Single‐Beat Estimation of Right Ventricular Contractility and Its Coupling to Pulmonary Arterial Load in Patients With Pulmonary Hypertension

Increased serotonin serum levels have been proposed to play a key role in pulmonary arterial hypertension (PAH) by regulating vessel tone and vascular smooth muscle cell proliferation. An intact serotonin system, which critically depends on a normal function of the serotonin transporter (SERT), is required for the development of experimental pulmonary hypertension in rodents exposed to hypoxia or monocrotaline. While these animal models resemble human PAH only with respect to vascular media remodeling, we hypothesized that SERT is likewise required for the presence of lumen-obliterating intima remodeling, a hallmark of human PAH reproduced in the Sugen hypoxia (SuHx) rat model of severe angioproliferative pulmonary hypertension. Therefore, SERT wild-type (WT) and knockout (KO) rats were exposed to the SuHx protocol. SERT KO rats, while completely lacking SERT, were hemodynamically indistinguishable from WT rats. After exposure to SuHx, similar degrees of severe angioproliferative pulmonary hypertension and right ventricular hypertrophy developed in WT and KO rats (right ventricular systolic pressure 60 vs. 55 mmHg, intima thickness 38 vs. 30%, respectively). In conclusion, despite its implicated importance in PAH, SERT does not play an essential role in the pathogenesis of severe angioobliterative pulmonary hypertension in rats exposed to SuHx.

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Effects of inhaled iloprost on right ventricular contractility, right ventriculo-vascular coupling and ventricular interdependence: a randomized placebo-controlled trial in an experimental model of acute pulmonary hypertension

Critical Care ◽

10.1186/cc7005 ◽

2008 ◽

Vol 12 (5) ◽

pp. R113 ◽

Cited By ~ 27

Author(s):

Steffen Rex ◽

Carlo Missant ◽

Piet Claus ◽

Wolfgang Buhre ◽

Patrick F Wouters

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Experimental Model ◽

Controlled Trial ◽

Ventricular Contractility ◽

Ventricular Interdependence ◽

Inhaled Iloprost ◽

Acute Pulmonary Hypertension

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Norepinephrine and dobutamine improve cardiac index equally by supporting opposite sides of the heart in an experimental model of chronic pulmonary hypertension

10.21203/rs.3.rs-458360/v1 ◽

2021 ◽

Author(s):

Janus Adler Hyldebrandt ◽

Nikolaj Bøgh ◽

Camilla Omann Christensen ◽

Peter Agger

Keyword(s):

Pulmonary Hypertension ◽

Cardiac Index ◽

Pulmonary Artery ◽

Right Ventricular ◽

Left Ventricular ◽

Ventricular Contractility ◽

End Diastolic Volume ◽

Chronic Pulmonary Hypertension ◽

Blood Pressures ◽

The Right

Abstract Background: Pulmonary hypertension is a significant risk factor in patients undergoing surgery. The combined effects of general anaesthesia and positive pressure ventilation can aggravate this condition and cause increased pulmonary blood pressures, reduced systemic blood pressures and ventricular contractility. Although perioperative use of inotropic support or vasopressors is almost mandatory for these patients, preference is disputed. In this study, we investigated the effects of norepinephrine and dobutamine and their ability to improve the arterio-ventricular relationship and haemodynamics in pigs suffering from chronic pulmonary hypertension.Method: Pulmonary hypertension was induced in five pigs by banding the pulmonary artery at 2–3 weeks of age. Six pigs served as controls. After 16 weeks of pulmonary artery banding, the animals were re-examined under general anaesthesia using biventricular conductance catheters and a pulmonary artery catheter. After baseline measurements, the animals were exposed to both norepinephrine and dobutamine infusions in incremental doses, with a stabilizing period in between the infusions. The hypothesis of differences between norepinephrine and dobutamine with incremental doses was tested using repeated two-way ANOVA and Bonferroni multiple comparisons post-test. Results: At baseline, pulmonary artery banded animals had increased right ventricular pressure (+39%, p=0.04), lower cardiac index (-23% p=0.04), lower systolic blood pressure (-13%, p=0.02) and reduced left ventricular end-diastolic volume (-33%, p=0.02). When incremental doses of norepinephrine and dobutamine were administered, the right ventricular arterio-ventricular coupling was improved only by dobutamine (p<0.05). Norepinephrine increased both left ventricular end-diastolic volume and left ventricular contractility to a greater extent (p<0.05) in pulmonary artery banded animals. While the cardiac index was improved equally by norepinephrine and dobutamine treatments in pulmonary artery banded animals, norepinephrine had a significantly greater effect on mean arterial pressure (p<0.05) and diastolic arterial pressure (p<0.05).Conclusion: While norepinephrine and dobutamine improved cardiac index equally, it was obtained in different manners. Dobutamine significantly improved the right ventricular function and the arterio-ventricular coupling. Norepinephrine increased systemic resistance, thereby improving arterial pressures and left ventricular systolic function by maintaining left ventricular end-diastolic volume.

