Insights Into Thiamine Supplementation in Patients With Septic Shock.

Septic shock is associated with unacceptably high mortality rates, mainly in developing countries. New adjunctive therapies have been explored to reduce global mortality related to sepsis. Considering that metabolic changes, mitochondrial dysfunction and increased oxidative stress are specific disorders within the path of septic shock, several micronutrients that could act in cellular homeostasis have been studied in recent decades. Thiamine, also known as vitamin B1, plays critical roles in several biological processes, including the metabolism of glucose, synthesis of nucleic acids and reduction of oxidative stress. Thiamine deficiency could affect up to 70% of critically ill patients, and thiamine supplementation appears to increase lactate clearance and decrease the vasopressor dose. However, there is no evident improvement in the survival of septic patients. Other micronutrients such as vitamin C and D, selenium and zinc have been tested in the same context but have not been shown to improve the outcomes of these patients. Some problems related to the neutrality of these clinical trials are the study design, doses, route, timing, length of intervention and the choice of endpoints. Recently, the concept that multi-micronutrient administration may be better than single-micronutrient administration has gained strength. In general, clinical trials consider the administration of a single micronutrient as a drug. However, the antioxidant defense is a complex system of endogenous agents in which micronutrients act as cofactors, and the physiological interactions between micronutrients are little discussed. In this context, the association of thiamine, vitamin C and corticoids was tested as an adjunctive therapy in septic shock resulting in a significant decrease in mortality. However, after these initial results, no other study conducted with this combination could reproduce those benefits. In addition, the use of low-dose corticosteroids is recommended in patients with septic shock who do not respond to vasopressors, which can affect the action of thiamine. Therefore, given the excellent safety profile, good biologic rationale and promising clinical studies, this review aims to discuss the mechanisms behind and the evidence for single or combined thiamine supplementation improving the prognosis of patients with septic shock.

Spondias mombin L. attenuates ventricular remodelling after myocardial infarction associated with oxidative stress and inflammatory modulation.

The objective of this study was to evaluate Spondias mombin L. (SM) pulp and its influence on cardiac remodelling after myocardial infarction (MI). Male Wistar rats were assigned to four groups: a sham group (animals underwent simulated surgery) that received standard chow (S; n = 20), an infarcted group that received standard chow (MI; n = 24), an infarcted group supplemented with 100 mg of SM/kg bodyweight/d, (MIS100; n = 23) and an infarcted group supplemented with 250 mg of SM/kg bodyweight/d (MIS250; n = 22). After 3 months of treatment, morphological, functional and biochemical analyses were performed. MI induced structural and functional changes in the left ventricle with worsening systolic and diastolic function, and SM supplementation at different doses did not influence these variables as analysed by echocardiography and an isolated heart study (P > .05). However, SM supplementation attenuated cardiac remodelling after MI, reducing fibrosis (P = .047) and hypertrophy (P = .006). Biomarkers of oxidative stress, inflammatory processes and energy metabolism were further investigated in the myocardial tissue. SM supplementation improved the efficiency of energy metabolism and decreased lipid hydroperoxide in the myocardium [group S (n = 8): 267.26 ± 20.7; group MI (n = 8): 330.14 ± 47.3; group MIS100 (n = 8): 313.8 ± 46.2; group MIS250: 294.3 ± 38.0 nmol/mg tissue; P = .032], as well as decreased the activation of the inflammatory pathway after MI. In conclusion, SM supplementation attenuated cardiac remodelling processes after MI. We also found that energy metabolism, oxidative stress and inflammation are associated with this effect. In addition, SM supplementation at the highest dose is more effective.

Ventricular remodeling induced by retinoic acid supplementation in adult rats.

Retinoic acid (RA) plays a role in regulating cardiac geometry and function throughout life. The aim of this study was to analyze the cardiac effects of RA in adult rats. Wistar rats were randomly allocated to a control group (n = 18) receiving standard rat chow and a group treated with RA (n = 14) receiving standard rat chow supplemented with RA for 90 days. All animals were evaluated by echocardiography, isolated papillary muscle function, and morphological studies. Whereas the RA-treated group developed an increase in both left ventricular (LV) mass and LV end-diastolic diameter, the ratio of LV wall thickness to LV end-diastolic diameter remained unchanged when compared with the control group. In the isolated papillary muscle preparation, RA treatment decreased the time to peak developed tension and increased the maximum velocity of isometric relengthening, indicating that systolic and diastolic function was improved. Although RA treatment produced an increase in myocyte cross-sectional area, the myocardial collagen volume fraction was similar to controls. Thus our study demonstrates that small physiological doses of RA induce ventricular remodeling resembling compensated volume-overload hypertrophy in rats.