RESUMEN

BACKGROUND: Dietary fish oil provides polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) and is associated with modified oxygen consumption, contractile fatigue and physiological responses to ischaemia or hypoxia in striated muscle. This study systematically investigated the membrane incorporation of fatty acids, with a focus on DHA, into skeletal muscle in relation to functional/metabolic differences and their responsiveness to fish oil doses. METHODS: Male Sprague-Dawley rats were randomised to isoenergetic diets (10% fat by weight). Human Western-style diets were simulated with 5.5% tallow, 2.5% n-6 PUFA sunflower seed oil and 2% olive oil (Control). High-DHA tuna oil exchanged for olive oil provided a Low (0.32%) or moderate (Mod) (1.25%) fish oil diet. Membrane phospholipid fatty acid composition was analysed in samples of five skeletal muscles selected for maximum variation in muscle fibre-type. RESULTS: Concentrations of DHA varied according to muscle fibre type, very strongly associated with fast oxidative glycolytic fibre population (r2 = 0.93; P < 0.01). No relationship was evident between DHA and fast glycolytic or slow oxidative fibre populations. Fish oil diets increased membrane incorporation of DHA in all muscles, mainly at the expense of n-6 PUFA linoleic and arachidonic acid. CONCLUSION: The exquisite responsiveness of all skeletal muscles to as little fish oil as the equivalent of 1-2 fish meals per week in a human diet and the selective relationship to fatigable muscle fibre-types supports an integral role for DHA in muscle physiology, and particularly in fatigue resistance of fast-twitch muscles. SUMMARY: Skeletal muscle fibres vary according to structural, metabolic and neurological characteristics and ultimately influences contractile function. This study sort to determine if the composition of phospholipid polyunsaturated fatty acids (PUFA), incorporated in their membranes, might also differ according to fibre type and when omega-3 PUFA are made available in the diet. We systematically demonstrated that the omega-3 PUFA, docosahexaenoic acid (DHA), incorporated into skeletal muscle membranes well above its provision in the diet and without competitive influence of high omega-6 PUFA concentrations, typical to the Western-style human diet. Notably, incorporation preferentially occurred according to metabolic characteristics of each muscle, supporting the notion that DHA plays an integral role in fast oxidative glycolytic muscle fibres.

Asunto(s)

Ácidos Docosahexaenoicos/metabolismo , Aceites de Pescado/administración & dosificación , Músculo Esquelético/química , Animales , Membrana Celular , Dieta Occidental , Grasas de la Dieta/administración & dosificación , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-6/metabolismo , Aceites de Pescado/química , Glucólisis , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley

RESUMEN

Dietary fish oil (FO) modulates muscle O2 consumption and contractile function, predictive of effects on muscle fatigue. High doses unattainable through human diet and muscle stimulation parameters used engender uncertainty in their physiological relevance. We tested the hypothesis that nutritionally relevant FO doses can modulate membrane fatty acid composition and muscle fatigue. Male Sprague-Dawley rats were randomised to control (10% olive oil (OO) by weight) or low or moderate FO diet (LowFO and ModFO) (HiDHA tuna fish oil) for 15 weeks (LowFO: 0.3% FO, 9.7% OO, 0.25% energy as EPA+DHA; ModFO: 1.25% FO, 8.75% OO, 1.0% energy as EPA+DHA). Hindlimb muscle function was assessed under anaesthesia in vivo using repetitive 5 s burst sciatic nerve stimulation (0.05 ms, 7-12 V, 5 Hz, 10 s duty cycle, 300 s). There were no dietary differences in maximum developed muscle force. Repetitive peak developed force fell to 50% within 62 (SEM 10) s in controls and took longer to decline in FO-fed rats (LowFO 110 (SEM 15) s; ModFO 117 (sem 14) s) (P<0.05). Force within bursts was better sustained with FO and maximum rates of force development and relaxation declined more slowly. The FO-fed rats incorporated higher muscle phospholipid DHA-relative percentages than controls (P<0.001). Incorporation of DHA was greater in the fast-twitch gastrocnemius (Control 9.3 (SEM 0.8) %, LowFO 19.9 (SEM 0.4), ModFO 24.3 (SEM 1.0)) than in the slow-twitch soleus muscle (Control 5.1 (SEM 0.2), LowFO 14.3 (SEM 0.7), ModFO 18.0 (SEM 1.4)) (P<0.001), which was comparable with the myocardium, in line with muscle fibre characteristics. The LowFO and ModFO diets, emulating human dietary and therapeutic supplement intake, respectively, both elicited muscle membrane DHA enrichment and fatigue resistance, providing a foundation for translating these physiological effects to humans.

