Effects of ω-3 polyunsaturated fatty acids on cardiac sarcolemmal Na+/H+ exchange

2002 ◽  
Vol 283 (4) ◽  
pp. H1688-H1694 ◽  
Author(s):  
Danny P. Goel ◽  
Thane G. Maddaford ◽  
Grant N. Pierce
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Specific Effect ◽  
Eicosapentanoic Acid ◽  
Cardiac Membranes ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion ◽  
Antiarrhythmic Actions

Myocardial ischemia-reperfusion activates the Na+/H+ exchanger, which induces arrhythmias, cell damage, and eventually cell death. Inhibition of the exchanger reduces cell damage and lowers the incidence of arrhythmias after ischemia-reperfusion. The ω-3 polyunsaturated fatty acids (PUFAs) are also known to be cardioprotective and antiarrhythmic during ischemia-reperfusion challenge. Some of the action of PUFAs may occur via inhibition of the Na+/H+ exchanger. The purpose of our study was to determine the capacity for selected PUFAs to alter cardiac sarcolemmal (SL) Na+/H+exchange. Cardiac membranes highly enriched in SL vesicles were exposed to 10–100 μM eicosapentanoic acid (EPA) or docosahexanoic acid (DHA). H+-dependent 22Na+ uptake was inhibited by 30–50% after treatment with ≥50 μM EPA or ≥25 μM DHA. This was a specific effect of these PUFAs, because 50 μM linoleic acid or linolenic acid had no significant effect on Na+/H+ exchange. The SL vesicles did not exhibit an increase in passive Na+ efflux after PUFA treatment. In conclusion, EPA and DHA can potently inhibit cardiac SL Na+/H+ exchange at physiologically relevant concentrations. This may explain, in part, their known cardioprotective effects and antiarrhythmic actions during ischemia-reperfusion.

scholarly journals Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury

2021 ◽  
Vol 22 (6) ◽  
pp. 2798
Author(s):  
Zoran Todorović ◽  
Siniša Đurašević ◽  
Maja Stojković ◽  
Ilijana Grigorov ◽  
Slađan Pavlović ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Time Course ◽  
Membrane Lipids ◽  
Lipid Analysis ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Enzyme Inactivation ◽  
Critical Event ◽  
Tissue Ischemia ◽  
Insight Into

Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.

scholarly journals Trop2 Guarantees Cardioprotective Effects of Cortical Bone-Derived Stem Cells on Myocardial Ischemia/Reperfusion Injury

2018 ◽  
Vol 27 (8) ◽  
pp. 1256-1268 ◽  
Author(s):  
Tianyu Li ◽  
Yunshu Su ◽  
Xiongli Yu ◽  
Durgahee S.A. Mouniir ◽  
Jackson Ferdinand Masau ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Myocardial Ischemia ◽  
Cortical Bone ◽  
Heart Function ◽  
Heart Diseases ◽  
Ischemia Reperfusion ◽  
Promising Therapeutic Approach ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion

Stem cell transplantation represents a promising therapeutic approach for myocardial ischemia/reperfusion (I/R) injury, where cortical bone-derived stem cells (CBSCs) stand out and hold superior cardioprotective effects on myocardial infarction than other types of stem cells. However, the molecular mechanism underlying CBSCs function on myocardial I/R injury is poorly understood. In a previous study, we reported that Trop2 (trophoblast cell-surface antigen 2) is expressed exclusively on the CBSCs membrane, and is involved in regulation of proliferation and differentiation of CBSCs. In this study, we found that the Trop2 is essential for the ameliorative effects of CBSCs on myocardial I/R-induced heart damage via promoting angiogenesis and inhibiting cardiomyocytes apoptosis in a paracrine manner. Trop2 is required for the colonization of CBSCs in recipient hearts. When Trop2 was knocked out, CBSCs largely lost their functions in lowering myocardial infarction size, improving heart function, enhancing capillary density, and suppressing myocardial cell death. Mechanistically, activating the AKT/GSK3β/β-Catenin signaling axis contributes to the essential role of Trop2 in CBSCs-rendered cardioprotective effects on myocardial I/R injury. In conclusion, maintaining the expression and/or activation of Trop2 in CBSCs might be a promising strategy for treating myocardial infarction, I/R injury, and other related heart diseases.

scholarly journals Cardioprotective Effects of Nutraceuticals: Focus on Omega-3 Polyunsaturated Fatty Acids

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3184
Author(s):  
Grazyna Sypniewska ◽  
Stefan Kruszewski
Keyword(s):  
Fatty Acids ◽  
Cardiovascular Diseases ◽  
Polyunsaturated Fatty Acids ◽  
Omega 3 ◽  
Cardioprotective Effects

Cardiovascular diseases are the leading cause of mortality worldwide [...]

