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 Pao2 was maintained >100 mm Hg. The control group received saline vehicle only (n = 6), the GBS group received GBS infusion only (n = 9), the enzymes (ENZ) group received polyethylene glycol-superoxide dismutase (PEG-SOD) and polyethylene glycol-catalase (PEG-CAT) treatment only (n = 6), and the ENZ+GBS group received PEG-SOD and PEG-CAT then GBS (n = 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 ENZ+GBS groups, respectively. Sixty minutes after the termination of the GBS infusion, PVR returned to baseline in the GBS group but did not in the ENZ+GBS 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.

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Abbreviations

CAT:

catalase

CI:

cardiac index (mL/kg/min)

ENZ:

enzymes

GBS:

group B streptococcus (Streptococcus agalactiae)

MAP:

mean systemic arterial pressure(mm Hg)

MPAP:

mean pulmonary arterial pressure (mm Hg)

PEG:

monomethoxy-polyethylene glycol

PEG-CAT:

polyethylene glycol-catalase

PEG-SOD:

polyethylene glycol-superoxide dismutase

PVRI:

pulmonary vascular resistance index (mm Hg·mL-1·kg-1·min-1)

ROS:

reactive oxygen species

SOD:

superoxide dismutase

SVRI:

systemic vascular resistance index(mm Hg·mL-1·kg-1·min-1)

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Author information

Correspondence to Jerri Curtis.

Additional information

Supported by funds from The Chief, Navy Bureau of Medicine and Surgery, Washington, D.C., Clinical Investigation Program sponsored this study #B97-077; Uniformed Services University of the Health Sciences #R086CT; Walter Reed Army Medical Center, Department of Clinical Investigation WU #6415.The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of the Army, Department of Defense, nor the U.S. Government.The research reported herein was conducted according to the principles set forth in the Guide for Care and Use of Laboratory Animals, Institute of Laboratory Animal Resources, National Research Council, HHS, Pub. No. (NIH) 85-23, revised 1985.Presented in part at the American Academy of Pediatrics Fall Meeting, October 1998; San Francisco, CA, U.S.A.

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Carpenter, D., Larkin, H., Chang, A. et al. Superoxide Dismutase and Catalase Do Not Affect the Pulmonary Hypertensive Response to Group B Streptococcus in the Lamb. Pediatr Res 49, 181–188 (2001) doi:10.1203/00006450-200102000-00009

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