Asunto(s)

Suplementos Dietéticos , Ácidos Docosahexaenoicos/metabolismo , Aceites de Pescado/administración & dosificación , Fibras Musculares Esqueléticas/metabolismo , Sustancias para Mejorar el Rendimiento/administración & dosificación , Fosfolípidos/metabolismo , Atún , Animales , Cardiotónicos/administración & dosificación , Ácidos Docosahexaenoicos/administración & dosificación , Estimulación Eléctrica , Corazón/fisiología , Miembro Posterior , Masculino , Fatiga Muscular , Fibras Musculares de Contracción Rápida/metabolismo , Fibras Musculares de Contracción Rápida/fisiología , Fibras Musculares Esqueléticas/fisiología , Fibras Musculares de Contracción Lenta/metabolismo , Fibras Musculares de Contracción Lenta/fisiología , Fuerza Muscular , Miocardio/metabolismo , Distribución Aleatoria , Ratas Sprague-Dawley , Nervio Ciático/metabolismo

RESUMEN

This study used a novel in vivo model to test the hypothesis that nutritive and non-nutritive blood flow distribution can still be observed under conditions of high vascular tone and oxygen delivery at rest and in metabolically active (twitch contracting) skeletal muscle. Experiments were performed in a constant flow autologous pump-perfused hindlimb in anaesthetised male Wistar rats. Agonists were tested at rest with a flow rate of 1ml x min(-1), and during hindlimb muscle twitch contractions (sciatic nerve stimulation: 6V, 1Hz, 0.05ms, 3min) at a flow rate of 2ml x min(-1). Oxygen consumption was determined from hindlimb venous and arterial blood samples. Resting perfusion pressure at 1ml x min(-1) was 92 + or - 3 mmHg (N=15) and oxygen consumption was 0.41 + or - 0.05 micromol x min(-1) x g(-1). Serotonin increased perfusion pressure and significantly decreased basal hindlimb oxygen consumption at rest. During acute muscle contraction this effect on oxygen consumption was diminished. Noradrenaline significantly increased perfusion pressure but had no significant effect on basal hindlimb oxygen consumption. Vasoconstriction that impacts upon muscle metabolism occurs in vivo, which potentially could be due to selective redistribution of blood flow. However, during muscle contraction local release of vasodilatory regulation can overcome exogenously-induced vasoconstriction. These results support the hypothesis that dual vascular pathways may explain differential vasoconstriction and how it impacts upon muscle metabolism.

Asunto(s)

Contracción Muscular/efectos de los fármacos , Relajación Muscular/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Animales , Relación Dosis-Respuesta a Droga , Miembro Posterior/irrigación sanguínea , Miembro Posterior/efectos de los fármacos , Miembro Posterior/metabolismo , Masculino , Músculo Esquelético/irrigación sanguínea , Músculo Esquelético/metabolismo , Perfusión , Presión , Ratas , Ratas Wistar , Flujo Sanguíneo Regional/efectos de los fármacos , Vasoconstrictores/administración & dosificación

RESUMEN

The concept that diet-induced changes in membrane lipids could modify heart function partly arose from observations that membrane composition and physical properties were closely associated with the capacity of the heart to respond appropriately to torpor and hibernation. Observations of natural hibernators further revealed that behavior of key membrane-bound enzymes could be influenced through the lipid composition of the cell membrane, either by changing the surrounding fatty acids through reconstitution into a foreign lipid milieu of different composition, or by alteration through diet. Myocardial responsiveness to beta-adrenoceptor stimulation, including initiation of spontaneous dysrhythmic contractions, was altered by both hibernation and dietary modulation of membrane fatty acids, suggesting modified vulnerability to cardiac arrhythmia. Subsequent studies using whole-animal models recognized that vulnerability to ventricular fibrillation decreased as the polyunsaturated: saturated fat (P:S) ratio of the diet increased. However, dietary fish oils, which typically contain at least 30% saturated fatty acids and only 30% long-chain n-3 (omega-3) polyunsaturated fatty acids (PUFA), exhibit antiarrhythmic effects that exceed the predicted influence of the P:S ratio, suggesting properties unique to the long-chain n-3 PUFA. Large-scale clinical trials and epidemiology have confirmed the arrhythmia prevention observed in vitro in myocytes, papillary muscles, and isolated hearts and in whole-animal models of sudden cardiac death. Some progress has been made towards a biologically plausible mechanism. These developments highlight nature's ability to provide guidance for the most unexpected applications.