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Acute Thromboembolic Pulmonary Hypertension In A Dog Model - Correlation Of Right Ventricular Ejection Fraction And Pulmonary Arterial Distensibility Measured By MRI

10.1164/ajrccm-conference.2011.183.1_meetingabstracts.a4979 ◽

2011 ◽

Author(s):

Naomi C. Chesler ◽

Alejandro Roldan-Alzate ◽

Heidi Kellihan ◽

Alex Frydrychowicz ◽

Daniel W. Consigny ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Ejection Fraction ◽

Right Ventricular ◽

Right Ventricular Ejection Fraction ◽

Ventricular Ejection ◽

Arterial Distensibility ◽

Ventricular Ejection Fraction ◽

Thromboembolic Pulmonary Hypertension ◽

Pulmonary Arterial ◽

Model Correlation

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The Clinical Impact of Flow Titration on Epoprostenol Delivery via High Flow Nasal Cannula for ICU Patients with Pulmonary Hypertension or Right Ventricular Dysfunction: A Retrospective Cohort Comparison Study

Journal of Clinical Medicine ◽

10.3390/jcm9020464 ◽

2020 ◽

Vol 9 (2) ◽

pp. 464 ◽

Cited By ~ 1

Author(s):

Jie Li ◽

Payal K. Gurnani ◽

Keith M. Roberts ◽

James B. Fink ◽

David Vines

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Gas Flow ◽

Ventricular Dysfunction ◽

Right Ventricular Dysfunction ◽

Constant Flow ◽

High Flow Nasal Cannula ◽

Refractory Hypoxemia ◽

Pulmonary Arterial ◽

Flow Titration

(1) Background: inhaled epoprostenol (iEPO) delivered via high-flow nasal cannula (HFNC) has been reported to be effective for pulmonary hypertension and right ventricular dysfunction. In vitro studies have identified HFNC gas flow as a key factor in trans-nasal aerosol delivery efficiency; however, little evidence is available on the clinical impact of flow titration on trans-nasal aerosol delivery. At our institution, iEPO via HFNC was initiated in 2015 and the concept of flow titration during iEPO via HFNC has been gradually accepted and carried out by clinicians in the recent years. (2) Methods: a retrospective review of the electronic medical records for all adult patients who received iEPO via HFNC in a tertiary teaching hospital. Pre- and post- iEPO responses were reported for patients whose HFNC flow was titrated or maintained constant during iEPO delivery. Positive response to iEPO was defined as the reduction of mean pulmonary arterial pressure (mPAP) > 10% for pulmonary hypertension patients or the improvement of oxygenation [pulse oximetry (SpO2)/fraction of inhaled oxygen (FIO2)] > 20%. The number of responders to iEPO was compared between groups with titrated vs constant flow. (3) Results: 51 patients who used iEPO to treat pulmonary hypertension and/or right ventricular dysfunction were reviewed. Following iEPO administration via HFNC, mPAP decreased (43.6 ± 11.7 vs. 36.3 ± 9.7 mmHg, p < 0.001). Among the 51 patients, 24 had concomitant refractory hypoxemia, their oxygenation (SpO2/FIO2) improved after iEPO delivery (127.8 ± 45.7 vs. 157.6 ± 62.2, p < 0.001). During iEPO initiation, gas flow was titrated in 25 patients and the remaining 26 patients used constant flow. The percentage of patients in the flow titration group who met the criteria for a positive response was higher compared to the group with constant flow (85.7% vs. 50%, p = 0.035). Pre- vs post-iEPO responses were significant in the flow titration group included improvement in cardiac output (p = 0.050), cardiac index (p = 0.021) and FIO2 reduction (p = 0.016). These improvements in hemodynamics and FIO2 were not observed in the constant flow group. (4) Conclusion: in patients with pulmonary hypertension and/or right ventricular dysfunction, trans-nasal iEPO decreased pulmonary arterial pressure. It also improved oxygenation in patients with combined refractory hypoxemia. These improvements were more evident in patients whose gas flow was titrated during iEPO initiation than those patients using constant flow.

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Right ventricular contractility in systemic sclerosis-associated and idiopathic pulmonary arterial hypertension

European Respiratory Journal ◽

10.1183/09031936.00135407 ◽

2008 ◽

Vol 31 (6) ◽

pp. 1160-1166 ◽

Cited By ~ 71

Author(s):

M. J. Overbeek ◽

J-W. Lankhaar ◽

N. Westerhof ◽

A. E. Voskuyl ◽

A. Boonstra ◽

...

