Alex Carll, an associate professor in the Department of Physiology, studies the impacts of ingredients in vape liquids in the laboratory. Rodrigo Cavallazzi, professor of medicine in the Division of Pulmonary, Critical Care and Sleep Disorders, treats patients as director of the medical intensive care unit at UofL Health – UofL Hospital.

UofL News spoke with Carll and Cavallazzi about their findings and insights to understand how work in the laboratory echoes patients’ experience with e-cigarettes.

UofL News: Dr. Carll, what is the focus of your research and what have you discovered about the effects of vaping?

Alex Carll: We test the impacts of inhaled electronic cigarette aerosols on heart function and blood pressure.��We have found that exposures to these aerosols in mice can rapidly disrupt heart rhythm, causing abnormal heart beats that occur either prematurely or are skipped.

Our studies in animal models indicate that vaping likely causes cardiac arrhythmias (abnormal heart beats) and does so by causing fight-or-flight stress responses. It increases blood pressure in humans and mice, as well. These abnormal heart beats can increase risk for fatal arrhythmias and sudden cardiac death, which have recently been associated with vaping in young adult patients.

Another mouse study from our group indicates that vaping during pregnancy may cause peripartum arrhythmias, with these effects continuing well after e-cigarette cessation.

UofL News: Dr. Cavallazzi, have you seen these types of effects in your patients?

Rodrigo Cavallazzi: When I see patients, my focus is more on the respiratory system, but it is definitely conceivable that patients who vape have several consequences to their cardiovascular system, including arrhythmias, based on the load of nicotine and other potentially toxic chemical substances��they are exposed to through vaping.��

UofL News: What are the symptoms you most often see in patients who vape?

Cavallazzi: I see respiratory symptoms such as cough, shortness of breath, chest tightness and wheezing, which I am certain can be attributed to vaping in some patients. I also see exacerbation of underlying lung diseases such as asthma and COPD.

Some of these patients end up in the ICU. I have seen a few patients with acute respiratory failure that I believe was due to a very serious condition called “e-cigarette or vaping product use-associated lung injury” (EVALI). These patients develop acute respiratory failure that sometimes resembles severe pneumonia or a severe Covid-19 infection. The medical literature indicates that this happens when tetrahydrocannabinol (THC, the principal��psychoactive constituent��of��cannabis) is added to an e-cigarette device and is��contaminated with vitamin E acetate. It also has been reported in patients inhaling nicotine only.

The effects mentioned in Dr. Carll’s studies seem to corroborate what other authors have written on the cardiovascular effects of inhaled nicotine and other potentially toxic chemical substances through e-cigarettes.��

UofL News: Dr. Carll, have you been involved in any human studies?

Carll: Yes, my lab has published two population studies detailing smoking’s adverse impacts on cardiac conduction, and we have associated some of our observations with long-term cardiovascular mortality.

Our population studies in smokers showed correlations between cotinine in the blood, a biomarker indicating nicotine exposure, and electrocardiogram (ECG) abnormalities. Some of these ECG abnormalities in smokers corresponded with over a 25-year follow-up period. Additionally, some of the ECG effects associated with smoking and nicotine corresponded with changes in the fight-or-flight stress hormones norepinephrine, epinephrine and dopamine. Dopamine itself also appeared responsible for shortening in the time between atrial and ventricular contraction.

I also have been involved in a yet-unpublished clinical trial focused on preventing smoking’s adverse impacts on heart conduction.

UofL News: Dr. Cavallazzi, how would the effects that Dr. Carll documented in the lab affect patients?

Cavallazzi: As a clinician, the chronic cardiovascular effects of combustible cigarette smoking I often see are myocardial infarction,��stroke and peripheral vascular disease. The latter manifests as difficulty walking and erectile dysfunction.

UofL News: How does the knowledge we have about the effects of cigarette smoking translate to vaping? And what do you tell your patients about the health impacts of vaping and smoking?

