Figure 5. Dichloroacetate (DCA) treatment increases blood pressure and improves microvascular dysfunction.

Septic animals were treated with DCA or vehicle 24 hours after cecal ligation and puncture (CLP) and assessed 6 hours after treatment. (A) Mean arterial pressure (MAP), measured via carotid artery cannulation, was significantly higher in CLP⁺ DCA vs. CLP⁺ vehicle group. (B) Mice treated with DCA (CLP⁺ DCA) or vehicle (CLP⁺ vehicle) were challenged with either normal saline (denoted as –LPS) or LPS (+LPS) i.p., and leukocyte and platelet adhesion were determined 4 hours later in the small intestine using intravital microscopy. CLP⁺ vehicle group did not show significant increase in leukocyte or platelet adhesion in response to LPS (+LPS) vs. normal saline (–LPS) stimulation and remained endotoxin tolerant. However, in CLP⁺ DCA groups, leukocyte and platelet adhesion increased significantly in response to LPS (vs. respective –LPS group), demonstrating endotoxin responsiveness. (C) E-selectin (left panel), ICAM1 (right panel) adhesion molecules, von Willebrand factor (VWF) endothelial marker, and nuclear DAPI staining show qualitatively increased E-selectin and ICAM1 expression in small intestinal tissue sections of CLP⁺ DCA vs. CLP⁺ vehicle group. IHC scale bar: 100 μm; A, n = 4 per group, t test. B, n = 5 in ±LPS vehicle and +LPS DCA, n = 4 in –LPS DCA. Assessed by 1-way ANOVA with Tukey post hoc multiple comparison test. C, n = 3. One exemplary result is shown. **P < 0.01; ***P < 0.001.