Wikipedia:Osmosis/Myocardial infarctions

Author: Tanner Marshall, MS

Editor: Rishi Desai, MD, MPH, Tanner Marshall, MS According to the world health organization, cardiovascular disease is the leading cause of death worldwide, as well as in the US. Of those, a large proportion are caused by heart attacks, also known as acute myocardial infarctions, or just myocardial infarctions, sometimes just called MI.

The word infarction means that some area of tissue has died due to a lack of blood flow, and therefore a lack of oxygen. “Myo” refers to the muscle, and “cardial” refers to the heart tissue. So with a heart attack, or MI, you have death of heart muscle cells because of a lack in blood flow, a process called necrosis.

Now the heart’s main job is to pump blood to your body’s tissues right? Well, the heart also needs blood, and so it also pumps blood to itself, using the coronary circulation. The coronary circulation is this system of small arteries and veins that help keep the heart cells supplied with fresh oxygen. Heart attacks happen when these small arteries become blocked and stop supplying blood to the heart tissue, and if this happens for long enough, heart tissue dies.

Almost all heart attacks are ultimately a result of endothelial cell dysfunction, which relates to anything that irritates or inflames the slippery inner lining of the artery—the tunica intima. One classic irritant are the toxins found in tobacco which float around in the blood and damage these cells.

That damage then becomes a site for atherosclerosis, a type of coronary artery disease where deposits of fat, cholesterol, proteins, calcium, and white blood cells build up and start to block blood flow to the heart tissue.

This mound of stuff has two parts to it, the soft cheesy-textured interior and the hard outer shell which is called the fibrous cap. Collectively this whole thing’s ominously called plaque. Usually, though, it takes years for plaque to build up, and this slow blockage only partially blocks the coronary arteries, and so even though less blood makes it to heart tissue, there’s still blood. Heart attacks happen when there’s a sudden complete blockage or occlusion of a coronary artery—so let’s see how that can happen.

Since these plaques sit right in the lumen of the blood vessel, they’re constantly being stressed by mechanical forces from blood flow, and interestingly it’s often the smaller plaques with softer caps rather than the larger ones with harder caps that are especially prone to break or get ripped off. Once that happens the inner cheesy filling which remember is this mix of fat, cholesterol, proteins, calcium, and white blood cells, is thrombogenic, and this means that it tends to form clots very quickly.

So platelets, or blood-clotting components in the blood, flow by and get excited; and they adhere to the exposed cheesy material. In addition to piling up, the platelets also release chemicals that enhance the clotting process.

Now this happens super fast, think about how quickly a small cut stops bleeding, that’s a very similar process—it happens in a matter of minutes, right? And now that coronary artery is fully occluded.

So now let’s change views a bit, If we take a slice of the heart like this, this side being posterior, or back, and this being anterior, or the front, with the left and right ventricles here, and then we have the three most commonly blocked arteries—the left anterior descending, or LAD which supplies blood to the anterior wall and septum of the left ventricle which accounts for 40-50% of cases, the right coronary artery, or the RCA which covers the posterior wall, septum and papillary muscles of the left ventricle—accounts for about 30-40% of cases, and finally, the left circumflex artery, or LCX which supplies to the lateral wall of the left ventricle —about 15-20% of cases. Notice that the majority of these areas supply the left ventricle—most heart attacks therefore involve the left ventricle, where the right ventricle and both atria—the upper chamber—aren’t as often affected.

Each of these areas is called the artery’s zone of perfusion. And, if we take a closer look at one of these zones, we’ll see that basically you’ve got the endocardium, which is the smooth membrane on the inside of the heart, and then the myocardium, all the heart muscle, and then, the epicardium, the outer surface of the heart, which is where the coronary arteries live.

Let’s say the LAD gets blocked, the area of perfusion is now at serious risk, and within about a minute, the muscle cells in this zone don’t see enough oxygen and become ischemic, and the muscle layer’s ability to contract is severely reduced. This initial stage is extremely sensitive, since the ischemic damage to cells in the perfusion zone is potentially reversible. After about 20-40 minutes, though, damage starts to become irreversible and the cells start to die, and this zone changes to a zone of necrosis, or dead tissue. Once lost, these cells will never return or regrow—that’s why quickly identifying and treating an MI quickly is super important.

The first area affected is the inner third of the myocardium, since it’s farthest from the coronary artery and the last area to receive blood, and it’s subject to higher pressures from inside the heart. If the blockage suddenly lyses or breaks down and blood flow returns, sometimes patients’ damage will be limited to the inner third, and this would be called a subendocardial infarct.

An ECG, or electrocardiogram, done at this point typically shows an ST-segment depression, or in other words, it doesn’t show ST segment elevation, so sometimes we call this an NSTEMI which stands for non-ST elevation myocardial infarction.

Other causes of this sort of subendocardial infarcts would be severe atherosclerosis and hypotension—anything that ultimately leads to poor perfusion of the heart tissue.

After about 3 to 6 hours, though, the zone of necrosis extends through the entire wall thickness, called a transmural infarct, which this time shows up as ST-segment elevation on ECG, which is why they’re sometimes called STEMIs, or ST elevation myocardial infarctions.

