TY - JOUR
T1 - Evaluation of delayed treatment of focal cerebral ischemia with three selective k-opioid agonists in cats
AU - Baskin, David S.
AU - Widmayer, Marsha A.
AU - Browning, Jeffrey L.
AU - Heizer, Marcia L.
AU - Schmidt, William K.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1994/10
Y1 - 1994/10
N2 - Background and Purpose: The purpose of this study was to determine the therapeutic efficacy of three κ-opioid agonists used for delayed treatment of experimental focal cerebral ischemia. Methods: Forty halothane- anesthetized cats underwent permanent occlusion of the right intracranial internal carotid, middle cerebral, and anterior cerebral arteries via a transorbital microsurgical approach. Six hours after occlusion, animals received a blinded bolus injection, and a subcutaneous osmotic pump was implanted to provide continuous release for 7 days. The injection and pump contained either saline or one of three κ-agonists: dynorphin (1-13), U- 50,488, or DuP E3800. Survival, neurological function, tissue damage, and brain weight were assessed. Results: As a group, κ-agonist-treated animals had higher survival (P<.02), less tissue damage (P<.02), and lower brain weight (P<.05) than saline controls. U-50,488 more effectively improved survival (P<.03) than dynorphin (P<.07) or E3800 (P<.07). Each of the three κ compounds improved tissue damage (dynorphin, P<.02; U-50,488, P<.05; E3800, P<.05). Greater improvement in neurological function was seen after treatment with dynorphin (P<.05) than with U-50,488 (P<.6) or E3800 (P<.7). The only significant reduction in brain weight was seen after dynorphin treatment (P<.01). Conclusions: Compounds that act at the κ subclass of opiate receptors are effective in increasing survival, improving neurological function, and decreasing tissue damage and edema in a cat model of focal cerebral ischemia. The current study provides support for the benefits of treatment of acute cerebrovascular ischemia with κ-opioid agonists. The agents may prove to be of superior clinical utility because of efficacy even when administered 6 hours after the onset of stroke.
AB - Background and Purpose: The purpose of this study was to determine the therapeutic efficacy of three κ-opioid agonists used for delayed treatment of experimental focal cerebral ischemia. Methods: Forty halothane- anesthetized cats underwent permanent occlusion of the right intracranial internal carotid, middle cerebral, and anterior cerebral arteries via a transorbital microsurgical approach. Six hours after occlusion, animals received a blinded bolus injection, and a subcutaneous osmotic pump was implanted to provide continuous release for 7 days. The injection and pump contained either saline or one of three κ-agonists: dynorphin (1-13), U- 50,488, or DuP E3800. Survival, neurological function, tissue damage, and brain weight were assessed. Results: As a group, κ-agonist-treated animals had higher survival (P<.02), less tissue damage (P<.02), and lower brain weight (P<.05) than saline controls. U-50,488 more effectively improved survival (P<.03) than dynorphin (P<.07) or E3800 (P<.07). Each of the three κ compounds improved tissue damage (dynorphin, P<.02; U-50,488, P<.05; E3800, P<.05). Greater improvement in neurological function was seen after treatment with dynorphin (P<.05) than with U-50,488 (P<.6) or E3800 (P<.7). The only significant reduction in brain weight was seen after dynorphin treatment (P<.01). Conclusions: Compounds that act at the κ subclass of opiate receptors are effective in increasing survival, improving neurological function, and decreasing tissue damage and edema in a cat model of focal cerebral ischemia. The current study provides support for the benefits of treatment of acute cerebrovascular ischemia with κ-opioid agonists. The agents may prove to be of superior clinical utility because of efficacy even when administered 6 hours after the onset of stroke.
KW - brain edema
KW - cats
KW - cerebral ischemia, focal
KW - opioid receptors
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U2 - 10.1161/01.STR.25.10.2047
DO - 10.1161/01.STR.25.10.2047
M3 - Article
C2 - 7916503
AN - SCOPUS:0028083252
SN - 0039-2499
VL - 25
SP - 2047
EP - 2053
JO - Stroke
JF - Stroke
IS - 10
ER -