By David N. Leff

Can a tipple a day keep the cardiologist away?

For the past quarter-century, people have been living and drinking with the idea that moderate regular consumption of an alcoholic beverage will ward off heart attack. This popular prescription arose from an epidemiologic survey in 1974 of individuals enrolled in the Kaiser-Permanente medical coverage plan, in Oakland, Calif.

"That study," recalled cardiologist Vincent Figueredo, "demonstrated that there was a U-shaped relationship between drinking vs. heart events. That is, there are fewer cardiac episodes in moderate consumers than in either abstainers or heavy drinkers." Since then, a lot of researchers have tried to tease out the biochemical or metabolic mechanism to affirm or deny this so far purely statistical finding that a bit of booze daily is good for your health.

"There are a couple of different mechanisms," Figueredo observed, "by which it is thought regular, moderate consumption of ethanol can be protective from a heart standpoint. The first mechanism — and it's well documented in large epidemiologic studies since 1974 — is that people who consume alcohol on a regular basis in moderation are less likely to have a heart attack than those who do not, or who drink heavily.

"And that's mostly due to beneficial effects on a subject's cholesterol levels. Your bad LDL cholesterol goes down; your good HDL cholesterol levels go up. Other additional benefits that probably protect against the heart attacks include less likelihood of the blood clotting, for example."

Figueredo is on the faculty at the University of New Mexico Health Sciences Center, in Albuquerque, and a clinical cardiologist at Lovelace Medical Center in the same city.

Alcohol Also May Increase Survival Chances

"What I'm suggesting," he told BioWorld Today, "is that there's a second protective mechanism, which is that people who regularly consume alcohol in moderation, if they do go on to have a heart attack, are more likely to survive it."

Here's how he explains that reverse risk factor:

"The idea is that with episodic exposure to ethanol there is a continual activation of adenosine receptor signaling, because of transient increases in adenosine. Adenosine is a substance," Figueredo pointed out, "that's produced by numerous cells in the body, including the endothelial cells lining the arteries.

"Alcohol actually blocks the transport of nucleosides [the units of DNA's double helix], of which adenosine is one. If you expose artery-lining cells to alcohol, this increases the adenosine because it can't be taken up by those cells. That adenosine then binds to its receptor, which results in vasodilation of the blood vessel, and possibly this protective effect."

Pursuing this process, Figueredo went on, "What this produces is a memory effect, at the cardiac cell level, presumably through specific isoenzymes of protein kinase C [PKC]. This memory effect is analagous to what cardiologists see with ischemic preconditioning. It's a way of protecting hearts against the injurious consequences of ischemic reperfusion — restoring blood flow to a blocked coronary artery. This protection involves producing brief episodes of alternate ischemia and reperfusion."

What this conditioning maneuver accomplishes, Figueredo said, "is to activate a number of signaling pathways, one of them being the adenosine pathway. All of these probably converge at the translocation of specific PKC isoenzymes. What PKC actually does," he allowed, "is unclear, but it's likely that its isoenzymes activate various enzymes and proteins within the cell. These probably ultimately mediate the preconditioning protection.

"What we find is that if we've done transient episodes of ischemia and reperfusion prior to the actual heart attack, during recovery there's better recovery of the heart muscle that was affected, and less cell death."

Figueredo is senior author of a research paper in the current Proceedings of the National Academy of Sciences (PNAS), dated July 7, 1998. Its title is "Activation of [epsilon] protein kinase C correlates with a cardioprotective effect of regular ethanol consumption."

For eight weeks, he and his co-authors fed nine guinea pigs a nutritious liquid diet laced 10 to 15 percent with alcohol — a dose mimicking the ethanol intake of moderate to heavy human tipplers. Nine control animals got the same diet, but minus the distilled spirit.

He and his co-authors then removed the hearts from both cohorts, stopped blood flow to the entire organ (thus simulating a heart attack), then reperfused the whole heart.

In hearts isolated from the moderate-drinking guinea pigs and perfused, left-ventricular pressure recovered to 42 percent of preischemic levels. Hearts from teetotalling control animals got back only 22 percent of their cardiac performance.

Ounces Of Prevention, One Glass A Day

"Drinking in moderation" may mean different things to different people.

A joint report in 1995 by the departments of Agriculture and Health and Human Services defined it as one to two drinks a day for men, one for women. If beer, 12 ounces; wine, five; distilled spirits, 1.5." (Figueredo defines himself as a "one-glass-of-wine-a-day person.")

He is now preparing to repeat this experiment in the beating hearts of live animals. "This should specifically confirm in vivo what we have showed in isolated hearts." he observed.

"Then, once we understand the mechanism by which regular ethanol consumption might be protective, we can try to find safer compounds that mimic that same effect. We could then give that compound to patients at risk for having heart attacks."

Figueredo concluded: "I'm not in any way suggesting people should go out and drink to protect their hearts. People who go out and exercise and eat right are probably going to protect their hearts more." *