- Two new, basic research studies in rodents (mice and rats) analyzed the impacts that alcohol may have on the heart.
- In a mouse study, abnormal heart rhythms that can occur after a pattern of repeated simulation of binge drinking may be related to a spike in a stress protein found in the heart. Researchers tested a heart-protective molecule to reduce the stress protein spike and the resulting irregular heart rhythms.
- In a study using rats that lacked estrogen production to simulate human menopause, alcohol exposure resulted in negative changes in heart function in animals receiving estrogen replacement.
An Anti-Arrhythmic Action and Novel Mechanisms of Alda-1 in Holiday Heart Syndrome
(Poster Presentation Mo065/Khanal)
Binge drinking (five drinks within two hours for men and four drinks within two hours for women) is common around the world. Recent research has also found the incidence of atrial fibrillation (AFib), the most common type of irregular heart rhythm or arrhythmia, continues to rise, according to the study.
“Around the holidays, opportunities for celebration – often accompanied by heavy drinking – occur during a brief period of time. Unfortunately, this sometimes sends revelers, even those with no previous heart condition, to the hospital with a racing or abnormally beating heart,” said Saugat Khanal, Ph.D., lead author of the study and a post-doctoral scholar in the department of physiology & cell biology at The Ohio State University College of Medicine in Columbus, Ohio. “Our study in mice explored the mechanism of alcohol-induced arrhythmia and a possible way to prevent it in the future.”
“Repeated binge drinking can lead to serious arrhythmias. This includes AFib, which is the most common type of arrhythmia.” Said Khanal. “AFib can raise the risk of stroke and heart failure. About one-third of new AFib diagnoses are related to alcohol use. Recurrence of AFib is common in habitual binge drinkers. The link between repeated binge drinking and arrhythmia at times of celebration is so well-known that medical professionals call it holiday heart syndrome which is caused by repeated binge drinking over the holidays.”
Previous animal research by this research team found binge-drinking-related arrhythmias are induced by elevations in a stress-induced protein called JNK2. This can cause heart cells to mishandle calcium and misfire, resulting in the heart beating too fast or irregularly. The new study suggests, for the first time, that the molecule Alda-1 may prevent the activation of JNK2 that leads to AFib.
The study found:
- In this study, more than 70% of the mice that were given alcohol mimicking binge drinking developed AFib, compared with none of those who also received the investigational cardiac protective agent Alda-1.
- Exposure to binge drinking levels of alcohol doubled levels of JNK2 activity compared to a control group that did not mimic binge-drinking. This activated JNK2 increased the AFib susceptibility in the mouse models mimicking binge drinking.
- Both JNK2 enzyme activity and calcium handling remained normal in the heart cells of the mice treated with Alda-1.
“Abstinence from alcohol can prevent most alcohol-associated AFib risks. Unfortunately, despite nationwide education efforts, binge drinking among all age groups continues to rise. Our findings suggest that developing new drugs, including Alda-1 and other JNK2-specific inhibitors, may be an effective anti-AFib strategy for people with holiday heart syndrome,” Khanal said.
The study was limited because researchers used a mouse model to replicate human holiday heart syndrome. Although the mouse model showed promising results, it may not have fully captured the complexities of binge drinking in humans and related cardiovascular consequences.
“Studies using larger animals will be a future direction to translate our exciting findings into clinical applications,” Khanal said.
Study background and details:
- Mice used in the study were divided into three groups: a holiday heart syndrome group, subject to four every-other-day doses of alcohol, mimicking holiday binge drinking in humans; an Alda-1 group, who received the alcohol regimen plus the cardioprotective agent Aldi-1; and controls, who received saline (no alcohol) or Alda-1 exposure.
- Outcome measures were obtained 24 hours after the last alcohol exposure. Measures used included:
- Electrophysiological studies assessed burst pacing-induced atrial arrhythmias;
- Calcium imaging studies investigated the impact of Alda-1 on JNK2-dependent Calcium mishandling; and
- Biochemical assays examined the effects of alcohol on ALDH2 expression and apoptotic signaling pathways.
Co-authors, their disclosures and funding sources are listed in the abstract.
Estrogen Modulation of Ethanol-Evoked Cardiac Oxidative Stress and Dysfunction: Role of Circadian Clock Period-2 and Ferroptosis in Estrogen Deficient Rats
(Poster Presentation Tu132/Ahmed and Abdel-Rahman)
The hormone estrogen helps keep blood vessels open and flexible and is generally thought to help protect women from heart disease. These higher estrogen levels may lead to fewer heart attacks and strokes in premenopausal women than in men of the same age. However, alcohol exposure worsens cardiovascular function more in women than men, researchers said. Also, in previous animal studies, alcohol has been confirmed to worsen heart function more in those animals with the highest estrogen levels.
This study explored whether several measures of heart function and the proteins that regulate it differed with regular alcohol exposure in female rats that received hormones to replenish their estrogen supply and those that did not.
The eight-week study included female rats with ovaries removed to simulate menopause (when the ovaries make virtually no estrogen). Researchers compared the menopausal rats who received regular alcohol exposure (delivered as 5% ethanol in a liquid diet) to those who were given alcohol and estrogen replacement.
The study found that, compared to those receiving alcohol alone, the menopausal rats treated with estrogen replacement plus alcohol had:
- both positive (lower weight gain and fat mass) and negative (higher blood pressure and heart rate) changes in measures related to heart health;
- a reduction in the heart’s ejection fraction, the heart’s ability to pump oxygen-rich blood to the rest of the body, as well as two other indicators of poorer pumping that may eventually result in heart failure; and
- disruption in circadian clock proteins, which are known to regulate heart function and other body processes, increased both oxidative stress (which can trigger plaque build-up in the arteries) and ferroptosis (a type of cell death that is a result of too much iron) in the heart’s cells.
“It was surprising to see the significant impact estrogen had on alcohol-induced heart dysfunction, despite its known cardioprotective effects. Premenopausal and menopausal women taking hormone replacement therapy should be cautious about alcohol consumption because it may be a factor in heart dysfunction,” said Syed Anees Ahmed, Ph.D., lead author of the study and a postdoctoral researcher in pharmacology and toxicology at the Brody School of Medicine at East Carolina University in Greenville, North Carolina.
The study findings are limited by the short duration and the use of an animal model. Because the study was conducted in rats, the results may not fully represent the longer-term impact of taking estrogen and regularly consuming alcohol in menopausal women as they age.
The American Heart Association recommends moderation in alcohol consumption for optimal cardiovascular health. If you don’t drink already, don’t start. If you do drink, talk with your doctor about the benefits and risks of consuming alcohol in moderation. Some people should not drink at all, like women who are pregnant or trying to get pregnant, people under age 21 and people with certain health conditions. The Association does not recommend drinking wine or any other form of alcohol to gain potential health benefits. Instead, take steps to lower cholesterol, control high blood pressure, manage weight, get enough physical activity, get plenty of sleep, stay away from tobacco and follow a healthy diet, as detailed in the Association’s Life’s Essential 8 recommendations.
Note: The studies featured in this article are research abstracts. Abstracts presented at American Heart Association’s scientific meetings are not peer-reviewed, and the findings are considered preliminary until published as full manuscripts in a peer-reviewed scientific journal.