REFLEX CARDIOVASCULAR EFFECTS OF CONTINUOUS PROSTACYCLIN ADMINISTRATION INTO AN ISOLATED IN-SITU LUNG IN THE DOG

Bolus administration of prostacyclin (PGI2), an inflammatory product produced by the arachidonic acid cyclooxygenase pathway, into the pulmonary circulation is known to stimulate pulmonary C-fibers and to produce transient reflex cardiovascular depression. We used an isolated perfused in situ left lung preparation to examine the reflex cardiovascular effects of continuous administration of PGI2 into the isolated pulmonary circulation of dogs. PGI2 was infused for 30 min (5 mug . kg-1 . min-1) into the innervated isolated left pulmonary circulation in six dogs and into the denervated isolated circulation in seven dogs. Mean arterial pressure and cardiac output were significantly decreased from baseline values during the final 20 min of PGI2 infusion. There were no significant changes in maximum rate of change of left ventricular pressure during systole and in heart rate. All variables returned to baseline levels within 15 min of discontinuation of PGI2 infusion. PGI2 infusion produced no significant measured hemodynamic changes in the denervated group. Control experiments demonstrated that the observed response was not affected by duration of the preparation, lung denervation, or infusion vehicle. These findings suggest that continuous infusion of PGI2 into the isolated pulmonary circulation produces sustained cardiovascular depression via a vagal reflex mechanism that is probably mediated by pulmonary C-fibers.