Nonenzymatic lipid mediators, neuroprostanes, exert the antiarrhythmic properties of docosahexaenoic acid

postprin

Assessment of contractility in intact ventricular cardiomyocytes using the dimensionless ‘Frank–Starling Gain’ index

This paper briefly recapitulates the Frank–Starling law of the heart, reviews approaches to establishing diastolic and systolic force–length behaviour in intact isolated cardiomyocytes, and introduces a dimensionless index called ‘Frank–Starling Gain’, calculated as the ratio of slopes of end-systolic and end-diastolic force–length relations. The benefits and limitations of this index are illustrated on the example of regional differences in Guinea pig intact ventricular cardiomyocyte mechanics. Potential applicability of the Frank–Starling Gain for the comparison of cell contractility changes upon stretch will be discussed in the context of intra- and inter-individual variability of cardiomyocyte properties

Evaluation of intravenous delivery of oxygenated DHA, 4(RS)-4-F4t-neuroprostane, in rodent

Poster Session 2: abstract no. 15

Non-enzymatic cyclic oxygenated metabolites of adrenic, docosahexaenoic, eicosapentaenoic and α-linolenic acids; bioactivities and potential use as biomarkers

International audienceCyclic oxygenated metabolites are formed in vivo through non-enzymatic free radical reaction of n-6 and n-3 polyunsaturated fatty acids (PUFAs) such as arachidonic (ARA C20:4 n-6), adrenic (AdA 22:4 n-6), α-linolenic (ALA 18:3 n-3), eicosapentaenoic (EPA 20:5 n-3) and docosahexaenoic (DHA 22:6 n-3) acids. These cyclic compounds are known as isoprostanes, neuroprostanes, dihomo-isoprostanes and phytoprostanes. Evidence has emerged for their use as biomarkers of oxidative stress and, more recently, the n-3PUFA-derived compounds have been shown to mediate bioactivities as secondary messengers. Accordingly, this review will focus on the cyclic oxygenated metabolites generated from AdA, ALA, EPA and DHA. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance

Pharmacokinetics of oxygenated DHA, 4(RS)-4-F4t-Neuroprostane in rodent brain

Poster Abstracts: no. 53Conference Theme: Lipidomics Impact on Metabolic, Cancer, Cardiovascular and Inflammatory DiseasesDocosahexaenoic acid (DHA) are predominantly abundant in cellular membranes of the central nervous system (CNS). The exact molecular mechanisms of how DHA exert its beneficial roles to the CNS remains largely unexplored, but is associated to the generation of anti-inflammatory enzymatic-derived lipid mediators, such as Resolvins (Rv) D1-6, Neuro-protectin D1 (NPD1/PD1), and Protectin DX (PDX), upon receptor-mediated signal transduction. Imbalance of reactive species in tissues spontaneously triggers non-enzymatic lipid peroxidation, especially the highly unsaturated fatty acid, DHA. Neuroprostanes (NeuroPs) are nonenzymatically derived lipid mediators from DHA oxygenation and are believed to be the gold standard for oxidative damage in the brain. These NeuroPs have a vital role to play in the pathogenesis of neurodegenerative diseases like the Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, as the levels of NeuroPs were elevated in the brains of these patients. Not until recently, a 4-series NeuroP (4(RS)-4-F4t-NeuroP), among the eight possible regioisomeric groups has demonstrated to possess anti-arrhythmic property in cellulo and in vivo. This study, for the first time, has further emphasized that not all isoprostanoids are unfavourable. Also, we identified that 4(RS)-4-F4t-NeuroP was the predominant isoprostanoids in normal pig and rat brain. To further probe on its functionality in the brain and its pharmacokinetics, we infused 4(RS)-4-F4t-NeuroP intravenously in male Sprague Dawley rats. The rats were sacrificed at eight different time points after injections: 0 (control), 5 s, 30 s, 1 h, 2 h, 4 h, 6 h and 24 h. Plasma was separated from the whole blood and organs were harvested immediately. The plasma concentration of 4(RS)-4-F4t-NeuroP was quantified throughout the time-course using the LCMS/MS. Our preliminary data suggest that the administration of 4(RS)-4-F4t-NeuroP is rapid with a fast rate of elimination, similar to those administrated with F2-Isoprostanes as previously reported by others

Non-enzymatic lipid mediators, neuroprostanes exerts the anti-arrhythmic properties of docosahexaenoic acid

Topic 19 - Electrophysiology, rythmology and pacing - D; paper no. 000