Platelet-activating factor is an extremely potent
lipid-inflammatory mediator implicated in the pathophysiologic mechanism of
reperfusion injury in a variety of organs. The purpose of this study, employing a porcine latissimus dorsi flap model, was to (1) examine the expression of
platelet-activating factor and (2) evaluate the possible benefit and mechanism of action of
platelet-activating factor antagonism in
musculocutaneous flap reperfusion injury. Experiment 1: In 6 pigs, bilateral flaps underwent 8 hours of arterial
ischemia followed by 12 hours of reperfusion. Biopsies were collected sequentially and analyzed immunohistochemically for
platelet-activating factor expression. Different processing techniques, however, were unable to detect specific tissue expression of
platelet-activating factor. Experiment 2: In 11 pigs, bilateral flaps underwent 8 hours of arterial
ischemia followed by 20 hours of reperfusion. A lipophilic
platelet-activating factor receptor antagonist (L-659,989) was administered as a single dose to treated flaps by a local intraarterial route prior to reperfusion. This treatment augmented the survival of both muscle (48.3 versus 19.7 percent) and skin (49.8 versus 42.0 percent) components of the flaps in a statistically significant fashion (p = 0.001). Experiment 3: In 3 pigs, a radiolabeled structural analogue of
L-659,989 (14C-L-680,573) was administered to flaps in a fashion similar to experiment 2. After 8 hours of
ischemia, sequential full-thickness flap biopsies were collected over the initial 6 hours of reperfusion. The radio-labeled
platelet-activating factor receptor antagonist was found to be highly concentrated within treated flaps, with gradual decay over the initial 6 hours of reperfusion. Experiment 4: Thirty minutes prior to completion of 8 hours of arterial
ischemia, autologous neutrophils labeled with
indium-111 were reintroduced into the systemic-circulation of 5 pigs. Prior to reperfusion, treated flaps received
L-659,989 as in experiment 2. Over the initial 4 hours of reperfusion, the flaps were imaged in situ by a
gamma camera at 3-minute intervals. The
platelet-activating factor receptor antagonist was found to significantly attenuate the accumulation of radioactivity within treated flaps.
CONCLUSION: