# Hemolysis and Nitric Oxide

> **NIH NIH K23** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $200,880

## Abstract

PROJECT SUMMARY / ABSTRACT
This application describes a five-year plan that will allow me to achieve independence as an investigator in the
field of anesthesia and critical care medicine. My project focuses on the deleterious effects of plasma
hemoglobin increased after prolonged cardiopulmonary bypass (CPB). I am an anesthesiologist at
Massachusetts General Hospital (MGH) and have a strong background in investigation in critical care
research. Dr. Fumito Ichinose, my primary mentor, is professor of anesthesia at Harvard Medical School and
cardiac anesthesiologist at the Department of Anesthesia at MGH. His research field focuses on the effects of
inhaled nitric oxide and hydrogen sulfide on the cardiovascular system. Dr. Taylor Thompson, my co-mentor, is
a pulmonologist at MGH and the Medical Director of the NHLBI-funded PETAL Network Clinical Coordinating
Center and served in that capacity for the ARDS Network for 20 years. He is a leader in conducting clinical
trials for the critically ill. An advisory committee of senior scientists able to provide additional expert guidance
includes Drs. Warren Zapol, Joseph Bonventre, Christopher Stowell and Marc Semigran. The research will be
performed at MGH and at Brigham and Women's Hospital.
Cardiopulmonary bypass is commonly used during open-heart surgery. However, it has been shown that
prolonged (> 90 minutes) CPB is associated with adverse outcomes. Specifically, long CPB has been
associated with acute kidney injury (AKI). My hypothesis is that prolonged CPB increases levels of circulating
plasma hemoglobin, which depletes plasma nitric oxide, in patients with endothelial dysfunction, in whom the
ability to replace nitric oxide is impaired. Administration of 80 part per million NO gas during and up to 24 hours
after cardiac surgery will (Aim I) reduce incidence of post-operative AKI (AIM IIa) block the avidity of plasma
free Oxy-Hb to consume plasma NO and (Aim IIb) preserve vascular responsiveness to vasodilation, despite
the presence of pre-existing endothelial dysfunction. I will test this hypothesis in a randomized, double-blind,
controlled clinical trial in 250 patients with endothelial dysfunction, undergoing cardiac surgery requiring
prolonged CPB. Patients will be randomized to receive 80 ppm NO or N2 through the membrane oxygenator,
while on CPB, and through the mechanical ventilator after weaning from the CPB.
During the award period I will attend a Master of Science at Harvard School of Public Health to improve my
knowledge and skills in clinical trials design and biostatistics. This research project will enhance both my
knowledge in critical care trial conduct and in translational medicine. The exposure to the advices of such
experienced mentors, the “hands-on” experience on clinical research and the formal training will equip me with
the critical expertise in the performance of clinical trials in critical care patients.

## Key facts

- **NIH application ID:** 9861255
- **Project number:** 5K23HL128882-04
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Lorenzo Berra
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $200,880
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9861255

## Citation

> US National Institutes of Health, RePORTER application 9861255, Hemolysis and Nitric Oxide (5K23HL128882-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9861255. Licensed CC0.

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