Cavallazzi: I tell them��the truth. Combustible cigarette smoking increases the risk of lung cancer development by 15 to 30 times. Up to 50% of people who smoke combustible cigarettes develop COPD. This is a much higher figure than previously thought.

Combustible cigarette smoking increases the risk of a heart attack by 4 to 7 times and increases the risk of other cancers and conditions, including peripheral vascular disease and stroke.

We are now starting to understand the risks of e-cigarette smoking: EVALI, exacerbation of asthma and COPD. There is data that daily users of e-cigarettes have more than double the odds of chronic lung disease, including chronic bronchitis, emphysema or COPD.

UofL News: How do you help your patients quit smoking or vaping?

Cavallazzi: I remind my patients that smoking combustible cigarettes or e-cigarettes is not a failure of character. It is never too late to quit smoking. Most people who quit for good tried a number of times before they were successful. Nicotine is highly addictive and is often listed as one of the most addictive substances out there.

Since nicotine is so addictive, I often offer pharmacological aids such as nicotine replacement – patches, gum and lozenges. The nicotine exposure obtained through these medications is sustained, low dose,��designed to be of short term (weeks), not inhaled and not combined with other potentially toxic chemical substances.

There are also other medications that are sometimes offered, including an antidepressant called bupropion, which is often combined with nicotine replacement. And there is a medication called varenicline, which acts on the nicotine receptors.

UofL News: Cigarette smoking has been declining since 1965, which is great news. But e-cigarettes are a relatively new product. What is the most concerning trend in the use of e-cigarettes?

Cavallazzi: Unfortunately, the rates of e-cigarette use are moving in the opposite direction. From 2014 to 2022, current e-cigarette users increased from 3.7% to 6.0% of adults. From 2011 to 2022, the rates went from 0.6% to 4.6% among middle school students and from 1.5% to 10.0% among high school students. This is concerning. These pre-adolescents and adolescents are more vulnerable, and some of the vape companies have marketed their products in ways that attract young users.

Carll: The e-cigarette market is constantly evolving to dodge regulations and enhance appeal, nicotine delivery and the potential for addiction. New untested products and chemical combinations are routinely deployed to users with minimal safety testing. While the long-term risks of current vaping products remain unclear, this real-world uncontrolled experiment continues with little regulation. Our research remains critical to inform users, practitioners and regulators about the overall risks of e-cigarettes and the specific device types, settings and ingredients that pose the greatest harms.

University of Louisville environmental medicine researchers are working to better understand how natural, social and personal environments affect health, particularly the cardiovascular system. In recent months, the National Institutes of Health have awarded four grants totaling $11.6 million to researchers affiliated with UofL’s to study factors affecting heart health. Through these projects, they hope to better understand how environmental exposures and tobacco products can affect the cardiovascular system, as well as how remodeling takes place in the heart after a heart attack.

“The unique and synergistic research collaborative we have built at the Envirome Institute already has resulted in new discoveries about the biological and the environmental factors that contribute to heart disease,” said Aruni Bhatnagar, chief of the UofL Division of Environmental Medicine and director of the Envirome Institute.��“Our studies funded by these new grants will lead to better understanding of the causes and progression of cardiovascular disease and new ways to protect and improve cardiovascular health.”

The new projects address the cardiovascular effects of newly introduced ingredients in electronic cigarette liquids, exposure to benzene, prenatal and infant exposure to combinations of substances and their impact on sleep in adolescence and the metabolic processes occurring after a heart attack that result in scarring in the heart.

One grant provides $3.3 million to investigate how exposure to benzene affects blood vessels. Sanjay Srivastava, professor of medicine who leads the project, said preliminary research shows that benzene worsens atherosclerosis, an underlying cause of cardiovascular disease and stroke. Atherosclerosis, a buildup of fatty deposits in arteries, reduces blood flow and flexibility of the arteries. Benzene is one of the top 20 pollutants from industrial sources in the United States, primarily from gasoline refineries. Outside industrial locations, exposure is higher near gas stations and from automobile exhaust and cigarette smoke. Benzene is known to cause cancer, but this is the first study to evaluate the effects of the chemical on heart disease, especially at levels typically experienced in the environment.

