Endotoxin-induced digital vasoconstriction in horses: associated changes in plasma concentrations of vasoconstrictor mediators.

The research explores the relationship between Lipopolysaccharide (LPS) infusion and reduced blood flow in horse’s digits, and it identifies the mediators responsible which include plasma 5-HT and Thromboxane B2 (TxB2). The study suggests potential anti-platelet therapy for prevention of laminitis associated with endotoxic conditions in horses.

Research Objective and Methodology

• The main objective of this study was to identify the vasoconstrictor mediators released following LPS infusion and to relate their appearance in horse’s plasma to digital blood flow alterations. The research aimed to understand the cause of reduced digital perfusion in horses, which is directly associated with an infusion of Lipopolysaccharide (LPS).
• The researchers conducted tests on six Thoroughbred horses. They administered a 30-minute infusion of LPS and monitored the blood flow in the lateral digital vessels using Doppler ultrasonography.
• Along with monitoring digital blood flow, the scientists also tracked the changes in hoof wall and coronary band surface temperatures (HWST and CBST). Concurrent measurements provided insights into the systemic effects of LPS infusion.
• Throughout the process, serial blood samples were collected, and the concentration of plasma LPS, tumour necrosis factor alpha (TNFalpha), 5-HT, thromboxane B2 (TxB2), and endothelin was measured.

Research Findings

• The research found that the maximum concentration of plasma LPS reached 13.2 pg/ml during the infusion, which was followed by an increase in plasma TNFalpha concentration. This suggests that the LPS infusion induces a response from the body’s immune system, leading to the production of TNFalpha, which is a primary cytokine involved in systemic inflammation.
• Post-infusion, digital arterial and venous blood flow decreased by 43% and 63% respectively, and there was a similar decrease in HWST and CBST.
• It was noted that the systemic blood pressure remained unaltered, suggesting that the changes in digital blood flow and temperature were a direct response to LPS infusion rather than a systemic effect on blood pressure.
• There was an increase in the concentrations of TxB2 and 5-HT at the occurrence of digital hypoperfusion. On the other hand, the concentration of plasma endothelin remained unchanged. This suggests that TxB2 and 5-HT, both of which are platelet-derived axes, are directly related to LPS-induced laminitis in horses.

Conclusions of the Study

• The study established a connection between the onset of digital hypoperfusion in horses and the increased levels of plasma 5-HT and TxB2. Hypoperfusion refers to a decrease in blood flow to a bodily organ or part, and laminitis is a painful condition affecting horses’ feet.
• Given that 5-HT and TxB2 are platelet-derived mediators, these findings suggest that platelet activity may play a crucial role in LPS-induced laminitis.
• As a result of these findings, the study supports the use of anti-platelet therapy in preventing laminitis in horses, particularly when associated with endotoxaemic conditions, such as bacterial infections.