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Urinary Trypsin Inhibitor Improves Peripheral Microcirculation and Bronchospasm Associated with Systemic Anaphylaxis in Rabbits In Vivo

Using intravital microscopy of the rabbit ear for quantitative studies of microvascular dynamics, we examined the impact of urinary trypsin inhibitor (UTI), a proteolytic enzyme inhibitor, on microvascular changes during immune complex-mediated anaphylaxis. A total of 50 rabbits, previously sensitized with horse serum, were anesthetized and mechanically ventilated with pentobarbital and isoflurane for the intravital microscopy. Rabbits were then challenged with intravenous injection of horse serum to induce systemic anaphylaxis. One minute after the challenge, each rabbit was randomly assigned to receive saline (group C), 50,000 units·kg−1 of UTI (group U1), or 150,000 units·kg−1 (group U2). There were no statistical differences between hemodynamic variables, including heart rate (HR), mean arterial pressure (MAP), and central venous pressure (CVP), among the survivors in each treatment group. Peak inspiratory pressure rose in all three groups but at a much higher rate in group C (P < 0.05). In contrast with the moderate effects of UTI on the above parameters, microscopic evaluation revealed a substantial difference among treatment groups: upon the initiation of anaphylaxis, the arteriole started to reduce in diameter, but UTI prevented vasoconstriction in the arteriole in a dose-dependent manner. Similar results were observed with blood flow velocity. Because flow rate was calculated as the product of blood flow velocity and vascular cross-sectional area proportional to the square of the vessel diameter, these results indicate that UTI preserves microvascular flow rate during anaphylaxis. Rabbit ear microcirculation is highly preserved in the UTI-treated groups during systemic anaphylactic shock.