Keyword(s):

Systemic Sclerosis ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Right Ventricular ◽

Idiopathic Pulmonary Arterial Hypertension ◽

Ventricular Contractility ◽

Pulmonary Arterial

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Exogenous Ghrelin Attenuates the Progression of Chronic Hypoxia-Induced Pulmonary Hypertension in Conscious Rats

Endocrinology ◽

10.1210/en.2007-0833 ◽

2007 ◽

Vol 149 (1) ◽

pp. 237-244 ◽

Cited By ~ 34

Author(s):

Daryl O. Schwenke ◽

Takeshi Tokudome ◽

Mikiyasu Shirai ◽

Hiroshi Hosoda ◽

Takeshi Horio ◽

...

Keyword(s):

Nitric Oxide ◽

Pulmonary Hypertension ◽

Right Ventricular ◽

Endothelial Nitric Oxide Synthase ◽

Ventricular Hypertrophy ◽

Chronic Hypoxia ◽

Right Ventricular Hypertrophy ◽

Pulmonary Arterial ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Chronic exposure to hypoxia, a common adverse consequence of most pulmonary disorders, can lead to a sustained increase in pulmonary arterial pressure (PAP), right ventricular hypertrophy, and is, therefore, closely associated with heart failure and increased mortality. Ghrelin, originally identified as an endogenous GH secretagogue, has recently been shown to possess potent vasodilator properties, likely involving modulation of the vascular endothelium and its associated vasoactive peptides. In this study we hypothesized that ghrelin would impede the pathogenesis of pulmonary arterial hypertension during chronic hypoxia (CH). PAP was continuously measured using radiotelemetry, in conscious male Sprague Dawley rats, in normoxia and during 2-wk CH (10% O2). During this hypoxic period, rats received a daily sc injection of either saline or ghrelin (150 μg/kg). Subsequently, heart and lung samples were collected for morphological, histological, and molecular analyses. CH significantly elevated PAP in saline-treated rats, increased wall thickness of peripheral pulmonary arteries, and, consequently, induced right ventricular hypertrophy. In these rats, CH also led to the overexpression of endothelial nitric oxide synthase mRNA and protein, as well as endothelin-1 mRNA within the lung. Exogenous ghrelin administration attenuated the CH-induced overexpression of endothelial nitric oxide synthase mRNA and protein, as well as endothelin-1 mRNA. Consequently, ghrelin significantly attenuated the development of pulmonary arterial hypertension, pulmonary vascular remodeling, and right ventricular hypertrophy. These results demonstrate the therapeutic benefits of ghrelin for impeding the pathogenesis of pulmonary hypertension and right ventricular hypertrophy, particularly in subjects prone to CH (e.g. pulmonary disorders).

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The Influence of Pulmonary Hemodynamics on Right Ventricular Function in Pulmonary Hypertension

Volume 1A: Abdominal Aortic Aneurysms; Active and Reactive Soft Matter; Atherosclerosis; BioFluid Mechanics; Education; Biotransport Phenomena; Bone, Joint and Spine Mechanics; Brain Injury; Cardiac Mechanics; Cardiovascular Devices, Fluids and Imaging; Cartilage and Disc Mechanics; Cell and Tissue Engineering; Cerebral Aneurysms; Computational Biofluid Dynamics; Device Design, Human Dynamics, and Rehabilitation; Drug Delivery and Disease Treatment; Engineered Cellular Environments ◽

10.1115/sbc2013-14440 ◽

2013 ◽

Author(s):

Vitaly O. Kheyfets ◽

Lourdes Rios ◽

Triston Smith ◽

Theodore Schroeder ◽

Jeffrey Mueller ◽

...

Keyword(s):

Fluid Dynamics ◽

Pulmonary Hypertension ◽

Shear Stress ◽

Right Ventricular ◽

Pulmonary Arteries ◽

Pulmonary Hemodynamics ◽

Arterial Hemodynamics ◽

Computational Fluid Dynamics Cfd ◽

Pulmonary Arterial ◽

Rv Function

Pulmonary arterial hypertension (PAH) is a degenerative disease that can lead to substantial morphometric remodeling of the pulmonary arteries. Previous studies have revealed coupling relationships between right ventricular (RV) function and pulmonary arterial hemodynamics. The objective of this study was to utilize computational fluid dynamics (CFD) to estimate spatially averaged Wall Shear Stress (WSS) for patients with PH and explore correlations between hemodynamics metrics and RV function.

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