Effect of endotoxin on cardiopulmonary function and biosynthesis of eicosanoids and TNFα in calves chronically depleted of copper

Abstract

We evaluated the acute cardiopulmonary and biochemical (i.e. plasma concentrations of eicosanoids and serum levels of TNFα) response to an infusion of Escherichia coli endotoxin (8 μg/kg i.v.) in cattle that were adequate or deficient in liver and plasma copper (Cu) concentrations. Young calves were chronically fed diets containing normal Cu (control; n = 4) and low Cu (n = 14). After ~6 months of dietary treatment, the calves were anesthetized and evaluated from 0-4 h during endotoxemia. At 0 h, plasma Cu concentrations averaged 32.4% (P < 0.05) of the control value (i.e. 0.81 ± 0.08 μg/ml). Endotoxin caused a transient, early (at 20.4 min) increase in mean pulmonary arterial pressure to 114% and 147% of baseline in normal and Cu depleted calves, respectively (P < 0.05). In Cu depleted calves, endotoxin significantly decreased heart rate (0.5-1 h) and cardiac index (0.5 h) as compared to normal calves. Endotoxin caused systemic hypotension and increased TXB2 production (at 0.5 h) and these changes were potentiated in Cu depleted calves. However, after 1 h there were no statistically significant differences between the two groups of calves for any cardiopulmonary parameter evaluated nor in plasma concentrations of eicosanoids and serum levels of TNFα. We conclude that chronic dietary depletion of Cu potentiates TXB ₂ biosynthesis and worsens the acute (≤1 h) cardiovascular response to endotoxin challenge in cattle.