Abnormal responses to pulmonary vasodilators in conscious dogs after left lung autotransplantation.

Abstract

We investigated the extent to which left lung autotransplantation (LLA) alters endothelium-dependent (bradykinin and acetylcholine) and endothelium-independent (sodium nitroprusside) vasodilation in the pulmonary circulation of conscious dogs. Continuous left pulmonary vascular pressure-flow (LPQ) plots were generated in conscious dogs 3-4 wk post-LLA and in sham-operated controls. LLA resulted in a marked upward shift in the baseline LPQ relationship compared with the control group (P < 0.01), i.e., LLA caused a chronic increase in pulmonary vascular resistance. The thromboxane analogue, U-46619, was used to acutely preconstrict the pulmonary circulation in control dogs, which shifted the control LPQ relationship to the same position measured post-LLA. Under these circumstances, bradykinin, acetylcholine, and nitroprusside caused pulmonary vasodilation in the control group, whereas these responses were either attenuated or reversed to vasoconstriction post-LLA. After acute preconstriction with U-46619 post-LLA, the pulmonary vasodilator responses to bradykinin and acetylcholine were again attenuated, but the response to nitroprusside was unaltered compared with control. These results indicate that a significant component of the chronic increase in pulmonary vascular resistance post-LLA is passively mediated and does not reflect an active increase in baseline vasomotor tone. Moreover, LLA results in an impairment in endothelium-dependent, but not endothelium-independent, pulmonary vasodilation in conscious dogs.