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J Thorac Cardiovasc Surg 2006;131:805-812
© 2006 The American Association for Thoracic Surgery

Cardiopulmonary Support and Physiology

Neurologic outcome after cardiopulmonary bypass with deep hypothermic circulatory arrest in rats: Description of a new model

Bettina Jungwirth, MD a , G. Burkhard Mackensen, MD a , b , * , Manfred Blobner, MD a , Frauke Neff, MD d , Bruno Reichart, MD c , Eberhard F. Kochs, MD a , Georg Nollert, MD, FAHA c

a Klinik für Anaesthesiologie, Technische Universität München, Klinikum rechts der Isar, Munich, Germany
d Institut für Allgemeine Pathologie und Pathologische Anatomie, Technische Universität München, Klinikum rechts der Isar, Munich, Germany
b Department of Anesthesiology, Duke University Medical Center, Durham, NC
c Herzchirurgische Klinik im Klinikum Großhadern, Ludwigs-Maximilian Universität München, Munich, Germany.

Received for publication July 29, 2005; revisions received October 27, 2005; accepted for publication November 8, 2005.

* Address for reprints: G. Burkhard Mackensen, MD, Department of Anesthesiology, Division of Cardiothoracic Anesthesiology and Critical Care Medicine, Duke University Medical Center, Durham, NC 27710. (Email: b.mackensen{at}duke.edu).

OBJECTIVE: Neurodevelopmental impairments after repair of congenital heart disease with cardiopulmonary bypass and deep hypothermic circulatory arrest continue to affect the lives of children. To date, the preclinical investigation of cerebral injury mechanisms related to deep hypothermic circulatory arrest has been restricted to expensive, personnel-demanding, and cumbersome large-animal models without validated neuropsychologic assessment. We aimed to establish a rodent recovery model of deep hypothermic circulatory arrest to overcome these disadvantages.

METHODS: Male rats (n = 34) were cannulated for cardiopulmonary bypass, cooled to a rectal temperature of 16°C to 18°C within 30 minutes, and assigned to deep hypothermic circulatory arrest durations of 0, 45, 60, 75, 90 (n = 6, respectively), or 105 (n = 4) minutes. After rewarming within 40 minutes, animals were weaned from cardiopulmonary bypass at 35.5°C. Neurologic and cognitive performance was assessed with the modified hole board test until postoperative day 14. Thereafter, brains were perfusion fixed and histologically analyzed.

RESULTS: Logistic regression analyses identified dose-dependent associations between survival, neurologic or cognitive function, and duration of deep hypothermic circulatory arrest. Functional and histologic deficits were detectable after clinically relevant deep hypothermic circulatory arrest durations. The overall neurologic function did not correlate with histologic outcome (r = 0.51, P > .05).

CONCLUSIONS: The current study presents a novel recovery model of cardiopulmonary bypass with deep hypothermic circulatory arrest in the rat. In contrast to studies in large animals, even clinically relevant deep hypothermic circulatory arrest durations up to 60 minutes resulted in detectable deficits. Consequently, this experimental model appears to be suitable to further elucidate the mechanisms associated with adverse cerebral outcome after cardiac surgery and deep hypothermic circulatory arrest and to investigate potential neuroprotective strategies.

Abbreviations and Acronyms CPB = cardiopulmonary bypass; DHCA = deep hypothermic circulatory arrest; MAP = mean arterial blood pressure; mHBT = modified hole board test




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