Burt Humburg posted Entry 2560 on September 3, 2006 07:30 AM.
Trackback URL: http://www.pandasthumb.org/cgi-bin/mt/mt-tb.fcgi/2554
We here at the Thumb are taking advantage of the long weekend to rest and recuperate: please don’t expect another review to be posted before Tuesday.
In the meantime, I’ve posted a review of modern cardiological techniques today. The backstory is that a few of the contributors to the Panda’s Thumb have, in their time, suffered chest pain or heart attacks. A question was recently asked about the difference between ballooning and stenting and, in an email of response, I ended up summarizing the history of invasive cardiology and thrombolytics in a brief essay. Below the fold, I post a version of that essay with hyperlinks to web resources where you can learn more about cardiology.
Best wishes for a great weekend from The Panda’s Thumb crew!
In the late-70’s, the pathophysiology of heart attacks was elucidated. Previously, it was thought that the vessels supplying the heart with oxygen, the coronary vessels, became progressively narrowed by fat deposition, a term known as atherosclerosis. This is a fairly straightforward conclusion, since autopsies of people with heart disease and angina (defined later in this paragraph) often show fatty buildup on the walls of arteries; it makes sense that as such buildups accumulate, the flow through the lumen of the vessel would reduce. Eventually, the amount of oxygen that the heart would need to function would become more than the amount of oxygen the blood flowing through that narrowed lumen could provide. On these occasions, victims would note chest pain, especially upon exertion. Such chest pain is known as angina.
This model or understanding of heart disease worked decently well for typical angina, but it did not explain nor did it predict those who died suddenly of coronary disease. In medical school, I heard an anecdote of a patient who was seen by a cardiologist due to a strong family history of coronary disease. For some reason, he underwent cardiac catheterization, in which contrast is injected into the coronary arteries, mapping any narrowing within the artery. During this procedure, he was found to have essentially full flow. Soon after his procedure, within a week or two, he suffered a fatal heart attack. Upon autopsy, the luman had completely occluded.
What was interesting about these kinds of cases, though, was that the lumens of these coronary vessels weren’t occluded by fat depostion from the walls of the arteries. Rather, they were occluded by clot. Unlike the old model, in which fat buildup on the walls of the vessels slowly but progressively built up until the lumen was occluded and flow was reduced, this was a situation in which a complete, flow-limiting clot formed within a very short period of time, probably within minutes to hours.
For this reason, cardiologists abandoned the “progressive fat deposition” model of acute coronary syndromes (in distinction to typical angina) and have replaced it with a new model of coronary artery disease. This new model or understanding involves the sudden buildup of clot in the coronary artery, which blocks flow downstream in that artery. This new model became the dominant explanation for sudden onset of chest pain. This model is explained at the Plavix website, under the section of Heart-Related Chest Pain, Heart Attack, Stroke and Poor Leg Circulation. But here’s the gist of it:
People who smoke or have strong family histories of cardiac disease or have diabetes or high cholesterol (see the American Heart Association’s website for a full list of known cardiac risk factors) tend to accumulate fat depositions on the walls of not just the coronary arteries, but all arteries in the body. (It is for this reason that the number one cause of death in people undergoing an operation for carotid disease is heart attack: carotids are arteries and if you’ve got disease in them, you’ll almost always have disease in the vessels of your heart.) These depositions of fat do not merely remain depositions of fat, but change over time (due to reasons that this article won’t review, but interested readers could review at Pathogenesis of Lesion Initiation). This changed fat is extremely thrombogenic - which is to say that a clot forms when normal blood is exposed to it. Thankfully, under normal circumstances, the endothelium of the vessel - the absolutely innermost layer of cells within a vessel - prevents this clot from forming. However, as the lumen of the vessel narrows, the turbulence in the flow increases. Eventually a portion of the endothelialized fat chips off, leaving the highly-thrombogenic changed lipids underneath. A clot forms, which reduces the flow of blood downstream in a very short time period; the patient feels sudden chest pain and the other effects of reduced coronary artery flow, including possibly life-threatening dysrhythmias or death.