Cardiac fibrosis is essential for upholding the structure of the heart after heart attack, but also tends to produce excessive scar tissue and stiffening of the heart. Bradford Hill is examining the processes behind stiffening and scarring in the heart following myocardial infarction. A $2.3 million grant is funding the professor of medicine’s work to investigate the metabolic processes underlying this process. Hill hopes the work will lead to a therapy that supports the repair process but also reduces excessive scarring, allowing heart attack patients to fare better down the road.

Clara Sears, assistant professor of environmental medicine, received a $2.1 million grant for a project to discover how exposure to mixtures of common chemicals and pollutants before birth and in infancy affects sleep health in adolescence. Ultimately, she hopes to understand whether exposures to phthalates (common components of plastics), metals and per-/polyfluoroalkyl substances (PFAS – known as “forever chemicals”) may be linked to cardiovascular issues later in life.

The largest of the grants, $3.9 million, will fund research into potential toxicity of new synthetic cooling compounds that are being used in electronic cigarette liquids. Daniel J. Conklin leads the project to learn whether these compounds are harmful to the cardiovascular and pulmonary systems when heated and inhaled. The compounds mimic the cooling effect of menthol, which can be irritating in high doses, but they have not been tested for safety or toxicity as inhaled substances. For this new project, Conklin, a professor of medicine who has studied the cardiovascular effects of e-cigarette and cigarette components for more than two decades, is testing the effects of the new constituents as well as documenting the impact of dual use – smoking conventional cigarettes along with vaping. The Food and Drug Administration’s Center for Tobacco Products will use the results of these studies to determine potential recommendations to regulate the products’ use.

“We are going to address the issue of dual use, where there are both cigarettes and e-cigarettes in use, because this is a very common phenomenon and the signals are coming that it’s actually worse than either one alone,” Conklin said.

“Our findings demonstrate that short-term exposure to e-cigarettes can destabilize heart rhythm through specific chemicals within e-liquids,” said Alex Carll, assistant professor in the UofL Department of Physiology who led the study. “These findings suggest that e-cigarette use involving certain flavors or solvent vehicles may disrupt the heart’s electrical conduction and provoke arrhythmias. These effects could increase the risk for atrial or ventricular fibrillation and sudden cardiac arrest.”

The researchers tested the cardiac impacts of inhaled e-cigarette aerosols solely from the main two ingredients in e-liquids (nicotine-free propylene glycol and vegetable glycerin) or from flavored retail e-liquids containing nicotine. They found that for all e-cigarette aerosols, the animals’ heart rate slowed during puff exposures and sped up afterwards as heart rate variability declined, indicating fight-or-flight stress responses. In addition, e-cigarette puffs from a menthol-flavored e-liquid or from propylene glycol alone caused ventricular arrhythmias and other conduction irregularities in the heart.

Conducted in collaboration with Daniel Conklin and Aruni Bhatnagar, professors in the UofL Division of Environmental Medicine, this work adds to a growing body of research on the potential toxicity and health impacts of e-cigarettes reported by the American Heart Association Tobacco Regulation and Addiction Center, for which UofL serves as the flagship institute.

“The findings of this study are important because they provide fresh evidence that the use of e-cigarettes could interfere with normal heart rhythms – something we did not know before,” Bhatnagar said. “This is highly concerning given the rapid growth of e-cigarette use, particularly among young people.”

As e-cigarette use has grown nationwide, the potential advantages and harms of vaping have been debated. Since vaping does not involve combustion, it exposes users and bystanders to little if any carbon monoxide, tar or cancer-causing nitrosamines compared with conventional cigarettes. However, e-cigarettes can deliver aldehydes, particles and nicotine at levels comparable to combustible cigarettes. Vaping might help smokers quit combustible cigarettes, but the appeal and addictiveness of e-cigarettes may encourage youth to vape amidst unknown long-term risks or take up smoking. More than 25% of high schoolers and 10% of middle schoolers in the U.S. reported using e-cigarettes before the pandemic.