Asunto(s)

Arritmias Cardíacas/dietoterapia , Arritmias Cardíacas/metabolismo , Membrana Celular/metabolismo , Muerte Súbita Cardíaca/prevención & control , Grasas de la Dieta/metabolismo , Grasas de la Dieta/uso terapéutico , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Omega-3/uso terapéutico , Aceites de Pescado/administración & dosificación , Corazón/fisiopatología , Animales , Arritmias Cardíacas/complicaciones , Muerte Súbita Cardíaca/etiología , Corazón/efectos de los fármacos , Humanos

RESUMEN

Epidemiologic studies, animal studies, and more recently, clinical intervention trials all suggest a role for regular intake of dietary fish oil in reducing cardiovascular morbidity and mortality. Prevention of cardiac arrhythmias and sudden death is demonstrable at fish or fish oil intakes that have little or no effect on blood pressure or plasma lipids. In animals, dietary intake of fish oil [containing both eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3)] selectively increases myocardial membrane phospholipid content of DHA, whereas low dose consumption of purified fatty acids shows antiarrhythmic effects of DHA but not EPA. Ventricular fibrillation induced under many conditions, including ischemia, reperfusion, and electrical stimulation, and even arrhythmias induced in vitro with no circulating fatty acids are prevented by prior dietary consumption of fish oil. The preferential accumulation of DHA in myocardial cell membranes, its association with arrhythmia prevention, and the selective ability of pure DHA to prevent ventricular fibrillation all point to DHA as the active component of fish oil. The antiarrhythmic effect of dietary fish oil appears to depend on the accumulation of DHA in myocardial cell membranes.

Asunto(s)

Antiarrítmicos/farmacología , Membrana Celular/metabolismo , Grasas Insaturadas en la Dieta/farmacología , Ácidos Grasos/metabolismo , Aceites de Pescado/farmacología , Miocardio/ultraestructura , Animales , Arritmias Cardíacas/prevención & control , Membrana Celular/química , Grasas Insaturadas en la Dieta/administración & dosificación , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/administración & dosificación , Ácido Eicosapentaenoico/metabolismo , Estimulación Eléctrica , Ácidos Grasos/análisis , Aceites de Pescado/administración & dosificación , Fibrilación Ventricular/prevención & control

RESUMEN

The influence of diets containing gamma-linolenic acid (GLA; 18:3n-6) on sciatic nerve conduction velocity (NCV) was determined in diabetic rats. NCV was lower in diabetic rats fed diets supplemented with olive oil or sunflower seed oil than in nondiabetic rats; rats supplemented with GLA during a 5-wk diabetic period, however, did not exhibit significantly lower NCV. The mean proportion of the phospholipid fatty acid linoleic acid (18:2n-6) was higher in the sciatic nerves of diabetic rats than in the nondiabetic groups irrespective of dietary lipid treatment. Additionally, the proportion of linoleic acid was higher in the diabetic rats fed sunflower oil than in all other groups. Dietary GLA supplementation did not significantly influence the fatty acid composition of nerve membrane phospholipids and there was no obvious correlation between the fatty acid composition of nerve membrane phospholipids and NCV. The content of fructose and glucose in sciatic nerves was higher, whereas that of myo-inositol was lower, in diabetic rats than in nondiabetic rats; however, this was not significantly influenced by dietary GLA. GLA administration did not significantly influence Na(+)-K(+)-exchanging ATPase or ouabain binding activity in sciatic nerve preparations, both of which remained nonsignificantly different in the diabetic and nondiabetic groups. The results suggest that dietary GLA can prevent the deficit in NCV induced by diabetes and that this effect is independent of the nerve phospholipid fatty acid profile, sugar and polyol content, Na(+)-K(+)-exchanging ATPase activity, and ouabain binding. GLA may prevent the deficit in NCV indirectly, possibly by its role as a precursor of vasodilatory prostaglandins. These results confirm that GLA is the active component of evening primrose oil.