From a historical perspective, this change in understanding of the pathophysiology of heart attacks caused a sea change in the way heart attacks were managed. Streptokinase had been known and well described since the 1930s - and lovers of history of science should not miss this biography of William Smith Tillett, who in addition to streptokinase also described C-reactive protein. Streptokinase is a drug that dissolves recently-formed clots, but few if any people used it for heart attacks. (Why would they if coronary disease was solely the result of lipid deposition?) But in the late 70’s, history saw a surge of articles identifying agents that dissolve these coronary clots - thrombolytics - with improved outcomes. Today, there are agents that break up clots that aren’t purified from bacteria and interested readers are invited to Google the search term “Tissue Plasminogen Activator” to learn more about them.
So that covers thrombolytics as a treatment for heart attacks, but most heart attacks today are treated with cardiac catheterization, at least if there’s a hospital nearby that performs them. Therefore, let’s back up a bit and talk about the advent of catheterizations. Even as of the late 70s, cardiac catheterizations were being attempted. It was already possible to snake a sterile catheter with a balloon at the end of it into a coronary artery, dilate the balloon to several atmospheres of pressure, and deflating the balloon which restored coronary flow. This procedure today is known as POBA, or “plain old balloon angioplasty.” (Seriously.)
However, POBA wasn’t all that successful. In many, perhaps even most, of the cases, the clot would return once again, sometimes within minutes. Keep in mind that most cardiologists were working off the model of progressive stenosis; thus, the intention was to develop techniques to keep the walls apart and stents were developed. A stent, pictured here, is a device that is threaded into a catheter with a balloon inside of it; when expanded or “deployed” by the dilation of the balloon, it becomes rigid and keeps the walls of the vessel held apart. This procedure is more than just angioplasty; such patients have now been “stented.”
But under the new model of heart disease described above, the reasons for that rapid reduction in flow are clear: by dilating the artery, the balloon can also disrupt the vessel wall, further exposing the blood to the thrombogenic fats and membranes underneath. In the course of time, it also became clear, as data from autopsies for people who lived for years with stents became available, that the endothelium that protected the thrombogenic intima from the blood eventually grew through the stent walls. This was a mixed blessing. On the one hand, the “endothelialization” of a stent makes it so that the stent, and especially the disrupted vessel wall under it, was no longer thrombogenic. However, in growing through the stent, the vessel lumen was once again narrowed, requiring procedures like a re-stenting to treat. Sometimes this growth was exuberant, such that restenting was needed within months.
A balance was needed whereby a stent could be deployed, clots that arise from the disruption of the artery wall in question could be prevented, and restenosis of the vessel could be delayed as long as possible. Many techniques were tried, such as using radiation to kill the endothelial cells nearest the clot. Nowadays, the stents cardiologists use are drug-eluting stents. In other words, the metal is encoated with medicines that poison the ability of the endothelium to grow through the stent. People who have such stents are given medicines like Plavix or aspirin in order to prevent clots for longer than they would need for simple bare-metal stents. Despite the use of drug eluting stents, endothelialization eventually takes place and even patients with drug-eluting stents only have to stay on medicines like Plavix or aspirin for at most a few months. (If there are other reasons to continue the medicine, they will remain on them longer, of course.)
With these and other advances, patients who suffer heart attacks do much better, especially if they do not hesitate to call 9-11 if they experience any of the warning symptoms. It remains only to say that most patients who die from heart attacks before they reach the hospital die because of fatal malignant dysrhythmias, like ventricular tachycardia or ventricular fibrillation. The treatment for these catastrophic complications is to defibrillate the heart (the thing you see on medical dramas where they all yell “Clear”). Nowadays, devices known as AEDs are available, which analyze the heart rhythms and administer a shock if it is needed.
I would encourage anyone, whether a reader of a pro-science website or a creationist website - to obtain CPR training.
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