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(Stroke. 1995;26:2127-2134.)
© 1995 American Heart Association, Inc.

Articles

Regional Prevalence and Distribution of Ischemic Neurons in Dog Brains 96 Hours After Cardiac Arrest of 0 to 20 Minutes

Ann Radovsky, DVM, PhD; Peter Safar, MD; Fritz Sterz, MD; Yuval Leonov, MD; Harvey Reich, MD Kazutoshi Kuboyama, MD

From the Safar Resuscitation Research Center and the Departments of Anesthesiology/Critical Care Medicine and Pathology, University of Pittsburgh (Penn) Medical Center.

Correspondence to Ann Radovsky, DVM, PhD, National Institute of Environmental Health Sciences, PO Box 12233, Mail Drop A0-01, Research Triangle Park, NC 27709. E-mail radovsky@niehs.nih.gov.

Background and Purpose In this established outcome model of cardiac arrest in dogs, we have used total (summed regional) brain histopathologic damage scores. The present study describes the regional progression of necrotic (ischemic) neuron prevalence with increasing duration of cardiac arrest. It tests the hypothesis that increases in the total prevalence of necrotic neurons better correspond to increasing arrest duration and better correlate with neurological deficit than do any individual regional scores.

Methods Blinded evaluation with light microscopy was used to score the prevalence (five categories) and note the distribution of necrotic neurons in dog brains 96 hours after normothermic ventricular fibrillation cardiac arrest followed by standard reperfusion and control of extracerebral variables. Six coronal brain sections including 19 regions were examined from dogs subjected to 0 (n=2), 5 (n=5), 10 (n=6), 12.5 (n=12), 15 (n=8), 17 (n=5), or 20 (n=1) minutes of cardiac arrest. Dogs were neurologically evaluated before death.

Results Necrotic neurons were widespread and scattered among normal neurons. Individual regions varied in their sensitivity to different durations of cardiac arrest. There were consistent increases in the mean prevalence of necrotic neurons with increased arrest duration in the hippocampal dentate gyrus and for cerebellar granule neurons. Regionally, the caudate nucleus had the best correlation with clinical neurological deficit (=+.85, P<.01).

Conclusions Compared with total (summed regional) necrotic neuron prevalence scores, increased regional prevalence scores for cerebellar granule neurons with increasing arrest duration were equally significant, and scores for the caudate nucleus had nearly the same correlation with individual clinical neurological deficit.

Key Words: animal models • cerebral ischemia • heart arrest • neuronal death • dogs

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