While reading the New York Times last week I came across an article announcing the passing of Dr. James W. Black, a noted Scottish pharmacologist, and while I am reluctant to write two drug-related blog posts in a row I feel obliged to dedicate a few words to his accomplishments.

(Of note, those of you fond of the world of pharmacology history may enjoy previous posts on nitroglycerin, warfarin, digitalis, and aspirin.  For those of you who have no interest in this, count yourself lucky)

Back in the mid-1950s doctors were eager to have more choices available to treat cardiac .  Nitroglycerin had existed in one form or another for several decades but fell short of providing adequate relief for many with coronary stenosis.  Coronary artery bypass surgery (CABG) was yet to be developed and the advent of catheter-based coronary repair (angioplasty, stenting) was decades away.

While most researchers in the field were looking for ways to increase the amount of oxygen-rich blood available for starving heart muscle, Dr. Black sought a different approach.  He theorized that one could improve a patient’s chest pain by decreasing the metabolic demand of the heart and consequently allowing the muscle to function on less blood. 

Scientists had already worked out the concept of cardiac muscle protein receptors that bind adrenalin and noradrenalin (epinephrine and norepinephrine), but the clinical scientific community was not focusing in this direction.  Dr. Black expanded on the existing research and sought a chemical that would specifically target the beta-adrenergic receptor—the trigger of the so-called “fight or flight” response.

His initial attempt yielded pronethalol, a substance that quite nicely blocked the beta-receptor and relaxed the contractile work of the heart.  Unfortunately this chemical was also quite toxic.  In 1964 Dr. Black developed the first safe and effective beta-blocker, and nine years later propranolol (Inderal) entered the US market as the pilot drug in a class that has come to be a mainstay in the world of cardiology.

For his work Dr. Black (and two others) was honored with the Nobel Prize in Medicine in 1988, but he didn’t stop there.

After his success with propranolol in 1964 he immediately launched an effort at producing a chemical that would block the production of stomach acid.  The fruit of his efforts to block the H2-receptor in the lining of the stomach was the drug cimetidine (Tagamet).  Those of you old enough to remember the “plop plop fizz fizz” jingle will recall what a breakthrough this development represented in 1979.  Thousands of patients suffering from ulcers and intractable reflux were spared the surgeon’s blade by adopting the use of this class of drugs (called H2 blockers—Zantac, Pepcid, and the like).

Dr. Black was knighted in 1981 and, after creating the world’s first blockade of stress on the heart and on the stomach, he spent some time as a university chancellor and then transitioned into retirement. I can’t think of another researcher who nearly single-handedly came up with two seminal medical therapies in unrelated fields.  It would be like Guglielmo Marconi discovering the transistor radio and the iPod.  Or like the Wright brothers developing the airplane and in-flight movies.  Or like Thomas Edison inventing the light bulb and the phonograph.  Oh, wait.  I guess Tom Edison did do that.

If only Dr. Black had enjoyed his youthful scientific curiosity longer I’m sure he’d have come up with cures for cancer, the common cold, baldness, and the nerdy desire to post blog articles every week.

Now it’s time to segue into the clinical portion of my article and focus a little on beta-blockers.  While propranolol was first in its class it is no longer widely used because of its frequent side effects.  It’s still prescribed to migraine sufferers, people with benign hand tremors and those who suffer from excessive perspiration when engaging in public speaking (I’ve never tried it for this but people tell me it works wonders).

Cardiac is considerably less common these days because most people with lifestyle-limiting coronary disease can receive full resolution of their symptoms with stent placement or bypass surgery.  Hypertension remains a common indication for the more modern beta-blockers such as metoprolol (Lopressor) and atenolol (Tenormin).  These medications can also treat the palpitations associated with atrial rhythm abnormalities such as atrial fibrillation.

Of interest is the use of beta-blockers in congestive heart failure.  As recently as the early nineteen nineties, when I started my internship, these drugs were regarded as contraindicated in patients with weak hearts.  It stands to reason if you think about it: adrenalin increases the frequency and vigor of cardiac contraction, and blocking this effect will slow and weaken the resulting pulse.  In medical school we were taught to assiduously avoid beta-blockers in these individuals.

But it turns out that just the opposite is true.  Think of beta-adrenergic stimulation (with adrenalin and noradrenalin) as the big, burly guy who beats the drum on the old Roman slave ships.  Sure, his incessant percussion frightens the frail slaves into rowing faster for a while, but after a time it just leads to early fatigue and failure of the system.  Patients with heart failure actually have higher than normal levels of adrenalin in their system—their bodies sense the low blood flow and release the hormone hoping to squeeze out a little more cardiac output.  Over time, though, the constant whipping of the heart leads to deterioration of the muscle cells and worsening of heart failure.