Asunto(s)

Diabetes Mellitus Experimental/fisiopatología , Neuropatías Diabéticas/prevención & control , Ácidos Grasos Insaturados/uso terapéutico , Conducción Nerviosa/efectos de los fármacos , Ácido gammalinolénico/uso terapéutico , Animales , Antiinflamatorios no Esteroideos/uso terapéutico , Centrifugación por Gradiente de Densidad , Neuropatías Diabéticas/dietoterapia , Electrofisiología , Ácidos Grasos Esenciales/uso terapéutico , Glucosa/análisis , Ácidos Linoleicos , Masculino , Conducción Nerviosa/fisiología , Oenothera biennis , Ouabaína/química , Fosfolípidos/análisis , Aceites de Plantas , Ratas , Ratas Wistar , Nervio Ciático/fisiopatología , ATPasa Intercambiadora de Sodio-Potasio/análisis , Estreptozocina

Asunto(s)

Arritmias Cardíacas/fisiopatología , Diabetes Mellitus Experimental/fisiopatología , Grasas Insaturadas en la Dieta , Grasas de la Dieta , Ácidos Grasos Omega-3/metabolismo , Miocardio/metabolismo , Animales , Arritmias Cardíacas/etiología , Arritmias Cardíacas/prevención & control , Diabetes Mellitus Experimental/metabolismo , Suplementos Dietéticos , Ácidos Docosahexaenoicos , Masculino , Aceite de Oliva , Aceites de Plantas , Ratas , Ratas Wistar , Factores de Tiempo

RESUMEN

This study tested the hypothesis that in vivo antiarrhythmic effects of dietary fish oil can be attributed directly to changes in myocardial properties. Sixty adult male rats were fed a fish oil diet (FO), an isoenergetic saturated fat diet (SAT) or a low fat reference diet (REF) for 16 wk. hearts isolated from these rats were perfused with washed porcine erythrocytes (0.4 hematocrit) in working heart mode. Dietary fish oil prevented reperfusion-induced ventricular fibrillation (VF) (% of rats with VF: REF 50%, SAT 80% P = 0.35, FO 0% P < 0.05 n = 10) and reduced arrhythmias in ischemia. In a separate set of hearts from rats fed the three diets, FO increased while SAT reduced the stimulation threshold for programmed electrical induction of VF during control perfusion compared with REF (mean +/- SD: REF 7.1 +/- 0.2 mA; SAT 5.8 +/- 0.2 mA, P < 0.001; FO 15.1 +/- 1.0 mA, P < 0.001, n = 10) and during subsequent ischemia (REF 5.9 +/- 0.2 mA; SAT 3.8 +/- 0.3 mA, P < 0.001; FO 8.9 +/- 0.2 mA, P < 0.001, n = 10). The isolated working heart model used physiological workload and oxygenation but excluded extracardiac influences. Dietary fish oil prevented the initiation and reduced the severity of arrhythmias in the isolated hearts in response to a variety of stimuli. These results establish that irrespective of any effects on blood pressure or platelet function in vivo, dietary fish oil directly affects myocardial properties which may contribute to observed clinical reductions in cardiac mortality associated with fish consumption.

Asunto(s)

Arritmias Cardíacas/prevención & control , Aceites de Pescado/farmacología , Corazón/fisiología , Miocardio/metabolismo , Animales , Arritmias Cardíacas/etiología , Membrana Celular/química , Membrana Celular/fisiología , Membrana Celular/ultraestructura , Ácidos Docosahexaenoicos/análisis , Ácidos Docosahexaenoicos/metabolismo , Ácido Eicosapentaenoico/análisis , Ácido Eicosapentaenoico/metabolismo , Estimulación Eléctrica , Ácidos Grasos Insaturados/metabolismo , Aceites de Pescado/uso terapéutico , Corazón/efectos de los fármacos , Masculino , Daño por Reperfusión Miocárdica/complicaciones , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/fisiopatología , Miocardio/patología , Miocardio/ultraestructura , Ratas , Ratas Wistar

