Sympathetic stimulation with physostigmine worsens outcome from incomplete brain ischemia in rats.
BACKGROUND
It has been suggested that anesthetics may protect the brain during incomplete cerebral ischemia by inhibition of sympathetic activity. This study evaluated whether physostigmine may increase plasma epinephrine and norepinephrine during carotid occlusion with hypotension and worsen ischemic outcome in rats and if this effect could be reversed by dexmedetomidine, an alpha 2-adrenergic agonist.


METHODS
Anesthesia was maintained with fentanyl (25 micrograms.kg-1.h-1) combined with 70% N2O ventilation in oxygen. Ischemia was produced by right carotid ligation combined with hemorrhagic hypotension to 30 mmHg for 30 min. Plasma epinephrine and norepinephrine were measured during ischemia. Neurologic outcome was evaluated for 3 days after ischemia. There were three groups: control (n = 10), physostigmine (1 mg/kg intraperitoneal 3 min before the start of ischemia, n = 10), and physostigmine plus dexmedetomidine (100 micrograms/kg intraperitoneally 15 min before the start of ischemia, n = 10). Brain tissue glutamate concentrations were measured by microdialysis in separate studies.


RESULTS
Compared to control rats, physostigmine increased plasma epinephrine and norepinephrine 10-fold and worsened neurologic outcome. The increases in epinephrine and norepinephrine were blocked by dexmedetomidine before treatment, and neurologic outcome was improved. Outcome was not correlated with blood glucose during ischemia (r = 0.11). Ischemia increased brain tissue glutamate from < 100 microM to 400 microM during ischemia. This increase was not altered by physostigmine treatment.


CONCLUSIONS
These results suggest that physostigmine worsens ischemic outcome by a mechanism that is associated with increases in plasma epinephrine and norepinephrine.
Schultz
J A
JA
Anesthesiology Department, University of Illinois, Chicago.
Hoffman
W E
WE
Albrecht
R F
RF
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D003956:Dialysis; D004837:Epinephrine / Q000097:blood; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010830:Physostigmine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
D001786:Blood Glucose; D005971:Glutamates; D018698:Glutamic Acid; D010830:Physostigmine; D009638:Norepinephrine; D004837:Epinephrine