Following
hypoxia-ischaemia (HI), an early
biomarker of insult severity is desirable to target neuroprotective
therapies to patients most likely to benefit; currently there are no
biomarkers within the 'latent phase' period before the establishment of secondary energy failure. Brief transient
phosphocreatine (PCr) recovery overshoot (measured absolutely or relative to
nucleotide triphosphate, NTP) following HI has been observed in cardiac and skeletal muscle; its significance however is unclear. To investigate cerebral PCr recovery levels after HI in relation to (i) baseline metabolism, (ii) insult severity, (iii) energy metabolism at recovery and (iv) subsequent metabolic derangement, cerebral NTP, PCr and
inorganic phosphate (relative to the exchangeable high-energy
phosphate pool) were measured serially in an in vivo model of perinatal asphyxial
encephalopathy using
phosphorus-31 magnetic resonance spectroscopy. Measures were compared either in all piglets or between 3 subgroups with no (n = 5, favourable outcome), moderate (n = 8, intermediate outcome) or severe (n = 5, unfavourable outcome) secondary energy failure at 24 h after HI. Maximum NTP, PCr and
inorganic phosphate recoveries were observed 2-8 h after HI. Following
resuscitation, in subjects with favourable outcome PCr recovered to higher than its baseline level (overshoot); in subjects with unfavourable outcome maximum PCr recovery was lower than baseline and lower than in subjects with favourable and intermediate outcomes. Recovery PCr correlated linearly and negatively with both acute insult severity and baseline PCr/NTP. These results suggest that recovery metabolism 2-8 h after HI may provide an early
biomarker of injury severity. PCr recovery overshoot in the developing brain may indicate a protective response to HI leading to cell recovery, survival and protection against subsequent stress. In addition, baseline cerebral metabolism (PCr/NTP) may identify vulnerable infants prior to invasive surgery.