# Contribution of Inflammation and Oxidative Stress in Pericardial Fluid to Postoperative Atrial Fibrillation After Cardiac Surgery

> **NIH VA I01** · ST. LOUIS VA MEDICAL CENTER · 2020 · —

## Abstract

Postoperative atrial fibrillation (POAF) is one of the most common complications following cardiac surgery.
Veterans are not spared from this frequent complication: the incidence of new onset atrial arrhythmias
requiring treatment ranges from 30% for patients undergoing coronary artery bypass grafting (CABG) to
64% for patients undergoing a combined CABG and mitral valve replacement. There is also an increased
incidence of postoperative stroke, increased length of intensive care unit and hospital stay, and a two fold
increase in ventricular tachycardia and fibrillation and it is tied to a higher rate of hospital and long-term
mortality. There has been essentially no reduction in the incidence or severity of the problem despite many
new prophylactic treatments introduced and adhered to in the last twenty years. It is notable that moderate-
dose steroid administration at the time of surgery, which directly suppresses systemic inflammation, has
consistently demonstrated decreased rates of atrial fibrillation in multiple studies. Unfortunately the side
effects of steroids prohibit routine use for this disease. There is a critical need for strategies to mitigate
this problem; our long term objective is to develop a treatment for postoperative atrial fibrillation
that is effective and can be used in the majority of patients undergoing surgery. Many studies have
shown significant changes in the peripheral blood which correlate with POAF. However, the contribution of
perturbations in the physiologic area housing the heart (the pericardial space) has been largely ignored.
Increased inflammation in the peripheral circulation including correlation with raised white blood cell counts
and higher levels of inflammatory markers has consistently demonstrated correlation with POAF after
cardiac surgery. Our preliminary data show that the kinetics of increase are similar to the peripheral blood
for some cytokines, but markedly different in others. Some of the inflammatory markers in the pericardial
fluid (PCF) are at much higher concentrations, by up to ten orders of magnitude or greater. This damage
likely contributes to the development of postoperative arrhythmias. Our first aim is to confirm that these high
local levels (i.e. pericardial) of specific cytokines and other cellular products contribute to the immense
problem of POAF. Aim 1 will allow confirmation that neutrophils, monocytes, and their products contribute
to POAF. Furthermore, we will identify the specific factors in the inflammatory pathway(s) that lead to the
arrhythmia and compromised cardiac function.
Based on preliminary data, our working hypothesis is that inflammatory stress in the pericardial
environment, driven by neutrophils and monocytes (which are the two vastly most abundant cell population
in the pericardial space at the time the majority of people develop POAF), directly affects atrial
electrophysiology, resulting in an increased probability of atrial fibrillation. In addition to deli...

## Key facts

- **NIH application ID:** 9858242
- **Project number:** 5I01CX001526-04
- **Recipient organization:** ST. LOUIS VA MEDICAL CENTER
- **Principal Investigator:** Spencer J Melby
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9858242

## Citation

> US National Institutes of Health, RePORTER application 9858242, Contribution of Inflammation and Oxidative Stress in Pericardial Fluid to Postoperative Atrial Fibrillation After Cardiac Surgery (5I01CX001526-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9858242. Licensed CC0.

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