Cardiac Phospholipids Research Articles

Phosphatidylcholine metabolism in isolated rat heart: modulation by ethanol and vitamin E

Prolonged ethanol administration has been reported to cause defects in cardiac performance and abnormal cardiac lipid contents. However, little is known regarding the short-term administration of ethanol to the perfused heart and its effect on cardiac phospholipid metabolism. In this study, the isolated Langendorff heart perfusion was used as a model to study the effects of ethanol and a combination of ethanol and vitamin E ( dl-α-tocopherol) on phospholipid metabolism. When perfused with 1% ethanol for 4 h, the major cardiac phospholipids were not altered but a 60% increase in lysophosphatidylcholine level was observed. Studies on the lysophosphatidylcholine metabolic enzymes revealed that phospholipase A (both phospholipase A 1 and A 2) activity was enhanced in the ethanol-perfused heart, but lysophospholipase and acyltransferase activities were unaffected by ethanol treatment. When the heart was perfused with 1% ethanol in the presence of 50–100 μM vitamin E, the ethanol-induced lysophosphatidylcholine accumulation was completely abolished. This was largely attributed to the attenuation of phospholipase A activities by vitamin E. In order to delineate the opposing effects of ethanol and vitamin E on phospholipid metabolism in the heart, phospholipase A activities in the subcellular fractions were determined in the presence of 0.5–2.0% ethanol or a combination of 1% ethanol and 0–100 μM vitamin E. Ethanol alone exhibited a biphasic effect on phospholipase A activity with maximum stimulation of enzyme activities at 1% concentration. When phospholipase A was assayed in 1% ethanol and vitamin E (25–100 μM), its activity was inhibited by vitamin E in a dose-dependent manner. The mechanism by which ethanol enhanced phospholipase A activities was further investigated with a partially purified enzyme from the rat heart cytosol. Kinetic studies with different concentrations of phosphatidylcholine revealed that at low substrate concentrations, ethanol was inhibitory to the reaction, whereas at high substrate concentrations, the reaction was enhanced by ethanol. Vitamin E (50 μM) completely abolished the ethanol-induced enhancement of enzyme activity in a noncompetitive manner. Since lysophosphatidylcholine is cytolytic at high concentration and its accumulation in the heart has been postulated as a biochemical cause of cardiac dysfunction, the level of the lysolipid in the heart must be under rigid control. Our result suggest that the modulation of cardiac phospholipase A activity is an important mechanism for the the regulation of lysophosphatidylcholine levels in the rat heart.

Alterations in polyunsaturated fatty acid composition of cardiac membrane phospholipids and alpha-1-adrenoceptor mediated phosphatidylinositol turnover

Alterations in polyunsaturated fatty acid composition of cardiac membrane phospholipids and alpha-1-adrenoceptor mediated phosphatidylinositol turnover

Inhibition of cardiac phospholipid N-methylation by oxygen free radicals: M. Kaneko, G. Paolillo, S. Majumder, C. Ou, V. Panagia and N.S. Dhalla. Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Departments of Physiology and Anatomy, University of Manitoba, Winnipeg, Canada R2H 2A6

Inhibition of cardiac phospholipid N-methylation by oxygen free radicals: M. Kaneko, G. Paolillo, S. Majumder, C. Ou, V. Panagia and N.S. Dhalla. Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Departments of Physiology and Anatomy, University of Manitoba, Winnipeg, Canada R2H 2A6

Effects of n-3 polyunsaturated fatty acids on coronary heart disease.

