Observations on the energy and redox state and protein synthetic rate in animal and human placentas.

Abstract

The energy and redox states of placentas in newly anesthetized or sacrificed guinea pigs and sheep were compared with that of human placentas immediately after delivery. Subsequently the effect of ischemia was observed in both human and animal placentas. The influence of perfusion, using a fluid containing oxygenated red cells (adult human) was studied in the human placenta. Adenine nucleotide precursors were added to the perfusion fluid in an attempt to improve the energy and redox states and the mixed protein synthetic rate of the tissue. The ATP and lactate concentrations in guinea pig placental tissue taken immediately after nembutal anesthesia were 1.16 and 3.59 mmol kg-1 wet weight respectively. One minute's ischemia caused a fall in ATP to 0.7 and a rise in lactate to 6.5 mmol kg-1. The concentration of ATP in human placental tissue, 30 secs to 3 minutes after delivery of the organ, was 0.52 and of lactate 4.8 mmol kg-1 wet weight, suggesting that some biochemical deterioration had already occurred. A further fall in ATP to 0.21 and rise in lactate to 6.4 mmol kg-1 wet weight took place during 20 mins of ischemia; thereafter the ATP level remained constant while the lactate continued to rise to 11 mmol kg-1 wet weight by 1 1/2 hours. The initial energy charge was similar in both animal and human placentas, 0.8-0.9, and was only reduced during prolonged hypoxia at 37 degrees C. Since the AMP did not rise to the same extent as in other tissues, it is suggested that the Atkinson equation used in the calculation of energy charge may not be applicable to the placenta, and that the most sensitive indication of deterioration in energy status is the swift fall in ATP concentration. Rapid establishment of maternal intervillous perfusion of an isolated lobule of the human placenta using ixygenated RBCS in the perfusion fluid, enabled the ATP and lactate levels to be maintained near to 'in vivo' values during one hour, with a protein turnover rate of 40% day-1, two thirds of that observed 'in vivo' in the sheep. The addition of 1.0-50 microM adenosine to the perfusion fluid improved the energy state of the tissue, but not its redox state nor protein synthetic rate. 1.5 microM inosine in the perfusion medium did not alter the energy state but caused a marked reduction in lactate production.