# Neurometabolic Outcomes of Different Cardiopulmonary Bypass Strategies

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $676,868

## Abstract

Project Description
 Patients with congenital cardiac diseases undergoing surgery requiring cardiopulmonary bypass (CPB)
are at risk for impaired neurodevelopmental progression due to time-related ischemia and exposure to toxic
levels of brain metabolites. Two competing CPB methodologies are currently practiced for certain
commonly occurring cardiac defects: 1) Deep Hypothermic Circulatory Arrest (DHCA), in which the pump is
turned off to provide a bloodless surgical field at the expense of no cerebral perfusion, and 2) Antegrade
Cerebral Perfusion (ACP), whereby selective perfusion of the brain is maintained throughout surgery.
Importantly, DHCA in cardiac surgery is strongly associated with long-term neurocognitive deficits in a
manner proportional to length of the circulatory arrest time. The alternative use of ACP for CPB, designed
as a strategy to protect the cerebral cortex, has become a common approach, though the value of ACP
over DHCA remains hotly debated, with well-designed and objective comparative studies lacking.
 Here we propose preclinical studies of a piglet model using MRI and dynamic proton magnetic
resonance spectroscopy (MRS) which measures metabolite activity in real time, to quantify alterations in
the brain’s metabolic state continuously over time during all phases of these CPB strategies. Preliminary
data reveal that DHCA causes marked alterations in brain energy metabolism, (e.g., a > 10-fold buildup in
brain lactate and a reduction in glucose), while no such derangement is seen with ACP. Importantly, post-
surgery quantitative spatial learning assessments will be used to identify metabolic markers most strongly
associated with poor clinical outcomes. Success of this project will demonstrate for the first time the
advantages of ACP over DHCA in preventing brain cellular injury-inducing metabolite derangements that
may hinder normal cognitive development. The real time continuous measurements used in this study will
also provide insights into underlying causes of the correlation between DHCA duration and neurological
injury. Data from these studies are expected to establish a benchmark for safety when DHCA or ACP is
required in the clinical setting. We anticipate that the results of this objective study in the piglet will be
directly and rapidly translatable to clinical practice. The Specific Aims are: 1) Using a CPB piglet model
we will image the brain metabolic state continuously in real time using MRS. The CPB model will
utilize the two commonly used forms of CPB, DHCA and ACP. Both DHCA and ACP will be
performed under varying conditions of temperature, flow and time, to determine the most effective
methodology to preserve a healthy brain metabolic state., and 2) To evaluate neurocognitive
outcomes and correlate with observed alterations in brain metabolism.

## Key facts

- **NIH application ID:** 10773170
- **Project number:** 5R01HL152757-04
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** FRANK HANLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $676,868
- **Award type:** 5
- **Project period:** 2021-02-15 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10773170

## Citation

> US National Institutes of Health, RePORTER application 10773170, Neurometabolic Outcomes of Different Cardiopulmonary Bypass Strategies (5R01HL152757-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10773170. Licensed CC0.

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