The purpose of this paper is to discuss the role of n-6 and n-3 polyunsaturated fatty acids in coronary heart disease (CHD). The level of n-6 and n-3 fatty acids in plasma and cardiac phospholipids was examined in relation to CHD in man. The fatty acid profile of cardiac phospholipids was also examined in relation to various risk factors of CHD, such as the composition of dietary fat, aging and stress. Life expectancy in Iceland is higher than in other Nordic countries, and the cardiovascular diseases mortality is lower in Iceland in the older age groups. There is a positive correlation between the level of arachidonic acid (AA) in plasma phospholipids (PL) in the normal population and cardiovascular disease mortality in Nordic countries. The level of AA in plasma PL is significantly higher in patients with CHD than in normal subjects. Dietary intake of fish or fish oil lowers cellular levels of AA and favorably influences eicosanoid metabolism in platelets and leukocytes. The roles of n-6 and n-3 fatty acids in heart muscle are less well understood. Rats fed diets containing either 10% butter, corn oil or cod liver oil showed markedly different fatty acid composition of individual phospholipids in sarcolemma. Dietary cod liver oil lowered the AA level in sarcolemmal phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) by 50% compared to butter or corn oil fed rats, replacing AA with docosahexaenoic acid (DHA). Adaptation to moderate to severe stress induced by repeated administration of catecholamines for 15 days resulted in marked but reversible alterations in the fatty acid profile of cardiac phospholipids. During severe stress the level of AA increased by 50% in PC replacing linoleic acid (LA), whereas in PE the DHA increased markedly replacing LA. Aging was accompanied by similar alterations in cardiac phospholipids, increased levels of AA in PC and increased DHA in PE. The incidence of ventricular fibrillation (VF) and sudden cardiac death induced by isoproterenol in adult rats fed different dietary fat was lowest in rats fed cod liver oil, with a low ratio of AA/DHA in cardiac phospholipids. Mortality due to VF was highest in rats fed corn oil with the highest ratio of AA/DHA. Sudden cardiac death in man was frequently associated with a higher ratio of AA/DHA than observed in people of the same age who died in accidents. The balance between n-6 and n-3 fatty acids in cellular phospholipids seems to play an important role in stress tolerance and survival.

Protection of rat myocardial phospholipid against peroxidative injury through superoxide- (xanthine oxidase)-dependent, iron-promoted fenton chemistry by the male contraceptive gossypol

Metal-promoted oxygen free-radical chemistry is a cause of tissue damage in many disease states, such as myocardial ischemia. The effect of gossypol, a polyphenolic plant pigment and male contraceptive, on the peroxidation of myocardial membrane phospholipid was studied and quantitatively characterized. As a result of exposure to xanthine oxidase (superoxide)-dependent, iron-promoted Fenton chemistry, cardiac phospholipid was readily peroxidized with defined kinetics. The peroxidation could be blocked by substances which interdict at specific points in the Fenton chemistry: Superoxide dismutase, α-tocopherol, the iron chelator desferrioxamine, and the xanthine oxidase substrate-analogs allopurinol and oxypurinol. The oxidative-injury system displayed a characteristic antiperoxidant response to each type of inhibitor. Gossypol, at low micromolar concentrations, profoundly altered the rate and extent of myocardial phospholipid peroxidation. Gossypol was ineffective as a xanthine oxidase inhibitor and as a Superoxide scavenger at concentrations that abolished myocardial lipid peroxidation. Since metal chelation was an effective means of preventing lipid peroxidation in this system only when the iron therein was completely chelated, the low anti-peroxidant ic 50 for gossypol, 1.1. μM, relative to the concentration of iron (100 μM) did not support a functionally significant antiperoxidant role for gossypol as an iron chelator. Rather, it appears that, at low micromolar gossypol concentrations which approximate the peak plasma concentrations in humans, the antiperoxidant effects of gossypol against superoxide-mediated, iron-promoted lipid damage rest with the ability of gossypol to intercept lipid radical intermediates as a “chain-breaking” aromatic phenol.

