Role of xanthine oxidase and leukocytes in postburn cardiac dysfunction.

BACKGROUND

Recent studies suggest that the cardiac dysfunction that occurs after a major burn is mediated by oxygen-derived free radicals. This hypothesis is based on the fact that superoxide dismutase and catalase, given with fluid resuscitation from burn injury, provided significant cardioprotection.

STUDY DESIGN

In this present study, rats received either enteral allopurinol or tungsten-enriched diets to determine if xanthine oxidase mediates postburn defects in cardiac contraction and relaxation. Polymorphonuclear neutrophil (PMN) were depleted to examine the contribution of PMN-derived factors to postburn cardiac dysfunction. Rats were divided into eight groups: groups 1 to 6 received regular chow, and groups 7 and 8 received tungsten-enriched diets for 14 days before study. Groups 2, 4, 6, and 8 were given a third-degree burn comprising 43 +/- 2 percent total body surface area and were resuscitated with Ringer's lactated solution for 24 hours (4 mL/kg/percent burn). In group 2, burned rats received fluid resuscitation alone; in group 4 (n = 10), rats were given allopurinol, 10 mg/kg daily by gastric lavage for five days preburn, group 6 (n = 11) received vinblastine (0.75 mg/kg) four days preburn, and group 8 (n = 11) received tungsten-enriched diets for 14 days before burn; sham burn controls included vehicle-treated (n = 10), allopurinol-treated (n = 8), PMN-depleted (n = 8), and tungsten-fed rats (n = 11) (groups 1, 3, 5, and 7, respectively).

RESULTS

Burn injury produced mild hypotension, hypothermia, bradycardia, and a significant decrease in left ventricular performance, despite aggressive fluid resuscitation (group 2). Allopurinol, tungsten-enriched diets, and PMN depletion partially attenuated burn-induced cardiac contractile dysfunction and improved left ventricular responsiveness to increases in preload, coronary flow rate and exogenous calcium.

CONCLUSIONS

Our data suggest that xanthine oxidase-derived oxygen metabolites and PMN-derived mediators contribute to postburn cardiac contractile deficits.