Pentoxifylline maintains vascular endothelial cell function during hyperdynamic and hypodynamic sepsis

Background. Although pentoxifylline produces various beneficial effects after endotoxemia or sepsis occurs, it is not known whether this agent attenuates the depressed endothelial cell function during sepsis. Therefore the aim of this study was to determine whether pentoxyifylline maintains vascular endothelial cell function (i.e., improves the release of endothelium-derived nitric oxide) during hyperdynamic and hypodynamic stages of polymicrobial sepsis. Methods. Rats were subjected to sepsis by cecal ligation and puncture (CLP), after which 3 ml/100 gm body wt normal saline solution was injected subcutaneously in these and 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 and 20 hours after CLP was performed (10-hour CLP, hyperdynamic sepsis; 20-hour CLP, hypodynamic sepsis), the thoracic aorta was isolated, cut into rings, and placed in organ chambers. Norepinephrine (2 x 10(-7) mol/L) was used to achieve near maximal tension. Dose responses for an endothelium-dependent vasodilator, acetylcholine, and an endothelium-independent vasodilator, nitroglycerine, were carried out. The changes 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 acetylcholine-induced vascular relaxation at both time points. In contrast, no significant reduction in nitroglycerine-induced vascular relaxation was seen in rats with sepsis irrespective of pentoxifylline treatment. Conclusions. Because pentoxifylline prevented endothelial cell dysfunction at 10 to 20 hours after CLP occurred, this agent appears to be a useful agent for maintaining vascular endothelial function during the hyperdynamic and hypodynamic stages of polymicrobial sepsis.