Acute and chronic pulmonary vasoconstriction after left lung autotransplantation in conscious dogs

Abstract

We investigated the acute and chronic effects of left lung autotransplantation (LLA) on the left pulmonary vascular pressure-flow (LP/Q) relationship in conscious dogs. Continuous LP/Q plots were generated in chronically instrumented conscious dogs 2 days, 2 wk, 1 mo, and 2 mo after LLA. Identically instrumented normal conscious dogs were studied at equal time points post-surgery. LLA had little or no effect on baseline systemic hemodynamics or blood gases. In contrast, compared with normal conscious dogs, striking active flow-independent pulmonary vasoconstriction was observed 2 days post-LLA. The slope of the LP/Q relationship was increased from a normal value of 0.275 +/- 0.021 to 0.699 +/- 0.137 mmHg.ml-1.min-1.kg-1 2 days post-LLA. Pulmonary vasoconstriction of similar magnitude was also observed on a chronic basis at 2 wk, 1 mo, and even 2 mo post-LLA. Pulmonary vasoconstriction post-LLA was not due to fixed resistance at the left pulmonary arterial or venous anastomotic sites. Finally, systemic arterial blood gases were unchanged when total pulmonary blood flow was directed to exclusively perfuse the transplanted left lung. Thus, LLA results in both acute and chronic pulmonary vasoconstriction in conscious dogs. LLA should serve as a useful stable experimental model to assess the specific effects of surgical transplantation on pulmonary vascular regulation.

Pulmonary Vascular Effects of Propofol at Baseline, during Elevated Vasomotor Tone, and in Response to Sympathetic α- and β-Adrenoreceptor Activation

“…The surgical technique for LLA has been described in detail. 2 Eight dogs underwent LLA via sequential divisions and anastomoses of the left pulmonary veins, left mainstem bronchus, and left main pulmonary artery. A wide circumhilar pericardial incision mobilized the left lung.…”

“…We also assessed the effects of propofol in an experimental model of left lung autotransplantation (LLA), which we have previously demonstrated results in a long-term increase in pulmonary vascular resistance. 2 Our second goal was to test the hypothesis that propofol anesthesia alters the pulmonary vascular response to sympathetic ␣and ␤-adrenoreceptor activation. Specifically, we hypothesized that propofol would potentiate the pulmonary vasoconstrictor response to ␣-adrenoreceptor activation, whereas it would attenuate the pulmonary vasodilator response to ␤-adrenoreceptor activation.…”

Endothelial defect mediates attenuated vasorelaxant response to isoproterenol after lung transplantation

“…The surgical procedure for LLA has been described previously in detail (18). Briefly, conditioned (microfilaria-free) mongrel dogs (20-30 kg) were premedicated with morphine sulfate (10 mg im) and anesthetized with pentobarbital sodium (20 mg/kg iv) and fentanyl citrate (15 µg/kg iv).…”

“…The role of the pulmonary circulation in this process remains to be elucidated. We have utilized an experimental model of left lung autotransplantation (LLA) to investigate the specific effects of surgical transplantation on mechanisms of pulmonary vascular regulation (18). We have observed in chronically instrumented dogs that LLA results in a marked and sustained increase in pulmonary vascular resistance (18) and is associated with abnormalities in neural (21,23), humoral (1), and local (22) mechanisms of pulmonary vascular regulation.…”

“…We have utilized an experimental model of left lung autotransplantation (LLA) to investigate the specific effects of surgical transplantation on mechanisms of pulmonary vascular regulation (18). We have observed in chronically instrumented dogs that LLA results in a marked and sustained increase in pulmonary vascular resistance (18) and is associated with abnormalities in neural (21,23), humoral (1), and local (22) mechanisms of pulmonary vascular regulation. Moreover, we have performed in vitro studies to investigate the cellular mechanisms involved in the enhanced pulmonary vasoconstrictor response to sympathetic ␣-adrenoreceptor activation and the attenuated pulmonary vasorelaxant response to endothelial activators (e.g., acetylcholine) post-LLA (4).…”