The lactate:pyruvate ratio affects hyperemia in humans following traumatic brain injury

Introduction

We have recently shown in rat middle cerebral arteries that the lactate:pyruvate (L:P) ratio, a modulator of the cellular NADH:NAD+ (redox potential), is a regulator of vascular function. Additionally, Ido et al. ² reported that cerebral blood flow (CBF) in activated rat brain is modified by changes in the L:P ratio: CBF was augmented when the ratio was raised and attenuated when the ratio was lowered. To further investigate this phenomenon, the relationship of cerebral parenchymal L:P ratio to cerebral perfusion after traumatic brain injury (TBI) was determined.

Methods

Thirty-five consented TBI patients (age 36 +/− 16, admission GCS 6.8 +/− 2.5, 74% male) were prospectively studied with cerebral microdialysis (CMA/Microdialysis, Stockholm, Sweden) and continuous jugular venous oxygenation (SjVO2), which was used as an indicator of cerebral perfusion status. 133Xenon cerebral blood flow studies (Ceretronix, Randers, Denmark) were conducted daily to verify the perfusion results of the SjVO2 measurements.

Results

A time dependent relationship between the L:P ratio and the first two phases of cerebral perfusion was observed. During the initial phase (<24 hours post injury) the mean hourly SjVO2 was 70+/−9.0% while during the second phase (24–48 hours), the SjVO2 rose significantly (p=0.0001) to 75+/−8.2%, indicative of increased cerebral perfusion. The L:P ratio did not correlate with SjVO2 during the initial phase (r=0.05, p=0.683) but was significantly positively correlated with SjVO2 during the next 24 hours (r=0.38, p=0.0001). No significant correlation between L:P ratio and SjVO2 was seen after 48 hours.

Discussion

This study showed that L:P ratio was a potent modulator of cerebral perfusion during the hyperemic phase following injury, thus suggesting an important contribution of the redox potential to vascular function. The effects of L:P ratio on cerebral perfusion are consistent both with (I) the need for higher flows to increase reoxidation of free NADH by LDH, and (II) the evidence that increased flows appear to exceed the need for oxygen and glucose to support increased energy metabolism.^{1, 2} Additionally, this study demonstrated the temporally variable nature of post-traumatic cerebral perfusion.