Interactions between ω3 polyunsaturated fatty acids and arginine on nutritional and immunological aspects in severe inflammation.

BACKGROUND & AIMS: Immune-enhancing diets (IEDs) contain a mixture of nutrients claimed to have immunological properties. Therefore, it seemed relevant to determine the effect of each of their components. The aim of this study was to examine the role of arginine (Arg) and ω3 polyunsaturated fatty acids (ω3 PUFAs) in the effect of an IED (Crucial(®)) in a validated rat model of inflammation induced by turpentine (TI). METHODS: Forty-two rats were randomized into five groups: AL (ad libitum), TI-EN (TI+standard enteral nutrition (EN): Sondalis(®)HP), TI-EN-Arg (TI+standard EN+Arg in equimolar concentration to Arg in the IED), TI-M-IED (TI+modified IED containing the same ω6/ω3 ratio as in standard EN) and TI-IED (TI+Crucial(®)). Blood was sampled to determine CD25 receptor density on lymphocytes. TNF-α, IL-6 and NO (production and expression) were evaluated on isolated macrophages. Mesenteric lymph nodes, spleen and liver were cultured for analysis of enterobacterial translocation and dissemination. RESULTS: CD25 density was decreased after TI and was corrected in the TI-EN-Arg, TI-M-IED and TI-IED groups (p<0.05). TI induced an alteration of macrophage mRNA expression of IL-6, TNF-α and iNOS, corrected in the TI-EN-Arg and TI-M-IED groups (p<0.05), but not by the IED. Enterobacterial translocation was observed in all treated groups, nevertheless the amount tended (p=0.054) to be lower in the TI-EN-Arg group. CONCLUSIONS: Arg and ω3 PUFAs make a major contribution to IED effects, but our study shows interaction between them on macrophage reactivity. This indicates that the individual properties of each pharmaconutrient are not additive in IEDs.

Effect of an immune-enhancing diet on lymphocyte in head-injured rats: what is the role of arginine?

OBJECTIVE: The benefit of immune-enhancing diets (IEDs) in the intensive care unit remains controversial. Considering their complexity, the role of each component, in particular arginine (Arg), in their properties is largely unknown. The aim of this study was to determine the role of arginine in the immunomodulatory effects of an IED (Crucial) in head-injured rats. DESIGN: Thirty-four rats were randomized into five groups: AL (ad libitum), HI (head-injured), HI-STD (HI + standard enteral nutrition, EN), HI-STD-Arg (HI + standard EN + Arg in equimolar concentration to Arg in IED), and HI-IED (HI + IED). These isocaloric and isonitrogenous diets were administered over 4 days. After death, the thymus was removed and weighed. The density of CD25, CD4 and CD8 on lymphocytes from blood and from Peyer patches was evaluated. Mesenteric lymph nodes, liver and spleen were cultured for analysis of enterobacterial translocation and dissemination. MEASUREMENTS AND RESULTS: HI induced an atrophy of the thymus which was not corrected by the standard diet (HI 0.27 +/- 0.03, HI-STD 0.35 +/- 0.03 vs. AL 0.49 +/- 0.02 g; p < 0.05). However, the standard diet supplemented with arginine limited the thymic atrophy and the IED restored thymus weight. CD25 density and interleukin-2 production were increased only in the HI-STD-Arg and HI-IED groups (p < 0.05). Head injury induced enterobacterial translocation and dissemination which were blunted only in the HI-STD-Arg group (p < 0.05). CONCLUSIONS: In this rat HI model, arginine appears to be safe, contributes to a large extent to the immunomodulatory effects of the IED, and seems to limit enterobacterial translocation and dissemination more efficiently alone than in an IED.

Does the ornithine-alpha-ketoglutarate ratio influence ornithine alpha-ketoglutarate metabolism in healthy rats?

Ornithine alpha-ketoglutarate (OKG) is a salt composed of 2 molecules of ornithine (ORN) and one molecule of alpha-ketoglutarate (alphaKG). OKG has been used successfully via oral, enteral, and parenteral routes to improve protein status in patients with chronic and acute protein depletion, but its mechanism of action, which is probably multifactorial, is still unclear. A specific metabolic interaction between alphaKG and ORN has been shown to be a key factor in the effects of OKG, but the impact of the ORN/alphaKG ratio (2 molecules of ORN for 1 molecule of alphaKG) has never been discussed. To clarify this point, young (3 weeks old) male Wistar rats in the postabsorptive state received 5 g/kg of either OKG or a mono-ornithine alphaKG (MOKG) salt (ORN/alphaKG ratio = 1:1) in amounts that were either isonitrogenous or isomolar to OKG, or a saline solution (controls) and were killed 1 hour later. In a second experiment, a kinetic study was performed in which rats were killed 1, 2, 3, or 6 hours after OKG, MOKG, or saline administration. Amino acid contents were analyzed in the plasma, liver, jejunal and ileal mucosae, and the extensor digitorum longus (EDL) muscle. The major metabolites detected after intake of OKG or MOKG (ie, ORN, proline [PRO], and glutamate; OKG and MOKG vs control, P < .05) together with the absence of increased arginine and citrulline levels suggested that ORN was mainly metabolized by the ORN aminotransferase pathway, leading to glutamate and PRO production with accumulation persisting at 6 hours postadministration. This study provides new and important data on the influence of the ORN/alphaKG ratio on OKG metabolism: MOKG-treated rats presented less intestinal ORN than OKG-treated rats (MOKG vs OKG, P < .05), suggesting that ORN/alphaKG ratio influences the rate of ORN availability and metabolism. In addition, the metabolic interaction between ORN and alphaKG (ie, in the presence of alphaKG, ORN metabolism is partially diverted toward PRO production), which is characteristic of OKG metabolism, still takes place even if the salt contains only 1 molecule of ORN instead of two.

Brady-tachy syndrome: rapid atrial pacing efficacy in preventing atrial fibrillation recurrence assessed by reliable electrograms: the prefib pilot study.

AIMS: Recent studies have tested different atrial pacing rates, modes, and sites for preventing atrial fibrillation (AF) recurrence. Present generation pacemakers offer reliable electrograms (EGMs) storage for optimizing the arrhythmia diagnosis. Based on these EGMs, the study objective was to assess the rate of AF recurrence at two different pacing rates. METHODS: Thirty patients suffering exclusively from symptomatic brady-tachy syndrome (BTS) resistant to > or =2 drugs, were implanted with a DDDR pacemaker. After a 5-days observation period, the DDD pacing rate was randomly programmed at 60 bpm (-15 bpm hysteresis) or at 80 bpm for 12 weeks. The two sequences were crossed over at the end of this fixed period or when earlier symptomatic AF recurred. Antiarrhythmics were maintained. Stored EGMs of > or =4 s duration identified all AF recurrence. RESULTS: Thirty patients (17 males, 77.2 +/- 8.1 years old) were included. One patient withdrew prematurely for severe heart failure associated with AF recurrence and rapid ventricular response. For the remainder of the 29 patients, fast atrial pacing neither provoked symptoms nor haemodynamic change. AF recurred in 16 patients paced at 60 (-15) bpm (mean time: 29 days; range 1-61) and in 9 patients paced at 80 bpm (mean time: 55 days; range 5-83) (P < 0.05). AF recurrence was asymptomatic in 50% of patients. CONCLUSIONS: These results confirm that rapid atrial pacing is 1) significantly effective for preventing AF recurrence in symptomatic BTS patients, and 2) haemodynamically well tolerated.