Burn induced cardiac dysfunction is reduced by pentoxifylline.

Abstract

Thermal injury impairs cardiac contractility and slows isovolumic relaxation; these myocardial defects persist despite adequate fluid resuscitation. Results of previous studies suggest that myocardial dysfunction occurring after thermal injury results from the byproducts of activated neutrophils and other inflammatory mediators. Pentoxifylline (PTX) (Hoechst-Roussel Pharmaceuticals) has been shown to modulate many of the deleterious effects mediated by the neutrophil. In the current study, isolated coronary perfused hearts of rats were used to determine if PTX improved cardiac dysfunction after burn injury. Parameters measured included left ventricular pressure (LVP), maximal rate of LVP rise (+dP/dt max) and fall (-dP/dt max). Full thickness scald burns averaging 40 percent of total body surface area (burn groups, n = 22) or zero percent for sham burns (n = 10) were produced using a template device. Ten rats with burns were not fluid resuscitated and served as untreated burns. An additional 12 burned rats received PTX intraperitoneally (50 milligrams per kilogram) 30 minutes, six hours and 20 hours after thermal insult. The results of ex vivo studies confirmed significant burn mediated cardiac dysfunction as indicated by a decrease in LVP (55 +/- 4 millimeters of mercury, p < 0.001), +/- dP/dt max (1,063 +/- 119 millimeters of mercury per second; 874 +/- 82 millimeters of mercury per second, p < 0.001) and a downward shift of LV function curves from those obtained for sham-burn hearts. However, hearts from burned rats treated with PTX had significantly higher LVP (76 +/- 3 millimeters of mercury, p < 0.001) and +/- dP/dt max (1,790 +/- 54 millimeters of mercury per second; 1,334 +/- 50 millimeters of mercury per second, p < 0.001) compared with hearts from untreated burned rats and generated LV function curves comparable with those calculated for sham-burned rats. The current data indicate that PTX attenuates postburn cardiac dysfunction and suggest a potential role for the adjunctive use of PTX after thermal injury.