Myocardial dysfunction is associated with activation of Na+/H+exchange immediately during reperfusion

1997 ◽  
Vol 273 (5) ◽  
pp. H2232-H2239 ◽  
Author(s):  
Thane G. Maddaford ◽  
Grant N. Pierce
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Vascular Wall ◽  
Right Ventricular Wall ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion ◽  
Dimethyl Amiloride ◽  
Whole Heart

Amiloride analogs block Na+/H+exchange and thereby protect the heart from myocardial ischemia-reperfusion injury. It is unclear whether drugs must be present before ischemia to be cardioprotective. After 60 min of global ischemia in the coronary-perfused right ventricular wall (RVW), as little as 1 min of exposure to dimethyl amiloride (DMA) immediately at the time of reperfusion protected the RVW. Delaying the drug attenuated the cardioprotection. If DMA was introduced in an ischemic solution near the end of ischemia, the cardioprotective effects were augmented. If the drug was washed out of the RVW vascular space before ischemia, cardioprotection was not observed. In contrast, in whole hearts, preischemic perfusion of the drug was necessary for cardioprotection and the cardioprotection remained even if the drug was washed out before ischemia. We conclude that Na+/H+exchange is active and contributes to contractile dysfunction during the first seconds of reperfusion. This is difficult to detect in the perfused whole heart, and the washout data suggest that this may be due to a limitation in drug delivery across the vascular wall. The data also suggest that the exchanger is not as active during ischemia itself as it is during reperfusion.

Mechanism of decreased adenosine protection in reperfusion injury of aging rats

2000 ◽  
Vol 279 (1) ◽  
pp. H329-H338 ◽  
Author(s):  
Feng Gao ◽  
Theodore A. Christopher ◽  
Bernard L. Lopez ◽  
Eitan Friedman ◽  
Guoping Cai ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Protective Effects ◽  
No Release ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion

The purpose of this study was to determine whether the protective effects of adenosine on myocardial ischemia-reperfusion injury are altered with age, and if so, to clarify the mechanisms that underlie this change related to nitric oxide (NO) derived from the vascular endothelium. Isolated perfused rat hearts were exposed to 30 min of ischemia and 60 min of reperfusion. In the adult hearts, administration of adenosine (5 μmol/l) stimulated NO release (1.06 ± 0.19 nmol · min−1 · g−1, P < 0.01 vs. vehicle), increased coronary flow, improved cardiac functional recovery (left ventricular developed pressure 79 ± 3.8 vs. 57 ± 3.1 mmHg in vehicle, P < 0.001; maximal rate of left ventricular pressure development 2,385 ± 103 vs. 1,780 ± 96 in vehicle, P < 0.001), and reduced myocardial creatine kinase loss (95 ± 3.9 vs. 159 ± 4.6 U/100 mg protein, P < 0.01). In aged hearts, adenosine-stimulated NO release was markedly reduced (+0.42 ± 0.12 nmol · min−1 · g−1 vs. vehicle), and the cardioprotective effects of adenosine were also attenuated. Inhibition of NO production in the adult hearts significantly decreased the cardioprotective effects of adenosine, whereas supplementation of NO in the aged hearts significantly enhanced the cardioprotective effects of adenosine. The results show that the protective effects of adenosine on myocardial ischemia-reperfusion injury are markedly diminished in aged animals, and that the loss in NO release in response to adenosine may be at least partially responsible for this age-related alteration.

C-peptide exerts cardioprotective effects in myocardial ischemia-reperfusion

2000 ◽  
Vol 279 (4) ◽  
pp. H1453-H1459 ◽  
Author(s):  
Lindon H. Young ◽  
Yasuhiko Ikeda ◽  
Rosario Scalia ◽  
Allan M. Lefer
Keyword(s):  
Cardiac Dysfunction ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
C Peptide ◽  
Cardiac Contractile ◽  
No Release ◽  
Cardiac Contractile Dysfunction ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion ◽  
Developed Pressure

Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in cardiac dysfunction. C-peptide, a cleavage product of proinsulin to insulin processing, induces nitric oxide (NO)-mediated vasodilation. NO is reported to attenuate cardiac dysfunction caused by PMNs after ischemia-reperfusion (I/R). Therefore, we hypothesized that C-peptide could attenuate PMN-induced cardiac dysfunction. We examined the effects of C-peptide in isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. C-peptide (70 nmol/kg iv) given 4 or 24 h before I/R significantly improved coronary flow ( P < 0.05), left ventricular developed pressure (LVDP) ( P < 0.01), and the maximal rate of development of LVDP (+dP/d t max) compared with I/R hearts obtained from rats given 0.9% NaCl ( P < 0.01). N G-nitro-l-arginine methyl ester (l-NAME) (50 μmol/l) blocked these cardioprotective effects. In addition, C-peptide significantly reduced cardiac PMN infiltration from 183 ± 24 PMNs/mm2 in untreated hearts to 44 ± 10 and 58 ± 25 PMNs/mm2 in hearts from 4- and 24-h C-peptide-treated rats, respectively. Rat PMN adherence to rat superior mesenteric artery exposed to 2 U/ml thrombin was significantly reduced in rats given C-peptide compared with rats given 0.9% NaCl ( P < 0.001). Moreover, C-peptide enhanced basal NO release from rat aortic segments. These results provide evidence that C-peptide can significantly attenuate PMN-induced cardiac contractile dysfunction in the isolated perfused rat heart subjected to I/R at least in part via enhanced NO release.

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