scholarly journals Ion Channel Involvement in Anoxic Depolarization Induced by Cardiac Arrest in Rat Brain

1995 ◽  
Vol 15 (4) ◽  
pp. 587-594 ◽  
Author(s):  
Yaxia Xie ◽  
Elke Zacharias ◽  
Patricia Hoff ◽  
Frank Tegtmeier

Anoxic depolarization (AD) and failure of ion homeostasis play an important role in ischemia-induced neuronal injury. In the present study, different drugs with known ion-channel-modulating properties were examined for their ability to interfere with cardiac-arrest-elicited AD and with the changes in the extracellular ion activity in rat brain. Our results indicate that only drugs primarily blocking membrane Na+ permeability (NBQX, R56865, and flunarizine) delayed the occurrence of AD, while compounds affecting cellular Ca2+ load (MK-801 and nimodipine) did not influence the latency time. The ischemia-induced [Na+]e reduction was attenuated by R56865. Blockade of the ATP-sensitive K+ channels with glibenclamide reduced the [K+]e increase upon ischemia, indicating an involvement of the KATP channels in ischemia-induced K+ efflux. The KATP channel opener cromakalim did not affect the AD or the [K+]e concentration. The ischemia-induced rapid decline of extracellular calcium was attenuated by receptor-operated Ca2+ channel blockers MK-801 and NBQX, but not by the voltage-operated Ca2+ channel blocker nimodipine, R56865, and flunarizine.

1993 ◽  
Vol 13 (4) ◽  
pp. 728-732 ◽  
Author(s):  
Miguel A. Pérez-Pinzón ◽  
Peter L. Lutz ◽  
Thomas J. Sick ◽  
Myron Rosenthal

Contrary to what is found in most vertebrates, the brains of certain turtle species maintain ATP levels and ion homeostasis and survive prolonged anoxia. The hypothesis tested here is that the release of adenosine and its binding to A1 receptors are essential for this anoxic tolerance. Studies were conducted in the isolated turtle cerebellum, which did release adenosine to the extracellular space during anoxia. When adenosine receptor antagonists [theophylline, 8-cyclopentyltheophylline (CPT), or 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)] were added to the superfusate under control conditions, they had no effect on extracellular potassium ion activity ([K+]o). During anoxia, however, these antagonists provoked maximal efflux of K+ (anoxic depolarization). Anoxic depolarization occurred earlier during anoxia with theophylline (a nonspecific adenosine receptor antagonist) than with CPT or DPCPX, which specifically block A1 receptors. Therefore, adenosine release and effects mediated by A1 receptors are essential to anoxia tolerance in turtle brain.


1989 ◽  
Vol 9 (6) ◽  
pp. 795-804 ◽  
Author(s):  
Jerry E. Fleischer ◽  
Akio Tateishi ◽  
John C. Drummond ◽  
Mark S. Scheller ◽  
Marjorie R. Grafe ◽  
...  

The excitatory amino antagonist MK-801 was administered to cats following resuscitation from cardiac arrest to evaluate its effect on neurologic and neuropathology outcome in a clinically relevant model of complete cerebral ischemia. In 29 cats studied, cardiac arrest (ventricular fibrillation) was maintained for 18 min and resuscitation was successfully performed in 21 cats. Four animals underwent a sham arrest. MK-801 or placebo was administered in a blinded, randomized manner. Beginning at 5 min post resuscitation (PR), MK-801 330 μg/kg over 2 min followed by 73 μg/kg/h for 10 h or the same volume of placebo was administered. Resuscitated animals remained paralyzed and sedated in an intensive care setting for 24–30 h PR. Neurologic examinations were performed at 2, 4, and 7 days PR by observers blinded to the treatment groups. Seventeen cats were entered into data analysis (nine MK-801-treated and eight placebo-treated). MK-801-treated animals had a significantly greater neurologic deficit score (NDS) rank (0 = normal, 100 = brain death) 2 days PR (mean rank 12.1 vs. 5.6; p = 0.008). This difference is most likely due to ongoing sedative actions of MK-801. There were no significant differences in NDS rank at 4 (10.3, MK-801 vs. 7.5, placebo) and 7 (9.6, MK-801 vs. 8.3, placebo) days PR. There were no significant differences in frontal cortex, hippocampus, occipital cortex, or cerebellar neuropathology between groups. Sham-arrested cats had normal neurologic and neuropathologic evaluations. In the circumstance of complete cerebral ischemia as employed in the current study, MK-801 had no beneficial effect upon neurologic or neuropathologic outcome.


1993 ◽  
Vol 108 (3) ◽  
pp. 577-582 ◽  
Author(s):  
S. Tacconi ◽  
E. Ratti ◽  
M.R. Marien ◽  
G. Gaviraghi ◽  
N.G. Bowery

2018 ◽  
Vol 31 (12) ◽  
pp. 1332-1338 ◽  
Author(s):  
Rong Xu ◽  
Yuan Xiao ◽  
Yan Liu ◽  
Bo Wang ◽  
Xing Li ◽  
...  

2007 ◽  
Vol 93 (4) ◽  
pp. L20-L22 ◽  
Author(s):  
Yevgen O. Posokhov ◽  
Philip A. Gottlieb ◽  
Michael J. Morales ◽  
Frederick Sachs ◽  
Alexey S. Ladokhin

Sign in / Sign up

Export Citation Format

Share Document