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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interest in the potential cardiovascular benefits of omega-3 long chain polyunsaturated fatty acids has been largely focused on possible antiatherothrombotic effects. In addition, however, definitive antiarrhythmic effects of these dietary omega-3 fatty acids have been reported by Charnock & McLennan. Our studies commenced with the observation that two of these fatty acids, eicosapentaenoic (C20:5n-3, EPA) and docosahexaenoic acid (C22:6n-3, DHA) prevented contracture and fibrillation of isolated neonatal cardiac myocytes when exposed to toxic levels of ouabain (0.1 mM). This protection was associated with prevention of excessively high intracellular calcium concentrations in the myocyte. Further, it was shown that these fatty acids modulate calcium currents through L-type calcium channels and that the effect occurs within a few minutes of adding EPA or DHA to the medium perfusing the cultured cardiac myocytes. Infusing an emulsion of the omega-3 fatty acids intravenously just prior to compression of a coronary artery in a conscious, prepared dog will prevent the expected subsequent ischemia-induced ventricular fibrillation.
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PMID:Omega-3 fatty acids and prevention of ventricular fibrillation. 778 57

There is evidence that dietary polyunsaturated fatty acids (PUFA) may protect against cardiovascular diseases, but the involvement of the cardiac muscle cell in this beneficial action remain largely unknown. The present study compared the respective influence of n-3 and n-6 PUFA on the function of cultured neonatal rat cardiomyocytes (CM). Cells were grown for 4 days in media enriched either n-3 (eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA) or n-6 (arachidonic acid, AA) PUFA. The PUFA n-6/n-3 ratio in the phospholipids was close to 1 and 20 in the n-3 and n-6 cells, respectively. The transmembrane potentials were recorded using microelectrodes and the contractions were monitored with a photoelectric device. In physiological conditions, the increase of n-6 PUFA level in the phospholipids resulted in a significant decrease in the maximal rate of initial depolarization (-16%). In opposition, the action potential amplitude and duration were not altered, and the cell contraction outline was not affected. Ischemia was simulated in vitro using a substrate-free, hypoxia-reoxygenation procedure in a specially designed gas-flow chamber. The progressive loss of electrical activity induced by the substrate-free, hypoxic treatment was affected by the n-6/n-3 ratio, since the n-6 rich CM displayed a slower depression of the AP amplitude and duration parameters. Conversely, the recovery of the resting potential (MDP) during reoxygenation was faster in n-3 CM, whereas the recovery of the contraction parameters was unaffected by the fatty acid composition of the cells. These results suggested that, in physiological conditions, the modification of long chain PUFA balance in the phospholipids of cardiac muscle cells may modulate the initial AP upstroke, which is governed by sodium channels. Moreover, the presence of n-3 PUFA appeared to accelerate the electrical depression during substrate-free hypoxia but in turn to allow a faster recovery upon reoxygenation.
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PMID:Influence of phospholipid long chain polyunsaturated fatty acid composition on neonatal rat cardiomyocyte function in physiological conditions and during glucose-free hypoxia-reoxygenation. 935 58

Studies have shown that fish oils, containing n-3 fatty acids, have protective effects against ischemia-induced, fatal cardiac arrhythmias in animals and perhaps in humans. In this study we used the whole-cell voltage-clamp technique to assess the effects of dietary, free long-chain fatty acids on the Na+ current (INa,alpha) in human embryonic kidney (HEK293t) cells transfected with the alpha-subunit of the human cardiac Na+ channel (hH1alpha). Extracellular application of 0.01 to 30 microM eicosapentaenoic acid (EPA, C20:5n-3) significantly reduced INa,alpha with an IC50 of 0.51 +/- 0.06 microM. The EPA-induced suppression of INa,alpha was concentration- and voltage-dependent. EPA at 5 microM significantly shifted the steady-state inactivation relationship by -27.8 +/- 1.2 mV (n = 6, P < 0.0001) at the V1/2 point. In addition, EPA blocked INa,alpha with a higher "binding affinity" to hH1alpha channels in the inactivated state than in the resting state. The transition from the resting state to the inactivated state was markedly accelerated in the presence of 5 microM EPA. The time for 50% recovery from the inactivation state was significantly slower in the presence of 5 microM EPA, from 2.1 +/- 0.8 ms for control to 34.8 +/- 2.1 ms (n = 5, P < 0.001). The effects of EPA on INa,alpha were reversible. Furthermore, docosahexaenoic acid (C22:6n-3), alpha-linolenic acid (C18:3n-3), conjugated linoleic acid (C18:2n-7), and oleic acid (C18:1n-9) at 5 microM and all-trans-retinoic acid at 10 microM had similar effects on INa,alpha as EPA. Even 5 microM of stearic acid (C18:0) or palmitic acid (C16:0) also significantly inhibited INa, alpha. In contrast, 5 microM EPA ethyl ester did not alter INa,alpha (8 +/- 4%, n = 8, P > 0.05). The present data demonstrate that free fatty acids suppress INa,alpha with high "binding affinity" to hH1alpha channels in the inactivated state and prolong the duration of recovery from inactivation.
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PMID:Fatty acids suppress voltage-gated Na+ currents in HEK293t cells transfected with the alpha-subunit of the human cardiac Na+ channel. 948 47

