Abstract 1786 Poster Session I, Saturday, 5/1 (poster 101)

Heme oxygenase (HO) catalyzes the degradation of heme into biliverdin and carbon monoxide (CO), which has been shown to contribute to vasoregulation in some experimental settings. In vitro studies have demonstrated that CO can stimulate soluble guanylate cyclase (sGC) and increase cyclic GMP (cGMP) levels in smooth muscle cells, as observed with nitric oxide (NO)-mediated vasodilation. Since inhaled NO (iNO) causes potent and sustained pulmonary vasodilation, we hypothesized that inhaled CO (iCO) may have similar effects on the perinatal lung. To determine whether iCO can lower pulmonary vascular resistance during the perinatal period, we studied the effects of iCO on five late gestation fetal lambs. Surgery was performed at 138-142 days (term=147d). Catheters were placed in the main pulmonary artery (PAP), aorta (AoP), and left atrium to measure pressure. An ultrasonic flow transducer was placed on the left pulmonary artery to measure blood flow to the left lung (Qp). Pulmonary vascular resistance (PVR) in the left lung was calculated as PAP-LAP/Qp. After baseline measurements, an endotracheal tube was placed and animals were mechanically ventilated using an hypoxic gas mixture (FiO2<0.10) to maintain fetal PaO2 constant. At the end of the 60 minute ventilation period (baseline), lambs received iCO at doses ranging from 5 to 2500 ppm at ten minute intervals. Comparisons were made with iNO (5 and 20 ppm), and combined iNO (5 ppm) and iCO (100 ppm). (Table)

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We found that iCO did not decrease PVR at any of the study doses. In contrast, low-dose iNO decreased PVR and the combination of iNO+iCO did not enhance the vasodilator response. We conclude: 1) that exogenous CO does not cause pulmonary vasodilation in the near-term ovine transitional circulation, and 2) iCO does not augment the pulmonary vasodilator response to low-dose iNO.