Afterload-induced diastolic dysfunction contributes to high filling pressures in experimental heart failure with preserved ejection fraction

Leite, Sara; Rodrigues, Sara; Tavares-Silva, Marta; Oliveira‐Pinto, José; Alaa, Mohamed; Abdellatif, Mahmoud; Fontoura, Dulce; Falcão-Pires, Inês; Gillebert, Thierry C.; Leite‐Moreira, Adelino F.; Lourenço, André P.

doi:10.1152/ajpheart.00397.2015

Cited by 36 publications

(30 citation statements)

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“…In the current study the interaction of DVI with increased LV afterload at −20 cmH 2 O is likely responsible for the reduced LVSV. While LV wall stress, as a measure of afterload, was not significantly elevated at −20 cmH 2 O, it may have been elevated to a physiologically relevant level to impair LV relaxation and contribute to a reduced LVEDV (Leite et al., ; Zile, Baicu, & Gaasch, ).…”

Section: Discussionmentioning

confidence: 99%

The haemodynamic response to incremental increases in negative intrathoracic pressure in healthy humans

Cheyne

Gelinas

Eves

2018

Experimental Physiology

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Negative intrathoracic pressure (nITP) generally augments venous return and left ventricular (LV) stroke volume (LVSV), though large increases in nITP, commonly seen in respiratory disease, attenuate LVSV. Despite this consistent finding, the degree of nITP required to reduce LVSV and the contributions of series and direct ventricular interaction (DVI) in mediating this response remain unclear. We hypothesized that nITP ≤-15 cmH O would augment LVSV, while nITP ≥-20 cmH O would reduce LVSV via DVI and increased afterload. Twenty-three healthy subjects were randomly given inspiratory loads during spontaneous breathing to generate -5, -10, -15, -20 and -25 cmH O. LV volumes, LV geometry, inferior vena cava collapsibility (cIVC) and LV end-systolic meridional wall-stress (LVESMWS) were assessed in the supine position using tri-plane echocardiography. LVSV remained unchanged up to -15 cmH O, but was significantly reduced at nITP ≥-20 cmH O (-12 ± 8% and -15 ± 11% at -20 and -25 cmH O, respectively, P < 0.05) due to significant reductions in LV end-diastolic volume (LVEDV), while LV end-systolic volume was unchanged. cIVC on inspiration was significantly increased at all levels of nITP, while LVESMWS only increased at -25 cmH O (P < 0.05). DVI, as indicated by a significant increase in the radius of septal curvature, occurred at nITP ≥-10 cmH O. In supine healthy humans, nITP ≤-15 cmH O does not significantly affect LV function, despite increased DVI. In contrast, nITP ≥-20 cmH O causes significant reductions in LVSV and LVEDV, which appear to be mediated by DVI and increased afterload at -25 cmH O. The impact of cIVC during nITP remains unclear.

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Section: Discussionmentioning

confidence: 99%

The haemodynamic response to incremental increases in negative intrathoracic pressure in healthy humans

Cheyne

Gelinas

Eves

2018

Experimental Physiology

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“…; Leite et al . ).We also calculated ESPVR and EDPVR during hypercapnia (

F_{IC O_{2}}

7%) and hypoxia (

F_{normalI O_{2}}

10%) exposure to estimate the effects of central and peripheral chemoreflex activation on cardiac function, respectively. Volumes were calibrated using arterial blood using the cuvette calibration method (Pacher et al .…”

Section: Methodsmentioning

confidence: 97%

Cardiac diastolic and autonomic dysfunction are aggravated by central chemoreflex activation in heart failure with preserved ejection fraction rats

