Interactions among inflammatory mediators on edema formation in the canine forelimb

Prostaglandin E1, 4 microgram/min, infused locally intra-arterially (ia) for 60 minutes into forelimbs perfused at constant pump controlled inflow produced decreases in perfusion pressure, increases in lymph total protein concentration (approximately equal to g/100 ml), and small increases in weight (23 g) owing to edema formation. Histamine, 16 microgram base/min, or bradykinin, 10 microgram base/min, infused locally ia for 60 minutes produced large increases in lymph flow, lymph total protein concentration, total protein transport, and weight (70 g and 130 g, respectively). However, the local ia infusion of prostaglandin E1, 4 microgram/min, together with histamine, 16 microgram base/min, or bradykinin, 10 microgram base/min, produced weight increases of 180 g and 236 g, respectively, and the rate of weight gain during the combination infusions greatly exceeded that produced by infusions of histamine or bradykinin alone. Moreover, the increases in lymph flow and in total protein transport far exceeded those produced by infusions of prostaglandin E1 and histamine or bradykinin alone or additively. The edema produced by the local ia infusion of prostaglandin E1, 4 microgram/min, together with bradykinin, 10 microgram base/min, was even more more marked in naturally perfused forelimbs. Similarly, the local ia infusion of histamine, 4 microgram base/min, or bradykinin, 0.8 microgram base/min, for 60 minutes into forelimbs perfused at constant inflow produced increases in lymph flow, lymph total protein concentration, total protein transport, and weight (38 g and 14 g, respectively). In contrast, histamine, 4 microgram base/min, and bradykinin, 0.8 microgram base/min, infused together locally ia for 60 minutes produced increases in weight of 118 g. The increase in lymph flow and total protein transport was considerably more marked during the combined infusions than during the infusions of histamine or bradykinin alone or additively.