Effects of free fatty acids on electrophysiological properties of ventricular myocardium

Lüderitz, Berndt; d’Alnoncourt, C. Naumann; Steinbeck, Gerhard

doi:10.1007/bf01471576

Cited by 19 publications

(3 citation statements)

References 36 publications

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“…The action potential shortening observed in the present study mirrors results obtained by others in whole tissue preparations. Palmitate (0.84 or 1.3 mM, complexed to 2% BSA), for example, has been shown to cause action potential shortening in papillary muscle [48]. Similarly, Willebrands and colleagues reported that perfusion of the isolated rat heart with palmitate (1–3 mM, complexed with 0.66 mM BSA) induced arrhythmias and reduced contractility in agreement with the present data [49].…”

Section: Discussionsupporting

confidence: 87%

Palmitate attenuates myocardial contractility through augmentation of repolarizing Kv currents

Haïm¹,

Wang²,

Flagg³

et al. 2010

Journal of Molecular and Cellular Cardiology

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There is considerable evidence to support a role for lipotoxicity in the development of diabetic cardiomyopathy, although the molecular links between enhanced saturated fatty acid uptake/ metabolism and impaired cardiac function are poorly understood. In the present study, the effects of acute exposure to the saturated fatty acid, palmitate, on myocardial contractility and excitability were examined directly. Exposure of isolated (adult mouse) ventricular myocytes to palmitate, complexed to bovine serum albumin (palmitate:BSA) as in blood, rapidly reduced (by 54±4%) mean (± SEM) unloaded fractional cell shortening. The amplitudes of intracellular Ca 2+ transients decreased in parallel. Current-clamp recordings revealed that exposure to palmitate:BSA markedly shortened action potential durations at 20, 50 and 90% repolarization. These effects were reversible and were occluded when the K + in the recording pipettes was replaced with Cs + , suggesting a direct effect on repolarizing K + currents. Indeed, voltage-clamp recordings revealed that palmitate:BSA reversibly and selectively increased peak outward voltage-gated K + (Kv) current amplitudes by 20 ± 2%, whereas inwardly rectifying K + (Kir) currents and voltage-gated Ca 2+ currents were unaffected. Further analyses revealed that the individual Kv current components I to,f , I K,slow and I ss , were all increased (by 12 ± 2 %, 37 ± 4 % and 34 ± 4, respectively) in cells exposed to palmitate:BSA. Consistent with effects on both components of I K,slow (I K,slow1 and I K,slow2 ) the magnitude of the palmitate-induced increase was attenuated in ventricular myocytes isolated from animals in which the Kv1.5 (I K,slow1 ) or the Kv2.1 (I K,slow2 ) locus was disrupted and I K,slow1 or I K,slow2 is eliminated. Both the enhancement of I K,slow and the negative inotropic effect of palmitate:BSA were reduced in the presence of the Kv1.5 selective channel blocker, diphenyl phosphine oxide-1 (DPO-1). Taken together, these results suggest that elevations in circulating saturated free fatty acids, as occurs in diabetes, can directly augment repolarizing myocardial Kv currents and impair excitation-contraction coupling.

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Section: Discussionsupporting

confidence: 87%

Palmitate attenuates myocardial contractility through augmentation of repolarizing Kv currents

Haïm¹,

Wang²,

Flagg³

et al. 2010

Journal of Molecular and Cellular Cardiology

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“…das Herz vor einer unnötigen Stoffwechselsteigerung bzw. sonstigen nicht essentiellen Trijodthyroninwirkung schützt und somit das Risiko von Arrhythmien vermindert (KURIEN et al 1971;LÜDERITZ et al 1976;STRANGE et al 1978;LÜDERITZ 1982).…”

Section: Schilddrüsenhormoneunclassified

Endokrines System und Schock: Therapeutische Perspektiven

Scriba¹,

Djonlagić²,

Müller-Esch³

1984

Schock

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“…The constituents in plasma are important in regulating cell function and maintaining homeostasis. For example, potassium affects cell excitability and severe depletion will cause muscle weakness and abnormalities of the cardiac impulse (3). To avoid the protein confounding effects of the cellular fractions of the blood on clinical biochemistry tests (1), the tests are often performed on cell-free samples, such as plasma or serum.…”

Section: Introductionmentioning

confidence: 99%

Design and Simulation of a Microfluidic Blood-Plasma Separation Chip Using Microchannel Structures

Huang

Pai

et al. 2009

Separation Science and Technology

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Current clinical methods for the separation of whole blood into blood cells and cell-free plasma are currently based on large facility equipment, such as centrifuges. The disadvantage of this process is that the patients must have assays performed at the hospital or laboratory where the separation facility is located. The present study presents a design for microfluidic chips with different microchannel structures, which utilizes backward facing step geometry and centrifugal force to extract the cell-free plasma from whole blood samples at the branch of the microchannel for further assay, avoiding the influence of blood cells. Numerical simulation was performed on a personal computer to analyze the effects of inlet velocity and the structures of the microchannel on the flow field and back-flow in the microchannel, as well as the efficiency of separation and the volumetric fraction of the flowrate of plasma extraction. The minimum radius of particles (R) that can be excluded from the side channel, and fraction of the volumetric flowrate were obtained to evaluate the efficiency of plasma extraction. Based on the numerical simulations, the design with both converging and bending channels was the best design among the four layouts proposed. In this design, the value of R could be set to less than the critical value (set as 1 mm because of the radius of platelets), and the volumetric fraction of the extraction flowrate was approximately 8.4% when Re was about 20. The preliminary experiments indicated the fluorescent particles with 2.5 mm in radius were successfully excluded from side (plasma outlet) channel of the microfluidic chip with converging a inlet channel and the bent microchannel, when the Reynolds number of the inlet flowrate equals 50.

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Effects of free fatty acids on electrophysiological properties of ventricular myocardium

Cited by 19 publications

References 36 publications

Palmitate attenuates myocardial contractility through augmentation of repolarizing Kv currents

Palmitate attenuates myocardial contractility through augmentation of repolarizing Kv currents

Endokrines System und Schock: Therapeutische Perspektiven

Design and Simulation of a Microfluidic Blood-Plasma Separation Chip Using Microchannel Structures

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