Numerous studies have demonstrated the benefit that comes from giving the heart a reprieve by adding certain types of beta-blockers such as carvedilol (Coreg) and extended-release metoprolol (Toprol XL).  Weak hearts can actually heal over time (to some degree, anyway) if you remove the stress of adrenalin.  In the world of congestive heart failure, beta-blockers have now emerged as the cornerstone of therapy.

I’ve been unable to find any interviews with Sir James Black in the last years of his life and I’d be interested to hear what he thought of the durability of his discoveries.  Decades later, beta-blockers and H2-blockers remain incredibly common and useful.  Dr. Black should be proud of his accomplishments.

There’s an iconic image from legendary medical illustrator Frank Netter, M.D. that I will never forget from my medical school days. It’s a picture of a man clutching his chest as he exits a restaurant to trudge into the snowy night. The artwork was originally published in 1969 as part of the CIBA Collection of Medical Illustrations that serves as the benchmark for anatomic art in the last half century. I’d venture that there is not a doctor on the planet who is not familiar with the artistic footprint of Dr. Netter.

This particular picture accompanies the section of the atlas pertaining to “ pectoris,” the chest pain that arises when the heart muscle is not getting an adequate supply of blood and oxygen. While the symptoms can be variable, is most often described as a squeezing pressure in the chest. As is typical of Dr. Netter’s style, his illustration captures many of the subtleties of the subject described. The man is middle-aged and mildly overweight and one can clearly see the burning ember of a cigarette butt he’s dropped into the snow. He is coming out of a restaurant and lumbering up a couple of steps into the driving winter wind. His right hand claws at his chest (see Levine sign) as his left hand loses its grip on his brief case.

In this illustration, Dr. Netter has made sure all the elements are there for a classic case of .

Risk factors? Check.

Exertion? Check.

Recent culinary indiscretion at a local pub? Check.

Driving snow and winter wind? Now it’s getting personal.

Those of us in the Midwest have had our share of arctic conditions over the last month as our temperatures hover well below freezing for what seems like an eternity and snow blankets our region to a degree that’s not been seen in years. The deep drifts have brought with them the familiar early morning buzz of snow blowers being reluctantly fired up for action, and, with that, come the admissions to the hospital of patients with heart attacks and chest pain.

While this is something I can’t quantify with any reliable objective data, my feeling is that I have seen more patients this year with heart conditions exacerbated by the elements than I’ve seen in years past. Is this just my imagination—my mind, being driven mad by the numbness of the arctic chill—or is there evidence linking a miserable winter to a rise in heart disease?

Indeed, solid research confirms the link between a bad winter and a rise in the rate of cardiac events. In one study, published in the British Journal of Medicine in 2004, researchers tracked temperature and climate data from 24 different countries in an attempt to establish a link between lousy weather and heart attacks. They discovered that a strong relationship exists between low temperature and the population’s rate of heart attacks and stroke. Their conclusions were so robust that they were able to provide an algorithm for determining what sort of rise in problems we can expect with cold air: “On average, a 5°C reduction in mean air temperature was associated with a 7% and 12% increase in the expected hospitalization rates of stroke and AMI (heart attack), respectively.” (How would it be if we added that to our evening weather broadcast? “And for tomorrow we can expect a high of 5 degrees, winds out of the north at 15 mph, and scattered heart attacks throughout the metro area.”)

Another study, published in the journal Circulation the same year, showed that the risk of cardiac-related death is at its absolute highest in the period between Christmas and New Years Day. The authors are careful to point out that it’s not clear whether the increased prevalence of heart attacks is due to the cold weather or the abundance of stale fruitcakes and spiked eggnog.

What, exactly, are the possible factors that lead to winter heart attacks in susceptible individuals? Here are some possibilities:

1. The body shunts more blood to the skin when the air is cold to maintain body temperature. To do this the heart needs to work harder to cycle the blood volume more quickly.
2. Depression, long linked to the cold darkness of winter, is known to be a risk factor for cardiovascular disease.
3. Flu and cold viruses can trigger inflammatory responses in the coronary arteries that can disrupt the delicate balance of coronary cholesterol plaques.
4. People generally exercise less when the weather is bad and slip into worse physical condition. Just this week Circulation published a study linking risk of cardiac death to the number of hours a person sits glued to American Idol.
5. People tend to eat more, smoke more, and gain more weight during the holiday season.

At the precise moment a person with occult coronary disease is at his deconditioned, flabbiest worst, he decides it’s time to man up and get out in the subzero temperature to perform his own stress test behind a 75-lb snow blower. It’s no surprise the night ends up with a trip to the cath lab.

I suppose the best way to avoid a January visit to the coronary care unit is to keep yourself in good shape during the rest of the year so that snow removal season isn’t such an extraordinary departure from your usual physical activity. Stay warm, get your flu shots, and watch your diet and your weight.

If there’s any question about your physical capability to shovel snow or rake ice off your roof, check with your doctor—it may be better to first try the conventional office-based stress test before you attempt the do-it-yourself-in-the-driveway method. I don’t think Dr. Netter needs any more modeling subjects for his medical atlases.