Aim: We aimed to assess the ability of natural and modified polyunsaturated fatty acids (PUFAs) to shorten QT interval in ex-vivo and in-vivo guinea pig hearts.
Methods: The effect of one natural (docosahexaenoic acid [DHA]) and three modified (linoleoyl glycine [Lin-GLY], docosahexaenoyl glycine [DHA-GLY], N-arachidonoyl taurine [N-AT]) PUFAs on ventricular action potential duration (APD) and QT interval was studied in a E4031 drug-induced long QT2 model of ex-vivo guinea pig hearts. The effect of DHA-GLY on QT interval was also studied in in-vivo guinea pig hearts upon intravenous administration. The effect of modified PUFAs on I was studied using Xenopus laevis oocytes expressing human KCNQ1 and KCNE1.
Results: All tested PUFAs shortened ADP and QT interval in ex-vivo guinea pig hearts, however, with different ability in restoring baseline APD/QT interval with specific modified PUFAs being most efficacious. Despite comparable ability in activating the human KCNQ1/KCNE1 channel, Lin-GLY was not as effective in shortening APD/QT interval as DHA-GLY in ex-vivo hearts. By constructing a guinea pig-like KCNE1, we found Lin-GLY to induce less activating effect compared with DHA-GLY on human KCNQ1 co-expressed with guinea pig-like KCNE1. Docosahexaenoyl glycine was studied in more detail and was found to shorten QT interval in in-vivo guinea pig hearts.
Conclusion: Our results show that specific PUFAs shorten QT interval in guinea pig hearts. The tendency of modified PUFAs with pronounced I channel activating effect to better restore QT interval suggests that modifying PUFAs to target the I channel is a means to improve the QT-shortening effect.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8633721 | PMC |
| http://dx.doi.org/10.1111/apha.13471 | DOI Listing |
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