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Myoglobinemia, Peripheral Arterial Disease, and Patient Mortality
Journal article   Peer reviewed

Myoglobinemia, Peripheral Arterial Disease, and Patient Mortality

Ottis Scrivner, Emma Fletcher, Carson Hoffmann, Feifei Li, Trevor Wilkinson, Dimitrios Miserlis, Robert S Smith, William T Bohannon, Roy Sutliff, William D Jordan, …
Journal of the American College of Surgeons, Vol.236(4), pp.588-598
04/2023
DOI: https://doi.org/10.1097/XCS.0000000000000554
PMID: 36656266
Web of Science ID: WOS:000960891300006

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Abstract

Peripheral arterial disease (PAD) causes leg muscle damage due to inadequate perfusion and increases cardiovascular events and mortality 2- to 3-fold. It is unclear if PAD is a biomarker for high-risk cardiovascular disease or if skeletal muscle injury harms arterial health. The objective of this work is to test if serum myoglobin levels (myoglobinemia) are a marker of PAD, and if so, whether myoglobin impairs vascular health. Patient blood samples were collected from PAD and control (no PAD) patients and interrogated for myoglobin concentrations and nitric oxide bioavailability. Patient mortality over time was captured from the medical record. Myoglobin activity was tested on endothelial cells and arterial function. Myoglobin is a biomarker for symptomatic PAD and was inversely related to nitric oxide bioavailability; 200 ng/mL myoglobin in vitro increased endothelial cell permeability in vitro and decreased nitrate bioavailability. Ex vivo, 100 ng/mL myoglobin increased vascular tone in naive murine aortas approximately 1.5 times, impairing absolute vessel relaxation. In vivo, we demonstrated that myoglobinemia caused impaired flow-mediated dilation in a porcine model. Patients presenting with myoglobin levels of 100 ng/mL or greater had significantly more deaths than those with myoglobin levels of less than 100 ng/mL. Using a combination of patient data, in vitro, ex vivo, and in vivo testing, we found that myoglobin is a biomarker for symptomatic PAD and a potent regulator of arterial health that can increase vascular tone, increase vascular permeability, and cause endothelial dysfunction, all of which may contribute to the vulnerability of PAD patients to cardiovascular events and death. This article was presented at the Southern Surgical Association 134th Annual Meeting, Palm Beach, FL, December 2022.

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