Mini heart attacks lessen damage from major ones

Researchers have discovered one potential mechanism by which briefly cutting off, then restoring, blood flow to arteries prior to a heart attack lessens the damage caused, according to a study published today in the journal Cardiovascular Research. The new mechanism points to how future drugs could provide protection ahead of heart attacks and strokes for those at highest risk. In the nearer term, the work may help to prevent damage caused as U.S. heart surgeons temporarily cut off blood flow 450,000 times each year to perform coronary artery bypass graft surgeries. Lastly, the discoveries hold clues to the value of the Mediterranean diet beyond red wine.

In severely diseased coronary arteries, fatty deposits in blood vessel walls become more likely to rupture, which releases proteins into the blood that cause blood clots and cut off blood flow. When a vessel becomes completely blocked (ischemia) the downstream tissue begins to die for lack of oxygen and nutrients. Worse yet, when blood flow is restored (reperfusion), the returning blood throws off cellular chemistry, creating as a side-product a burst of highly reactive "free radicals" that tear apart cell components and cause cells to self-destruct. Later in the process, the immune system attacks the cardiac tissue damaged by ischemia and reperfusion, causing inflammation which can lead to heart failure.

In 1986 then medical student Chuck Murry at Duke University first described a technique called ischemic preconditioning (IPC), which quickly cuts off then restores blood flow to the heart. He found that IPC somehow protected heart tissue against the damage caused by subsequent, prolonged blood vessel blockages. An emerging theory holds that this natural early warning system of IPC has evolved to protect against heart attack. Labs worldwide are seeking to re-create or strengthen this natural protection against ischemia/reperfusion (IR) injury. In the current study, researchers for the first time determined that IPC caused more of a key molecule, nitro-linoleic acid (LNO2), to be made in ischemic cells.

"LNO2 appears to be important in the mechanism by which IPC triggers the body's natural defense mechanisms against heart attack before the major attack comes," said Paul S. Brookes, Ph.D., associate professor of Anesthesiology and of Pharmacology and Physiology at the University of Rochester Medical Center. "Obviously, this natural response, when it follows a major heart attack, is often too little too late. Our hope is that boosting the effect in patients at high risk, perhaps by administering LNO2 beforehand, will reduce heart attack damage in the future. Even sooner, we may be able dramatically reduce reperfusion injury suffered in surgical settings."

Study Details

Going into the study, the mechanisms underlying IPC protection were controversial, but a consensus had emerged recently that mitochondria were involved. The cell's powerhouse, mitochondria use oxygen to convert nutrients into cellular energy supply.