RESUMEN

Previous research showed that dietary fish oil was potently antiarrhythmic in rats but olive oil was not. This study was designed to test the hypothesis that canola oil, another major dietary source of oleic acid additionally containing the (n-3) polyunsaturated fatty acid alpha-linolenic acid [18:3(n-3)], can reduce vulnerability to cardiac arrhythmia in rats. Rats were randomly assigned to one of four experimental diet groups for 12 wk. The fat source in the diets was 12% olive (63% oleic acid), canola (55% oleic, 8% alpha-linolenic acid), soybean [50% linoleic 18:2(n-6), 7% alpha-linolenic acid] or sunflower seed oil (64% linoleic acid). Arrhythmias were induced by coronary artery occlusion and reperfusion. Incidence of ventricular fibrillation, mortality and arrhythmia score during reperfusion were significantly lower in rats fed the diet containing canola oil than in those fed the olive oil diet. No difference in the severity of arrhythmias was seen in groups fed diets containing soybean or sunflower seed oils. Analysis of myocardial phospholipid fatty acids showed that consumption of canola oil decreased the ratio of (n-6)/(n-3) polyunsaturated fatty acids relative to the other diets, as does dietary fish oil. These results suggest that regular substitution of canola oil for other dietary lipid sources may assist in reducing the likelihood of a transient ischemic event leading to life-threatening cardiac arrhythmias, but the effectiveness of alpha-linolenic acid is reduced by high levels of linoleic acid.

Asunto(s)

Arritmias Cardíacas/prevención & control , Dieta , Ácidos Grasos Monoinsaturados/farmacología , Ácidos Grasos/metabolismo , Miocardio/metabolismo , Animales , Arritmias Cardíacas/metabolismo , Ácidos Grasos/análisis , Ácidos Grasos Monoinsaturados/análisis , Ácidos Grasos Insaturados/metabolismo , Ácidos Linolénicos/análisis , Ácidos Linolénicos/normas , Masculino , Miocardio/química , Ácidos Oléicos/análisis , Ácidos Oléicos/farmacología , Aceite de Oliva , Fosfolípidos/metabolismo , Aceites de Plantas/análisis , Aceites de Plantas/farmacología , Distribución Aleatoria , Aceite de Brassica napus , Ratas , Aceite de Soja/análisis , Aceite de Soja/farmacología , Aceite de Girasol

RESUMEN

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.

Asunto(s)

Grasas Insaturadas en la Dieta/farmacología , Ácidos Grasos Omega-3/farmacología , Ácidos Grasos Insaturados/farmacología , Fibrilación Ventricular/tratamiento farmacológico , Animales , Arritmias Cardíacas/fisiopatología , Estimulación Eléctrica , Electrofisiología , Ácidos Grasos Omega-6 , Femenino , Haplorrinos , Isquemia/fisiopatología , Isoproterenol/farmacología , Masculino , Miocardio/química

RESUMEN

OBJECTIVE: The aim was to investigate (1) the relationship between atrial natriuretic factor (ANF) release and the extent of ischaemia-hypoxia, and (2) the potential role of eicosanoids in ANF release during global ischaemia, particularly the cyclo-oxygenase derivatives (prostaglandins) and the lipoxygenase derivatives (leukotrienes). METHODS: Using an isolated perfused, spontaneously beating rat heart, global ischaemia was achieved by the reduction of perfusion flow rate relative to basal flow rate. ANF was measured by radioimmunoassay. RESULTS: A decrease in perfusion flow rate by 75-80% to a final value of 2-2.5 ml.min-1.g-1 heart (n = 6) caused a gradual but sustained increase of ANF release which reached a plateau after 12 min, attaining a peak value of 89.9 (SEM 26.6)% over baseline. A decrease in perfusion flow rate by 55-60% (n = 5) also resulted in an increased ANF secretion, with a peak of 125.6(23.2)% over baseline at 14 min. A decrease in perfusion flow rate by 25-30% to a final value of 5-6.75 ml.min-1.g-1 heart (n = 4) showed no change in ANF release. The mean basal value of ANF release was 8.23(2.39) ng.min-1.g-1 heart (n = 26). In a separate series of experiments using a reduction of 55-60% in perfusion flow rate but with the addition to the perfusion medium of the specific cyclo-oxygenase inhibitor meclofenamate 10 microM (n = 5) or the lipoxygenase inhibitor nordihydroguaiaretic acid 10 microM (n = 5), no increase in ANF release occurred during the period of global ischaemia. Neither inhibitor affected ANF release during basal perfusion rates (7-9 ml.min-1.g-1 heart). CONCLUSIONS: ANF released in response to global ischaemia is likely to be mediated by prostanoids generated via the cyclo-oxygenase pathway and leukotrienes generated via the lipoxygenase pathway. Both pathways may provide important paracrine/autacoid regulatory roles for the protection of the heart during ischaemia by stimulating ANF release, with the subsequent beneficial effects of the peptide on peripheral tissues, ultimately leading to a reduction in load on the heart.

