The most common cause of heart attacks is
coronary artery disease (also known as coronary heart disease). Coronary arteries supply oxygen rich blood
to the heart. This arteries can slowly become narrow from
a build-up of plaque, consisting of fat, cholesterol and other substances. This process of plaque build-up over the years
is called atherosclerosis and the resulting condition is coronary artery disease. Eventually, an area of the plaque can rupture. The body tries to repair the tear by forming
a blood clot on the surface of the plaque. This blood clot can partially or completely
block blood flow through the affected coronary artery. The heart tissue supplied by the coronary
artery dies due to lack of oxygen and other nutrients. This is called heart attack. Earlier the available treatments for heart
attacks were mostly preventive and palliative rather than curative. Oxygen was administered for shortness of breath,
intravenous fluids were given to prevent dehydration, morphine was given to ease pain and complete
bed rest was advised. Aspirin and some oral anticoagulants were
tried but there was no reduction in mortality rates. [title] [title] The treatment of heart attacks took a fortunate turn in 1933, when the wonder drug streptokinase was serendipitously discovered by Dr. W S Tillet. Dr. Tillet in course of one of his
experiments, observed that the bacteria Streptococci aggregated together to form clumps in test tubes that contained human plasma. Tillet wondered what was happening. So he set up
a new experiment. He added calcium to oxalated human plasma to form blood clots. Some of
these test tubes contained Streptococci bacterial culture. Tillet noticed that clots in test tubes containing Streptococci dissolved with passage of time. He thus concluded that the
bacterium Streptococcus produced some substance that dissolved blood clots. In 1934, Garner
and Tillet successfully isolated this substance and showed that it was a protein secreted
by the bacterium Streptococcus. The substance was later named streptokinase. In 1958, use
of streptokinase in treatment of heart attacks was started.
[title] In the normal process of blood clot formation,
a prothrombin activator is released at the site of injury. This in presence of calcium
converts blood protein, prothrombin to thrombin. Thrombin in turn converts fibrinogen to fibrin.
The protein fibrin forms a mesh entrapping red blood cells, thus forming a blood clot.
It was earlier thought that streptokinase acted by directly degrading fibrin. But it
was later seen that streptokinase acts in a more indirect way. Streptokinase forms a
complex with plasminogen, another plasma protein. The streptokinase-plasminogen interaction
results in a conformational change in plasminogen. Plasminogen is activated. It auto cleaves
itself and is converted to plasmin. Plasmin degrades fibrin and dissolves blood clots
thus clearing the obstruction in the affected coronary artery and restoring blood flow to
the affected heart tissue during heart attack. [title]
There are some risks associated with administration of streptokinase injection. There is a risk
of haemorrhage (excessive bleeding) at the puncture site and other sites such as gastrointestinal
tract and brain. But these bleeding complications are common only in elderly patients or when
the streptokinase dose is too high. There is also a small risk of an allergic reaction
to the streptokinase molecule due to its bacterial origin.
[title] There are other plasminogen activators available
now like tissue plasminogen activator (tPA) and urokinase. Tissue plasminogen activator
is produced using recombinant animal cells and urokinase is purified from urine. Of the
three major plasminogen activators, streptokinase is most efficient as it is stable for longer
time in human body. Also streptokinase is least expensive of the three. It is almost
ten times cheaper than tissue plasminogen activator. Hence, despite the widespread use
of tissue plasminogen activator in developed nations, streptokinase remains essential to
the management of heart attacks in developing nations.
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