likely plays an important role in the analgesic action produced by activation of the descending noradrenergic system and α2-adrenergic agonists.

scholarly journals Right ventricular function and its coupling with the pulmonary circulation in acute heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Barki ◽  
M Losito ◽  
M.M Caracciolo ◽  
F Bandera ◽  
M Rovida ◽  
...  
Keyword(s):  
Heart Failure ◽  
Acute Heart Failure ◽  
Acute Phase ◽  
Pulmonary Circulation ◽  
Heart Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Response To Treatment ◽  
The Right ◽  
B Lines

Abstract Background The right ventricle (RV) is extremely sensitive to hemodynamic changes and increased impedance. In acute heart failure (AHF), the development of pulmonary venous congestion and the increase of left ventricular (LV) filling pressures favors pulmonary vascular adverse remodeling and ultimately RV dysfunction, leading to the onset of symptoms and to a further decay of cardiac dynamics. Purpose The aim of the study was to evaluate RV morphology and functional dynamics at admission and discharge in patients hospitalized for AHF, analyzing the role and the response to treatment of the RV and its coupling with pulmonary circulation (PC). Methods Eighty-one AHF patients (mean age 75.75±10.6 years, 59% males) were prospectively enrolled within 24–48 hours from admission to the emergency department (ED). In either the acute phase and at pre-discharge all patients underwent M-Mode, 2-Dimensional and Doppler transthoracic echocardiography (TTE), as well as lung ultrasonography (LUS), to detect an increase of extravascular lung water (EVLW) and development of pleural effusion. Laboratory tests were performed in the acute phase and at pre-discharge including the evaluation of NT-proBNP. Results At baseline we observed a high prevalence of RV dysfunction as documented by a reduced RV systolic longitudinal function [mean tricuspid annular plane systolic excursion (TAPSE) at admission of 16.47±3.86 mm with 50% of the patients exhibiting a TAPSE&lt;16mm], a decreased DTI-derived tricuspid lateral annular systolic velocity (50% of the subjects showed a tricuspid s' wave&lt;10 cm/s) and a reduced RV fractional area change (mean FAC at admission of 36.4±14.6%). Furthermore, an increased pulmonary arterial systolic pressure (PASP) and a severe impairment in terms of RV coupling to PC was detected at initial evaluation (mean PASP at admission: 38.8±10.8 mmHg; average TAPSE/PASP at admission: 0.45±0.17 mm/mmHg). At pre-discharge a significant increment of TAPSE (16.47±3.86 mm vs. 17.45±3.88; p=0.05) and a reduction of PASP (38.8±10.8 mmHg vs. 30.5±9.6mmHg, p&lt;0.001) was observed. Furthermore, in the whole population we assisted to a significant improvement in terms of RV function and its coupling with PC as demonstrated by the significant increase of TAPSE/PASP ratio (TAPSE/PASP: 0.45±0.17 mm/mmHg vs 0.62±0.20 mm/mmHg; p&lt;0.001). Patients significantly reduced from admission to discharge the number of B-lines and NT-proBNP (B-lines: 22.2±17.1 vs. 6.5±5 p&lt;0.001; NT-proBNP: 8738±948 ng/l vs 4227±659 ng/l p&lt;0.001) (Figure 1). Nonetheless, no significant changes of left atrial and left ventricular dimensions and function were noted. Conclusions In AHF, development of congestion and EVLW significantly impact on the right heart function. Decongestion therapy is effective for restoring acute reversal of RV dysfunction, but the question remains on how to impact on the biological properties of the RV. Funding Acknowledgement Type of funding source: None

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