22 May 2009

The Secret of Sudden Death

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Recent research points out how calcium ions can help preventing sudden heart death

Unlocking the mystery of that 5% of sudden cardiac deaths which are not caused by any apparent anatomic abnormality points to a group of inherited gene mutations in the heart’s ion channels. In its effort to prevent these fatalities, which unfortunately are not always preceded by premonitory symptoms, international research has recently focused on the mechanisms of the calcium ion (Ca2+) transport, which somebody has described as the “simplest and most versatile intracellular messenger known”.

For well over a decade, science has made a lot of progress in the understanding of the so-called “calcium ion sparks”, which are responsible for cardiac excitation/ contraction coupling, and these investigations have provided valuable insights into cardiac arrhythmias, hypertension and heart failure.

It has been discovered that not only there are several intracellular proteins clearly showing calcium ion dependence, but a number of arrhythmias, too. There can be several gene mutations, and when it comes to preventing sudden arrhythmia deaths the real challenge is to identify them in time to take preventative action, as the American Academy of Family Physicians summed it up back in 2003.

Research is getting closer to this goal. In a healthy heart, arrhythmias can be caused by drugs, such as the antihistamine terfenadine, or electrolyte imbalances like hypokalemia or hypomagnesemia; an Austrian team from Graz recently showed that even a vitamin D deficiency can play a role; or else the reason can be either myocarditis or an endocrine disorder. All these are associated with the prolongation of the electrocardiographic QT interval. The same occurs in the case of the congenital long QT syndrome, which is responsible for some of the highest rates of sudden nocturnal deaths in Southern Asia and the Pacific Rim countries.

The average age of a person dying of inherited long QT syndrome is 32 years. This is is well known in the Philippines, Japan and Thailand, where it is called “sleep death” and can run in families to a frightening degree.

In 2005, a US study led by Duke University determined the molecular mechanism that can lead to sudden death in seemingly healthy young people. The fatal arrhythmia syndrome they discovered is caused by a mutation of the gene that codes for the protein ankyrin-B, which is important in maintaining calcium equilibrium within heart cells.

Ankyrin-B forms a complex with three other proteins allowing the orderly passage of ions in and out of the cell, the most important of which is calcium. Its entry causes the contraction of the cell, but it needs to be pumped out before the next heartbeat, or else it can cause damage to the cell. Loss of calcium regulation within heart cells can make a person vulnerable to arrythmia. Today’s challenge is about proving we can fix this faulty mechanism.



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