Asunto(s)

Factor Natriurético Atrial/biosíntesis , Diterpenos , Eicosanoides/fisiología , Isquemia Miocárdica/metabolismo , Miocardio/metabolismo , Animales , Modelos Animales de Enfermedad , Ginkgólidos , Frecuencia Cardíaca/efectos de los fármacos , Lactonas/farmacología , Masculino , Masoprocol/farmacología , Ácido Meclofenámico/farmacología , Contracción Miocárdica/efectos de los fármacos , Perfusión , Factor de Activación Plaquetaria/antagonistas & inhibidores , Ratas , Ratas Endogámicas , Tasa de Secreción/efectos de los fármacos

RESUMEN

The aim of this study was to develop an erythrocyte-perfused isolated working heart model of global ischemia that would allow controllable reductions in coronary perfusion pressure but with maintained afterload to facilitate the temporal association of myocardial ischemia with ventricular contractile or metabolic dysfunction. Isolated working rat hearts were perfused at 37 degrees C with a washed, resuspended porcine erythrocyte perfusate (40% hematocrit) at a preload of 10 mmHg and afterload of 75 mmHg, paced at 300 beats per min. A bifurcation above the aorta permitted imposition of two one-way valves, one opened by ventricular ejection in systole and closed by aortic afterload in diastole, the other closed by aortic pressure from ventricular ejection but opened to allow coronary perfusion in diastole according to an adjustable pressure head (75 mmHg initially). Ischemia was imposed by lowering the coronary perfusion pressure to 35 mmHg while maintaining diastolic afterload at 75 mmHg. The presence of erythrocytes provides oxygen delivery in the normal physiological range. This model permits the severity of ischemia to be graded by any specified level. The maintained afterload model of ischemia is a simple enhancement of the isolated working heart permitting a separation of workload and coronary perfusion pressure variables. This provides greater control over and direct monitoring of experimental ischemic events in progress.

Asunto(s)

Eritrocitos/fisiología , Modelos Biológicos , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatología , Animales , Corazón/fisiología , Técnicas In Vitro , Masculino , Miocardio/metabolismo , Oxígeno/sangre , Oxígeno/metabolismo , Consumo de Oxígeno/fisiología , Perfusión , Ratas , Ratas Wistar , Porcinos

RESUMEN

This study compared monounsaturated oleic acid with n-6 and n-3 polyunsaturated fatty acids (PUFAs) for their ability to modify the vulnerability to cardiac arrhythmias during ischemia or reperfusion in rats. Replacement of saturated animal fat in the diet with oleic acid-rich olive oil did not significantly alter the incidence of ventricular fibrillation or other cardiac arrhythmias. Replacement with either n-6-rich sunflower seed oil or n-3-rich fish oil reduced the incidence and severity of arrhythmias occurring in ischemia. The fish oil significantly reduced reperfusion arrhythmias independently of antecedent ischemic arrhythmias. Fatal ventricular fibrillation was significantly reduced by n-6 (8%; n = 25) and n-3 (0%; n = 24) PUFA but not by monounsaturates (36%; n = 25) compared with saturated fat (42%; n = 24). The results suggest that dietary replacement of saturated fats by n-6 and especially n-3 PUFA but not monounsaturated fatty acids can reduce the likelihood of an ischemic event leading to sudden cardiac death.