Effect of Dietary Salmon Oil Feeding on Rat Heart Lipid Status

For 2 mo rats were fed a salmon oil diet (12.5%, wt/wt) supplemented with 4.5% (wt/wt) corn oil, a corn oil diet (17%, wt/wt) or a low fat diet (4.4%, wt/wt). Cardiac lipids were analyzed and fatty acid composition of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was determined. Ventricular biopsies were taken for ultramicroscopic examination. Serum cholesterol, triglyceride, phospholipid and vitamin E concentrations were significantly lower in rats fed salmon oil than in those fed the other two diets, whereas serum transaminases and vitamin A were not significantly affected. Cardiac protein, phospholipid, triglyceride and cholesterol concentrations were unaffected by diet. Cardiac phospholipid composition remained unchanged and no significant changes in lyso-PC or lyso-PE levels were observed. However, the salmon oil diet produced a markedly lower n-6/n-3 ratio in both PE and PC than in the other two diets. This was the result of replacement of n-6 polyunsaturated fatty acids (PUFA), primarily 20:4n-6 with n-3 PUFA, primarily 22:6n-3. The unsaturation index of PC and PE was higher with the salmon oil diet than with the other two diets. Ventricular biopsies of rats fed salmon oil showed mild lipid accumulation associated with some lipofuscin-like material. It is suggested that, in rat heart, fish oil led to a moderate accumulation of lipids, the composition of which may include long-chain monounsaturated fatty acids and a degradative form of peroxidized lipids.

Dietary menhaden oil: effects on the rate and magnitude of modification of phospholipid fatty acid composition of mouse heart and brain.

1. Male CD-1 white mice, 18-20 g body-weight, were given semi-purified diets containing 100 g menhaden oil (MO) or hydrogenated coconut oil (HCO)/kg for 23 d. Mice were killed on days 0, 3, 5, 7, 14, 23. After 23 d of MO supplementation the remaining mice were switched to the HCO diet for an additional 10 d. 2. The progressive change(s) in the polyunsaturated fatty acid (PUFA) composition of cardiac and brain phospholipid classes were followed during the MO supplementation and depletion periods. 3. The content of fatty acids 20:5n-3, 22:5n-3 and 22:6n-3 increased immediately following ingestion of the MO diet and continued to increase at a steady rate in both heart and brain phospholipid classes. 4. In general, the period required to reach steady-state was 1 week for n-3 PUFA and 18:2n-6, and 2 weeks for 20:4n-6. 5. Cessation of MO consumption for 10 d resulted in marked decreases in the content of n-3 PUFA and increases in n-6 PUFA in cardiac phospholipids in particular. Brain phospholipids were less responsive. 6. The results suggest that dietary fish oil must be consumed for at least 1 week before maximum changes in PUFA composition are observed, and fish oil ingestion must be continuous to maintain elevated n-3 PUFA levels in heart and brain phospholipids.

In vivo stimulation of cardiac phospholipid N-methylation by isoproterenol: Y. Taira, V. Panagia, K.R. Shah, N.S. Dhalla. Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Departments of Physiology and Anatomy, University of Manitoba, Winnipeg, Canada R2H 2A6

In vivo stimulation of cardiac phospholipid N-methylation by isoproterenol: Y. Taira, V. Panagia, K.R. Shah, N.S. Dhalla. Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Departments of Physiology and Anatomy, University of Manitoba, Winnipeg, Canada R2H 2A6

Long-term saturated fat feeding induced changes in rat myocardial phospholipid fatty acids are reversed by cross-over to polyunsaturated diets: Differences between n-3 and n-6 lipid supplements

The reversal of long-term saturated fat feeding induced changes in cardiac phospholipids by cross-over to different polyunsaturated lipid diets was investigated. Rats were maintained on standard pellets supplemented (12% w/w) with sheep fat (SF) for 9 months and then crossed-over to either n-6 enriched sunflower seed oil (SSO) or n-3 polyunsaturated tuna fish oil (TFO) supplemented diets and fed for a further 9 months. A third group of rats was fed the SF diet continuously. Although there were no differences in body weights at the time of cross-over, at sacrifice the TFO supplemented rats were found to be heavier (p<0.05) than the SSO diet fed group. The cross-over to different polyunsaturated diets significantly altered the fatty acid composition of cardiac phospholipids. However, the nature and extent of these changes varied considerably between the n-3 and n-6 lipid supplements. For example, in total phospholipids, linoleic acid proportion was increased in the SSO group whilst a considerable reduction was apparent following the TFO diet. In contrast, only the n-3 diet altered the proportion of arachidonic acid (20:4, n-6) in cardiac membranes. Nevertheless, the extent of displacement of 20:4 by n-3 acids showed some class specificity, with phosphatidylethanolamine (PE) displaying the greatest reduction. The incorporation of n-3 unsaturated eicosapentaenoic (20:5) acid into cardiac phospholipids was relatively small (<1%) compared to docosahexaenoic acid (DHA; 22:6, n-3) which amounted to 16% in phosphatidylcholine, 25% in diphosphatidylglycerol and up to 40% in PE following n-3 supplementation, demonstrating a specificity between different phospholipid classes for the incorporation and/or conversion of dietary fatty acids. The observations of the present study clearly indicate that dietary intervention with polyunsaturated lipid supplements in mature animals results in considerable changes in membrane lipid composition depending on the type of unsaturation.

