Pulmonary vasoconstriction induced by mitral valve obstruction in sheep

We hypothesizedthat left atrial hypertension results in pulmonary vasoconstriction,which is obscured by the expected passive decrease in pulmonaryvascular resistance. The objectives of this study were todemonstrate and quantify the vasoconstrictive changes that occur in thepulmonary circulation during experimental left atrial hypertension, todetermine the site of vasoconstriction, and to explore its mechanism.Sheep were instrumented for measurement of pulmonary arterial (Ppa),left atrial (Pla), and systemic arterial pressures (Psa) with a Foleyballoon catheter to variably obstruct the mitral valve. Distalpulmonary arterial wedge pressure (Ppaw) was determined by using a 5-FrSwan-Ganz catheter that was advanced until it wedged with the balloondeflated. Cardiac output (CO) was estimated by thermodilution;pulmonary vascular resistances (PVR) were calculated as mean (Ppa  Pla)/CO = total PVR, (Ppa  Ppaw)/CO = upstream PVR, and(Ppaw  Pla)/CO = downstream PVR. We studied 15 awake sheep atbaseline and during increases in Pla of 10 and 20 cmH₂O, with and without inhalationof ~36 parts per million of nitric oxide. Left atrial hypertensionresulted in elevation of Ppa. CO decreased only slightly at both levels of Pla elevation. Nitric oxide inhalation caused a significant decreasein PVR, which was greater as Pla increased. This vasodilator effect wasmost striking in downstream vessels. Experiments with phentolamine,atropine, and ibuprofen failed to reveal the mechanism of the reactivepulmonary vasoconstriction.