Two new, key animal studies shed light on alcohol consumption and the heart. The first study may explain why drinking too much alcohol sometimes causes an irregular heartbeat and a possible way to prevent it. The second study investigated why alcohol may have a negative impact on heart function in women receiving estrogen replacement therapy. Both studies are preliminary research for posters presented at the 2024 American Heart Association Basic Cardiovascular Science Sessions. The meeting is in Chicago, July 22–25, 2024, and offers the latest research on innovations and discoveries in cardiovascular science.
Binge drinking (five drinks within two hours for men and four drinks within two hours for women) is common worldwide. Recent research also found that the incidence of atrial fibrillation (AFib), the most common type of irregular heart rhythm or arrhythmia, continues to rise, according to the study.
“During the holidays, opportunities to celebrate – often accompanied by heavy drinking – appear at short notice. Unfortunately, this sometimes sends revelers, even those with no prior heart disease, to the hospital with an irregular or irregular heartbeat.” said Saugat Khanal, Ph.D., lead author of the study and a postdoctoral fellow in the department of physiology and 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 heavy drinking can lead to serious arrhythmias. This includes AFib, which is the most common type of arrhythmia.” Hanal said.
AFib can increase the risk of stroke and heart failure. About a third of new AFib diagnoses are related to alcohol use. Recurrence of AFib is common in habitual heavy drinkers. The link between repeated excessive alcohol consumption and arrhythmia during festive periods is so well known that medical professionals call it holiday heart syndrome, which is caused by repeated excessive alcohol consumption during the holidays.”
Saugat Khanal, Postdoctoral Fellow, Department of Physiology and Cell Biology, The Ohio State University College of Medicine in Columbus
Previous animal research by this research group found that arrhythmias associated with excessive alcohol consumption are caused by increases in a stress-induced protein called JNK2. This can cause heart cells to mishandle calcium and misfire, causing the heart to beat too fast or irregularly. The new study suggests, for the first time, that the molecule Alda-1 can prevent the activation of JNK2 that leads to AFib.
The study found:
- In this study, more than 70% of mice given alcohol to mimic binge drinking developed AFib, compared to none of those also given the investigational heart protective agent Alda-1.
- Exposure to binge drinking levels doubled the levels of JNK2 activity compared to a control group that did not mimic binge drinking. This activated JNK2 increased AFib susceptibility in mouse models mimicking excessive alcohol consumption.
- Both JNK2 enzyme activity and calcium handling remained normal in cardiac cells of Alda-1-treated mice.
“Abstaining from alcohol can prevent most alcohol-related AFib risks. Unfortunately, despite nationwide education efforts, binge drinking in all age groups continues to increase. Our findings suggest that the development of young drugs, including Alda-1 and other specific JNK2 inhibitors, may be an effective anti-AFib strategy for people with holiday heart syndrome,” Khanal said.
The study was limited because the 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 complexity of excessive alcohol consumption in humans and the associated cardiovascular consequences.
“Studies using larger animals will be a future direction to translate our exciting findings into clinical applications,” Khanal said.
Background and study details:
- The mice used in the study were divided into three groups: a group with holiday heart syndrome, which was subjected to four doses of alcohol every other day, which mimics holiday binge drinking in humans; an Alda-1 group, which received the alcohol regimen plus the cardioprotective agent Aldi-1. and controls, which received saline (no alcohol) or Alda-1 exposure.
- Outcome measures were taken 24 hours after the last alcohol exposure. Measures used included:
- Electrophysiological studies evaluated atrial arrhythmias induced by burst pacing.
- Calcium imaging studies investigated the effect of Alda-1 on JNK2-dependent calcium mishandling. and
- Biochemical analyzes examined the effects of alcohol on ALDH2 expression and apoptotic signaling pathways.
Co-authors, their disclosures and sources of funding are listed in the abstract.
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 in men, the 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 investigated 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 involved female rats that had their ovaries removed to simulate menopause (when the ovaries essentially stop producing estrogen). The researchers compared menopausal rats given regular exposure to alcohol (administered as 5% ethanol in a liquid diet) with those given alcohol and estrogen replacement.
The study found that, compared to those given only alcohol, 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 decrease 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 can eventually lead to 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 cause plaque to build up in the arteries) and apoptosis (a type of cell death that is result of excess iron ) in heart cells.
“It was surprising to see the significant effect that estrogen had on alcohol-induced cardiac dysfunction, despite its known cardioprotective effects. Premenopausal and menopausal women receiving hormone replacement therapy should be cautious about alcohol consumption because it may is a factor in cardiac dysfunction,” he 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 long-term impact of taking estrogen and regular alcohol consumption in postmenopausal women as they age.
The American Heart Association recommends moderation in alcohol consumption for optimal cardiovascular health. If you don’t already drink, don’t start. If you drink, talk to your doctor about the benefits and risks of drinking alcohol in moderation. Some people should not drink at all, such as women who are pregnant or trying to become pregnant, people under 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 eat a healthy diet as outlined in the recommendations of Life’s Essential 8 of the Union.
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