The effects of dietary mackerel oil on plasma and cell membrane lipids, on hemodynamics and cardiac arrhythmias during recurrent acute ischemia in the pig.

Fish-oil nutrition leads to a change in fatty acid composition of cellular membranes. To investigate whether this affects cardiac responses to acute myocardial ischemia, pigs were fed a 9.1% (w/w) mackerel-oil (n = 8) or 9.1% (w/w) lard-fat diet (n = 8). Eight weeks mackerel-oil feeding reduced plasmacholesterol (51%) and triglyceride (48%), while the n-6 fatty acids of cardiac and platelet membrane phospholipids were partially replaced by n-3 fatty acids. After 8 weeks the animals were anesthetized and the left anterior descending coronary artery was occluded 6 times for a period of 5 min at 15 min intervals. Recovery of cardiac function and the incidence of cardiac arrhythmias were similar for both dietary groups. However, during the last reperfusions, hyperemic responses were less in magnitude and shorter lasting in the lard-fat (81 +/- 17 ml/min) than in the mackerel-oil group (129 +/- 18 ml/min). This may be caused by a difference in thromboxane synthesis, as coronary venous blood thromboxane B2 levels were higher in the lard-fat (77 +/- 6 pg/ml) than in the mackerel-oil group (19 +/- 7 pg/ml, P less than 0.05) during peak hyperemia. The low baseline levels of both thromboxane B2 and 6-keto prostaglandin F1alpha in fish-oil fed animals originate from the reduced content of precursor fatty acid in the membrane phospholipids. In conclusion, despite marked changes in membrane fatty acid composition induced by prolonged feeding with fish oil, no modification of recovery of cardiac function and of incidence of cardiac arrhythmias was found during acute recurrent ischemia.

The influence of fish oil diet and norepinephrine treatment on fatty acid composition of rat heart phospholipids and the positional fatty acid distribution in phosphatidylethanolamine.

The effect of chronic norepinephrine (NE) administration with increasing dosage from 1-4 mg/kg over a period of 2 weeks was studied on cardiac phospholipids and their fatty acid distribution in rats. Animals were fed a control diet or a 10% cod liver oil (CLO)-enriched diet. The relative distribution of various polyunsaturated fatty acids esterified to the 1- and 2-position of the phosphatidylethanolamine fraction was estimated. NE stress during control feeding significantly reduced the total phospholipid content in rat heart. No differences in the phospholipid class distribution were found. However, CLO feeding as well as chronic NE administration resulted in a decrease of omega 6 fatty acids, mainly C 18:2 omega 6 and C 20:4 omega 6, which was compensated with an increase in omega 3 fatty acids, mainly C 20:5 omega 3 and C 22:6 omega 3. The changes in fatty acid composition qualitatively agree with those reported by Gudbjarnason et al. (23), except that the mortality in our NE-treated control or CLO-fed groups was considerably lower. It can probably be attributed to a different mode of NE administration. On the other hand, at the end of the CLO feeding period in rats treated with NE or not, comparing with control fed rats without NE treatment, the incidence rate of ST segment elevation in electrocardiogram (ECG) recorded under light diethylether-induced anesthesia was higher. Independent of whether the fatty acid composition of myocardial phospholipids was dietary or pharmacologically manipulated, most of the polyunsaturated fatty acids were found at the 2-position of the phosphatidylethanolamine molecules. The polyunsaturated fatty acids account for 45-50% of the fatty acyl residues and preferentially occupy the 2-position, where they can exchange for each other.