The purpose of the present investigation was to determine whether the beneficial effects of polyunsaturated fatty acids (PUFA) may influence ischemia-reperfusion-induced alterations of myocardial alpha- and beta-adrenoceptor (alpha-AR, beta-AR) responsiveness. This study was carried out using monolayer cultures of neonatal rat ventricular myocytes in a substrate-free, hypoxia-reoxygenation model of ischemia. The cardiomyocytes (CM) were incubated during 4 days in media enriched either with n-6 PUFA (arachidonic acid, AA) or with n-3 PUFA (eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA). The n-6/n-3 ratio in n-3 CM was close to 1.2, compared to 20.1 in n-6 CM. The contractile parameters of n-6 CM and n-3 CM were similar in basal conditions as well as during hypoxia and reoxygenation. In basal conditions, the phospholipid (PL) enrichment with long chain n-3 PUFA resulted in an increased chronotropic response to isoproterenol (ISO) and to phenylephrine (PHE). After posthypoxic reoxygenation, the chronotropic response to beta-AR activation in n-6 CM was significantly enhanced as compared with the control response in normoxia. In opposition, the ISO-induced rise in frequency in n-3 CM in control normoxia and after reoxygenation was similar. In these n-3 CM, the changes in contractile parameters, which accompanied the chronotropic response, were also similar in reoxygenation and in normoxic periods, although the rise in shortening velocity was slightly increased after reoxygenation. In response to PHE addition, only the chronotropic effect of n-6 CM appeared significantly enhanced after hypoxic treatment. These results suggested that increasing n-3 PUFA in PL reduced the increase in alpha- and beta-AR functional responses observed after hypoxia-reoxygenation. This effect may partly account for the assumed cardiac protective effect of n-3 PUFA, through the attenuation of the functional response to catecholamines in the ischemic myocardium.
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PMID:Cross-influence of membrane polyunsaturated fatty acids and hypoxia-reoxygenation on alpha- and beta-adrenergic function of rat cardiomyocytes. 1038 Jan 17

In animal feeding studies, and probably in humans, n-3 polyunsaturated fatty acids (PUFAs) prevent fatal ischemia-induced cardiac arrhythmias. We showed that n-3 PUFAs also prevented such arrhythmias in surgically prepared, conscious, exercising dogs. The mechanism of the antiarrhythmic action of n-3 PUFAs has been studied in spontaneously contracting cultured cardiac myocytes of neonatal rats. Adding arrhythmogenic toxins (eg, ouabain, high Ca(2+), lysophosphatidylcholine, beta-adrenergic agonist, acylcarnitine, and the Ca(2+) ionophore) to the myocyte perfusate caused tachycardia, contracture, and fibrillation of the cultured myocytes. Adding eicosapentaenoic acid (EPA: 5-15 micromol/L) to the superfusate before adding the toxins prevented the expected tachyarrhythmias. If the arrhythmias were first induced, adding the EPA to the superfusate terminated the arrhythmias. This antiarrhythmic action occurred with dietary n-3 and n-6 PUFAs; saturated fatty acids and the monounsaturated oleic acid induced no such action. Arachidonic acid (AA; 20:4n-6) is anomalous because in one-third of the tests it provoked severe arrhythmias, which were found to result from cyclooxygenase metabolites of AA. When cyclooxygenase inhibitors were added with the AA, the antiarrhythmic effect was like those of EPA and DHA. The action of the n-3 and n-6 PUFAs is to stabilize electrically every myocyte in the heart by increasing the electrical stimulus required to elicit an action potential by approximately 50% and prolonging the relative refractory time by approximately 150%. These electrophysiologic effects result from an action of the free PUFAs to modulate sodium and calcium currents in the myocytes. The PUFAs also modulate sodium and calcium channels and have anticonvulsant activity in brain cells.
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PMID:Prevention of fatal cardiac arrhythmias by polyunsaturated fatty acids. 1061 72

