Abstract 225

Aprotinin (Apr) is a serine protease inhibitor shown to reduce post-operative bleeding following cardiopulmonary bypass. A retrospective study of children undergoing single ventricle repair of congenital heart lesions at our institution found that the pulmonary vascular pressure gradient was lower in patients treated with Apr. This led us to prospectively measure the effects of Apr on pulmonary vascular resistance (PVR) in isolated, blood-perfused piglet lungs. In the first protocol, the direct vasodilator effects of Apr on hypoxic PVR were determined in 9 control lungs (CON). CON lungs were ventilated with 21% then 6% O2. Pulmonary vascular dose-responses to APR (300-30,000 units/kg) were then determined and compared with responses to similar volumes of saline. In the second protocol, effects of Apr on cardiopulmonary bypass - induced changes in PVR were determined. Piglets were placed on cardiopulmonary bypass for 3 hours with 1 hour of aortic cross-clamp. Piglets received either Apr ≈ 350,000 units/kg iv and ≈ 350,000 units/kg in the bypass circuit (CPB+Apr, n=4) or no Apr (CPB, n=4). After bypass, lungs were isolated and perfused for 60 min under normoxic then hypoxic conditions. Data shown are mean ± se total pressure gradient (ΔPt = pulmonary artery pressure - left atrial pressure) in mmHg measured at constant flow (100 ml/kg.min) for the CON, CPB, and CPB+Apr lungs. Data were compared by ANOVA (p significant at 0.05). (Table) Apr did not alter ΔPt at any concentration in hypoxic CON lungs (data not shown). Hypoxic ΔPt decreased by 0.9 ± 1.7 mmHg after the highest dose of Apr and by 0.4 ± 0.7 mmHg after saline suggesting that Apr did not cause direct pulmonary vasodilation. Normoxic and hypoxic ΔPt were both lower in CON lungs (*) compared to lungs studied after cardiopulmonary bypass, but there was no difference in normoxic or hypoxic ΔPt between CPB and CPB+Apr groups. Thus, Apr did not appear to alter the increase in normoxic and hypoxic PVR seen in isolated perfused lungs during the first hour following cardiopulmonary bypass. However, effects of Apr such as decreased inflammatory response or diminished blood product requirements likely continue beyond the first hour and may have contributed to the apparently lower PVR seen 6-12 hours after cardiopulmonary bypass in our clinical study.

Table 1 No caption available
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This study was supported by Dr. Elaine C. Kohler Fund for Healing, the Children's Hospital of Wisconsin Foundation, and Bayer Corporation.