So the difference between NSTEMIs and STEMIs is that NSTEMIs don’t have ST-segment elevation, and these are caused by partial infarct of the wall, whereas STEMIs have ST-segment elevation and involve the whole wall thickness.

Patients that have an MI will most commonly have severe and crushing chest pain or pressure, that might radiate up to the left arm or jaw, they might have diaphoresis or sweating, nausea, fatigue, and dyspnea. All of these are either a direct result of an end-organ like the heart or the brain not getting enough perfusion—so think chest pain and dizziness. Or from the sympathetic response from the body to help the heart work harder and preserve blood pressure—so think sweating and clammy skin. Many people also have referred pain where the nerves in the heart are irritated, but that pain can be felt in the jaw, shoulder, arm, or back instead.

In addition to an ECG, labs can be very useful in diagnosing an MI. When there’s been irreversible damage to heart cells, their membranes become damaged and the proteins and enzymes inside escape, and can enter the bloodstream. Three key ones are troponin I, Troponin T, and CK-MB, which is a combination of creatine kinase enzymes M and B. d Both troponin I and T levels can be elevated in the blood within 2-4 hours after infarction, and usually peak around 48 hours, but stay elevated for 7-10 days. CK-MB starts to rise 2-4 hours after infarction, peaks around 24 hours, and returns to normal after 48 hours.

Since CK-MB returns to normal more quickly, it can be useful to diagnose reinfarction, a second infarction that happens after 48 hours but before troponin levels go back to normal. A second heart attack happens following 10% of MIs.

A major complication with MIs are arrhythmias, or abnormal heart rhythms, with the highest risk being immediately following an MI, since the damage or injury can disrupt how the cells conduct electrical signals. Kind of along the same lines, depending on how much contractile or muscle tissue is affected, patients’ hearts might not be able to pump enough blood to the body, resulting in cardiogenic shock. In the days following an infarction, the tissue around the infarcted area becomes inflamed and is invaded by neutrophils, which can lead to pericarditis, inflammation of the pericardium. In the next couple weeks, macrophages invade the tissue, and the healing process begins with the formation of granulation tissue, which is new connective tissue that’s yellow and soft. At this phase, the tissue’s most at risk of myocardial rupture. After 2 weeks to several months, the cardiac tissue scarring process finishes, and the resulting tissue becomes grayish-white in color. Since the scar tissue doesn’t help pump blood, over time the remaining heart muscle can grow or change shape to try and compensate for these lost cells and pump harder, but they ultimately continue to fail, which can lead to heart failure.

Now a potentially life-saving treatment that can be performed immediately following an MI, is fibrinolytic therapy, which uses medications to break down fibrin in blood clots.

An angioplasty might also be done, which is a minimally invasive endovascular procedure where a deflated balloon inserted into the blockage then inflated to open the artery up. And finally a percutaneous coronary intervention might also be performed, where a tiny catheter is used to place a stent in the coronary artery to physically open up a blood vessel.

Each of these focuses on re-establishing blood flow to the the dying heart heart cells—since time is tissue. If early enough following blockage, some of these cells that haven’t entered into the irreversible stage can be salvaged and saved, while the others will be destroyed and removed. This can improve both short and long-term function as well as prevent further damage and reduce the overall zone of necrosis.

Now an important complication of re-establishing perfusion, or reperfusion therapy, is reperfusion injury, where tissue is damaged by returning blood flow. And, this is thought to happen because of a couple mechanisms. First, blood flowing back to cells brings this influx of calcium, and since calcium leads to muscle contraction, the irreversibly damaged cells contract, and since they’ve been irreversibly damaged, they get stuck like that and can’t relax.

This shows up on histology as this characteristic contraction band necrosis.

Also though, blood brings along oxygen, right? Yeah it does. But, that oxygen, paradoxically, can actually lead to more cellular damage. The conditions in an ischemic heart seem to cause an increased conversion of the returning oxygen to reactive oxygen species, which go on to damage more heart cells.

In addition to reestablishing blood flow though, there are a number of medications that might be given in the acute setting including antiplatelet meds like aspirin, anticoagulants like heparin, nitrates which relax the coronary arteries and help lower preload, beta blockers that slow down the heart rate and thereby cardiac demand, pain medication to help relieve the discomfort, and statins which help improve a patient’s lipid profile. Now there are many individual factors to consider when it comes to acute management of a myocardial infarction, and of course many long term issues to consider as well—the most important of which is to address the underlying risk factors like an improved diet and quitting smoking.

All right, time for a quick recap… heart attack, also known as myocardial infarction, or MI, is the death of heart muscle cells due to the lack of blood flow, most commonly caused by atherosclerosis of the coronary arteries. The most common symptoms of MI include crushing chest pain or pressure that might radiate up to the left arm or jaw, sweating, nausea, and dyspnea. Treatment of MI includes re-establishing blood flow using medications, angioplasty, or percutaneous coronary intervention. Underlying risk factors should be addressed for long term management.

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