PENTOXIFYLLINE IMPROVES THE TISSUE OXYGEN EXTRACTION CAPABILITIES DURING ENDOTOXIC-SHOCK

Pentoxifylline (PTX), a xanthine derivative used in the treatment of c irculatory insufficiency, has been found to have protective effects in different models of sepsis. We hypothesized that this drug might impr ove the cellular oxygen availability following endotoxin challenge by increasing oxygen delivery (DO2) and/or tissue oxygen extraction. The oxygen extraction capabilities were studied during a reduction in bloo d flow induced by cardiac tamponade. Fourteen anesthetized, ventilated , and paralyzed dogs, received intravenous 2 mg/kg of Escherichia coli endotoxin followed by a continuous infusion of 20 ml/kg.h of saline. 30 min later tamponade was induced by repeated bolus injections of war m saline into the pericardial space. Seven dogs were pretreated with P TX as an intravenous bolus of 20 mg/kg, followed by a continuous infus ion at 20 mg/kg.h, and the other seven dogs served as a control group. PTX largely attenuated the systemic and pulmonary vasoconstriction ob served in the control group and resulted in significant increases in c ardiac index, DO2 and oxygen consumption VO2). PTX also improved venti lation/perfusion matching in the lungs as indicated by a higher PaO2 a nd PVO2 and a lower venous admixture than in the untreated group durin g cardiac tamponade (both p < .05). In addition, the critical DO2 (DO2 crit) was lower and the critical oxygen extraction ratio was higher in the PTX treated than in the control group (9.1 +/- 1.8 vs. 11.6 +/- 2 .4 ml/kg.min, and 70.6 +/- 14.0 vs. 49.3 +/- 14.6%, both p < .05). The VO2/DO2 dependency slope was also steeper in the PTX-treated than in the control group (.80 +/- .28 vs. .43 +/- .19, p < .05). The peak tum or necrosis factor-cw (TNF) release was significantly attenuated by PT X (185 +/- 70 vs. 260 +/- 80 pg/ml, p < .05). Thus, the addition of PT X to fluid therapy can increase PaO2 DO2 and global oxygen extraction capabilities when cardiac index is progressively reduced in the endoto xic dog. These effects were attributed to the vasodilating and antiinf lammatory effects of PTX.