Asunto(s)

Arritmias Cardíacas/prevención & control , Grasas de la Dieta/administración & dosificación , Ácidos Grasos Monoinsaturados/uso terapéutico , Ácidos Grasos Insaturados/uso terapéutico , Ácidos Grasos/administración & dosificación , Daño por Reperfusión Miocárdica/complicaciones , Animales , Arritmias Cardíacas/etiología , Membrana Celular/metabolismo , Ácidos Grasos/metabolismo , Ácidos Grasos Monoinsaturados/administración & dosificación , Ácidos Grasos Insaturados/administración & dosificación , Aceites de Pescado/administración & dosificación , Aceites de Pescado/uso terapéutico , Isquemia Miocárdica/complicaciones , Miocardio/metabolismo , Aceite de Oliva , Aceites de Plantas/administración & dosificación , Aceites de Plantas/uso terapéutico , Ratas , Ratas Sprague-Dawley , Aceite de Girasol

RESUMEN

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)

Asunto(s)

Muerte Súbita Cardíaca/etiología , Grasas de la Dieta/metabolismo , Ácidos Grasos Insaturados/metabolismo , Fibrilación Ventricular/metabolismo , Función Ventricular Izquierda/efectos de los fármacos , Animales , Callithrix/metabolismo , Muerte Súbita Cardíaca/prevención & control , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/farmacología , Eicosanoides/metabolismo , Ácidos Grasos Insaturados/administración & dosificación , Ácidos Grasos Insaturados/farmacología , Aceites de Pescado/administración & dosificación , Aceites de Pescado/metabolismo , Aceites de Pescado/farmacología , Imagen de Acumulación Sanguínea de Compuerta , Corazón/efectos de los fármacos , Corazón/fisiología , Hemodinámica/efectos de los fármacos , Humanos , Lípidos de la Membrana/metabolismo , Miocardio/metabolismo , Fosfolípidos/metabolismo , Aceites de Plantas/administración & dosificación , Aceites de Plantas/metabolismo , Aceites de Plantas/farmacología , Volumen Sistólico/efectos de los fármacos , Aceite de Girasol , Fibrilación Ventricular/complicaciones

RESUMEN

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.

Asunto(s)

Grasas Insaturadas en la Dieta/administración & dosificación , Volumen Sistólico/fisiología , Animales , Callithrix , Gasto Cardíaco/efectos de los fármacos , Epinefrina/farmacología , Aceites de Pescado , Imagen de Acumulación Sanguínea de Compuerta , Corazón/diagnóstico por imagen , Corazón/efectos de los fármacos , Corazón/fisiología , Masculino , Aceites de Plantas , Volumen Sistólico/efectos de los fármacos , Aceite de Girasol

RESUMEN

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.

Asunto(s)

Grasas de la Dieta/farmacología , Fibrilación Ventricular/fisiopatología , Animales , Callithrix , Estimulación Cardíaca Artificial , Enfermedad Coronaria/fisiopatología , Umbral Diferencial , Electrocardiografía , Isoproterenol/farmacología

RESUMEN

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.

Asunto(s)

Callithrix/metabolismo , Grasas de la Dieta/metabolismo , Ácidos Grasos/metabolismo , Miocardio/metabolismo , Análisis de Varianza , Animales , Peso Corporal , Encéfalo/metabolismo , Colesterol/sangre , Riñón/metabolismo , Metabolismo de los Lípidos , Hígado/metabolismo , Masculino , Músculos/metabolismo , Especificidad de Órganos , Triglicéridos/sangre , Vitamina E/sangre

RESUMEN

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.

Asunto(s)

Grasas de la Dieta/farmacología , Eicosanoides/biosíntesis , Miocardio/metabolismo , Animales , Epoprostenol/biosíntesis , Grasas/química , Ácidos Grasos/análisis , Ácidos Grasos/farmacología , Ratas , Ratas Endogámicas , Tromboxano A2/biosíntesis

RESUMEN

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.

Asunto(s)

Arritmias Cardíacas/etiología , Enfermedad Coronaria/complicaciones , Grasas Insaturadas en la Dieta/farmacología , Grasas de la Dieta/farmacología , Aceites de Plantas/farmacología , Animales , Arritmias Cardíacas/prevención & control , Grasas de la Dieta/efectos adversos , Modelos Animales de Enfermedad , Masculino , Aceite de Palma , Ratas , Ratas Endogámicas

RESUMEN

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.

Asunto(s)

Eicosanoides/biosíntesis , Aceites de Pescado/administración & dosificación , Animales , Grasas de la Dieta/sangre , Epoprostenol/biosíntesis , Técnicas In Vitro , Riñón/metabolismo , Miocardio/metabolismo , Fosfolípidos/sangre , Ácidos Prostanoicos/orina , Ratas , Ratas Endogámicas , Tromboxano A2/biosíntesis , Vitamina E/metabolismo