Isoproterenol inhibits the increase in microvascular membrane permeability produced by bradykinin

Bradykinin (BRADY) is hypothesized to cause the "capillary leak" syndrome in patients with sepsis, trauma, and burns. Our purpose was to determine if isoproterenol (ISO) reversed a BRADY-produced accelerated loss of intravascular fluid and protein into the interstitium of skin. An increase in microvascular permeability in canine hind paw skin was sustained by a continuous femoral artery infusion of BRADY (0.2 micrograms/kg/min). After 2 hours of BRADY, skin lymph flow (LYM FLOW microliters/min) increased nine-fold and skin lymph-to-plasma total protein concentration ratio (RTP) was substantially increased. Mean blood flow in the femoral arteries was increased four-fold by the BRADY infusion. After 2 hours of BRADY-induced increased permeability, five of the ten dogs were started on intravenous ISO (2 micrograms/min continuously) which increased heart rate from 182 +/- 15 to 222 +/- 11 beats/min. ISO reversed the increase in RTP produced by the BRADY. After 8 hours of BRADY, there was less tissue albumin in the dogs given ISO (14.5 +/- 2.0 vs. 29.5 +/- 6.6 mg/gram dry wgt, p less than 0.05 unpaired t-test). ISO can reverse the sustained increase in skin microvascular permeability produced by BRADY.