Learning and memory is preserved after induced asanguineous hyperkalemic hypothermic arrest in a swine model of traumatic exsanguination

doi:10.1067/msy.2002.125787

Surgery

Volume 132, Issue 2, August 2002, Pages 278-288

Presented at the Society of University Surgeons 63rd Annual Meeting, Honolulu, Hawaii, February 14-16, 2002.

https://doi.org/10.1067/msy.2002.125787 Get rights and content

Abstract

Background. Induced asanguineous hypothermic metabolic arrest (suspended animation) could provide valuable time to repair major vascular injuries if safely induced in patients with trauma. We report a novel method of doing this in a swine model of uncontrolled lethal hemorrhage (ULH) that resulted in preservation of learning ability and memory. Methods. Yorkshire swine (100 to 125 lb) underwent ULH before rapid intra-aortic infusion of a hypothermic (4°C), hyperkalemic (70 mEq/L) organ preservation solution by a left thoracotomy. Cooling continued until core temperature reached 10°C, and this was maintained for 60 minutes using low-flow cardiopulmonary bypass. Vascular injuries were repaired during this state of suspended animation, which was then reversed, and the animals were observed for 6 weeks. Cognitive functions were tested by training animals to retrieve food from color-coded boxes. Postoperatively, the ability to remember this task and a 75-point objective neurologic scale were used to test neurologic function. In experiment I, ULH was caused by lacerating thoracic aorta (n = 9). Five preoperatively untrained animals were trained to perform the task and compared with control animals (n = 15), and 4 preoperatively trained animals were tested for memory retention postoperatively. In experiment II, ULH was induced by creating an iliac artery and vein injury (n = 15). Animals were kept in shock for 15, 30, and 60 minutes before the induction of hypothermia. Results. In experiment I, surviving animals (7/9) were neurologically intact, and their capacity to learn new skills was no different than for control animals. All pretrained animals demonstrated complete memory retention. In experiment II, survival with 15, 30, and 60 minutes of shock were 80%, 60%, and 80%, respectively. All animals (except 1) in the 60-minute group were neurologically intact and displayed normal learning capacity. Conclusions. Induction of hypothermic metabolic arrest (by thoracotomy) for repair of complex traumatic injuries is feasible with preservation of normal neurologic function, even after extended periods of shock from an intra-abdominal source of uncontrolled hemorrhage. (Surgery 2002;132:278-88.)

Section snippets

Material and methods

The institutional Animal Care and Use Committee approved this study. All research was conducted in compliance with the Animal Welfare Act and other federal statutes, guides, and regulations relating to animals and experiments involving animals.¹⁰ Strict aseptic technique was used for all surgical procedures.

Hemodynamic and physiologic parameters

There was a sharp decrease in the mean arterial pressure in all the animals at the start of uncontrolled hemorrhage (Fig 1).

. Mean arterial blood pressures during the experiment. Data presented as group mean ± SEM. No shock before aortic injury (solid circle), hemorrhage from aortic injury over 5 minutes without any iliac injury; 15 minutes shock (circle), iliac injury and 15 minutes of uncontrolled hemorrhage before aortic injury; 30 minutes shock (solid triangle), iliac injury and 30 minutes of

Discussion

This experiment demonstrated that therapeutic profound hypothermia can be induced rapidly and safely through an EDT even after 60 minutes of uncontrolled hemorrhagic shock. Maintenance of total body hypothermic metabolic arrest with low-flow CPB using acellular organ preservation solutions for 60 minutes was associated with excellent survival and preservation of cognitive functions. In this 6-week survival model we noted a remarkable absence of long-term disability and a low incidence of

Acknowledgements

We would like to acknowledge the invaluable guidance provided by Norman Rich, MD, David Burris, MD, John Kirkpatrick, MD, Peter Safar, MD, and Michael Taylor, PhD, and excellent support by Petros Kouridakis, MD, Sylvester Slater, and Daniel Bellin, BS, during this project.

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^*: Supported by a grant from the Office of Naval Research-MDA905-97-Z-007.

^**: The opinions and assertions contained herein are the private ones of the authors and are not to be construed as official or reflecting the views of the Department of Defense at large. This manuscript was prepared by US Government employees and, therefore, cannot be copyrighted and may be copied with restriction.

^*: Reprint requests: Hasan B. Alam, MD, Department of Surgery, Room A-3021, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD 20814.

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Society of University SurgeonsLearning and memory is preserved after induced asanguineous hyperkalemic hypothermic arrest in a swine model of traumatic exsanguination*,**,*

Abstract

Section snippets

Material and methods

Hemodynamic and physiologic parameters

Discussion

Acknowledgements

J Am Coll Surg

Ann Thorac Surg

Appl Anim Behav Sci

J Surg Res

Cryobiology

Four minute limit for cardiac resuscitation

JAMA

Cerebral resuscitation from cardiac arrest: pathophysiologic mechanisms

Crit Care Med

Safety and efficacy of hypothermic cardiopulmonary bypass and circulatory arrest for operations on the descending thoracic and thoracoabdominal aorta

Ann Thorac Surg

The therapeutic potential of regulated hypothermia

Emerg Med J

Influence of deep hypothermia on the tolerance of the isolated cardiomyocyte to ischemia-reperfusion

J Mol Cell Cardiol

Induced hypothermia during emergency department thoracotomy: an animal model

J Trauma

Complete recovery after normothermic hemorrhagic shock and profound hypothermic circulatory arrest of 60 minutes in dogs

J Trauma

Society of University Surgeons
Learning and memory is preserved after induced asanguineous hyperkalemic hypothermic arrest in a swine model of traumatic exsanguination*,**,*