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J S Charnock

Publications and source records attributed to J S Charnock.

At least 19 recordsLinked to original sources
PubMed2000

Gamma-linolenic acid provides additional protection against ventricular fibrillation in aged rats fed linoleic acid rich diets.

Ligation of the coronary artery in rats produces severe ventricular fibrillation (VF) and malignant cardiac arrhythmia. Mortality increases with the age of the animal. Diets rich in saturated fatty acids (SF) but low in linoleic acid (LA) increase, but diets high in LA and low in SF decrease the severity of VF and mortality in older animals. The effects of an LA enriched diet can be blocked by inhibition of cyclooxygenase suggesting that conversion of LA to eicosanoids is central to the development of VF. Conversion of LA to gamma-linolenic acid (GLA) via delta-6 desaturase is the first step in the process. The activity of delta-6 desaturase declines with age. Thus inclusion of GLA in the diet of older animals may provide an additional benefit over LA alone. Dietary supplements of evening primrose oil (EPO) to one year old rats reduced ischaemic VF more than a supplement of sunflower seed oil (SSO) without GLA. Substitution of borage oil (more GLA than EPO but less LA than either EPO or SSO) was without additional benefit.

Aging↗
PubMed1999

Omega-3 polyunsaturated fatty acids and ventricular fibrillation: the possible involvement of eicosanoids.

Increased dietary omega-3 polyunsaturated fatty acids (PUFAs) reduce the incidence and severity of ventricular fibrillation (VF) in laboratory animals subjected to partial ischaemia and reduce the risk of cardiac arrest in humans after myocardial infarction. In whole animals there is considerable evidence which suggests that incorporation of these fatty acids into cardiac membrane phospholipids influences the production of a variety of eicosanoids having opposing arrhythmogenic or anti-arrhythmogenic properties, and that the balance of these actions is shifted in favour of an anti-arrhythmogenic state by feeding fish oil dietary supplements rich in omega-3 PUFA. However, differences in eicosanoid biosynthesis between species, between tissues of the same species and even between different intracellular sites within cells of the same tissue could influence experimental outcomes. The importance of further studies with the most appropriate whole animal models or tissues is emphasized, as is the difference between the structural integrity of cardiac muscle and cardiomyocytes in vitro.

Animals↗
PubMed1995

Dietary lipid modification of myocardial eicosanoids following ischemia and reperfusion in the rat.

Several different edible oils were compared for their ability to modify eicosanoid biosynthesis following experimentally-induced myocardial ischemia and reperfusion in the rat. Two types of palm oil [neutralized, bleached, and deodorized (NBDPO) and refined, bleached, and deodorized (RBDPO)] and partially hydrogenated soybean oil (SBO) were tested against a diet supplemented with sunflower seed oil (SSO) rich in n-6 polyunsaturated fatty acids (PUFA). Fish oil (FO) rich in n-3 PUFA, with its known cardioprotective actions, served as an internal reference point for the study. Test oils were fed as a 12% (w/w) supplement for nine months before the induction of myocardial ischemia and reperfusion. Palm oil diets exerted effects indistinguishable from the SBO group against cardiac arrhythmia, which occurred following alterations to coronary blood flow. Arrhythmic potentials, as expressed by a hierarchical scale (0-9) of arrhythmia score, were: SSO, 1.5 +/- 0.5; FO, 0.9 +/- 0.4; SBO, 3.1 +/- 0.5*; NBDPO, 3.2 +/- 0.5*; RBDPO, 3.3 +/- 0.6*; *P < 0.05 vs. SSO. Following ischemia and reperfusion, both SSO and RBDPO groups tended to show an increase in myocardial prostacyclin, with the effect being more prominent in the RBDPO group (SSO, 10%; RBDPO, 25%). Thromboxane production was reduced in the FO group. Interestingly, cardiac muscle from both FO and palm oil groups displayed a reduced capacity to produce 12-hydroxyeicosatetraenoic acid SSO, 591 +/- 95.8; SBO, 375.5 +/- 48.9; NBDPO, 287.2 +/- 64.7*; RBDPO, 230.9 +/- 80.2**; FO, 203.7 +/- 81.4** (ng/g dry wt, *P < 0.05, **P < 0.01). No clear relationship was seen between the availability of 20:4n-6 in myocardial phospholipids and eicosanoid profile. Data suggests that fatty acid composition of edible oils is not the only determinant of arrhythmic vulnerability and eicosanoid production.

Animals↗
PubMed1994

Lipids and cardiac arrhythmia.