Competition of n-3 and n-6 polyunsaturated fatty acids in the isolated perfused rat heart.

When perfused with exogenous arachidonic acid (AA) or eicosapentaenoic acid (EPA), the rat heart incorporated these fatty acids into phospholipids, chiefly as phosphatidylcholine. The pattern of fatty acid incorporation at any given concentration of fatty acid in the perfusate was not different between n-3 and n-6 polyenoates. When rat hearts were perfused with the same amounts but different mixtures of EPA and AA, the incorporation of EPA showed a marked increase proportional to the EPA/AA ratio present in the perfusate. Results indicated that cardiac muscle phospholipids incorporate n-3 and n-6 polyenoates equally effectively and hence enrichment of n-3 polyenoate can displace AA in the cardiac phospholipid pool.

The composition of cardiac phospholipids in rats fed different lipid supplements.

Changes in dietary lipid intake are known to alter the fatty acid composition of cardiac muscle of various animals. Because changes in cardiac muscle membrane structure and function may be involved in the pathogenesis of arrhythmia and ischemia, we have examined the effects of dietary lipid supplements on the phospholipid distribution and fatty acid composition of rat atria and ventricle following 20 weeks feeding of diets supplemented with either 12% sunflower-seed oil or sheep fat. Neither lipid supplement produced significant changes in the proportions of cholesterol, total phospholipids or phosphatidylcholine, phosphatidylethanolamine or diphosphatidylglycerol,--the phospholipid classes that together account for more than 90% of the total phospholipids of rat cardiac muscle. Significant changes were found in the profiles of the unsaturated fatty acids of all 3 phospholipid components of both atria and ventricle. Although similar, the changes between these tissues were not identical. However, in general, feeding a linoleic acid-rich sunflower seed oil supplement resulted in an increase in the omega-6 family of fatty acids, whereas feeding the relatively linoleic acid-poor sheep fat supplement decreased the level of omega-6 fatty acids but increased the levels of the omega-3 family, resulting in major shifts in the proportions of these families of acids. In particular, the ratio of arachidonic acid: docosahexaenoic acid (20:4,omega-6/22:6,omega-3), which is higher in all phospholipids of atria than ventricle, is increased by feeding linoleic acid, primarily by increasing the level of arachidonic acid in the muscle membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of partially hydrogenated marine oils on the mitochondrial function and membrane phospholipid fatty acids in rat heart.

The influence of dietary partially hydrogenated marine oils containing docosenoic acid on rat heart mitochondrial membrane phospholipid fatty acid composition was studied with particular reference to cardiolipin and oxidative phosphorylation. Five groups of male weanling rats were fed diets containing 20% (w/w) peanut oil (PO), partially hydrogenated peanut oil (HPO), partially hydrogenated Norwegian capelin oil (HCO), partially hydrogenated herring oil (HHO), and rapeseed oil (RSO) for 10 weeks. All the cardiac phospholipids investigated were influenced by the experimental diets. An increased amount of arachidonic acid observed in phosphatidylethanolamine (PE) after feeding partially hydrogenated oils suggests a changed regulation of the arachidonic acid metabolism in comparison with PO treatment. 22:1 originating from the dietary oils was incorporated only to a small extent into phosphatidylcholine (PC) and PE. A selective incorporation of 18:1 isomers into the 1- and 2-positions of PC and PE with respect to geometry and position of the double bond was observed. Large amounts of 18:1 trans were incorporated into the 1-position of PC and PE, irrespective of the amount of 18:2 supplemented to the diets, replacing a considerable proportion of stearic acid in this position. After feeding HHO and RSO, the content of 22:1 in mitochondrial cardiolipin of rat heart was found to be 3% (mainly cetoleic acid) and 10% (mainly erucic acid), respectively, indicating a high affinity for cis isomers of 22:1, but also a considerable resistance against incorporation of trans isomers was observed. The ability of rat cardiac mitochondria to oxidize palmitoylcarnitine and to synthesize ATP was depressed after feeding HHO and RSO. Dietary cis isomers of 22:1 seem to have a specific ability to interfere with cardiac ATP synthesis and also to alter the fatty acid composition of cardiolipin of rat heart.

