Fetal ductus arteriosus ligation. Pulmonary vascular smooth muscle biochemical and mechanical changes

To evaluate the smooth muscle mechanical and biochemical changes associated with persistent pulmonary hypertension syndrome of the newborn, we studied 31 fetal sheep in which the ductus arteriosus was ligated at 125 days of gestation. Sixty-one noninstrumented and six sham-operated fetuses served as controls. All animals were delivered by cesarean section at 137-140 days of gestation, and the experimental group had the ductus arteriosus ligated for 12 +/- 3 days. The ligated group demonstrated a higher mean (+/- SEM) pulmonary artery pressure (72.3 +/- 3.8 versus 54.1 +/- 2 mm Hg, p < 0.01) and right ventricular mean free wall weight (12.5 +/- 0.7 versus 6.8 +/- 0.3 g, p < 0.01) as compared with the sham-operated group. Significant changes in the pulmonary vascular smooth muscle of the ligated group were observed. The myosin content of vessels from the second through fifth generation demonstrated a significant increase in actin and myosin content (p < 0.01), but given their disproportional changes, the noninstrumented group demonstrated a lower actin/myosin ratio than the experimental group (p < 0.01). Changes in the myosin heavy chain isoform stoichiometry, characterized by an increase in both the mean high/low myosin heavy chain isoform ratio (1.8 +/- 0.3 versus 1.0 +/- 0.1, p < 0.05) and the nonmuscle isoform as a percentage of the total myosin heavy chain (12.4 +/- 0.7% versus 2.7 +/- 0.9%, p < 0.01), were also observed in the ligated as compared with the noninstrumented animals. In addition, the muscle Mg-ATPase activity was significantly (p < 0.05) reduced in the experimental group.(ABSTRACT TRUNCATED AT 250 WORDS)