Evaluation of lactate production and clearance kinetics by 1H NMR in a model of brief repetitive cerebral ischemia.

Pilots of high-performance aircraft are subject to repeated transient cerebral ischemia during high-gravitational stress maneuvers. Previously we have demonstrated that repeated episodes of transient cerebral ischemia and reflow are cumulative and lactate accumulations appear to be exponential. To evaluate the metabolic events determining the kinetics of lactate accumulation, and therefore the rates of substrate utilization, we have used in vivo 1H nuclear magnetic resonance with a 5-s time resolution to measure lactate production and clearance. The individual rates for each animal were then used to predict the accumulation of lactate in the same animal during 30 episodes of ischemia and reflow. Lactate accumulation was modeled as the balance between a zero-order production process during the ischemic period and a first-order clearance process. The predicted lactate accumulation showed excellent agreement with the observed time course, validating the predictive power of the simple model used. The highly reproducible nature of this model and its accuracy in predicting lactate accumulation should enable more accurate studies of the deleterious effects of lactate accumulation in cerebral ischemia by providing a highly reproducible means for generating a specific level of lactate accumulation.