Evidence for a carbachol stimulated phosphatidylinositol effect in heart

Incubation of canine heart slices with 32P-inorganic phosphate in physiological medium resulted in the incorporation of 32P into a number of cardiac phospholipids. Carbachol, a non-hydrolyzable acetylcholine analogue, selectively increased 32P-incorporation into phosphatidic acid and phosphatidylinositol in slices of right auricle 80 and 70% respectively. This effect of carbachol was half-maximal at 5-10 microM and was inhibited completely by atropine. Carbachol did not affect labeling of other phospholipids in right auricle and did not affect the labeling of any phospholipid in slices of left auricle or right or left ventricle. These results provide evidence for a muscarinic receptor mediated phospholipid effect which appears to be localized in the right atrial region of canine heart.

Basic phospholipase A 2 from Naja nigricollis snake venom: Phospholipid hydrolysis and effects of electrical and contractile activity of the rat heart

To clarify the mechanism of the cardiotoxic action of the basic phospholipase A 2 from Naja nigricollis snake venom, its effects were tested on the rat heart, including hydrolysis of cardiac phospholipids, electrocardiogram, (Na + K)-ATPase activity, resting and action potentials, and cardiac contractility. Its effects contrasted with those of a noncardiotoxic acidic phospholipase from Naja naja atra snake venom. Only the N. nigricollis enzyme exhibited cardiotoxic effects in isolated perfused rat hearts. The cardiotoxic effects occurred with low levels of phospholipid hydrolysis, phosphatidylserine being hydrolyzed to the greatest extent. Although high concentrations of either phospholipase decreased (Na + K)-ATPase activity in vitro, this reaction did not account for the cardiotoxic effects observed in isolated perfused hearts. In rat atrial preparations the cardiotoxic enzyme depolarizes the cells, decreases action potential amplitude and overshoot, decreases time to 50 and 90% repolarization of action potential, and prolongs the latency to initiation of the action potential. Simultaneously recorded contractile activity showed prolonged latency to initiation of contraction, increased time to peak force of contraction, and decreased amplitude of contraction. These effects were mimicked by caffeine and 7.5 m m Ca 2+ in the bathing medium. The cardiotoxic effects were blocked by Mn 2+ (Mn 2+ also reversed cardiotoxic actions) and 4.0 m m Ca 2+, but not by lanthanum, tetrodotoxin, lidocaine, acetylcholine, or cyanide. Manganese added to rat atrial preparations before N. nigricollis phospholipase decreased hydrolysis of phosphatidylserine. These results suggest that the N. nigricollis enzyme exerts its cardiotoxic action by increasing intracellular Ca 2+ levels. The cardiotoxic effects correlate with, but may not be related to, phosphatidylserine hydrolysis.

Lipid metabolism in riboflavin-deficient rats

1. The increase in activation coefficient (stimulated: basal activity) of erythrocyte NAD(P)H2: glutathione oxidoreductase (EC 1.6.4.2) and reduction in hepatic flavin concentration which occurred in riboflavin-deficient weanling rats were not markedly or consistently affected by differences in the concentration of lipid in the diet nor by differences in the total proportion of saturated or polyunsaturated fatty acids in the dietary lipid. 2. Their gain in body-weight was, however, reduced when the dietary lipid concentration was increased from 30 to 200 g/kg and liver: body-weight and hepatic triglyceride content were correspondingly increased, suggesting a functionally-deleterious effect of high fat intake in the deficient animals. This was especially severe when the diets contained cottonseed oil, which appeared to be toxic for the deficient animals. 3. Comparisons between fatty acid profiles of hepatic phospholipids of deficient, pair-fed and ad lib,-fed control animals indicated that the increase in proportion of 18:2 omega 6 and the decrease in proportion of 20:4 omega 6 observed in deficient animals were due specifically to riboflavin deficiency, whereas certain other changes were probably caused by inanition. The changes in 18:2 omega 6 and 20:4 omega 6 were observed at both low and high levels of lipid intake and at both low and high levels of dietary lipid polyunsaturation. Similar changes in fatty acid profiles were observed in renal, erythrocyte membrane, and plasma phospholipids, but were not seen in cardiac phospholipids, 4. A consistent increase in proportion of 18:2 omega 6 was also observed in the hepatic triglycerides, together with a decrease in proportion of 16:0. 5. It is concluded that acute riboflavin deficiency affects lipid metabolism in a characteristic manner, probably by interfering with beta-oxidation of fatty acids, but that diets of high lipid content do not significantly increase the extent of flavin depletion.