In any discussion of lipids and heart disease it is beneficial from the outset to recognise that at least three different pathological processes may be involved. The first of these is atherosclerosis which involves the deposition of "fat" in the coronary vessels, another is thrombogenesis which describes the formation of blood clots in the coronary vessels, and the third is arrhythmia which refers to disorders in the beating of the heart which may become sufficiently serious to cause sudden cardiac death (SCD). Also it is this disturbance in the rhythmic beating of the heart which is responsible for much of the mortality from 'heart attacks' which occur 'outside-of-hospital' in societies like U.S.A., U.K. and Australia. It is this latter condition of cardiac arrhythmia which is the major concern of this review. Because it is often difficult to differentiate the role of lipids in 'heart disease' in man, it has frequently been assumed that all dietary fatty acids have similar effects on the different processes involved, and many unwarranted generalisations have been made which have led to conflicts of opinion amongst physicians and confusion in the lay public. From the animal studies discussed in this review, it is apparent that dietary fatty acids have an important role to play in determining the vulnerability of the myocardium to develop serious ventricular fibrillation (VF) and potentially lethal cardiac arrhythmia. In general, diets rich in saturated fatty acids promote a state of myocardial vulnerability, whilst diets rich in PUFA significantly diminish the probability of developing lethal disorders in cardiac rhythm when the heart is placed under pharmacological (or emotional) stress, or deprived of sufficient blood flow and supply of oxygen. Very recent experiments with the monounsaturated fatty acid (MUFA) oleic acid clearly demonstrate that, at least in rats subjected to ligation of their coronary artery, this acid is not 'neutral' as has been suggested by some for its role in atherosclerosis, but in fact is indistinguishable from saturated fatty acids in its effect in promoting arrhythmia during either regional ischaemia or reperfusion arrhythmia in this animal model of SCD.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Comparative efficacy of n-3 and n-6 polyunsaturated fatty acids in modulating ventricular fibrillation threshold in marmoset monkeys.

Programmed electrical stimulation in anesthetized marmoset monkeys was used to examine relative antiarrhythmic efficacies of dietary n-3 and n-6 polyunsaturated fatty acids (PUFAs) from fish and plant oils. Diets contained 31% of energy (en%) as fat, comprising 15 en% saturated fat and 7 en% PUFAs, obtained by blending sheep fat with sunflower seed (SF/SSO) or fish oil (SF/FO) and a base diet. After 16-wk feeding, ventricular fibrillation (VF) was inducible in 6 of 10 animals on each diet under control conditions. The VF threshold (VFT) was significantly elevated in the SF/FO group (33.3 +/- 3.1 mA; n = 6) compared with the SF/SSO group (14.3 +/- 4.9 mA; n = 6). VFT, reduced during acute myocardial ischemia with 10 of 10 animals inducible per diet, remained significantly higher with SF/FO feeding. The SF/FO diet contained 3.8 en% as n-3 PUFAs, which was incorporated as 31% of myocardial membrane fatty acids. Dietary n-3 PUFA reduced vulnerability of normal or ischemic myocardium to arrhythmias in a nonhuman primate.

Animals↗
PubMed1992

Dietary modulation of lipid metabolism and mechanical performance of the heart.

Sudden Cardiac Death resulting from sustained ventricular fibrillation or malignant cardiac arrhythmia has been linked to the type of dietary fat intake in several economically well developed countries where high levels of saturated fatty acids are common. Experimental studies with the small non-human primate marmoset monkey have clearly demonstrated the health benefit of substituting polyunsaturated fatty acids (PUFA's) for dietary saturated fatty acids. Heart rate and blood pressure are lowered, while the left ventricular ejection fraction and the electrical threshold for the induction of ventricular fibrillation are both increased after prolonged feeding of PUFA enriched diets. All these changes in heart function reduce the risk of developing malignant cardiac arrhythmias. The fatty acid composition of cardiac membrane phospholipids is profoundly altered by these changes in dietary lipid intake. In particular the proportions of arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are altered in such a way that the production of myocardial eicosanoids is affected. Although the changes in proportion of these long-chain PUFA's in cardiac phosphatidyl ethanolamine and phosphatidyl inositol are not identical, the shift in balance between these substrates or inhibitors of cyclo-oxygenase activity leads to relatively greater production of prostacyclin (PGI2) than thromboxane (TXA2).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Dietary lipid modulation of ventricular fibrillation threshold in the marmoset monkey.

