U-74,500A inhibition of burn-induced cardiac dysfunction

Our previous studies suggest that oxygen-derived free radicals, particularly the hydroxyl radical, play a major role in cardiac dysfunction which is characteristic of burn injury. In this present study, we examined the effects of U-74,500A (U7), a 21-aminosteroid, nonglucocorticoid on ventricular contraction and relaxation recovery from burn injury. Parameters measured included left ventricular pressure (LVP) and the maximal rate of LVP rise (+dP/dt max) and fall (-dP/dt max). Full-thickness burns comprising 45% of the total body surface area (burn groups, N = 69) or 0% for controls (Group 1, N = 8) were produced in guinea pigs. In Group 2, 20 burned guinea pigs were not fluid resuscitated (vehicle only) and served as untreated burns; in Group 3, 11 burned guinea pigs received U7 alone (2.5 mg/kg in 0.01 N HCl iv). Eleven burned guinea pigs were resuscitated with vehicle plus 4 ml lactated Ringer's (LR)/kg/% burn for 24 hr (Group 4); in Group 5, 14 guinea pigs were treated with U7 as described for Group 3 followed immediately by LR for 24 hr as described for Group 4. In Group 6, U7 was administered immediately postburn as described for Group 3; and LR resuscitation, begun 1 hr postburn, was continued for 24 hr (N = 14). Compared to controls, untreated burn injury significantly impaired cardiac function as indicated by a fall in LVP (74 +/- 3 vs 60 +/- 4 mm Hg, P less than 0.05) and +/- dP/dt max (1126 +/- 51 vs 1011 +/- 39 and 1159 +/- 53 vs 993 +/- 59 mm Hg/sec, P less than 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)