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

OBJECTIVE: We sought to determine the relationship between the degree of histologic changes in the brain, heart, kidney, and liver in fetal lambs after severe asphyxia and to analyze the role of oxidative stress in the pathogenesis of fetal multiple organ failure. STUDY DESIGN: Eight chronically instrumented near-term fetal lambs were asphyxiated by partial umbilical cord occlusion for approximately 60 minutes until the fetal arterial pH reached <6.9 and the base excess reached <-20 mEq/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, kidney, and liver were collected 72 hours after asphyxia, processed, and histologically examined after hematoxylin and eosin staining. Fetal brain histologic features were classified into 5 grades, with 5 being the most severe damage. 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, glutathione, lactate, and glucose. RESULTS: Myocardial changes of necrosis, phagocytosis, and contraction bands 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 kidney all asphyxiated cases showed tubular necrosis, but glomeruli were generally spared. Of the measures of oxidative stress, only liver tissue levels of thiobarbituric acid-reactive substances and superoxide dismutase were significantly higher in the asphyxiated group than in the control group, but there was no correlation with the degree of damage. Lactate level was higher only in the heart in the asphyxiated fetuses. CONCLUSION: Renal tubular damage was seen with all degrees of asphyxia, despite 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.