---
title: "3‑Hydroxybutyrate Raises Cardiac Contractility in Rats via Non–β‑Adrenergic Mechanisms"
id: "biorxiv-19-inotropic-effects-of-3-hydroxybutyrate-in-a-rodent-heart-pressure-volume-and"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-19-inotropic-effects-of-3-hydroxybutyrate-in-a-rodent-heart-pressure-volume-and"
content_type: "clinical_feed_article"
specialty: "Cardiology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.15.751359v1?rss=1"
published_at: "2026-09-21T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# 3‑Hydroxybutyrate Raises Cardiac Contractility in Rats via Non–β‑Adrenergic Mechanisms
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-19-inotropic-effects-of-3-hydroxybutyrate-in-a-rodent-heart-pressure-volume-and
- **Specialty:** [Cardiology](https://medichelpline.com/clinical-feed/cardiology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.15.751359v1?rss=1)
- **Published At:** 2026-09-21T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Administration of **3‑hydroxybutyrate (3‑OHB)** increases cardiac output in experimental models, but it was unclear whether this reflects direct myocardial **inotropy** or peripheral vasodilation. - The study combined in vivo left ventricular pressure‑volume analysis and ex vivo isolated LV trabeculae experiments in adult male HanSD rats to distinguish myocardial from systemic effects. - In vivo pressure‑volume data showed that 3‑OHB increased left ventricular end‑systolic elastance by 34%, improved ventriculo‑arterial coupling by 65%, and raised LV efficiency by 28%, consistent with a direct positive inotropic effect. - Isolated LV trabeculae perfused with 1 mmol/L 3‑OHB at 1 Hz pacing developed increased twitch force in both healthy and heart failure groups; the increase was larger in healthy hearts (+55.8%) than in the HF group (+35.6%), with p = 0.014 for the group difference. - The inotropic response to 3‑OHB was not further increased by isoprenaline coadministration and was not blocked by beta‑1 adrenergic blockade (metoprolol) or inhibition of adenylyl cyclase (2,5‑dideoxyadenosine), indicating independence from **beta‑adrenergic** and **cAMP‑dependent** signaling. - Authors interpret the data as evidence that 3‑OHB directly enhances myocardial contractile performance, most compatible with a **bioenergetic** mechanism rather than receptor‑mediated inotropy. - The findings support consideration of 3‑OHB as a candidate inotropic agent with a mechanism distinct from conventional cAMP‑dependent inotropes. - The report is a preprint and has not undergone peer review. Funding sources and competing interest declarations were reported by the authors.
## Clinical Analysis & Structured Key Points
Inotropic effects of 3-hydroxybutyrate in a rodent heart: pressure-volume and isolated rat ventricular trabeculae analysis | bioRxiv Skip to main content New Results Inotropic effects of 3-hydroxybutyrate in a rodent heart: pressure-volume and isolated rat ventricular trabeculae analysis View ORCID Profile Jan Kropacek , View ORCID Profile Thu Thao Nguyen , Ema Hajkova , View ORCID Profile Matej Molnar , View ORCID Profile Luca Monzo , View ORCID Profile Matus Miklovic , View ORCID Profile Vojtech Melenovsky doi: https://doi.org/10.64898/2026.09.15.751359 Jan Kropacek 1 Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine - IKEM, Prague, Czech Republic; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Jan Kropacek Thu Thao Nguyen 1 Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine - IKEM, Prague, Czech Republic; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Thu Thao Nguyen Ema Hajkova 1 Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine - IKEM, Prague, Czech Republic; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Matej Molnar 1 Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine - IKEM, Prague, Czech Republic; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Matej Molnar Luca Monzo 2 Universite de Lorraine, Centre dInvestigations Cliniques Plurithematique 1433 and Inserm U1116, CHRU Nancy, FCRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Luca Monzo Matus Miklovic 1 Centre for Experimental Medicine, Institute