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Sökning: onr:"swepub:oai:lup.lub.lu.se:30b538ae-e43c-4936-b441-1827ad8b8008" > Retained Metabolic ...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00006298naa a2200481 4500
001oai:lup.lub.lu.se:30b538ae-e43c-4936-b441-1827ad8b8008
003SwePub
008230905s2023 | |||||||||||000 ||eng|
0247 a https://lup.lub.lu.se/record/30b538ae-e43c-4936-b441-1827ad8b80082 URI
0247 a https://doi.org/10.1161/CIRCULATIONAHA.122.0621662 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
1001 a Watson, William D.u University of Oxford,University of Cambridge4 aut
2451 0a Retained Metabolic Flexibility of the Failing Human Heart
264 1c 2023
300 a 15 s.
520 a Background: The failing heart is traditionally described as metabolically inflexible and oxygen starved, causing energetic deficit and contractile dysfunction. Current metabolic modulator therapies aim to increase glucose oxidation to increase oxygen efficiency of adenosine triphosphate production, with mixed results. Methods: To investigate metabolic flexibility and oxygen delivery in the failing heart, 20 patients with nonischemic heart failure with reduced ejection fraction (left ventricular ejection fraction 34.9±9.1) underwent separate infusions of insulin+glucose infusion (I+G) or Intralipid infusion. We used cardiovascular magnetic resonance to assess cardiac function and measured energetics using phosphorus-31 magnetic resonance spectroscopy. To investigate the effects of these infusions on cardiac substrate use, function, and myocardial oxygen uptake (MVo2), invasive arteriovenous sampling and pressure-volume loops were performed (n=9). Results: At rest, we found that the heart had considerable metabolic flexibility. During I+G, cardiac glucose uptake and oxidation were predominant (70±14% total energy substrate for adenosine triphosphate production versus 17±16% for Intralipid; P=0.002); however, no change in cardiac function was seen relative to basal conditions. In contrast, during Intralipid infusion, cardiac long-chain fatty acid (LCFA) delivery, uptake, LCFA acylcarnitine production, and fatty acid oxidation were all increased (LCFA 73±17% of total substrate versus 19±26% total during I+G; P=0.009). Myocardial energetics were better with Intralipid compared with I+G (phosphocreatine/adenosine triphosphate 1.86±0.25 versus 2.01±0.33; P=0.02), and systolic and diastolic function were improved (LVEF 34.9±9.1 baseline, 33.7±8.2 I+G, 39.9±9.3 Intralipid; P<0.001). During increased cardiac workload, LCFA uptake and oxidation were again increased during both infusions. There was no evidence of systolic dysfunction or lactate efflux at 65% maximal heart rate, suggesting that a metabolic switch to fat did not cause clinically meaningful ischemic metabolism. Conclusions: Our findings show that even in nonischemic heart failure with reduced ejection fraction with severely impaired systolic function, significant cardiac metabolic flexibility is retained, including the ability to alter substrate use to match both arterial supply and changes in workload. Increasing LCFA uptake and oxidation is associated with improved myocardial energetics and contractility. Together, these findings challenge aspects of the rationale underlying existing metabolic therapies for heart failure and suggest that strategies promoting fatty acid oxidation may form the basis for future therapies.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Kardiologi0 (SwePub)302062 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cardiac and Cardiovascular Systems0 (SwePub)302062 hsv//eng
653 a adenosine triphosphate
653 a heart failure
653 a magnetic resonance spectroscopy
653 a metabolism
7001 a Green, Peregrine G.u University of Oxford4 aut
7001 a Lewis, Andrew J.M.u University of Oxford4 aut
7001 a Arvidsson, Peru Lund University,Lunds universitet,Klinisk fysiologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Hjärt-MR-gruppen i Lund,Forskargrupper vid Lunds universitet,Clinical Physiology (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Cardiac MR Group,Lund University Research Groups,Skåne University Hospital,University of Oxford4 aut0 (Swepub:lu)med-pea
7001 a De Maria, Giovanni Luigiu Oxford University Hospitals NHS Foundation Trust4 aut
7001 a Arheden, Håkanu Lund University,Lunds universitet,Klinisk fysiologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Hjärt-MR-gruppen i Lund,Forskargrupper vid Lunds universitet,Clinical Physiology (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Cardiac MR Group,Lund University Research Groups4 aut0 (Swepub:lu)klfy-har
7001 a Heiberg, Einaru Lund University,Lunds universitet,Klinisk fysiologi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Hjärt-MR-gruppen i Lund,Forskargrupper vid Lunds universitet,WCMM- Wallenberg center för molekylär medicinsk forskning,LTH profilområde: Teknik för hälsa,LTH profilområden,Lunds Tekniska Högskola,Clinical Physiology (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund Cardiac MR Group,Lund University Research Groups,WCMM-Wallenberg Centre for Molecular Medicine,LTH Profile Area: Engineering Health,LTH Profile areas,Faculty of Engineering, LTH4 aut0 (Swepub:lu)klin-eh0
7001 a Clarke, William T.u University of Oxford4 aut
7001 a Rodgers, Christopher T.u University of Cambridge4 aut
7001 a Valkovič, Ladislavu University of Oxford4 aut
7001 a Neubauer, Stefanu University of Oxford4 aut
7001 a Herring, Neilu University of Oxford4 aut
7001 a Rider, Oliver J.u University of Oxford4 aut
7102 a University of Oxfordb University of Cambridge4 org
7730 t Circulationg 148:2, s. 109-123q 148:2<109-123x 0009-7322
8564 u http://dx.doi.org/10.1161/CIRCULATIONAHA.122.062166x freey FULLTEXT
8564 8u https://lup.lub.lu.se/record/30b538ae-e43c-4936-b441-1827ad8b8008
8564 8u https://doi.org/10.1161/CIRCULATIONAHA.122.062166

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