Additional research by Carll and Matthew Nystoriak, an associate professor of medicine at UofL, to determine the effects of vape flavorings on the heart recently received $3.6 million in research funding from the National Institutes of Health.

“Our team’s findings that specific ingredients in e-cigarette liquids promote arrhythmias indicates there is an urgent need for more research into the cardiac effects of these components in both animals and humans,” Carll said.

Perhaps early 20s? Maybe even 16?

“The average chronic smoker begins smoking at 13.7 years old,” says Daniel Conklin, PhD. “And if you know anything about averages, that’s … not good.”

Conklin, a professor of medicine at the University of Louisville, specializes in cardiovascular research and what environmental pollutants do to our bodies. At this month’s Beer with a Scientist, Conklin will discuss smoking and what we do (and don’t) know about the harm caused by electronic cigarettes.

“Essentially, we’re trying to separate fact from fiction. We’re currently part of an American Heart Association Tobacco Regulation Center to investigate emerging tobacco products and their potential to cause harm to the cardiovascular system,” Conklin said. “We’re trying to figure out the best way to regulate these products.”

Scientists have known that conventional tobacco products are associated with cardiovascular disease risk since the 1960s, Conklin said. However, with new technology comes a new generation of health risks and the emerging science showing what vaping does to the body may shock you.

Conklin’s talk will begin at 7 p.m. on Wednesday, May 15, at , 8023 Catherine Lane. A 30-minute presentation will be followed by an informal Q&A session.

E-cigarettes come in all kinds of flavors, like mango, cotton candy or creme brûlée.��

But a new study from Boston University and the University of Louisville��shows inhaling those flavors could be bad for your cardiovascular health.��

Researchers found short-term exposure to some flavor additives may cause adverse health effects, such as blood vessel dysfunction that could lead to hypertension.

These results were published in a journal of the American Heart Association (AHA):.��

Daniel J. Conklin, PhD, a professor of cardiovascular medicine at UofL and an author on the study, said little is known about the health effects of e-cigarettes compared to what we know about regular cigarettes.

Despite many still containing nicotine and some with high levels of nicotine, such as JUUL, he said e-cigarette devices are often seen as a cessation tool or as a “safer” alternative because e-cigarettes contain fewer .

“But we can’t rule out risks for other diseases just because cancer risk is reduced,” he said.��

In 2016, the U.S. ��reported that 15.4 percent of adults said they had ever used an e-cigarette and 3.2 percent said they were current users.

But Conklin said e-cigarettes appear to have gained the most traction with teenagers and young adults. According to the , high school students use e-cigarettes more than adults and more than they use traditional cigarettes.

“That’s the most disconcerting aspect, because long-term tobacco use starts in the youth with addiction to nicotine,” he said. “So, many public health advocates are worried we’re looking at addicting a new generation.”

Green is a second-year student in the UofL School of Dentistry. UofL News had the chance to talk to her about her motivation and her goals.��

UofL News: What motivated you to invest in health and social justice?

Ashton Green: I’ve always been very aware that the best way to be useful in society is to serve those around you. I have also always had an interest in the field of health care. In my initiative to address local health care disparities, I think my target area would deal primarily with cigarette smokers because in Kentucky smoking is a huge issue. ��Part of my motivation for choosing to focus on smoking also stems from my family. Some of my mother’s side of the family is from Kentucky and we have lost several relatives due to lung cancer and esophageal cancer. Smoking and diseases that stem from it are very personal to me and I want to come up with a resource that I feel the greater community can easily use and learn from. Hopefully this knowledge can contribute to cultural change. The impact might be small at first, but I feel that if you target one area you have the ability to focus on it and expand it to make greater change later.