for Clinical and Experimental Medicine - IKEM, Prague, Czech Republic; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Matus Miklovic Vojtech Melenovsky 3 Department of Cardiology, Institute for Clinical and Experimental Medicine - IKEM, Prague, Czech Republic Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Vojtech Melenovsky For correspondence: vome{at}ikem.cz Abstract Info/History Metrics Supplementary material Preview PDF Abstract An administration of 3 hydroxy-butyrate (3-OHB) in experimental animals or humans is associated with an increase of cardiac output (CO), but whether this hemodynamic benefit reflects direct myocardial inotropy or heart unloading due to peripheral vasodilation remains unclear. It is also unknown if myocardial effects are due to engagement of receptor-mediated inotropic response, or due to improvement of myocardial bioenergetics. To address these questions, we studied integrated cardiovascular response (pressure-volume analysis of the left ventricle) and isolated left ventricular (LV) trabeculae from normotensive male HanSD rats (age 20-30 weeks) after administration of 3-OHB (1 mmol/l) and drugs targeting adrenergic and cAMP-dependent signaling - metoprolol, adenylyl cyclase inhibitor 2,5-dideoxyadenosine and isoprenaline, during Tyrode solution perfusion and 1 Hz pacing. Pressure-volume analysis demonstrated increased left ventricular end-systolic elastance (+34%), improved ventriculo-arterial coupling (+65%) and increased LV efficiency (+28%), indicating direct inotropic effect of 3OHB. In isolated LV trabeculae, 3-OHB increased twitch force in both groups, but increase was greater in healthy hearts (+55.8%) than in the HF group (+35.6%) (p = 0.014). The inotropic effect of 3-OHB was not further augmented by coadministration of isoprenaline and was not attenuated by beta-1 adrenergic blockade or cAMP inhibition. Results suggest that 3-OHB directly improves LV inotropy and by a mechanism that is independent of receptor-mediated beta-adrenergic signaling, most consistent with a direct bioenergetic pathway. These findings support 3-OHB as a candidate inotropic agent with a mechanistic profile distinct from conventional cAMP-dependent inotropes. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared Ministry of Health, Czech Republic — conceptual development of research organization, Institute for Clinical and Experimental Medicine - IKEM , IN 00023001 Ministry of Health of the Czech Republic, in cooperation with the Czech Health Research Council — National Institute CarDia , NW26A-CARDIA Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license . Back to top Previous Posted September 21, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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Share Inotropic effects of 3-hydroxybutyrate in a rodent heart: pressure-volume and isolated rat ventricular trabeculae analysis Jan Kropacek , Thu Thao Nguyen , Ema Hajkova , Matej Molnar , Luca Monzo , Matus Miklovic , Vojtech Melenovsky bioRxiv 2026.09.15.751359; doi: https://doi.org/10.64898/2026.09.15.751359 Share This Article: Copy Citation Tools Inotropic effects of 3-hydroxybutyrate in a rodent heart: pressure-volume and isolated rat ventricular trabeculae analysis Jan Kropacek , Thu Thao Nguyen , Ema Hajkova , Matej Molnar , Luca Monzo , Matus Miklovic , Vojtech Melenovsky bioRxiv 2026.09.15.751359; doi: https://doi.org/10.64898/2026.09.15.751359 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Areas All Articles Animal Behavior and Cognition (8016) Biochemistry (18744) Bioengineering (14893) Bioinformatics (44455) Biophysics (22611) Cancer Biology (19728) Cell Biology (26906) Clinical Trials (138) Developmental Biology (13970) Ecology (21008) Epidemiology (2067) Evolutionary Biology (25457) Genetics (16172) Genomics (23517) Immunology (18717) Microbiology (42520) Molecular Biology (18064) Neuroscience (93504) Paleontology (700) Pathology (2982) Pharmacology and Toxicology (5100) Physiology (8117) Plant Biology (16000) Scientific Communication and Education (2095) Synthetic Biology (4560) Systems Biology (10237) Zoology (2391)
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