Programmed electrical stimulation was used to examine the ability of long-term dietary lipid modulation to influence myocardial vulnerability to the induction of ventricular fibrillation in adult marmoset monkeys (Callithrix jacchus). Marmosets fed diets supplemented (to a total of 28.5% of the energy as fat) with polyunsaturated fatty acid (PUFA)-rich tuna fish oil or sunflower seed oil had significantly elevated mean ventricular fibrillation threshold compared with those fed a saturated animal fat supplemented diet or a reference diet not supplemented with fat (11.2% of the energy as fat). Fibrillation threshold was reduced during acute myocardial ischemia induced by coronary artery occlusion but still remained higher in the PUFA-fed animals than either the control or the ischemic threshold in reference or saturated fat supplemented animals. Dietary tuna fish oil was associated with a low incidence of sustained fibrillation episodes and no fatalities. These results indicate that myocardial substrate vulnerability to arrhythmic stimuli is increased during ischemia in a nonhuman primate model but dietary PUFA can reduce vulnerability under both normal and ischemic conditions. Reduced dietary fat intake alone was without effect.

Animals↗
PubMed1992

Differences in fatty acid composition of various tissues of the marmoset monkey (Callithrix jacchus) after different lipid supplemented diets.

1. The fatty acid composition of different muscles, organs and blood components of the marmoset monkey were examined after long-term feeding of several well defined lipid supplemented diets. 2. Similarities between the fatty acid composition of cardiac and skeletal muscles which persisted after all diets suggest that biopsy of skeletal muscle may have an important diagnostic value in this and other primate species. 3. The relationship between the dietary intake of individual fatty acids and their proportions in different tissues is both complex and variable. 4. However, the lipid metabolism of Callithrix jacchus recommends this small non-human primate as a most suitable species for the study of lipid nutrition.

Analysis of Variance↗
PubMed1992

Dietary fat modulation of left ventricular ejection fraction in the marmoset due to enhanced filling.

OBJECTIVE: The aim was to investigate the influence of long term dietary fish oil consumption on cardiac function in a non-human primate, to elucidate further the basis of the apparently reduced cardiovascular disease mortality associated with its consumption in man. METHODS: Adult male marmoset monkeys (Callithrix jacchus) were fed diets supplemented with polyunsaturated fatty acids (PUFA) of marine (tuna fish oil) or plant (sunflower seed oil) origin, saturated animal fat (sheep perirenal fat), or a low fat reference diet for 24 months. Cardiac function was assessed using radionuclide angiography under pentobarbitone anaesthesia with a counts based adaptation for ventricular volume estimations. Measures were made at rest and during infusion of adrenaline. RESULTS: The mean left ventricular ejection fraction was greater in the tuna fish oil group [55.0(SEM 1.1)% n = 7] and the sunflower seed oil group [58.1(2.4)% n = 8] than in the reference group [48.5(1.4)% n = 9] and the sheep fat group [47.6(1.8)% n = 8]. This was associated with a more than 25% greater end diastolic volume and 40-70% increases in stroke volume in tuna fish or sunflower seed oil fed animals. There was no evidence of cardiac hypertrophy. In contrast, adrenaline increased stroke volume and ejection fraction by increasing emptying, thus reducing residual end systolic. Tuna fish oil fed animals had a low resting heart rate. When this was raised to comparable levels by adrenaline, lower pressure-rate indices and greater cardiac minute work suggested higher myocardial energy efficiency in PUFA fed animals compared with the reference and sheep fat groups. CONCLUSIONS: Dietary fish oil and sunflower seed oil increased the left ventricular ejection fraction in the marmoset monkey by enhancing ventricular filling, thus providing an energy sparing promotion of diastolic relaxation.

Animals↗
PubMed1991

Differences between in vivo and in vitro production of eicosanoids following long-term dietary fish oil supplementation in the rat.

The effects of different lipid supplements on endogenous and exogenous production of eicosanoids were investigated in the rat following a 12-month pre-feeding period. The urinary excretion of tetranorprostanemonoic (TPM) and tetranorprostanedioic (TPD) acids was measured as an index of endogenous production whilst myocardial release of PGI2 and TXA2 was estimated under in vitro conditions. Compared to the reference group, n-3 PUFA rich tuna fish oil (TFO) fed rats displayed a near doubling of endogenous (TPM + TPD) synthesis; however, myocardial production was reduced by 32% (PGI2) and 55% (TXA2). Sheep fat supplementation also caused a 62% rise in urinary tetranor metabolites but in contrast to TFO feeding, myocardial production in vitro also showed a significant increase (P less than 0.05). Considerable changes in PUFA profile of plasma, heart and kidney occurred as a result of dietary lipid treatment and in addition a high tissue specificity was also noted with regard to the incorporation and conversion of dietary n-3 PUFA. For example, the heart showed a low EPA (1.2%) and high DHA (28.0%), whereas their proportions in the kidney were near equal (6-7%). As only the TFO diet exerted a significant effect on the proportion of AA, the changes in eicosanoid production cannot be fully explained on the basis of precursor/inhibitor availability. The results probably reflect the complex interactions between fatty acid substrates, release mechanisms and biosynthetic enzymes.

