Age-dependent effects of gradual decreases in cerebral perfusion pressure on the neurochemical response in swine.
OBJECTIVE
There is still a lack of knowledge on the age-dependent relation between a reduction in cerebral perfusion pressure (CPP) and compromised brain perfusion leading to excessive transmitter release and brain damage cascades. The hypothesis is that an age-dependent lower threshold of cerebral blood flow (CBF) autoregulation determines the amount and time course of transmitter accumulation.


METHODS
This was a prospective randomized, blinded animal study performed in a university laboratory involving eight newborn and 11 juvenile anesthetized pigs.


METHODS
Striatal dopamine, glutamate, glucose, and lactate were monitored by microdialysis. For CPP manipulation, the cisterna magna was infused with artificial cerebrospinal fluid to control intracranial pressure at the maintained arterial blood pressure (stepwise CPP decrease in 15-min stages to 50, 40, 30, and finally 0 mmHg).


RESULTS
Juvenile pigs showed a gradual decrease in CBF between 50 mmHg CPP (CPP-50) and 30 mmHg CPP (CPP-30), but a significant CBF reduction did not occur in newborn piglets until CPP-30 (P < 0.05). At CPP-30, brain oxidative metabolism was reduced only in juveniles, concomitantly with elevations in dopamine and glutamate levels (P < 0.05). In contrast, newborn piglets exhibited a delayed and blunted accumulated of transmitters and metabolites (P < 0.05).


CONCLUSIONS
The lower limit of CBF autoregulation was associated with modifications in neurochemical parameters that clearly occurred before brain oxidative metabolism was compromised. Early indicators for mild to moderate hypoperfusion are elevated levels of lactate and dopamine, but elevated levels of glutamate appear to be an indicator of brain ischemia. The shift to the left of the lower autoregulatory threshold is mainly responsible for the postponed neurochemical response to decrements in the CPP in the immature brain.
Institute of Molecular Cell Biology, Universitätsklinikum Jena, Friedrich Schiller University, 07745, Jena, Germany.
Bernd
B
Walter
Kristina
K
Aisenpreis
Harald G
HG
Fritz
Jens
J
Soukup
Michael
M
Eiselt
Reinhard
R
Bauer
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure; D001923:Brain Chemistry / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D007427:Intracranial Pressure / Q000502:physiology*; D017551:Microdialysis; D011446:Prospective Studies; D011897:Random Allocation; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013552:Swine
D017981:Receptors, Neurotransmitter