Left-Ventricular Energetics in Pulmonary Arterial Hypertension-Induced Right-Ventricular Hypertrophic Failure

Han, June‐Chiew; Guild, Sarah-Jane; Pham, Toan; Nisbet, Linley A.; Tran, Kenneth; Taberner, Andrew J.; Loiselle, Denis S.

doi:10.3389/fphys.2017.01115

Cited by 28 publications

(21 citation statements)

References 48 publications

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“…These include decreased heart rate, decreased mean arterial blood pressure and, most importantly, a 3‐fold increase in RV systolic pressure (Han et al . ).…”

Section: Methodsmentioning

confidence: 97%

Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae

Pham

Nisbet

Taberner

et al. 2018

The Journal of Physiology

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Pulmonary arterial hypertension (PAH) greatly increases the afterload on the right ventricle (RV), triggering RV hypertrophy, which progressively leads to RV failure. In contrast, the disease reduces the passive filling pressure of the left ventricle (LV), resulting in LV atrophy. We investigated whether these distinct structural and functional consequences to the ventricles affect their respective energy efficiencies. We studied trabeculae isolated from both ventricles of Wistar rats with monocrotaline-induced PAH and their respective Control groups. Trabeculae were mounted in a calorimeter at 37°C. While contracting at 5 Hz, they were subjected to stress-length work-loops over a wide range of afterloads. They were subsequently required to undergo a series of isometric contractions at various muscle lengths. In both protocols, stress production, length change and suprabasal heat output were simultaneously measured. We found that RV trabeculae from PAH rats generated higher activation heat, but developed normal active stress. Their peak external work output was lower due to reduced extent and velocity of shortening. Despite lower peak work output, suprabasal enthalpy was unaffected, thereby rendering suprabasal efficiency lower. Crossbridge efficiency, however, was unaffected. In contrast, LV trabeculae from PAH rats maintained normal mechano-energetic performance. Pulmonary arterial hypertension reduces the suprabasal energy efficiency of hypertrophied right ventricular tissues as a consequence of the increased energy cost of Ca cycling.

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“…These include decreased heart rate, decreased mean arterial blood pressure and, most importantly, a 3‐fold increase in RV systolic pressure (Han et al . ).…”

Section: Methodsmentioning

confidence: 97%

Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae

Pham

Nisbet

Taberner

et al. 2018

The Journal of Physiology

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“…Experimental protocols. The experiment commenced with the trabecula stimulated at 4 Hz to replicate the intrinsic rate of beating of the rat heart ex vivo (18). The trabecula was required to undergo both work-loop and isometric contractions.…”

Section: Methodsmentioning

confidence: 99%

Solving a century-old conundrum underlying cardiac force-length relations

Han

Pham

Taberner

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

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In the late 19th century, Otto Frank presented a diagram (Frank O. Z Biol 37: 483–526, 1899) showing that cardiac end-systolic pressure-volume relations are dependent on the mode of contraction: one for isovolumic contractions that locate above that for afterloaded ejecting contractions. Conflicting results to Frank’s have been subsequently demonstrated in various species, both within and among preparations, ranging from the whole hearts to single myocytes, showing a single pressure-volume or force-length relation that is independent of the mode of contraction. Numerous explanations for these conflicting results have been proposed but are mutually contradictory and hence unsatisfying. The present study aimed to explore how these conflicting findings can be reconciled. We thus explored the cardiac force-length relation across a wide spectrum of both preloads and afterloads, encompassing the physiological working range. Experiments were performed using isolated ventricular trabeculae at physiological temperature and stimulus frequency. The force-length relation obtained from isometric contractions was indeed located above a family of those obtained from shortening contractions. Low preload conditions rendered the relation contraction mode independent. High afterload conditions also showed a comparable effect. Our exploration allowed us to reveal the loading conditions that can explain the apparent single, contraction mode-independent, force-length relation that is in contrast with that presented by Frank. Resolving this century-old cardiac conundrum highlights the caution that must be taken when using the end-systolic force-length relation to illustrate as well as to understand the concepts of the Frank-Starling law of the heart, “potential energy,” and cardiac contractility. NEW & NOTEWORTHY Our exploration of the cardiac force-length relation under wide ranges of preload and afterload has allowed us to reconcile conflicting results in the literature regarding its length dependency. We show that the relation is dependent on the mode of contraction but can appear to be otherwise under certain conditions. This finding highlights the need for caution when using the force-length relation to understand key concepts in cardiac physiology.

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“…Pulmonary hypertension (PH) is a kind of refractory rare lung diseases, distal pulmonary arterial remodeling is the characteristic of it [16][17][18]. The pathogenesis of PH is not clear yet, and no effective therapy is available for it.…”

Section: Discussionmentioning

confidence: 99%

The protective of baicalin on pulmonary hypertension vascular remodeling through regulation of TNF-α signaling pathway

Xue¹,

Jiang²,

Sun³

et al. 2020

Preprint

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Background: Pulmonary hypertension (PH) is a life-threatening disease, so far no effective method for it. Baicalin can attenuate pulmonary artery pressure and reduce right ventricular hypertrophy in PH, however, the potential mechanism remains unexplored. Therefore, the main aim of the present study was to investigate the protective effect and of baicalin on experimental PH vascular remodeling, and reveal the underlying mechanism.Methods: Monocrotaline (MCT)-induced PH rats models was established, and baicalin was given by intragastric administration. Six weeks later, right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) were recorded, lung tissue hematoxylin-eosin (H&E) staining was analysis to reveal the effect of baicalin on MCT-induced PH. In Vitro, we established TNF-α induced pulmonary artery smooth muscle cells (PASMCs) to detect the inhibition of baicalin on vascular remodeling. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunofluorescence were used to detect the mRNA and protein expressions.Results: Our results indicated that baicalin could significantly attenuate MCT induced the RVSP and the right ventricular hypertrophy index (RVHI); inhibit pulmonary vascular remodeling and lung fibrosis. Moreover, our results showed baicalin could significantly decrease the expression of inflammatory cytokines, but increase the protein expression of bone morphogenetic protein type II receptor (BMPR2), ID1 and Smad1//5/8.Conclusion:Taken together, our present study confirmed the mechanism of baicalin against PH was associated with inhibition of TNF-α signaling pathway.

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Left-Ventricular Energetics in Pulmonary Arterial Hypertension-Induced Right-Ventricular Hypertrophic Failure

Cited by 28 publications

References 48 publications

Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae

Pulmonary arterial hypertension reduces energy efficiency of right, but not left, rat ventricular trabeculae

Solving a century-old conundrum underlying cardiac force-length relations

The protective of baicalin on pulmonary hypertension vascular remodeling through regulation of TNF-α signaling pathway

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