Are Opioid Use and Cardiovascular Function Linked?

Researchers investigate effects of chronic opioid use on cardiac muscle cells

Innovations in Congenital Heart | Fall 2019

It’s clear that opioid misuse and addiction has led to a national health crisis, with more than 130 people dying each day from opioid-related overdose, according to the Centers for Disease Control and Prevention. While there is increased public awareness of the devastating effects of acute opioid use, the health consequences of chronic exposure are not well-known.

An investigational collaboration between University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine is under way to identify whether there is an association between cardiac function and opioids, including morphine, hydrocodone and synthetics such as fentanyl and methadone.

There have been a number of potential links between chronic opioid use and cardiac disease,” says Eric Devaney, MD, Chief of Pediatric Cardiac and Thoracic Surgery at UH Rainbow Babies & Children's Hospital and Clinical Professor at the School of Medicine. “What we are trying to do in our lab is identify whether this is a direct or secondary effect and determine the specific mechanism.”

CARDIAC MYOCYTES

Utilizing a Sprague Dawley rat model, researchers are studying the potential physiology of cardiac myocytes. “We are trying to determine if there are effects on cardiac muscle function in the face of opioid exposure in a normal state, an ischemic state and a state of heart failure,” says Dr. Devaney. “We are also looking at if there are sex-dependent differences related to opioids and cardiovascular function.” Data collection is measuring cardiac muscle contractility, arrhythmogenicity and how intracellular calcium is managed, which is a determinant of how cardiac muscle cells function.

“When you look at the literature related to opioid use and cardiac health, you find association studies that are often inconclusive and contradictory,” says Matt Klos, PhD, Co-Director of the UH Rainbow Babies & Children's Hospital Pediatric Cardiac Surgery Laboratory and Adjunct Clinical Instructor at the School of Medicine. “We wanted to use a reduction model to determine if we see any changes in cardiac function to gain a better understanding.”

Each cell has three major receptors, and testing the various forms of opioids will provide insight on how each combination of receptors might be influencing cardiac function. As the study continues, a next step will be to develop a transgenic animal model.

OPIOID PROJECT RESEARCH AWARD

Kayla Hicks, a medical student at the School of Medicine working on the opioid project, recently won first place in the Starr Medical Student and Resident Research Forum for her poster presentation, Sex Dependent Differences in Cardiac Myocyte Excitation-Contraction Coupling after Chronic Stimulation of the Delta or Kappa Opioid Receptors during Normoxic and Hypoxic Conditions. Sponsored by the Association of Women Surgeons (AWS), the contest facilitates interaction and idea exchange among students interested in surgery, surgical residents and faculty members of various institutions. Each year, 10 medical students and 10 residents are invited to present their research posters at the AWS Annual Conference. Held in conjunction with the American College of Surgeons Clinical Congress, the contest is supported by donations to the AWS Foundation.

OPIOID ADDICTION PROLONGED RISK

“One of the interesting aspects of this epidemic is that when we treat opioid addiction, we often treat it by using an opioid substitute such as methadone that is taken long-term and gradually weaned off,” says Dr. Devaney. “Because an increasing number of patients are going to be exposed to chronic opioid therapy, we need to know what the ongoing risks are for cardiovascular function.

"The project has been under way during the past year, and an abstract of preliminary data has been accepted by the American Heart Association for publication.

For more information, please call 216-553-1947 or email Dr. Devaney at Peds.Innovation@UHhospitals.org.