Inhaled carbon monoxide does not cause pulmonary vasodilation in the late-gestation fetal lamb

Grover, Theresa R., Robyn L. Rairigh, Jeanne P. Zenge, Steven H. Abman, and John P. Kinsella. Inhaled carbon monoxide does not cause pulmonary vasodilation in the late-gestation fetal lamb. Am J Physiol Lung Cell Mol Physiol 278: L779-L784, 2000.--As observed with nitric oxide (NO), carbon monoxide (CO) binds and may activate soluble guanylate cyclase and increase cGMP levels in smooth muscle cells in vitro. Because inhaled NO ([I.sub.NO]) causes potent and sustained pulmonary vasodilation, we hypothesized that inhaled CO ([I.sub.CO]) may have similar effects on the perinatal lung. To determine whether [I.sub.CO] can lower pulmonary vascular resistance (PVR) during the perinatal period, we studied the effects of [I.sub.CO] on late-gestation fetal lambs. Catheters were placed in the main pulmonary artery, left pulmonary artery (LPA), aorta, and left atrium to measure pressure. An ultrasonic flow transducer was placed on the LPA to measure blood flow to the left lung. After baseline measurements, fetal lambs were mechanically ventilated with a hypoxic gas mixture (inspired [O.sub.2] fraction [is less than] 0.10) to maintain a constant fetal arterial [PO.sub.2]. After 60 min (baseline), the lambs were treated with [I.sub.CO] [5-2,500 parts/million (ppm)]. Comparisons were made with [I.sub.NO] (5 and 20 ppm) and combined [I.sub.NO] (5 ppm) and [I.sub.CO] (100 and 2,500 ppm). We found that [I.sub.CO] did not alter left lung blood flow or PVR at any of the study doses. In contrast, low-dose [I.sub.NO] decreased PVR by 47% (P [is less than] 0.005). The combination of [I.sub.NO] and [I.sub.CO] did not enhance the vasodilator response to [I.sub.NO]. To determine whether endogenous CO contributes to vascular tone in the fetal lung, zinc protoporphyrin IX, an inhibitor of heme oxygenase, was infused into the LPA in three lambs. Zinc protoporphyrin IX had no effect on baseline PVR, aortic pressure, or the pressure gradient across the ductus arteriosus. We conclude that [I.sub.CO] does not cause vasodilation in the near-term ovine transitional circulation, and endogenous CO does not contribute significantly to baseline pulmonary vascular tone or ductus arteriosus tone in the late-gestation ovine fetus. nitric oxide; heme oxygenase; persistent pulmonary hypertension of the newborn; pulmonary hypertension