Pentoxifylline prevents the transition from the hyperdynamic to hypodynamic response during sepsis

Yang, Shaolong, Mian Zhou, Douglas J. Koo, Irshad H. Chaudry, and Ping Wang. Pentoxifylline prevents,; the transition from the hyperdynamic to hypodynamic response during sepsis. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H1036-H1044, 1999.--The cardiovascular response to sepsis includes an early, hyperdynamic phase followed by a late, hypodynamic phase. Although administration of pentoxifylline (PTX) produces beneficial effects in sepsis, it remains unknown whether this agent prevents the transition from the hyperdynamic to the hypodynamic response during the progression of sepsis. To study this, male adult rats were subjected to polymicrobial sepsis by ceca] ligation and puncture (CLP). At 1 h after CLP, PTX (50 mg/kg body wt) or vehicle was infused intravenously over 30 min. At 20 h after CLP (i.e., the late stage of sepsis), cardiac output and organ blood flow were measured by radioactive microspheres. Systemic and regional (i.e., hepatic, intestinal, and renal) oxygen delivery (D[O.sub.2]) and oxygen consumption (V[O.sub.2]) were determined. Moreover, plasma levels of lactate and alanine aminotransferase (ALT) were measured, and histological examinations were performed. In additional animals, the necrotic cecum was excised at 20 h after CLP, and mortality was monitored for 10 days thereafter. The results indicate that cardiac output, organ blood flow, and systemic and regional D[O.sub.2] decreased by 36-65% (P [is less than] 0.05) at 20 h after CLP. Administration of PTX early after the onset of sepsis, however, prevented reduction in measured hemodynamic parameters and increased systemic and regional D[O.sub.2] and V[O.sub.2] by 50-264% (P [is less than] 0.05). The elevated levels of lactate (by 173%, P [is less than] 0.05) and ALT (by 718%, P [is less than] 0.05), as well as the morphological alterations in the liver, small intestine, and kidneys during sepsis were attenuated by PTX treatment. In addition, PTX treatment decreased the mortality rate from 50 to 0% (P [is less than] 0.05) after CLP and cecal excision. Because PTX prevents the occurrence of hypodynamic sepsis, this agent appears to be a useful adjunct for maintaining hemodynamic stability and preventing lethality from sepsis. cecal ligation and puncture; regional blood flow; cardiovascular responses; oxygen delivery; oxygen consumption; lactate