Animals↗
PubMed1991

Changes in myocardial eicosanoid production following long-term dietary lipid supplementation in rats.

Recent studies demonstrate a strong link between the type of fat consumed and arrhythmogenesis and implicate altered production of eicosanoids as a potential mechanism. Thus, in a preliminary study designed to evaluate this hypothesis, five dietary lipid supplements--sunflower seed oil (SSO), chemically refined palm oil (PO I), physically refined palm oil (PO II), sheep fat (SF), and a 1:1 blend of SF and fish oil (SF-FO)--were compared for their effects on membrane-lipid composition and eicosanoid synthesis after a 12-mo pre-feeding period. Polyunsaturated fatty acids (PUFAs) of the myocardium showed significant alterations in response to dietary lipid treatment. Nevertheless, prostacyclin production was unaffected whereas both SF-FO and POI diets caused a significant inhibition of myocardial thromboxane A2 (TXA2). It is speculated that n-3 (omega-3) PUFAs may act as specific inhibitors of TXA2 synthetase whereas the PO I effect is unlikely to be mediated via fatty acids. These preliminary data are worthy of further investigation.

Animals↗
PubMed1991

Dietary fats and oils in cardiac arrhythmia in rats.

The effect of long-term feeding of various dietary fats and oils on cardiac arrhythmia was studied in an animal model of sudden cardiac death. After confirmation that a dietary supplement of saturated animal fat (SF) increased the animals' susceptibility to develop cardiac arrhythmia under ischemic stress whereas the polyunsaturated fatty acids of sunflower seed oil (SSO) reduced this susceptibility, we found that diets supplemented with either chemically refined palm oil (PO-I) or physically refined palm oil (PO-II) gave results that were generally intermediate in value between the SF and the SSO groups. However, during reperfusion of a previously ischemic heart, both PO-I- and PO-II-supplemented diets appeared to be as effective as SSO in reducing ventricular premature beats. In addition, the incidence of animals displaying severe ventricular fibrillation was much less after palm-oil feeding than it was after SF feeding. These preliminary results warrant further investigation of the potential antiarrhythmic effects of commercial palm oil.

Animals↗
PubMed1991

Differential effects of dietary fish oil on myocardial prostaglandin I2 and thromboxane A2 production.

Marmoset monkeys (Callithrix jacchus) were maintained for 24 mo on a standard primate diet [reference (Ref) diet] or this diet supplemented (8% wt/wt) with either sheep fat (SF), sunflower seed oil (SSO), or tuna fish oil (TFO). The polyunsaturated fatty acids (PUFA) of myocardial phospholipids demonstrated significant alterations as a result of the dietary (n-3) or (n-6) lipid supplementation. The reduction (P less than 0.05) in prostaglandin (PG) I2 in PUFA diet-fed groups (SSO, 113.8 +/- 7.8; TFO, 87.9 +/- 8.2 compared with Ref, 153.9 +/- 7.4 pg/mg dry wt) seems to be due to the rate limitation of the endogenous substrate, because the addition of exogenous arachidonic acid (AA) has obliterated the dietary difference. However, AA did not increase the basal PGI2 production in the Ref or SF dietary groups, which differed from that for thromboxane (Tx) A2 where 2- to 5-fold stimulation was observed. It is suggested that there exists a preferential channeling mechanism to direct AA derived from phospholipase hydrolysis of membrane phospholipids toward PGI2 synthesis. Conversely, the bulk of the AA for TxA2 biosynthesis appears to be supplied by a cytosolic nonesterified fatty acid pool. The effective replacement of AA of this pool and a specific inhibition of TxA2 synthetase enzyme complex by the (n-3) PUFA of fish oil are offered as likely mechanisms for the greater inhibition of TxA2 compared with PGI2 production observed in the present and previous studies. The present data on myocardial eicosanoids correlate well with the beneficial qualities of (n-3) and (n-6) dietary PUFA on cardiac function that we have reported previously.

Animals↗
PubMed1990

Absence of coronary or aortic atherosclerosis in rats having dietary lipid modified vulnerability to cardiac arrhythmias.

