Affiliation:
1. the Department of Neurology, The University of Texas Medical School, Houston, Tex.
Abstract
Background and Purpose
In search of a better treatment for acute ischemic stroke, we evaluated the use of lubeluzole and hemodilution with diaspirin cross-linked hemoglobin (DCLHb) therapy to test whether treatment with two complementary acting compounds provides more potent protection than either treatment alone.
Methods
We used unilateral reversible middle cerebral artery (MCA) and common carotid artery (CCA) occlusion of various durations in Long-Evans rats to produce ischemic cortical lesions. We calculated the average maximal lesion volume (Vol
max
) and the time required to produce half maximal lesion size (T
50
) in control animals (n=31) and evaluated the effects on cerebral perfusion and infarct size of treatment with lubeluzole (n=23), hemodilution (to 30% hematocrit) with albumin (n=17) or DCLHb (n=23), and combined lubeluzole+DCLHb therapy initiated 15 minutes after MCA/CCA occlusion.
Results
The Vol
max
produced by MCA/CCA occlusion in control animals was 138.5±7.7 mm
3
, and T
50
was 98.5±10.2 minutes. Lubeluzole alone reduced Vol
max
by 53% with no significant effect on T
50
. In contrast to lubeluzole, DCLHb hemodilution prolonged T
50
by 68% with no significant effect on Vol
max
. Prolongation of T
50
by DCLHb was not due to hemodilution itself, since a similar degree of hemodilution with albumin had no effect. Finally, combined lubeluzole+DCLHb rescued 72% of the tissue and augmented the effect of lubeluzole alone by 40% (Vol
max
, 66.3±13.0 versus 39.4±12.2 mm
3
) while prolonging T
50
by 31%.
Conclusions
Combination therapy for acute stroke using compounds with complementary action can result in more complete attenuation of neuronal damage and demonstrates the possible clinical utility of combined neuroprotective and reperfusion therapies.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Advanced and Specialized Nursing,Cardiology and Cardiovascular Medicine,Neurology (clinical)
Cited by
60 articles.
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