Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest

Purpose of the Study: Determine the effect of deep vs low vs moderate hypothermia on
neurocognitive function, brain functional connectivity, and leukocyte SUMOylation patterns
after surgical circulatory arrest.

Hypothesis: Deep hypothermia is superior to moderate hypothermia in reducing postoperative
cognitive decline and preserving brain functional connectivity and that low hypothermia is
non-inferior to deep hypothermia.

Design and Procedures: 273 informed and consenting patients who are scheduled for elective
proximal aortic reconstructive surgery (ascending aorta + aortic valve or root) with
concomitant proximal hemi- or total arch replacement via median sternotomy will be randomized
to deep (<20°C), low (20.1°C-24°C), or moderate (24.1°C-28°C) hypothermia during circulatory
arrest. Cognitive testing using a standard battery will occur preoperatively (baseline), at 4
weeks, and at 1 year after surgery. Neuroimaging procedures before surgery, and at 4 weeks
and 1 year after surgery will consist of high-resolution anatomic, resting-state fMRI
(rs-fMRI) and magnetic resonance spectroscopy (MRS) sequences. To characterize leukocyte
activation, whole blood will be drawn at 5 time points: at baseline (prior to surgery),
before circulatory arrest, 10 minutes after reperfusion, 10 minutes after CPB, and 4 hours
after CPB.

Inclusion Criteria:

- Patients who are scheduled for elective proximal aortic reconstructive surgery
(ascending aorta + aortic valve or root) with concomitant proximal hemi- or total arch
replacement via median sternotomy

Exclusion Criteria:

- < 40 years of age

- History of symptomatic cerebrovascular disease, eg, prior stroke with residual deficit

- Alcoholism (> 2 drinks/day)

- Psychiatric illness (any clinical diagnoses requiring therapy)

- Drug abuse (any illicit drug use in the past 3 months)

- Hepatic insufficiency (liver function tests > 1.5 times the upper limit of normal)

- Severe pulmonary insufficiency (requiring home oxygen therapy)

- Renal failure (serum creatinine > 2.0 mg/dL)

- Claustrophobic fear

- Unable to read and thus unable to complete the cognitive testing

- Pregnant women

- Patients who score < 24 on a baseline Mini Mental State Examination (MMSE) or ≥ 27 on
the baseline Center for Epidemiological Studies Depression (CES-D) scale

- Patients who have pre-existing unsafe implants for 3 Tesla magnetic resonance imaging
(MRI).