Laboratory studies have shown that saturated fats in the diet increase vulnerability to ventricular fibrillation and other cardiac arrhythmias while polyunsaturates, especially the n-3 fatty acids of fish oils, are antiarrhythmic. Similarly, dietary saturated fat has been implicated in the development of coronary atherosclerosis while polyunsaturated fatty acids are reported to provide protection. In the present study, dietary fat supplements known to influence arrhythmic vulnerability after long term feeding in the rat were tested for their propensity to induce or prevent changes in the aorta or coronary vasculature. It was found that dietary supplementation for 15 months with saturated fat (from sheep fat) or n-6 (sunflower seed oil) or n-3 (fish oil) polyunsaturated fatty acids made no difference to the development of vascular changes in coronary arteries or aorta of the rat despite some significant differences in plasma triglyceride and cholesterol levels. The vascular lesions observed were minimal even in non-supplemented age-matched reference animals. They consisted of focal intimal thickening and slight mucopolysaccharide accumulation with no evidence of progression to fibrotic lesions or calcium accumulation and there were no fatty deposits observed. It is concluded that significant atherosclerosis-induced chronic myocardial ischaemia in no way contributes to dietary lipid modulation of arrhythmic vulnerability in the rat.

Animals↗
PubMed1990

Reversal of the arrhythmogenic effects of long-term saturated fatty acid intake by dietary n-3 and n-6 polyunsaturated fatty acids.

This study investigated whether the adverse influences of dietary saturated animal fatty acids (SF) on vulnerability to cardiac arrhythmias in rats could be modified by crossover in maturity to diets rich in polyunsaturated fatty acids (PUFAs). The arrhythmia model was coronary artery occlusion and reperfusion under anesthesia. Animals were fed commercial stock diet (4% fat wt:wt) supplemented (12% wt:wt) with fat (final diets, 35% energy as fat). Of rats fed the SF diet for 9 and 18 mo, ventricular fibrillation (VF) occurred in 71% during occlusion and in 86% on reperfusion. Mortality from VF was 0% after 9 mo on the SF diet but 67% after 18 mo. Dietary crossover to n-3 (tuna-fish oil) or n-6 (sunflower-seed oil) PUFA-supplemented diets at 9 mo reduced arrhythmias (VF incidence less than 30% in occlusion and reperfusion) and mortality (0%). The n-3 PUFAs were most effective. Dietary interventions can be effective even when introduced in mature, high-risk animals and may be of benefit in reducing risk of sudden cardiac death.

Age Factors↗
PubMed1989

In vivo formation of metabolites of prostaglandins I2 and I3 in the marmoset monkey (Callithrix jacchus) following dietary supplementation with tuna fish oil.

Recent studies have shown that ingestion of eicosapentaenoic acid (EPA) in man results in the formation of 'trienoic' prostanoids which amy partly explain the potent antithrombotic/antiatherogenic properties of long-chain polyunsaturated n-3 fatty acids (PUFAs). However, endogenous formation of cyclooxygenase metabolites of EPA has not been demonstrated in an animal model, and in vitro studies indicate a clear species difference in the conversion of EPA to PGI3. Thus, in the present study, the in vivo formation of PGI3 following long-term dietary tuna fish oil supplementation was investigated in a small non-human primate - the marmoset monkey (Callithrix jacchus). The excretion of major urinary metabolites 2,3-dinor-6-keto-PGF1 alpha (PGI2-M) and delta 17-2,3-dinor-6-keto-PGF1 alpha (PGI3-M) was estimated as an index of total body synthesis of PGI2 and PGI3, respectively. Following extraction, dinor prostanoid metabolites were separated by capillary gas chromatography and identified by negative ion chemical ionization mass spectrometry. Supplementation of the standard (reference) diet with either sheep fat or sunflower seed oil did not alter the body production of PGI2-M. However, following the tuna fish oil-enriched diet, there occurred not only an increase in urinary PGI2-M (reference 70.7 +/- 9.0; tuna fish oil 115.5 +/- 12.1 ng/g creatinine, P less than 0.05), but also a considerable formation of PGI3-M (62.9 +/- 5.3 ng/g creatinine), which was not seen in any other dietary group; in addition, the urinary level of immmunoreactive 2,3-dinor-thromboxane B2/3 was reduced after ingestion of tuna fish oil. These urinary changes were accompanied by a rise in plasma phospholipid-bound EPA and docosahexaenoic acid (DHA). In addition, tuna fish oil supplementation resulted in a significant reduction in plasma cholesterol (53%) and triacylglycerols (44%). The present study provides for the first time experimental evidence for the in vivo formation of PGI3 in an animal model and also confirms the earlier observations in man following dietary fish oil supplementation.

Animals↗