Vaughan W G, Horton J W, White D J
Department of Surgery, University of Texas Southwestern Medical Center, Dallas 75235-9031.
Surg Gynecol Obstet. 1993 May;176(5):459-68.
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.
热损伤会损害心脏收缩力并减缓等容舒张；尽管进行了充分的液体复苏，这些心肌缺陷仍然存在。先前研究的结果表明，热损伤后发生的心肌功能障碍是由活化的中性粒细胞和其他炎症介质的副产物引起的。己酮可可碱（PTX）（赫斯特-罗素制药公司）已被证明可以调节由中性粒细胞介导的许多有害作用。在当前的研究中，使用大鼠离体冠状动脉灌注心脏来确定PTX是否能改善烧伤后的心脏功能障碍。测量的参数包括左心室压力（LVP）、LVP上升的最大速率（+dP/dt max）和下降速率（-dP/dt max）。使用模板装置造成平均占全身表面积40%的全层烫伤（烧伤组，n = 22）或假烫伤为0%（n = 10）。10只烧伤大鼠未进行液体复苏，作为未治疗的烧伤组。另外12只烧伤大鼠在热损伤后30分钟、6小时和20小时腹腔注射PTX（50毫克/千克）。离体研究结果证实了烧伤介导的显著心脏功能障碍，表现为LVP降低（55±4毫米汞柱，p < 0.001）、+/- dP/dt max降低（1,063±119毫米汞柱/秒；874±82毫米汞柱/秒，p < 0.001）以及左心室功能曲线相对于假烧伤心脏的曲线向下移位。然而，与未治疗的烧伤大鼠心脏相比，接受PTX治疗的烧伤大鼠心脏的LVP（76±3毫米汞柱，p < 0.001）和+/- dP/dt max（1,790±54毫米汞柱/秒；1,334±50毫米汞柱/秒，p < 0.001）显著更高，并且产生的左心室功能曲线与假烧伤大鼠计算的曲线相当。当前数据表明PTX可减轻烧伤后心脏功能障碍，并提示PTX在热损伤后辅助使用的潜在作用。