UofL News: Explain one experience that drives you to make a difference.

Green: Upon first moving here I wasn’t quite aware of how intense the problem of smoking is. One time while walking home from school I passed by the hospital. As I walked by, I saw patients in hospital gowns and some carrying IV poles standing outside smoking cigarettes. As you can imagine, this was such a confusing sight, but in that moment I realized people must not be aware of how detrimental smoking actually is. I was definitely shocked that day. I remember calling my mom about it and saying, ‘You won’t believe what I just saw.’ That was pretty eye-opening.

UofL News: What would you like to accomplish as a Health and Social Justice Scholar?

Green:��I want to create something that is sustainable long after I graduate. I have a few ideas I would like to speak with my mentor about and get the ball rolling. I definitely want to address smoking cessation and create a resource that will last long after I’m gone, because the point is to make permanent, positive change if you can. I have some ideas that I am really excited about.

Editor’s note: UofL News also had the opportunity to talk to Health and Social Justice Scholar��Mallika Sabharwal. .��

About the Health and Social Justice Scholars program

Introduced in the spring of 2016, the Health and Social Justice Scholars Program engages professional students with local communities and faculty mentors to bring about changes to benefit underserved populations in the Louisville area.��For more information, visit .

Infertility can be devastating for those who long to have a child. Aside from the financial burden of infertility treatment, couples can face anxiety, depression and a variety of other health problems. Data from a Centers for Disease Control and Prevention U.S. National Health Statistics Report conducted from 2006-2010 found nearly 11 percent, or 6.7 million, of women ages 15 to 44 have an impaired ability to get pregnant or carry a baby to term and 6 percent, or 1.5 million, of married women ages 15��to��44 are infertile. ��

Kira Taylor, PhD, MS, assistant professor, Department of Epidemiology and Population Health in the UofL School of Public Health and Information Sciences, says exposure to tobacco smoke may be more harmful in women who carry the slow metabolizer form of NAT2, a gene that plays an important role in metabolism of toxins present in tobacco smoke and other hazardous substances.��

“We think that if a woman carries the slow form of the NAT2 gene, cigarette toxins will be metabolized and excreted more slowly, thus exacerbating the effects of smoking hazards – including making infertility problems more pronounced,” Taylor said.

Taylor and her research team will consider ovarian reserve – a woman’s remaining egg count – and in vitro fertilization success rates as they relate to the cumulative impact of smoking, exposure to secondhand smoke, and finally a combination of exposure to tobacco smoke and presence of the NAT2-slow gene.

Participants will provide a urine sample, which will be used to assess NAT2 genotype and recent exposure to cigarette smoke, and they will answer a questionnaire regarding lifetime exposure to cigarette smoke. Researchers will assess ovarian reserve through hormone levels and ultrasound, and success rates of in vitro fertilization procedures will be recorded.

“The results of this study will add to a growing body of evidence for the role of current smoking, past smoking and passive smoking on ovarian reserve and in vitro fertilization,” Taylor said. “We hope to determine for the first time whether the observed effects of smoking are stronger among women carrying the slow version of NAT2.”��

Study co-investigators include Henry Bohler, MD, associate professor, Department of Obstetrics, Gynecology and Women’s Health, and practicing physician with the University of Louisville Physicians Fertility Center; David Hein, PhD, professor and chair,��; and Rachel Neal, PhD, associate professor, Department of�� .

If Taylor and her colleagues find an interaction between NAT2 and smoking with regard to ovarian reserve or in vitro fertilization, it could pave the way for more accurate analyses of the effects of smoking. In addition, the NAT2-slow gene may be a biomarker for fertility specialists to consider as a predictor of in vitro fertilization success or failure. In the future, it also may be possible to treat individuals who are more genetically susceptible – those with the slow NAT2 gene – using personalized medicine in the form of drug or gene therapy to mitigate the effects of exposure to harmful substances.