ALTERED PULMONARY MICROVASCULAR REACTIVITY AFTER TOTAL CARDIOPULMONARY BYPASS

Pulmonary vascular resistance is frequently elevated after cardiac ope rations in which cardiopulmonary bypass is used. In our study of the p ossible contribution of altered pulmonary microvascular reactivity to this condition, sheep were heparinized, cannulated via the aorta and r ight atrium, and placed on total cardiopulmonary bypass. After 90 minu tes of total cardiopulmonary bypass and pulmonary arterial occlusion, the sheep were removed from cardiopulmonary bypass, and their lungs we re perfused normally for 60 minutes. Noninstrumented animals were used as controls. To evaluate the effect of 90 minutes of extracorporeal c irculation without reduced pulmonary perfusion, we studied additional sheep after they underwent right heart bypass with a pump-oxygenator. Pulmonary microarterial vessels (130 to 230 mum in diameter) from each group were examined in vitro in a pressurized (20 mm Hg), no-flow sta te with video microscopic imaging and electronic dimension analysis. A fter preconstriction of vessels with the thromboxane A2 analog U46619 by 30 % to 40 % of the baseline diameter, vasoactive drugs were applie d extraluminally. Serotonin caused control microvessels to dilate. In the presence of the nitric oxide synthetase inhibitor N(G)-methyl-L-ar ginine, this was converted to a significant contractile response. Acet ylcholine alone had minimal effect on control vessels. However, in the presence of the cyclooxygenase inhibitor indomethacin, acetylcholine caused a significant relaxation response. After total cardiopulmonary bypass and pulmonary reperfusion, pulmonary microvessels contracted si gnificantly when exposed to acetylcholine and serotonin, compared with respective control responses. Both these contractile responses were i nhibited in the presence of indomethacin. Endothelium-independent resp onses to sodium nitroprusside and U46619 and dilation responses to ade nosine were not altered after cardiopulmonary bypass. Extracorporeal c irculation with continued pulmonary arterial perfusion (right heart by pass group) had no effect on microvascular responses. In conclusion, t otal cardiopulmonary bypass with associated reduced pulmonary perfusio n causes significant alterations of endothelium-dependent pulmonary mi crovascular responses because of the increased release of a constricto r prostanoid substance and possibly because of reduced release of endo thelium-derived relaxing factor.