Isoproterenol Inhibits the Increase in Microvascular Membrane Permeability Produced by Bradykinin

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Abstract
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 μg/kg/min). After 2 hours of BRADY, skin lymph flow (LYM FLOW jil/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 μg/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 < 0.05 unpaired t-test). ISO can reverse the sustained increase in skin microvascular permeability produced by BRADY.

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