From the Wellcome Surgical Institute (J.A.G., I.M.M.), the Department of
Medicine and Therapeutics (K.R.L., J.L.R., A.F.D.), and the Department of
Statistics (J.M.) of the University of Glasgow (Scotland) and Novartis Pharma
Ltd. (A.S., M.R.), Basel, Switzerland.
Correspondence to I. Mhairi Macrae, PhD, Wellcome Surgical Institute & Hugh Fraser Neuroscience Laboratories, University of Glasgow, Garscube Estate, Glasgow G 61, 1QH, Scotland, UK. E-mail m.macrae{at}udcf.gla.ac.uk
Background and
Purpose—Susceptibility to cerebral infarction was compared in
stroke-prone spontaneously hypertensive (SHRSP), normotensive
Wistar-Kyoto (WKY) rats, and F1 hybrids derived from a
SHRSP/WKY cross.
Methods—The proximal left middle cerebral artery (MCA) was
occluded under anesthesia and infarct volume assessed 24
hours later by magnetic resonance imaging and confirmed 5 days later by
quantitative histopathology. Total hemispheric infarct volume was
expressed as a percentage of the total brain volume.
Results—Infarct volumes measured by MRI in adult SHRSP
(19.5±2.0%) and F1 hybrid rats (19.4±1.9%) were
significantly greater than in WKY (11.1±2.4; CI [6.07, 10.76]) and
(5.93, 10.52), respectively, P<.001). Sensitivity to an
ischemic insult was unrelated to blood pressure: although
systolic blood pressures differed between young versus adult
male SHRSP and between female versus male SHRSP and F1
hybrids, infarct volumes were equal. A close correlation was found
between infarct volumes measured by MRI and histology
(r=.92, P<.0001).
Conclusions—Outcome to MCA occlusion (MCAO) measured with MRI
provides a reproducible and nonterminal quantitative phenotypic marker
of stroke susceptibility in the SHRSP. This is the first study to
employ MCAO with MRI to quantify stroke susceptibility in
F1 hybrid rats and indicates a dominant mode of inheritance
for this phenotype.
Department
of Physiology,
University of Michigan Medical School,
Ann Arbor, Michigan
© 1998 American Heart Association, Inc.
Original Contributions
Susceptibility to Cerebral Infarction in the Stroke-Prone Spontaneously Hypertensive Rat Is Inherited as a Dominant Trait
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