Cardiac dysfunction occurs after thermal injury but the pathogenesis is unclear; leukocytes have been implicated in the pathogenesis of multiorgan dysfunction after burn injury. White blood cell activation and entry into tissue involve the use of a number of adhesion molecules, including intercellular adhesion molecule (ICAM)-1, CD54. We asked the question: will administration of the monoclonal antibody (R6.5) directed against ICAM-1 alter the cardiac dysfunction which we have previously shown to occur after thermal injury? Previously instrumented New Zealand White rabbits were anesthetized and given a full-thickness burn over 30% of the total body surface area by applying brass probes heated to 100°C to the animals' backs for 15 sec. Animals were monitored for 24 hr and given lactated Ringer's (LR) solution (4 cc/kg/% burn, Parkland formula) with additional LR given to maintain cardiac output and urine output. Three experimental groups were studied: sham burn controls had catheters placed and were monitored for 24 hr (N = 8); burn rabbits were divided into vehicle treated (saline, 1 ml/kg, N = 6) or R6.5 treated (2 mg/kg, N = 6). Vehicle or antibody was administered 30 min postburn and every 8 hr until 24 hr postburn; at this time, rabbits were sacrificed and hearts were harvested for in vitro assessment of contractile performance (Langendorff). Compared to values measured in sham burn controls, burn injury caused cardiac contractile depression as indicated by a fall in left ventricular pressure (LVP) (77 ± 2 vs 56 ± 3 mm Hg, P = 0.01), +dP/dt (1223 ± 64 vs 842 ± 64 mm Hg/sec, P = 0.001), and -dP/dt (973 ± 63 vs 666 ± 42 mm Hg/sec, P = 0.01). Administration of R6.5 significantly improved cardiac contractile function compared to the vehicle-treated burns as indicated by higher LVP (67 ± 2 mm Hg, P > 0.05), +dP/dt (1017 ± 33 mm Hg/sec, P > 0.05), and -dP/dt (858 ± 40 mm Hg/sec, P > 0.05) than values measured in vehicle-treated burns. These results suggest that ICAM-1-mediated WBC activation and/or tissue entry are involved in the pathogenesis of cardiac dysfunction following thermal injury.
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