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From the Departments of Anesthesiology and Critical Care Medicine (S.L.,
P.T., Y.X.), Pathology (R.L.H.), and Pharmacology (Y.X.), University of
Pittsburgh (Pa).
Correspondence to Yan Xu, PhD, W-1358 Biomedical Science Tower, University of Pittsburgh, Pittsburgh, PA 15261. E-mail xu{at}smtp.anes.upmc.edu
Background and Purpose—Because
noninvasive physiological monitoring of cerebral
blood flow, metabolic integrity, and brain ion and water
homeostasis can now be accomplished with new, state-of-the-art MR
spectroscopy and imaging techniques, it is appropriate to develop
controllable and reproducible animal models that permit prolonged
circulatory arrest and resuscitation in the magnet and also allow for
studies of long-term survival and outcome. We have developed such a
model in rats that involves minimal surgical preparations and can
achieve resuscitation remotely within precisely controlled
time.
Methods—Cardiac arrest was induced by asphyxiation, the duration
of which ranged from 8 to 24 minutes. Resuscitation was achieved
remotely by a slow, intra-aortic infusion of oxygenated
blood (withdrawn either from the same rat before asphyxia or from a
healthy donor rat) along with a resuscitation cocktail containing
heparin (50 U/100 g), sodium bicarbonate (0.1 mEq/100 g), and
epinephrine (4 µg/100 g). The body temperature was measured
by a tympanic thermocouple probe and was controlled either by a heating
pad (constant tympanic temperature=37°C) or by warm ambient air
(constant air temperature=37°C). Interleaved
31P/1H nuclear magnetic resonance (NMR)
spectroscopy was used in a selected group of rats to measure the
cerebral metabolism before and during approximately 20
minutes of circulatory arrest and after resuscitation.
Results—The overall success rate of resuscitation, irrespective
of the duration of cardiac arrest, was 82% (51 of 62). With a
programmed infusion pump, the success rate was even higher (95%). The
survival time for rats subjected to 15 and 19 minutes of asphyxia with
core temperature tightly controlled was significantly lower than that
with ambient temperature control (P<0.001 and
P<0.04, respectively). High-quality NMR spectra can be
obtained continuously without interference from the resuscitation
effort. Final histological examinations taken 5 days
after resuscitation showed typical neuronal damages, similar to those
found in other global ischemia models.
Conclusions—Because the no-flow time and resuscitation time can
be precisely controlled, this outcome model is ideally suited for
studies of ischemic and reperfusion injuries in the brain and
possibly in other critical organs, permitting continuous assessment of
long-term recovery and follow-up in the same animals.
Departments
of Anesthesia and Radiology and the
Cardiovascular Research Institute University of
California at San Francisco San Francisco, California
© 1998 American Heart Association, Inc.
Original Contributions
A Reproducible Model of Circulatory Arrest and Remote Resuscitation in Rats for NMR Investigation
Editorial Comment
This article has been cited by other articles:
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