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.

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.

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.

Mount Gambier drinking water and birth defects. A laboratory study in rats after earlier epidemiological findings.

Experimental studies in pregnant rats failed to demonstrate the presence of a teratogenic agent in water from the Mount Gambier Blue Lake or from several local bores, even when the water from each of those two sources was concentrated tenfold and fivefold, respectively, by freeze drying. The experimental data thus failed to corroborate the previously reported epidemiological evidence of an increased risk of human teratogenesis in pregnant women who were drinking water from these sources. The growth of rat embryos in culture on serum taken from pregnant women in the Mount Gambier region was identical, regardless of the source of drinking water consumed by the individual donors. The findings do not suggest the presence of a teratogen in Mount Gambier water supplies; however, they should be regarded with the caution which is necessarily associated with teratology studies conducted across the boundaries of species.

Teratogenic effect of extended administration of N-nitrosoethylurea and ethylurea/nitrite in rats.

N-Nitrosoethylurea (ENU) and ethylurea (EU) with sodium nitrite (NaNO2) were administered daily by mouth to Hooded Wistar rats. Doses ranged from 1-50 mg ENU/kg body weight (day-1) and from 20-70 mg EU/kg body weight day-1 and extended over days 7 to 16 inclusive of pregnancy. Severe teratogenesis occurred in animals which received from 10 mg ENU/kg day-1. Fetal death predominated at intakes above 12.5 mg ENU/kg body wt. Many organ systems were affected by ENU, but developmental anomalies of the nervous system were most common, especially anophthalmia and hydrocephalus. With EU and nitrite severe teratogenesis was noted at levels above 50 mg EU/kg body weight. Maximum teratogenic potency was obtained when nitrite was administered at approximately 50% of the level of the EU dose. Terata arising from treatment with EU/nitrite were similar to those caused by ENU. However, unlike ENU-treated animals, litters from the EU/nitrite study were either severely malformed or barely affected at all. The erratic nature of the teratogenesis following treatment with EU/nitrite was not influenced by the presence of food in the stomach at the time of dosing. For both substances administered over a 10-day period, the threshold dose needed for obvious teratogenicity was considerably less than in all previously reported single-dose studies.