The relationship between plasma lipid peroxidation products and primary graft dysfunction after lung transplantation is modified by donor smoking and reperfusion hyperoxia

Joshua M Diamond; Mary K Porteous; L Jackson Roberts 2nd; Nancy Wickersham; Melanie Rushefski; Steven M Kawut; Rupal J Shah; Edward Cantu 3rd; David J Lederer; Shampa Chatterjee; Vibha N Lama; Sangeeta Bhorade; Maria Crespo; John McDyer; Keith Wille; Jonathan Orens; Ann Weinacker; Selim Arcasoy; Pali D Shah; David S Wilkes; Chadi Hage; Scott M Palmer; Laurie Snyder; Carolyn S Calfee; Lorraine B Ware; Jason D Christie; Lung Transplant Outcomes Group

doi:10.1016/j.healun.2015.12.012

The relationship between plasma lipid peroxidation products and primary graft dysfunction after lung transplantation is modified by donor smoking and reperfusion hyperoxia

J Heart Lung Transplant. 2016 Apr;35(4):500-507. doi: 10.1016/j.healun.2015.12.012. Epub 2016 Jan 7.

Authors

Joshua M Diamond¹, Mary K Porteous¹, L Jackson Roberts 2nd², Nancy Wickersham³, Melanie Rushefski¹, Steven M Kawut^{1

4

5}, Rupal J Shah⁶, Edward Cantu 3rd⁷, David J Lederer⁸, Shampa Chatterjee⁹, Vibha N Lama¹⁰, Sangeeta Bhorade¹¹, Maria Crespo¹², John McDyer¹², Keith Wille¹³, Jonathan Orens¹⁴, Ann Weinacker¹⁵, Selim Arcasoy⁸, Pali D Shah¹⁴, David S Wilkes¹⁶, Chadi Hage¹⁶, Scott M Palmer¹⁷, Laurie Snyder¹⁷, Carolyn S Calfee^{6

18}, Lorraine B Ware^#¹⁹, Jason D Christie^#^{1

4}; Lung Transplant Outcomes Group

Affiliations

¹ Pulmonary, Allergy, and Critical Care Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
² Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, Tennessee.
³ Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University, Nashville, Tennessee.
⁴ Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Philadelphia, PA.
⁵ Penn Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
⁶ Department of Medicine, University of California, San Francisco, California.
⁷ Division of Cardiovascular Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.
⁸ Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, New York.
⁹ Department of Physiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Philadelphia, PA.
¹⁰ Division of Pulmonary, Allergy, and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan.
¹¹ Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois.
¹² Division of Pulmonary, Allergy, and Critical Care, University of Pittsburgh, Pittsburgh, Pennsylvania.
¹³ Division of Pulmonary and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
¹⁴ Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Johns Hopkins University Hospital, Baltimore, Maryland.
¹⁵ Division of Pulmonary and Critical Care Medicine, Stanford University, Palo Alto, California.
¹⁶ Division of Pulmonary, Allergy, Critical Care, and Occupational Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
¹⁷ Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University, Raleigh-Durham, North Carolina.
¹⁸ Departments of Medicine and Anesthesia, University of California, San Francisco, California.
¹⁹ Departments of Medicine and Pathology, Microbiology and Immunology, Vanderbilt University, Nashville, Tennessee.

^# Contributed equally.

Abstract

Background: Donor smoking history and higher fraction of inspired oxygen (FIO2) at reperfusion are associated with primary graft dysfunction (PGD) after lung transplantation. We hypothesized that oxidative injury biomarkers would be elevated in PGD, with higher levels associated with donor exposure to cigarette smoke and recipient hyperoxia at reperfusion.

Methods: We performed a nested case-control study of 72 lung transplant recipients from the Lung Transplant Outcomes Group cohort. Using mass spectroscopy, F2-isoprostanes and isofurans were measured in plasma collected after transplantation. Cases were defined in 2 ways: grade 3 PGD present at day 2 or day 3 after reperfusion (severe PGD) or any grade 3 PGD (any PGD).

Results: There were 31 severe PGD cases with 41 controls and 35 any PGD cases with 37 controls. Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (28.6 pg/ml vs 19.8 pg/ml, p = 0.03). Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (29.6 pg/ml vs 19.0 pg/ml, p = 0.03) among patients reperfused with FIO2 >40%. Among recipients of lungs from donors with smoke exposure, plasma F2-isoprostane (38.2 pg/ml vs 22.5 pg/ml, p = 0.046) and isofuran (66.9 pg/ml vs 34.6 pg/ml, p = 0.046) levels were higher in severe PGD compared with control subjects.

Conclusions: Plasma levels of lipid peroxidation products are higher in patients with severe PGD, in recipients of lungs from donors with smoke exposure, and in recipients exposed to higher Fio2 at reperfusion. Oxidative injury is an important mechanism of PGD and may be magnified by donor exposure to cigarette smoke and hyperoxia at reperfusion.

Keywords: F2-isoprostane; ischemia reperfusion; isofuran; lipid peroxidation; lung transplantation; primary graft dysfunction.

Publication types

Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Biomarkers / blood
Female
Follow-Up Studies
Humans
Hyperoxia / blood*
Hyperoxia / etiology
Lipid Peroxidation
Lung Transplantation / adverse effects*
Male
Postoperative Complications*
Primary Graft Dysfunction / blood*
Primary Graft Dysfunction / etiology
Reperfusion Injury / blood
Reperfusion Injury / complications*
Retrospective Studies
Smoking / adverse effects*
Time Factors
Tissue Donors

Substances

Biomarkers

Abstract

Publication types

MeSH terms

Substances

Grants and funding