Lower Omega 3 Index is a Marker of Increased Propensity of Hypertensive Rat Heart to Malignant Arrhythmias
Lower Omega 3 Index is a Marker of Increased Propensity of Hypertensive Rat Heart to Malignant Arrhythmias
Year: 2013
Authors: Bacova, B. Sec, P. Radosinska, J. Certik, M. Vachulova, A. Tribulova, N.
Publication Name: Physiol Res.
Publication Details: Volume 62; Issue 1; Pages S201 – S208
Abstract:
Polyunsaturated omega 3 fatty acids are important components of cell membrane affecting its function and their deficiency is deleterious to health. We have previously shown that spontaneously hypertensive rats (SHR) are prone to life- threatening arrhythmias that are reduced by n 3 PUFA intake. Purpose of this study was to explore plasma and red blood c ells (RBC) profile of n 3 and n 6 PUFA as well as to determine n 3 index, a risk factor for sudden cardiac death, in aged SHR and the effect of n 3 PUFA intake. Male and female 12 month old SHR and age matched Wistar rats fed with n 3 PUFA (200 mg per kg BW per day per 2 month) were compared with untreated rats. Composition of n 3 PUFA alpha linolenic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as well as n 6 PUFA: linoleic acid and arachidonic acid was analyzed by gas chromatography. Results showed sex and strain related differences of basal n 3 and n 6 PUFA levels in plasma and RBC as well as in response to n 3 PUFA intake. Comparing to Wistar rats n 3 index, expressed as a percentage of EPA plus DHA of total fatty acids, was lower in SHR and it increased due to consumption of n 3 PUFA. Findings support our hypothesis that lower n 3 index may be also a marker of increased propensity of the hypertensive rat heart to malignant arrhythmias. (Authors abstract)
Sudden cardiac death (SCD) accounts for more than 15 per cent of all deaths in Europe, and therefore is a major health problem. SCD is the major cause of death due to ventricular tachyarrhythmias, particularly ventricular fibrillation (VF). It may be caused by various arrhythmogenic factors. One of these factors is myocardial hypertrophy.
Data from clinical and experimental studies support the hypothesis that consumption of n 3 PUFA lowers the risk of cardiovascular diseases and SCD . Based on the scientific evidence it was proposed a new risk factor for SCD, the n 3 index. It is measured in red blood cells (RBC) and is expressed as a percentage of EPA plus DHA of total fatty acids. n 3 PUFA intake protects young and old spontaneously hypertensive rats (SHR) from VF. Protection was associated with treatment induced improvement of cell membrane and intercellular junction integrity as well as up-regulation of myocardial electrical coupling protein, connexin 43. This study was aimed to explore plasma and RBC profile of n 3 and n 6 PUFA as well as to determine n 3 index in aged male and female SHR and the effect of n 3 PUFA intake. The study found that there are strain and sex dependent differences in n 3 and n 6 PUFA levels in both plasma and RBC. More importantly, n 3 index, i.e. EPA plus DHA was lower in SHR when compared to Wistar rats and it was enhanced due to n 3 PUFA supplementation. It should be noted that n 3 and n 6 PUFA profile found in plasma reflects short term, whereas in RBC rather long term changes in dietary fatty acids intake. Comparing to males the plasma n 3 but not n 6 PUFA content was lower in females either Wistar or SHR. It may indicate that the rate of n 3 PUFA metabolism is faster in females even if they are old. Women also have a greater capacity than man to synthesize n 3 PUFA from their essential fatty acid precursor ALA. ALA was higher in females than males regardless the strain. In contrast, RBC levels of AA (important representative of n 6 PUFA) were much lower in females than males SHR as well as Wistar rats. Furthermore LA (precursor of n 6 PUFA) was low in female Wistar but not SHR. Sex related differences point out the role of sex hormones in regulation of PUFA metabolism. Different to ALA (which does not exhibit strain differences) the levels of EPA or DHA were lower in SHR comparing to Wistar rats regardless the sex. Consequently, n 3 index was lower in SHR than Wistar rats. Two