Toledo

Andrade

Lucero

et al. 2017

The Journal of Physiology

184

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Key pointsr Heart failure with preserved ejection fraction (HFpEF) is associated with disordered breathing patterns, and sympatho-vagal imbalance.r Although it is well accepted that altered peripheral chemoreflex control plays a role in the progression of heart failure with reduced ejection fraction (HFrEF), the pathophysiological mechanisms underlying deterioration of cardiac function in HFpEF are poorly understood.r We found that central chemoreflex is enhanced in HFpEF and neuronal activation is increased in pre-sympathetic regions of the brainstem.r Our data showed that activation of the central chemoreflex pathway in HFpEF exacerbates diastolic dysfunction, worsens sympatho-vagal imbalance and markedly increases the incidence of cardiac arrhythmias in rats with HFpEF.Abstract Heart failure (HF) patients with preserved ejection fraction (HFpEF) display irregular breathing, sympatho-vagal imbalance, arrhythmias and diastolic dysfunction. It has been shown that tonic activation of the central and peripheral chemoreflex pathway plays a pivotal role in the pathophysiology of HF with reduced ejection fraction. In contrast, no studies to date have addressed chemoreflex function or its effect on cardiac function in HFpEF. Therefore, we tested whether peripheral and central chemoreflexes are hyperactive in HFpEF and if chemoreflex activation exacerbates cardiac dysfunction and autonomic imbalance. Sprague-Dawley rats (n = 32) were subjected to sham or volume overload to induce HFpEF. Resting breathing variability, chemoreflex gain, cardiac function and sympatho-vagal balance, and arrhythmia incidence were studied. HFpEF rats displayed [mean ± SD; chronic heart failure (CHF) vs. Sham, respectively] a marked increase in the incidence of apnoeas/hypopnoeas (20.2 ± 4.0 vs. 9.7 ± 2.6 events h −1 ), autonomic imbalance [0.6 ± 0.2 vs. 0.2 ± 0.1 low/high frequency heart rate variability (LF/HF HRV )] and cardiac arrhythmias (196.0 ± 239.9 vs. 19.8 ± 21.7 events h −1 ). Furthermore, HFpEF rats showed increase central chemoreflex sensitivity but not peripheral chemosensitivity. Accordingly, hypercapnic stimulation in HFpEF rats exacerbated increases in sympathetic outflow to the heart (229.6 ± 43.2% vs. 296.0 ± 43.9% LF/HF HRV , normoxia vs. hypercapnia, respectively), incidence of cardiac arrhythmias (196.0 ± 239.9 vs. 576.7 ± 472.9 events h −1 ) and diastolic dysfunction (0.008 ± 0.004 vs. 0.027 ± 0.027 mmHg μl −1 ). Importantly, the cardiovascular consequences of central chemoreflex activation were related to sympathoexcitation since * These authors contributed equally to this work. these effects were abolished by propranolol. The present results show that the central chemoreflex is enhanced in HFpEF and that acute activation of central chemoreceptors leads to increases of cardiac sympathetic outflow, cardiac arrhythmogenesis and impairment in cardiac function in rats with HFpEF.

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“…Methods based on volume‐normalized data acquired in various species are also better when applied to groups rather than individuals, have bias in the high and low pressure range, and limitations in HFpEF . Lastly, contractile reserve is impaired in HFpEF and should also be appraised in experimental models, sudden afterload unmasks low contractile reserve …”

Section: Assessment Of Heart Failure With Preserved Ejection Fractionmentioning

confidence: 99%

An integrative translational approach to study heart failure with preserved ejection fraction: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology

Lourenço

Leite‐Moreira

Balligand

et al. 2017

European J of Heart Fail

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As heart failure with preserved ejection fraction (HFpEF) rises to epidemic proportions, major steps in patient management and therapeutic development are badly needed. With the current position paper we seek to update our view on HFpEF as a highly complex systemic syndrome, from risk factors and mechanisms to long-term clinical manifestations. We will revise recent advances in animal model development, experimental set-ups and basic and translational science approaches to HFpEF research, highlighting their drawbacks and advantages. Directions are provided for proper model selection as well as for integrative functional evaluation from the in vivo setting to in vitro cell function testing. Additionally, we address new research challenges that require integration of higher-order inter-organ and inter-cell communication to achieve a full systems biology perspective of HFpEF.

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Afterload-induced diastolic dysfunction contributes to high filling pressures in experimental heart failure with preserved ejection fraction

Cited by 36 publications

References 32 publications

The haemodynamic response to incremental increases in negative intrathoracic pressure in healthy humans

The haemodynamic response to incremental increases in negative intrathoracic pressure in healthy humans

Cardiac diastolic and autonomic dysfunction are aggravated by central chemoreflex activation in heart failure with preserved ejection fraction rats

An integrative translational approach to study heart failure with preserved ejection fraction: a position paper from the Working Group on Myocardial Function of the European Society of Cardiology

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