The Effects of cGMP on Fetal Sheep Pulmonary Blood Flow and Lung Liquid Production

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This study was designed to determine the effects of a membrane permeant phosphodiesterase-resistant analog of cGMP on lung liquid production and pulmonary blood flow at the time of birth. Experiments were performed on seven fetal sheep prepared for chronic measurements of lung liquid production (Jv), pulmonary blood flow (Qp) and pressure, as well as systemic pressure. Injection of either 8-bromo-cGMP or saline were made via a catheter inserted in the left pulmonary artery. Experiments consisted of 1 h of control, 1 h of infusion, and 2 h of recovery. Data were analyzed by ANOVA and Newman-Keuls test. After infusion of 8-bromo-cGMP, Jv was decreased by 70 and 44% from control in h 3 and 4, respectively. Qp was elevated by 100 mL/min in h 2 and 3 and continued to be elevated by 50 mL/min in h 4. Saline infused animals showed no significant changes in Qp and Jv. This study demonstrates that 8-bromo-cGMP decreases lung liquid production and increases pulmonary blood flow in near term fetal sheep. Although blood flow increased in h 2, lung liquid production did not decrease at this time, suggesting a time dissociation between changes in pulmonary blood flow and lung liquid production. Thus, it is possible that a common transduction pathway involving cGMP may be responsible for lung liquid reduction and elevation of pulmonary blood flow at birth. However, Qp and Jv may not be causally related.

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