Reduction of myocardial necrosis in male albino rats by manipulation of dietary fatty acid levels

A comprehensive statistical analysis had shown a significant correlation between the incidence of myocardial lesions in male albino rats and the concentration of certain dietary fatty acids. To test this result under controlled conditions, male rats were fed for 16 weeks diets containing 20% by weight soybean oil or a low erucic acid rapeseed (LEAR) oil. Both dietary oils contained substantial amounts of linolenic acid, and both groups developed a high incidence of myocardial necrosis. The addition of dietary saturated fatty acids to the oil in the form of cocoa butter significantly lowered the incidence of heart lesions in both groups. The addition of cocoa butter resulted in increased absorption of saturates and increased growth. Replacement of the cocoa butter by at least an equal amount of synthetic triolein resulted in no significant changes in the cardiopathogenic response compared to the original oils, thus ensuring that the reduction in heart lesions associated with the addition of cocoa butter was not due to dilution of cardiopathogenic compounds in the original vegetable oils. These results support the hypothesis that myocardial lesions in male rats are related to the balance of dietary fatty acids and not to cardiotoxic contaminants in the oils. Changes in the dietary fatty acids did not appear to influence the proportion of the cardiac phospholipids, but their fatty acid composition was markedly influenced. Dietary linolenic acid affected the C22 polyunsaturated fatty acids (PUFA) and dietary saturates increased the level of saturates in cardiac phospholipids. The level of arachidonic acid and total C22 PUFA did not appear to be affected by diet.

Influence of physical training on the effects of dietary oils on cardiac morphology and phospholipids in rats.

Male wistar rats fed purified diets containing 15% sunflower oil (SF) by weight, high erucic acid rapeseed oil (HEAR) or low erucic acid rapeseed oil (LEAR) for 12 weeks and subjected to a moderate treadmill running program were compared with sedentary animals fed the same diets on the basis of cardiac morphology and complete analysis of cardiac phospholipids. HEAR caused the highest incidence and number of heart lesions both in untrained and trained rats but in the latter there was a highly significant increase of the lesions. LEAR gave a higher incidence of lesions than SF in untrained rats but not in trained ones. If compared to SF, HEAR and LEAR increased cardiac diphosphatidylglycerol (DPG) and sphingomyelin (SM) content (mg/g wet tissue) and decreased phosphatidylcholines (PC) and phosphatidylethanolamines (PE) in untrained rats. Marked changes in the fatty acid pattern of these phospholipids were also observed. PE and PC in trained and untrained rats fed HEAR or LEAR contained elevated levels of C 22:5 (n-3) and C 22:6 (n-3) fatty acids whereas the C 22:4 (n-6) and C 22:6 (n-6) polyenes disappeared. Monoenes (C 18:1, C 20:1 or C 22:1) largely incorporated in DPG of rats fed the cruciferous oils. In SM levels of saturated fatty acids (C 16:0, C 18:0, C 20:0) and of n-9 monoenes (C 18:1, C 20:1, C 22:1, C 24:1) were higher in rats fed HEAR or LEAR than in those feds SF. These changes were mainly related to the high level of n-9 monoenes (oleic, eicosenoic and erucic acids) as well as to the high ratio linolenic/linoleic acid present in cruciferous oils. Physical training interacted with the effects of these dietary oils on the cardiac phospholipid composition. The relation between changes in phospholipid composition and the incidence and the number of cardiac lesions is discussed.

The effect of dietary fatty acids on the incidence of cardiac lesions and changes in the cardiac phospholipids in male rats

The effect of dietary fatty acids on the incidence of cardiac lesions and changes in the cardiac phospholipids in male rats