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The effect of Riociguat on cardiovascular function and efficiency in healthy, juvenile pigs

INTRODUCTION: Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of pulmonary hypertension. Its effect on cardiometabolic efficiency is unknown. A potential cardiac energy sparing effect of this drug could imply a positive prognostic effect, particularly in patients with...

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Autores principales: Næsheim, Torvind, How, Ole‐Jakob, Myrmel, Truls
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507463/
https://www.ncbi.nlm.nih.gov/pubmed/32918535
http://dx.doi.org/10.14814/phy2.14562
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author Næsheim, Torvind
How, Ole‐Jakob
Myrmel, Truls
author_facet Næsheim, Torvind
How, Ole‐Jakob
Myrmel, Truls
author_sort Næsheim, Torvind
collection PubMed
description INTRODUCTION: Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of pulmonary hypertension. Its effect on cardiometabolic efficiency is unknown. A potential cardiac energy sparing effect of this drug could imply a positive prognostic effect, particularly in patients with right heart failure from pulmonary hypertension. METHOD: We infused Riociguat in six healthy juvenile pigs and measured the integrated cardiovascular effect and myocardial oxygen consumption. To assess the interplay with NO‐blockade on cardiac function and efficiency we also administered the NO‐blocker L‐ NAME to the animals after Riociguat. RESULTS AND DISCUSSION: Infusion of 100 µg/kg Riociguat gave modest systemic vasodilatation seen as a drop in coronary and systemic vascular resistance of 36% and 26%, respectively. Right and left ventriculoarterial coupling index (Ees/Ea), stroke work efficiency (SWeff), and the relationship between left ventricular myocardial oxygen consumption (MVO(2)) and total mechanical work (pressure–volume area; PVA) were unaffected by Riociguat. In contrast, systemic and pulmonary vasoconstriction induced by L‐NAME (15 mg/kg) shifted the Ees/Ea ratio toward reduced SWeff in both systemic and pulmonary circulation. However, there was no surplus oxygen consumption, that was measured by the MVO(2)/PVA relationship after L‐NAME in Riociguat‐treated pigs. This suggests that Riociguat can reduce the NO‐related cardiometabolic inefficiency previously observed by blocking the NO pathway.
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spelling pubmed-75074632020-09-28 The effect of Riociguat on cardiovascular function and efficiency in healthy, juvenile pigs Næsheim, Torvind How, Ole‐Jakob Myrmel, Truls Physiol Rep Original Research INTRODUCTION: Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of pulmonary hypertension. Its effect on cardiometabolic efficiency is unknown. A potential cardiac energy sparing effect of this drug could imply a positive prognostic effect, particularly in patients with right heart failure from pulmonary hypertension. METHOD: We infused Riociguat in six healthy juvenile pigs and measured the integrated cardiovascular effect and myocardial oxygen consumption. To assess the interplay with NO‐blockade on cardiac function and efficiency we also administered the NO‐blocker L‐ NAME to the animals after Riociguat. RESULTS AND DISCUSSION: Infusion of 100 µg/kg Riociguat gave modest systemic vasodilatation seen as a drop in coronary and systemic vascular resistance of 36% and 26%, respectively. Right and left ventriculoarterial coupling index (Ees/Ea), stroke work efficiency (SWeff), and the relationship between left ventricular myocardial oxygen consumption (MVO(2)) and total mechanical work (pressure–volume area; PVA) were unaffected by Riociguat. In contrast, systemic and pulmonary vasoconstriction induced by L‐NAME (15 mg/kg) shifted the Ees/Ea ratio toward reduced SWeff in both systemic and pulmonary circulation. However, there was no surplus oxygen consumption, that was measured by the MVO(2)/PVA relationship after L‐NAME in Riociguat‐treated pigs. This suggests that Riociguat can reduce the NO‐related cardiometabolic inefficiency previously observed by blocking the NO pathway. John Wiley and Sons Inc. 2020-09-12 /pmc/articles/PMC7507463/ /pubmed/32918535 http://dx.doi.org/10.14814/phy2.14562 Text en © 2020 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Næsheim, Torvind
How, Ole‐Jakob
Myrmel, Truls
The effect of Riociguat on cardiovascular function and efficiency in healthy, juvenile pigs
title The effect of Riociguat on cardiovascular function and efficiency in healthy, juvenile pigs
title_full The effect of Riociguat on cardiovascular function and efficiency in healthy, juvenile pigs
title_fullStr The effect of Riociguat on cardiovascular function and efficiency in healthy, juvenile pigs
title_full_unstemmed The effect of Riociguat on cardiovascular function and efficiency in healthy, juvenile pigs
title_short The effect of Riociguat on cardiovascular function and efficiency in healthy, juvenile pigs
title_sort effect of riociguat on cardiovascular function and efficiency in healthy, juvenile pigs
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507463/
https://www.ncbi.nlm.nih.gov/pubmed/32918535
http://dx.doi.org/10.14814/phy2.14562
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