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Ventricular Fibrillation-Induced Cardiac Arrest in the Rat as a Model of Global Cerebral Ischemia

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Abstract

Cardiopulmonary arrest remains as one of the leading causes of death and disability in Western countries. Although ventricular fibrillation (VF) models in rodents mimic the “square wave” type of insult (rapid loss of pulse and pressure) commonly observed in adult humans at the onset of cardiac arrest (CA), they are not popular because of the complicated animal procedure, poor animal survival, and thermal injury. Here, we present a modified, simple, and reliable VF-induced rat model of CA that will be useful in studying the mechanisms of CA-induced delayed neuronal death, as well as the efficacy of neuroprotective drugs. CA was induced in male Sprague Dawley rats using a modified method of von Planta et al. (J Appl Physiol 65:2641–2647, 1988). In brief, VF was induced in anesthetized, paralyzed, and mechanically ventilated rats by an alternating current delivered to the entrance of the superior vena cava into the heart. Resuscitation was initiated by administering a bolus injection of epinephrine and sodium bicarbonate followed by mechanical ventilation and manual chest compressions and countershock with a 10-J direct current. Neurological deficit score was higher in the CA group compared to the sham group during early reperfusion periods, suggesting brain damage. Significant damage in the CA1 hippocampus (21 % normal neurons compared to control animals) was observed following histopathological assessment at 7 days of reperfusion. We propose that this method of VF-induced CA in the rat provides a tool to study the mechanism of CA-induced neuronal death without compromising heart functions.

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Acknowledgments

This study was supported by NIH grants NS45676, NS054147, NS34773, NS05820, and NS073779. We would like to thank Dr. Maritza Martinez and Mr. Oleksandr Dashkin for the technical assistance, and Prof. Brant Watson for the critical reading of this manuscript.

Conflict of Interest

Kunjan R. Dave, David Della-Morte, Isabel Saul, Ricardo Prado, and Miguel A. Perez-Pinzon declare that they have no conflicts of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Authors and Affiliations

  1. Cerebral Vascular Disease Research Laboratories, Department of Neurology, Leonard M. Miller School of Medicine, University of Miami, 1420 NW 9th Avenue, TSL/203E, Miami, FL, 33136, USA

    Kunjan R. Dave, David Della-Morte, Isabel Saul, Ricardo Prado & Miguel A. Perez-Pinzon

  2. Neuroscience Program, Leonard M. Miller School of Medicine, University of Miami, Miami, FL, 33136, USA

    Miguel A. Perez-Pinzon

  3. Department of Advanced Biotechnologies and Bioimaging, IRCCS San Raffaele, Rome, Italy

    David Della-Morte

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  1. Kunjan R. Dave
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  2. David Della-Morte
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  3. Isabel Saul
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  4. Ricardo Prado
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  5. Miguel A. Perez-Pinzon
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Correspondence to Kunjan R. Dave.

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Dave, K.R., Della-Morte, D., Saul, I. et al. Ventricular Fibrillation-Induced Cardiac Arrest in the Rat as a Model of Global Cerebral Ischemia. Transl. Stroke Res. 4, 571–578 (2013). https://doi.org/10.1007/s12975-013-0267-0

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  • DOI: https://doi.org/10.1007/s12975-013-0267-0

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