Epidemiologic studies, animal studies, and more recently, clinical intervention trials all suggest a role for regular intake of dietary fish oil in reducing cardiovascular morbidity and mortality. Prevention of cardiac arrhythmias and sudden death is demonstrable at fish or fish oil intakes that have little or no effect on blood pressure or plasma lipids. In animals, dietary intake of fish oil [containing both eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3)] selectively increases myocardial membrane phospholipid content of DHA, whereas low dose consumption of purified fatty acids shows antiarrhythmic effects of DHA but not EPA. Ventricular fibrillation induced under many conditions, including ischemia, reperfusion, and electrical stimulation, and even arrhythmias induced in vitro with no circulating fatty acids are prevented by prior dietary consumption of fish oil. The preferential accumulation of DHA in myocardial cell membranes, its association with arrhythmia prevention, and the selective ability of pure DHA to prevent ventricular fibrillation all point to DHA as the active component of fish oil. The antiarrhythmic effect of dietary fish oil appears to depend on the accumulation of DHA in myocardial cell membranes.
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PMID:Myocardial membrane fatty acids and the antiarrhythmic actions of dietary fish oil in animal models. 1183 83

Omega-3 fatty acid therapy is a promising intervention for the secondary prevention of coronary artery disease (CAD). Omega-3 fatty acids have properties that promote atherosclerotic plaque stability and decrease the incidence of ischemia-driven cardiac arrhythmias. A large number of clinical trials conducted in patients with CAD or prior myocardial infarction (MI) have examined hard cardiovascular end points, including total mortality, cardiovascular mortality, sudden death, and nonfatal MI. Several intermediate cardiovascular end-point studies have also examined whether ventricular arrhythmias can be suppressed in patients with implantable cardioverter defibrillators (ICDs). Significant reductions in total mortality and sudden death--20% to 50%--have been found in studies using doses of 0.85 to 4.0 g/day, with treatment durations from 12 to 42 months. Favorable trends toward reduction in the incidence of arrhythmic events have been demonstrated in some, but not all, ICD studies. Omega-3 fatty acid therapy shows a general positive trend toward benefit in reducing life-threatening events after MI and in patients with ICDs who have ischemic arrhythmias. Results of the recent Japan EPA Lipid Intervention Study (JELIS) in a large cohort (N = 18,645) of Japanese men and women suggest significant benefits in the reduction of unstable angina and nonfatal coronary events. The totality of evidence supports a strong role for omega-3 fatty acids derived from fish oil in secondary prevention through a presumptive role as an antiarrhythmic agent and through an ability to promote plaque stabilization.
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PMID:Secondary prevention of coronary artery disease with omega-3 fatty acids. 1691 18

Many studies indicate that dietary omega-3 polyunsaturated fatty acids (PUFAs) have the cardioprotective properties. But majority of experiments were carried out with using omega-3 PUFAs from marine fish oil. The purpose of this study was to determine effects of the plant-derived omega-3 PUFA (alpha-linolenic acid (a-LA) on postischemic myocardial dysfunction, lipid peroxidation and antioxidant enzymes activity. Male Wistar rats (250-300 g) were divided into 4 groups (n = 10-12 each). In control group (1) were intact rats. The hearts from 2-nd group of animal were exposed to 20 min of global ischemia followed by 40 min reperfusion according to the Langendorff technique. The 3-rd and 4-th groups of animal received of the plant-derived oil (a-LA), which is a precursor of eicosapentaenoic acid and was used as a dietary supplement in dose 0.1 mg/kg per day for 4 weeks. The hearts from 4-th group of animal were also exposed to ischemia/ reperfusion. Analysis of myocardial phospholipid fatty acid content showed that consumption of the plant-derived 6-LA for 4 weeks changes fatty acid profile through incorporation of b-LA in cell membranes. It also reduced content of omega-6 PUFAs in membrane phospholipids. In 3-rd group content of a-LA and EPA were increased by 1.5- and 3.5-times, respectively, whereas content of AA was reduced by 1.7-times. The development of ischemia/ reperfusion in 2-nd group caused increase of free AA content in heart tissue by 3.5-times, whereas in 4-th group this increase was only by 1.4-time. Ischemia/reperfusion of the isolated rat heart in 4-th group was accompanied by reduced leukotriene C4 and thromboxane B2 production in 3-times and 1.9-times, respectively in comparison to 2-nd group. The time of myocardial function recovery after ischemia (heart rate, left ventricular development pressure), was shorter compare to 2-nd group. Also in 4th group end-diastolic pressure and coronary perfusion pressure during reperfusion period were significantly lower. Dietary omega-3 PUFAs resulted in remarkable decrease of reperfusion arrhythmias in 4-th group (in 3.8-times) and limited the oxidative stress through decrease free radical and lipid peroxidation production. In this group of animals the activity of antioxidant enzymes (superoxide dismutase and catalase) after ischemia/reperfusion were higher than in 2-nd group. We suggest that dietary supplement of the plant-derived alpha-LA for 4 weeks have cardioprotective effects similar to the effects of fish oil.
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PMID:[The effects of alpha-linolenic acid on the functioning of the isolated heart during acute myocardial ischemia/reperfusion]. 1717 34