month lasting supplementation with n 3 PUFA ethyl ester resulted in significant increase of both plasma and RBC levels of EPA and or DHA in Wistar and particularly SHR. An increase of EPA and DHA was accompanied by reduction on ALA levels perhaps due to its enhanced metabolism and conversion to EPA or DHA. AA to EPA ratio was higher in SHR than Wistar rats while decreased due to n 3 PUFA intake. Of note, reduced ratio AA per EPA shifts the spectrum of ecosanoids production toward increase in tromboxane A3 and PGI3 at the expense of TXA2 and PGI2. This shift was found to reduce risk of fatal arrhythmias. In conclusion, this study revealed for the first time that n 3 index is lower in male and female SHR comparing to Wistar rats but increased due to n 3 PUFA intake. It should be emphasized the inverse association of n 3 index with occurrence of malignant arrhythmias in SHR. Findings support the hypothesis that lower n 3 index may be a marker of increased propensity of the heart to SCD due to malignant arrhytmia. (Editors comments)
Data from clinical and experimental studies support the hypothesis that consumption of n 3 PUFA lowers the risk of cardiovascular diseases and SCD . Based on the scientific evidence it was proposed a new risk factor for SCD, the n 3 index. It is measured in red blood cells (RBC) and is expressed as a percentage of EPA plus DHA of total fatty acids. n 3 PUFA intake protects young and old spontaneously hypertensive rats (SHR) from VF. Protection was associated with treatment induced improvement of cell membrane and intercellular junction integrity as well as up-regulation of myocardial electrical coupling protein, connexin 43. This study was aimed to explore plasma and RBC profile of n 3 and n 6 PUFA as well as to determine n 3 index in aged male and female SHR and the effect of n 3 PUFA intake. The study found that there are strain and sex dependent differences in n 3 and n 6 PUFA levels in both plasma and RBC. More importantly, n 3 index, i.e. EPA plus DHA was lower in SHR when compared to Wistar rats and it was enhanced due to n 3 PUFA supplementation. It should be noted that n 3 and n 6 PUFA profile found in plasma reflects short term, whereas in RBC rather long term changes in dietary fatty acids intake. Comparing to males the plasma n 3 but not n 6 PUFA content was lower in females either Wistar or SHR. It may indicate that the rate of n 3 PUFA metabolism is faster in females even if they are old. Women also have a greater capacity than man to synthesize n 3 PUFA from their essential fatty acid precursor ALA. ALA was higher in females than males regardless the strain. In contrast, RBC levels of AA (important representative of n 6 PUFA) were much lower in females than males SHR as well as Wistar rats. Furthermore LA (precursor of n 6 PUFA) was low in female Wistar but not SHR. Sex related differences point out the role of sex hormones in regulation of PUFA metabolism. Different to ALA (which does not exhibit strain differences) the levels of EPA or DHA were lower in SHR comparing to Wistar rats regardless the sex. Consequently, n 3 index was lower in SHR than Wistar rats. Two month lasting supplementation with n 3 PUFA ethyl ester resulted in significant increase of both plasma and RBC levels of EPA and or DHA in Wistar and particularly SHR. An increase of EPA and DHA was accompanied by reduction on ALA levels perhaps due to its enhanced metabolism and conversion to EPA or DHA. AA to EPA ratio was higher in SHR than Wistar rats while decreased due to n 3 PUFA intake. Of note, reduced ratio AA per EPA shifts the spectrum of ecosanoids production toward increase in tromboxane A3 and PGI3 at the expense of TXA2 and PGI2. This shift was found to reduce risk of fatal arrhythmias. In conclusion, this study revealed for the first time that n 3 index is lower in male and female SHR comparing to Wistar rats but increased due to n 3 PUFA intake. It should be emphasized the inverse association of n 3 index with occurrence of malignant arrhythmias in SHR. Findings support the hypothesis that lower n 3 index may be a marker of increased propensity of the heart to SCD due to malignant arrhytmia. (Editors comments)
