Hypoxanthine and lactate concentrations in lambs during hypoxic and stagnant hypoxia

Abstract

To determine the suitability of plasma hypoxanthine as a marker of tissue hypoxia, we studied the relationship of arterial plasma hypoxanthine and blood lactate concentrations to the cumulative O2 deficit during hypoxemia and low cardiac output (hypoxic and stagnant hypoxia, respectively). Eight intact, chronically catheterized lambs were studied using ketamine sedation. Comparable reductions in O2 transport and consumption were produced with each form of hypoxia. Lactate was linearly related to O2 deficit during both forms of hypoxia, although the slope of the regression was greater for low cardiac output (0.049) than hypoxemia (0.032). Hypoxanthine was linearly related to cumulative O2 deficit only during low cardiac output. During hypoxemia, hypoxanthine concentration initially increased but plateaued with further increases in O2 deficit. The discrepancy in response of hypoxanthine was most likely caused by differences in the rate of elimination between stagnant and hypoxic hypoxia. We concluded that plasma hypoxanthine concentration was not a reliable marker for tissue hypoxia because it differed with the cause of O2 deprivation and did not necessarily reflect the severity of O2 deprivation.

Response to Low Cardiac Output: Developmental Differences in Metabolism during Oxygen Deficit and Recovery in Lambs

“…Blood lactate concentration increased linearly with both time and O2 deficit in all studies and never reached a plateau during low output. A linear relationship between arterial lactate concentration and time (as well as 0 2 deficit) has been reported previously for both stagnant hypoxia (3) and hypoxia (3,23,25). The use of lactate concentration as a marker of "tissue hypoxia" is controversial (26)(27)(28).…”

“…It has been traditional to attribute lactic acidemia to overproduction of lactic acid by hypoxic tissues; however, lactate accumulation is more accurately viewed as the balance between increased production rates and decreased removal rates (26)(27)(28). Although we measured neither lactate production nor lactate use in our studies, we would expect that the lactate accumulation we detected is caused by both increased production and decreased removal rates (3,(26)(27)(28). With the large decreases in whole body 0 2 consumption and cardiac output we produced, it is likely that some tissues, e.g.…”

“…We used the calculated O2 deficit as a common measure of 0 2 lack during the low cardiac output period to compare the metabolic responses during the low cardiac output and recovery in the two age groups. We chose the level of reduction in cardiac output based on previous studies (3,12) to be sure that: I) it would be well below the critical level of O2 delivery, 2) lactate would be produced, and 3) this state would be tolerated for periods up to 60 min. To ensure that the disruptions were comparable, in every study at both ages, we acutely decreased cardiac output so that the whole body O2 consumption was reduced by one third (38.1 % decrease at 2 wk and 35.1% decrease at 8 wk) with respect to baseline and was maintained at a nearly steady state.…”

“…Oxygen consumption and C 0 2 production were measured by a flow-through system in which ambient air was drawn at a constant rate through a face mask and was mixed with expired gas from the nose and mouth. The fractional concentrations of 0 2 and C 0 2 were monitored continuously for calculation of Oz consumption and C 0 2 production as described previously (3,9). Blood gas tensions and pH were measured by standard electrodes at 37°C (Radiometer America Inc., Westlake, OH) and corrected to body temperature.…”

“…This is a potential mechanism for the greater tolerance of young animals to hypoxic stresses. (Pediatr Res 26: 180-187, 1989) When 0 2 supply to the tissues is critically reduced by hypoxemia, anemia, or low cardiac output, whole body O2 consumption decreases and an O2 deficit accumulates throughout the hypoxic period (1)(2)(3). With restoration of 0 2 supply, there is a transient excess in O2 consumption above the initial baseline level and it has been suggested that this excess represents "repayment" of some or all of the O2 deficit (4,5) in a manner analogous to exercise (6).…”