Superoxide Dismutase and Catalase Do Not Affect the Pulmonary Hypertensive Response to Group B Streptococcus in the Lamb

Abstract

The purpose of this study was to determine whether treatment with conjugated antioxidant enzymes could attenuate or abolish pulmonary hypertension induced by group B streptococcus (GBS). Lambs, 3-7 d old, were anesthetized and ventilated. Intravascular catheters were placed in the left ventricle, descending aorta, right atrium, and pulmonary artery for continuous monitoring of intravascular pressures. Cardiac output was measured with radiolabeled microspheres. Measurements were obtained at baseline and 15 and 60 min into a 60-min GBS infusion, and 60 min after GBS was stopped. Blood gas values were held constant and Pao 2 was maintained Ͼ100 mm Hg. The control group received saline vehicle only (n ϭ 6), the GBS group received GBS infusion only (n ϭ 9), the enzymes (ENZ) group received polyethylene glycol-superoxide dismutase (PEG-SOD) and polyethylene glycol-catalase (PEG-CAT) treatment only (n ϭ 6), and the ENZϩGBS group received PEG-SOD and PEG-CAT then GBS (n ϭ 9). Plasma samples were obtained to confirm increased superoxide dismutase and catalase activities in the groups receiving enzymes. Compared with baseline, pulmonary vascular resistance increased by 119% and 101% at 15 min and 87% and 81% at 60 min in the GBS and ENZϩGBS groups, respectively. Sixty minutes after the termination of the GBS infusion, PVR returned to baseline in the GBS group but did not in the ENZϩGBS group. Enzyme infusions resulted in at least a ninefold increase in plasma enzyme activities. As opposed to previously published data from endotoxin models, PEG-CAT and PEG-SOD were ineffective in altering the GBS-induced pulmonary hypertensive response in this model. This suggests that acute administration of antioxidant enzymes may not be effective in ameliorating GBS-induced pulmonary hypertension. Morbidity and mortality remain unacceptably high in newborn infants infected with GBS despite aggressive use of antibiotics, both intrapartum and immediately following delivery (1). Many infants infected with this organism develop pulmonary hypertension (2), even in the face of blood cultures that have quickly become sterile. In many of these infants, the high morbidity and mortality is a result of the pulmonary hypertension. There are no unique or specific

Role of Superoxide Anion on Basal and Stimulated Nitric Oxide Activity in Neonatal Piglet Pulmonary Vessels

“…In a lamb model of PPHN, Steinhorn et al (9) demonstrated that a single intratracheal dose of SOD reduced pulmonary vascular resistance and improved the pulmonary vasodilatory action of inhaled NO ⅐ . In contrast, Carpenter et al (10) did not observe changes in pulmonary vascular resistance after i.v. infusion of SOD in 3-to 7-d-old lambs.…”

Inhaled nitric oxide induced NOS inhibition and rebound pulmonary hypertension: a role for superoxide and peroxynitrite in the intact lamb

“…After a 30-min recovery, either PEG diluted in 5 ml of normal saline (n ϭ 6, vehicle control) or PEG-SOD (n ϭ 7) was delivered through the left pulmonary artery catheter. The dose of PEG-SOD (1,000 -2000 U/kg every 6 h) was based upon previous studies that demonstrate a sustained significant increase in plasma SOD activity (8,32). Either PEG or PEG-SOD was given every 6 h to complete a total of four doses.…”

Group B streptococcal phospholipid causes pulmonary hypertension

“…Biochemical fractionation procedures were linked in series to develop an initial purification protocol, which was modified to give the final protocol described here. At each step, fractions were assayed for pulmonary arterial hypertensive activity in 3-to 12-day-old lambs of Ϸ5 kg, as described (7). We previously demonstrated that pulmonary arterial pressure measurements were a valid surrogate for measurement of pulmonary vascular resistance in this animal model (7).…”

“…At each step, fractions were assayed for pulmonary arterial hypertensive activity in 3-to 12-day-old lambs of Ϸ5 kg, as described (7). We previously demonstrated that pulmonary arterial pressure measurements were a valid surrogate for measurement of pulmonary vascular resistance in this animal model (7). Fractions were infused peripherally into the femoral vein, not directly into the pulmonary artery.…”