Protective Effects of Sodium Pyruvate during Systemic Inflammation Limited to the Correction of Metabolic Acidosis.

Protective effects by exogenous sodium pyruvate already have been described in various experimental models of injury, among others during intestinal ischemia-reperfusion injury, hemorrhagic shock, and shock secondary to systemic inflammation (endotoxemic shock). Low doses of sodium pyruvate reduced signs of inflammation, enhanced systemic blood pressure, and ameliorated metabolic acidosis when administered in a prophylactic manner during endotoxemic shock. In the present study, we investigated whether low-dosed infusions of sodium pyruvate exhibited beneficial effects when applied therapeutically after the induction of systemic inflammation. Lipopolysaccharide was infused at a rate of 0.5 mg/kg × h over a period of 360 min to induce systemic inflammation in male Wistar rats. Sodium pyruvate (single dose 50 mg/kg × 15 min) was administered intravenously 180 and 270 min after starting of the lipopolysaccharide infusion. Systemic/vital parameters (e.g., systemic blood pressure and breathing rate) and blood/plasma parameters (e.g., acid-base parameters; electrolytes; glucose and lactate concentration; hemolysis; aminotransferase activities; and parameters of coagulation) were determined in regular intervals. Lipopolysaccharide infusion led to metabolic acidosis, hypoglycemia, electrolyte as well as hemostatic disturbances, and hemolysis. Except for the acid-base status (amelioration of metabolic acidosis) and the plasma chloride concentration (reduction of hyperchloremia), the additional infusion of sodium pyruvate failed in significantly improving lipopolysaccharide-dependent alterations (e.g. vital, blood and plasma parameters). Protective effects of a delayed administration of the metabolizable anion pyruvate during systemic inflammation, hence, are limited to its function as alkalizer to counteract metabolic acidosis.

Melatonin reduces changes to small intestinal microvasculature during systemic inflammation.

BACKGROUND: Systemic inflammation is known to impair the microcirculation in intestine and other organs as a result of multifactorial events. Here, we show that melatonin selectively reduces changes to the small intestinal microvasculature during systemic inflammation. MATERIALS AND METHODS: Lipopolysaccharide (LPS) was infused at a rate of 0.5 mg/kg × h to induce systemic inflammation in male Wistar rats. Melatonin (single dose: 3 mg/kg × 15 min) was intravenously administered before as well as 120 and 240 min after the beginning of the LPS infusion. Systemic parameters were determined in regular intervals. Small intestine, liver, and kidney were histologically (structure of the microvessels, intravascular blood accumulation, and hemorrhages) and immunohistochemically (mast cells, granulocytes, and macrophages) analyzed. RESULTS: Continuous infusion of LPS resulted in dilated microvessels with intravascular blood accumulation (congestion) in liver and small intestine, the latter being particularly pronounced. Blood vessel walls remained intact, there were no hemorrhages. Melatonin significantly reduced these changes to the microvasculature in small intestine, but not in liver. It further reduced mast cell and granulocytes count in small intestine enhanced by LPS. However, except for the systemic blood pressure, melatonin neither improved LPS-dependent changes to systemic parameters nor mortality. CONCLUSIONS: Changes to the microvasculature during systemic inflammation are most pronounced in small intestine. Melatonin selectively diminishes these changes to small intestinal microvasculature, probably by reducing the local immune cells recruitment. However, changes to the small intestine are not decisive for the survival. We assume that the therapeutic benefit of melatonin is more likely in local intestinal inflammation.