Histologic and biochemical study of the brain, heart, kidney, and liver inasphyxia caused by occlusion of the umbilical cord in near-term fetal lambs

OBJECTIVE: We sought to determine the relationship between the degree of hi stologic changes in the brain, heart, kidney, and liver in fetal lambs afte r severe asphyxia and to analyze the role of oxidative stress in the pathog enesis of fetal multiple organ failure. STUDY DESIGN: Eight chronically instrumented near-term fetal lambs were asp hyxiated by partial umbilical cord occlusion for approximately 60 minutes u ntil the fetal arterial pH reached <6.9 and the base excess reached <-20 mE q/L. An additional 6 fetuses were used as sham-asphyxiated controls. Fetal heart rates, blood pressure, fetal breathing movements, and arterial blood gases and acid-base states were serially monitored. The brain, heart, kidne y, and liver were collected 72 hours after asphyxia, processed, and histolo gically examined after hematoxylin and eosin staining. Fetal brain histolog ic features were classified into 5 grades, with 5 being the most severe dam age. The other organs were examined histologically by pathologists who were blinded to the treatment. Each organ was assayed for tissue concentrations of thiobarbituric acid-reactive substances, superoxide dismutase, glutathi one, lactate, and glucose. RESULTS: Myocardial changes of necrosis, phagocytosis, and contraction band s occurred in only 2 of the most severely (grade 5) brain-damaged fetuses. The same 2 cases showed fatty changes and congestion in the liver. In the k idney all asphyxiated cases showed tubular necrosis, but glomeruli were gen erally spared. Of the measures of oxidative stress, only liver tissue level s of thiobarbituric acid-reactive substances and superoxide dismutase were significantly higher in the asphyxiated group than in the control group, bu t there was no correlation with the degree of damage. Lactate level was hig her only in the heart in the asphyxiated fetuses. CONCLUSION: Renal tubular damage was seen with all degrees of asphyxia, des pite variable brain damage. Histologic changes in the myocardium and liver were seen only with the most severe brain damage. Oxidative stress appears to play a role in the pathogenesis of liver damage.