A heart attack occurs when the flow of blood to the heart is blocked. The blockage is most often a buildup of the “plaque” in the arteries that feed the heart (coronary arteries). Sometimes a plaque can rupture and form a clot that blocks blood flow. The interrupted blood flow can damage or destroy part of the heart muscle.
A heart attack (myocardial infarction) can be fatal, but treatment has improved dramatically over the years. It's crucial to seek emergency medical help if you think you might be having a heart attack.
There are several life-saving treatments that can open the blocked artery that is causing the heart attack. The blocked artery can be either opened by injecting clot-dissolving drugs into a vein (“fibrinolysis”) or through a procedure called “angioplasty.” Angioplasty is performed in a special part of the hospital called a “cath lab”. Angioplasty may involve the placement of a small wire device called a “stent,” (“percutaneous coronary intervention,” or PCI). A stent is inserted into the artery to help it remain open after the clot is removed. The best outcomes occur when primary PCI is performed with a door-to-balloon time of less than 90 minutes.
“Reperfusion therapy”, which uses clot-dissolving drugs or mechanical means to unblock clogged arteries, has long been the most effective treatment for heart attack. Though it significantly reduces heart damage, patients treated with this therapy still experience some damage, about half of which actually results from the treatment itself. This is because the rapid restoration of blood flow into oxygen-deprived heart tissues can lead to a swift rise in “free radicals”. When left unchecked, this surge of free radicals induces “oxidative stress”, which can cause heart muscle cell death and heart injury as part of a condition known as “ischemia/reperfusion injury”.
Though scientists have long considered necrosis to be a passive, unavoidable form of cell death, recent studies have suggested that some forms of it happen in a highly regulated manner that could potentially be targeted for treatment. Little has been known about how this type of cell death is regulated which prompted Dr Cheng of the Washington State University to take a closer look.
Genetic approach: Cheng and his team had previously screened more than 20,000 genes to look for ones that appeared to either suppress or promote necrotic cell death. One gene that stood out to them as warranting further study was PRKAR1A, which helps regulate PKA activity by encoding a protein known as PKA regulatory subunit R1alpha.
So the researchers conducted a series of experiments to validate whether the R1alpha protein can regulate necrotic cell death in a rodent model. They found that turning off the PRKAR1A gene increased cell death. Mice lacking the gene also had more heart injury and worse heart function after heart attack, as compared to wild-type mice.
Cheng explained that, under normal circumstances, the rapid increase of free radicals after heart attack treatment triggers the heart to launch its antioxidant defense system, the built-in protective mechanism that helps keep free radicals in check. What their new study findings suggest is that the antioxidant defense system cannot be launched as effectively when the R1alpha protein is removed from the heart, resulting in more oxidative stress, which leads to cell death and heart injury. Cheng hopes that their research would eventually allow them to test a compound in humans that targets the R1alpha protein in a favourable manner.
First and foremost it is necessary that we are aware that sudden myocardial ischaemia – reperfusion induces injury to “cardiomyocytes” and initiates various forms of cell death that contributes to more damage in myocardial infarction. Then, we must remain aware that myocardial ischaemia – reperfusion also induces injury to the coronary microcirculation, including capillary rupture and haemorrhage. So let’s keep thinking beyond the gains of establishing immediate perfusion with an angioplasty or clot-busting – a phenomenon to which we had not paid much attention thus far.
“Reperfusion injury”, sometimes called ischemia-reperfusion injury (IRI) or reoxygenation injury, is the tissue damage caused when blood supply returns to tissue (re- + perfusion) after a period of ischemia or lack of oxygen (anoxia or hypoxia). The absence of oxygen and nutrients from blood during the ischemic period creates a condition in which the restoration of circulation results in inflammation and oxidative damage through the induction of oxidative stress rather than (or along with) restoration of normal function.
We are of course doing extremely well by offering primary angioplasty or clot-busting to our patients who are admitted within the “golden hour”. But IRI takes its toll by leading to myocardial necrosis in the reperfused myocardium and this must remain uppermost in our mind.
Cheng’s study is a pioneering one and could be a trend-setter to resolutely limit the IRI (ischemia reperfusion injury), preserving as much healthy myocardial muscle as possible.
This article (which incidentally) got a big thumbs up from my friend Dr Theodore Abraham, Professor of Cardiology, Chief and Director at the University of California in San Francisco not only wishes to share recent medical information with our learned colleagues but also yearns to tell our patients how medical research is always trying new advances to ameliorate the life of our heart patients-- a saga of heroism!
(Dr Francisco Colaço is a seniormost consulting physician, pioneer of Echocardiography in Goa)