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It has been proven that dietary eicosapentaenoic acid (C20:5 n-3 or EPA) protects the heart against the deleterious effects of sepsis in female rats. We do not know if this is the case for male rodents. In this case, the efficiency of other n-3 polyunsaturated fatty acids (PUFAs) remains to be determined in both female and male rats. This study aimed at (i) determining whether dietary EPA is cardioprotective in septic male rats, (ii) evaluating the influence of dietary &alpha, linolenic (C18:3 n-3 or ALA) on cardiac function during this pathology, and (iii) finding out the physiological and molecular mechanisms responsible for the observed effects. Sixty male rats were divided into three dietary groups. The animals were fed a diet deficient in n-3 PUFAs (DEF group), a diet enriched with ALA (ALA group) or a diet fortified with EPA (EPA group) for 6 weeks. Thereafter, each group was subdivided into 2 subgroups, one being subjected to cecal ligation and puncture (CLP) and the other undergoing a fictive surgery. Cardiac function was determined in vivo and ex vivo. Several parameters related to the inflammation process and oxidative stress were determined. Finally, the fatty acid compositions of circulating lipids and cardiac phospholipids were evaluated. The results of the ex vivo situation indicated that sepsis triggered cardiac damage in the DEF group. Conversely, the ex vivo data indicated that dietary ALA and EPA were cardioprotective by resolving the inflammation process and decreasing the oxidative stress. However, the measurements of the cardiac function in the in vivo situation modulated these conclusions. Indeed, in the in vivo situation, sepsis deteriorated cardiac mechanical activity in the ALA group. This was suspected to be due to a restricted coronary flow which was related to a lack of cyclooxygenase substrates in membrane phospholipids. Finally, only EPA proved to be beneficial in sepsis. Its action necessitates both resolution of inflammation and increased coronary perfusion. In that sense, dietary ALA, which does not allow the accumulation of vasodilator precursors in membrane lipids, cannot be protective during the pathology.

Diabetes is characterized by a high mortality rate which is often associated with heart failure. Green tea and eicosapentaenoic acid (EPA) are known to lessen some of the harmful impacts of diabetes and to exert cardio-protection. The aim of the study was to determine the effects of EPA, green tea extract (GTE), and a combination of both on the cardiac consequences of diabetes mellitus, induced in Wistar rats by injection of a low dose of streptozotocin (33 mg/kg) combined with a high fat diet. Cardiac mechanical function, coronary reactivity, and parameters of oxidative stress, inflammation, and energy metabolism were evaluated. In the context of diabetes, GTE alone limited several diabetes-related symptoms such as inflammation. It also slightly improved coronary reactivity and considerably enhanced lipid metabolism. EPA alone caused the rapid death of the animals, but this effect was negated by the addition of GTE in the diet. EPA and GTE combined enhanced coronary reactivity considerably more than GTE alone. In a context of significant oxidative stress such as during diabetes mellitus, EPA enrichment constitutes a risk factor for animal survival. It is essential to associate it with the antioxidants contained in GTE in order to decrease mortality rate and preserve cardiac function.

Several meta-analyses describing the effect of n-3 polyunsaturated fatty acids on the survival rate of the victims of an acute coronary event do not clearly support a beneficial impact of these fatty acids. Yet, animal studies consistently show n-3 PUFA-induced protection against ischemia-reperfusion-induced myocardial injuries. The impact on reperfusion arrhythmias of these PUFAs is more controversial. The literature shows the anti-arrhythmic properties of circulating n-3 PUFAs. However, when these fatty acids are incorporated in the cardiac membrane, they protect the myocardial tissue vis a vis cellular damage but they can be either pro- or anti-arrhythmic during reperfusion, depending on the severity of tissue injuries. The latter elements can explain the lack of beneficial effect observed in the meta-analyses, but a proper use of n-3 PUFAs may provide advantages in terms of survival rate. This review discusses the different results obtained in humans and animals and presents several strategies to enhance the beneficial effects of n-3 PUFAs.

Topic 1 — Inflammation — A Topic 1 — Inflammation — ATopic 1 — Inflammation — A; IntroductionSepsis triggers the failure of cardiac mitochondria and this deleterious effect could be prevented by omega-3 polyunsaturated fatty acids (PUFA).ObjectivesTo evaluate the influence of eicosapentaenoic acid (C20: 5 omega-3 or EPA) on the mechanical and mitochondrial functions of the heart during early sepsis.MethodsFour month-old female Wistar rats were subdivided in 4 groups (n = 8 per group) according to: (i) the 4-week diet given (deficient in omega-3 PUFA [DEF] or enriched with EPA); (ii) the surgery performed (caecal ligation at 1 cm of the apex of the heart and puncture in order to induce sepsis [CLP] or sham). The cardiac mechanical function was studied in vivo by NMR 48 h after the surgery. Immediately after, part of the myocardium was used in order to extract mitochondria and another part was frozen in order to subsequently analyse the fatty acid composition of cardiac phospholipids.ResultsThe EPA groups display a large decrease in the omega-6/omega-3 PUFA ratio of cardiac phospholipids. Sepsis increases the mRNA expression of IL-1beta in the DEF group but not in the EPA one. The mechanical function is altered neither by the diets nor by the surgeries. The DEF/CLP animals have a deficient oxidative phosphorylation compared to the DEF/Sham rats: reduced mitochondrial oxygen consumption (−42%, P < 0.001) and ATP production (−37%, P < 0.05). The sepsis-induced mitochondrial damages in this group is due to an increase reactive oxygen species (ROS) release (+130 and +63% for the ROS/respiration and ROS/ATP ratios, P < 0.01 and P < 0.05, respectively). The dietary EPA prevents these damages (P < 0.05).ConclusionA sufficient EPA intake favours the upholding of the mitochondrial function during early sepsis, which could delay the subsequent development of heart failure. We plan to verify this beneficial effect of EPA in Humans affected by acute endocarditis.

This work was supported by 2 grants attributed by the Fédération Française de Cardiologie and society ADETEC of patients with a previous cardiac surgery; If it is sustained for several days, sepsis can trigger severe abnormalities of cardiac function which leads to death in 50% of cases. This probably occurs through activation of toll‐like receptor‐9 by bacterial lipopolysaccharides and overproduction of proinflammatory cytokines such as TNF‐α and IL‐1β. In contrast, early sepsis is characterized by the development of tachycardia. This study aimed at determining the early changes in the cardiac function during sepsis and at finding the mechanism responsible for the observed changes. Sixty male Wistar rats were randomly assigned to two groups, the first one being made septic by cecal ligation and puncture (sepsis group) and the second one being subjected to the same surgery without cecal ligation and puncture (sham‐operated group). The cardiac function was assessed in vivo and ex vivo in standard conditions. Several parameters involved in the oxidative stress and inflammation were determined in the plasma and heart. As evidenced by the plasma level of TNF‐α and gene expression of IL‐1β and TNF‐α in the heart, inflammation was developed in the sepsis group. The cardiac function was also slightly stimulated by sepsis in the in vivo and ex vivo situations. This was associated with unchanged levels of oxidative stress, but several parameters indicated a lower cardiac production of reactive oxygen species in the septic group. In conclusion, despite the development of inflammation, early sepsis did not increase reactive oxygen species production and did not reduce myocardial function. The depressant effect of TNF‐α and IL‐1β on the cardiac function is known to occur at very high concentrations. The influence of low‐ to moderate‐grade inflammation on the myocardial mechanical behavior must thus be revisited.