Pulmonary vasomotor dysfunction is produced with chronically high pulmonary blood flow.

This study examined the hypothesis that chronic high pulmonary blood flow produces dysfunction of the mechanisms of pulmonary vasorelaxation. A 3:1 left-to-right shunt was created in dogs by bilateral femoral artery-femoral vein shunts with use of 6 mm polytetrafluoroethylene grafts. Isolated pulmonary artery rings were studied at the following times: 3 days (n = 2), 2 weeks (n = 4), and 5 months (n = 6). Control animals had no shunt. The following mechanisms of pulmonary vasorelaxation were studied in isolated pulmonary artery rings (4 rings from each dog): (1) endothelium-dependent cyclic guanosine monophosphate-mediated relaxation (response to acetylcholine), (2) endothelium-independent cyclic guanosine monophosphate-mediated relaxation (response to sodium nitroprusside), and (3) beta-adrenergic cyclic adenosine monophosphate-mediated relaxation (response to isoproterenol). Statistical analysis was done by analysis of variance. This model of high pulmonary flow did not produce an increase in pulmonary arterial pressure or transpulmonary gradient. However, chronic high pulmonary flow produced progressive dysfunction of all three of these mechanisms of pulmonary vasorelaxation. By 5 months of high pulmonary flow, acetylcholine produced only 36% +/- 6% relaxation versus 95% +/- 5% in control animals (p < 0.05). Likewise, sodium nitroprusside produced only 69% +/- 6% relaxation versus 100% in control animals (p < 0.05). Finally, isoproterenol produced only 55% +/- 5% relaxation versus 94% +/- 6% in control animals (p < 0.05). We conclude that dysfunction of the mechanisms of pulmonary vasorelaxation may contribute to exaggerated perioperative pulmonary vasoconstriction in the setting of chronic high pulmonary blood flow.