PENTOXIFYLLINE MAINTAINS VASCULAR ENDOTHELIAL-CELL FUNCTION DURING HYPERDYNAMIC AND HYPODYNAMIC SEPSIS

Background. Although pentoxifylline produces various beneficial effect s after endotoxemia or sepsis occurs, it is not known whether this age nt attenuates the depressed endothelial cell function during sepsis. T herefore the aim of this study was to determine whether pentoxyifyllin e maintains vascular endothelial cell function (i.e., improves the rel ease of endothelium-derived nitric oxide) during hyperdynamic and hypo dynamic stages of polymicrobial sepsis. Methods. Rats were subjected t o sepsis by cecal ligation and puncture (CLP), after which 3 ml/100 gm body wt normal saline solution was injected subcutaneously in these a nd rats in a sham-operated group. At 1 hour after the onset of sepsis, pentoxifylline (50 mg/kg body wt) or an equal volume of normal saline solution was infused intravenously during a 30 minute period. At 10 a nd 20 hours after CLP was performed (10-hour CLP, hyperdynamic sepsis; 20-hour CLP, hypodynamic sepsis), the thoracic aorta was isolated, cu t into rings, and placed in organ chambers. Norepinephrine (2 x 10(-7) mol/L) was used to achieve near maximal tension. Dose responses for a n endothelium-dependent vasodilator, acetylcholine, and an endothelium -independent vasodilator, nitroglycerine, were carried out. The change s in percentage relaxation in the aortic rings by these agonists were then determined. Results. Endothelium-dependent (acetylcholine-induced ) vascular relaxation decreased significantly at 10 and 20 hours after CLP. Administration of pentoxifylline, however, maintained acetylchol ine-induced vascular relaxation at both time points. In contrast, no s ignificant reduction in nitroglycerine-induced vascular relaxation was seen in rats with sepsis irrespective of pentoxifylline treatment. Co nclusions. Because pentoxifylline prevented endothelial cell dysfuncti on at 10 to 20 hours after CLP occurred, this agent appears to be a us eful agent for maintaining vascular endothelial function during the hy perdynamic and hypodynamic stages of polymicrobial sepsis.