Polyunsaturated fatty acids (PUFAs) such as docosahexaenoic and eicosapentaenoic acids (DHA, EPA) exert ischemic anti-arrhythmic effects. However, their mechanism of action remains unknown. The present study was designed to investigate their potential effect on the regulation of the late sodium current as the basis for their ischemic anti-arrhythmic activity. Human isoforms of wild-type SCN5A and DeltaKPQ-mutated cardiac sodium channels were stably transfected in HEK 293 cells and, the resulting currents were recorded using the patch clamp technique in whole cell configuration. In addition to their effect to inhibit peak I(Na), acute application of DHA and EPA blocked veratridine-induced late sodium current (late I(Na-Verat)) in a concentration--dependent manner with IC(50) values of 2.1 +/- 0.5 microM and 5.2 +/- 0.8 microM,for DHA and EPA, respectively. Channels availability was reduced, resulting in a significant leftward shift of the steadystate inactivation curve by -10.0 +/- 2.1 mV and -8.5 +/- 0.2 mV for DHA and EPA, respectively. Similar inhibitory effects of DHA and EPA were also observed on late I(Na-KPQ). In addition to their role as blocking agents of peak I(Na), DHA and EPA reduced human late I(Na). These results could explain the antiarrhythmic properties of DHA and EPA during ischemia or following ischemia-reperfusion.
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PMID:Direct protective effects of poly-unsaturated fatty acids, DHA and EPA, against activation of cardiac late sodium current: a mechanism for ischemia selectivity. 1789 22

Postprandial lipemia is associated with elevated risk of cardiovascular disease. Very little data exists regarding postprandial response in subjects with metabolic syndrome (MetS). The current study was conducted within the LIPGENE EU Integrated Project. Patients were randomized to one of the four isocaloric fatty meals (Oral Fat Tolerance Tests, OFTT): (A) high-fat, saturated fatty acid (SFA)-rich (HFSA), (B) high-fat, monounsaturated fatty acid (MUFA)-rich (HFMUFA), (C) low-fat, high-complex carbohydrate with 1.24 g high oleic sunflower oil supplement (LFHCC) and (D) low-fat high-complex carbohydrate with 1.24 g long chain n-3 poly-unsaturated fatty acid (LC n-3 PUFA) supplement (LFHCCn-3). The total and incremental areas under the curve (tAUC and iAUC) of plasma lipid and lipoprotein, Ischemia Modified Albumin (IMA) and LDL density were examined in patients with MetS to define effect of OFTT. All types of OFTT transiently increased plasma triglyceride and LDL density (LDLdens). It was paralleled by temporal decrease in total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C). This last effect was partly alleviated in LFHCCn-3 test. A reversible increase of IMA was statistically significant only in the course of HSFA and HMUFA tests. EPA and DHA supplement in combined high complex-carbohydrate meal may attenuate adverse effect of tested meal on LDL particle profile and plasma ischemia modified albumin. No expected associations between measures of central adiposity (waist, WHR), adipose tissue insulin resistance (Adipo-IR), and postprandial responses of TG, TC, LDL-C, HDL-C, LDLdens and IMA/Alb ratio were found in subgroup analysis.
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PMID:Lipoprotein profile, plasma ischemia modified albumin and LDL density change in the course of postprandial lipemia. Insights from the LIPGENE study. 2023 37


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