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Age-dependent effects of gradual decreases in cerebral perfusion pressure on the neurochemical response in swine.

Abstract：

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. DESIGN AND SETTING:This was a prospective randomized, blinded animal study performed in a university laboratory involving eight newborn and 11 juvenile anesthetized pigs. INTERVENTION: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). MEASUREMENTS AND MAIN 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.

journal_name

Intensive Care Med

journal_title

Intensive care medicine

authors

Walter B,Aisenpreis K,Fritz HG,Soukup J,Eiselt M,Bauer R

doi

10.1007/s00134-010-1846-0

subject

Has Abstract

pub_date

2010-06-01 00:00:00

pages

1067-75

issue

eissn

0342-4642

issn

1432-1238

journal_volume

pub_type

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Age-dependent effects of gradual decreases in cerebral perfusion pressure on the neurochemical response in swine.