Myocardial Infarction And Tissue Plasminogen Activator Biology Essay

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Myocardial infarction, or commonly known as heart attack, is the development of myocyte necrosis due to insufficient coronary blood flow for an extended period of time (Craft et al. 2011). It is one of the leading causes of death in Australia. To illustrate, in 2008, 11,122 deaths was registered under heart attack and this figure accounted a total of 7.7% of all causes of death (Australian Bureau of Statistics 2010). One of the possible treatments is fibrinolysis therapy using tissue plasminogen activator (tPA). It functions to convert inactive plasminogen into plasmin, which then degrades fibrin into soluble fragments (Bonow et al. 2012).

Hemostasis Process

Hemostasis is a spontaneous process that stops bleeding from a damaged blood vessel. When a blood vessel is injured, vasoconstriction will occur immediately, followed by formation of platelet plug and blood coagulation (clotting). When the blood vessel is repaired, blood clot will then be dissolved by plasmin that originates from the conversion of plasma proenzyme plasminogen. This conversion is activated by tissue plasminogen activator that is produced by endothelial cells (Widmaier, Raff & Strang 2006).

Normal Physiology of the Heart

Heart is the most important organ in blood cardiovascular system, which functions to pump blood throughout our body for exchanges of nutrients, oxygen and metabolic waste. It is divided into left and right halves by septum, and each half consisting of an atrium and a ventricle. Right atrium receives deoxygenated blood from venae cavae whereas the right ventricle pumps the blood into the lungs for oxygenation. Meanwhile, oxygenated blood from the lungs is received by left atrium and pumped away from the heart to all parts of the body by left ventricle (see Fig. 1) (Silverthorn 2010). This pumping action is achieved by the contraction of cardiac muscle that constitutes the myocardium. The oxygen required by cardiac muscle to remain alive and functioning is supplied by coronary arteries that branch away from aorta. However, a coronary artery blockage may occur and cause ischemia heart diseases such as myocardial infarction (Widmaier Raff & Strang 2006).

Figure 1 Diagrammatic section of a heart and its blood flow (Widmaier, Raff & Strang 2006).

Pathophysiology of Myocardial Infarction

A cause of myocardial infarction is coronary artery occlusion. Due to genetic reasons or lifestyle factors, cholesterol is gradually buildup beneath the endothelium at many points in the arteries in a process known as atherosclerosis. Often, these areas of deposits become calcified and develop into atherosclerotic plaque due to invasions of fibrous tissue (Hall 2011). Because of shear forces, inflammation, secretion of macrophage-derived enzymes, immune cell activation and cell apoptosis, the plaque formed is disrupted, and subsequently causes quick formation of thrombus (Craft et al. 2011). The atherosclerosis plaque or the thrombus formed may block the coronary arteries completely and thus prevent blood from flowing past them to supply oxygen (see Fig. 2) (Zieve & Chen 2010). Due to depletion of oxygen for an extended period of time, the cardiac muscle becomes permanently damaged or dies and myocardial infarction is resulted (Zieve & Chen 2010).

FIGURE 2 Thrombus formation leads to myocardial infarction (Craft et al. 2011).

Angina pectoris is the major symptom of myocardial infarction (Zieve & Chen 2010). Oxygen deprivation resulted by the coronary artery blockage often gives rise to the rapid loss of potassium ion from the intracellular environment of cardiac muscle. This causes the myocardial cells to lose contractility and hence leads to ventricular fibrillation (Hall 2011; Craft et al. 2011). This reduces cardiac performance as well as blood pressure. As a negative feedback mechanism, α-receptors and β-receptors of the sympathetic system are stimulated to increase heart rate and peripheral resistance respectively. However, these mechanisms worsen the cardiac situation and cause the patient to experience severe angina pain (Luellmann, Mohr & Hein 2011). In fact, sudden ventricular fibrillation also causes fatality in most people (Hall 2011). Other symptoms of myocardial infarction may include cough, fainting, nausea, vomiting, shortness of breath and sweating (Zieve & Chen 2010).

Different from normal hemostasis, myocardial infarction is often resulted from damage to endothelial cells. Blood clotting mechanism is stimulated as usual but endothelial cells’ anticlotting functions are interfered. Hence, tissue plasminogen activator (tPA) is used as a fibrinolytic agent to treat acute myocardial infarction (Widmaier, Raff & Strang 2006).

The role of Tissue Plasminogen Activator (tPA) in treating Myocardial Infarction

FIGURE 4 Mechanism of fibrinolytic drugs (Kipshidze et al. 2007).

Apart from body synthesis, tPA can now be synthesized using genetic engineering and some examples are alteplase, tenecteplase and reteleplase (Luellmann, Mohr & Hein 2011). A native tPA is a serine protease made up of one polypeptide chain but it is converted by plasmin into two-chain form (Bonow et al. 2012). Despite structural differences, both single- and two- chain tPA function as enzyme in converting inactive plasminogen (Glu-plasminogen or Lys-plasminogen) present in the blood into plasmin (see Fig.4) (Luellmann, Mohr & Hein 2011; Bonow et al. 2012). This is achieved by the cleavage of a single peptide bond in the single-chain Glu- or Lys- plasminogen to form an active two-chain plasmin (Bonow et al. 2012).

The enzymatic activity of tPA is relatively low when fibrin is absent. However, with the presence of fibrin, its enzyme activity increases by at least three orders of magnitude. This is because fibrin can act as a template that binds plasminogen and tPA together and the binding promotes their interaction (Bonow et al. 2012).

Plasmin formed will function as an enzyme that digests fibrin of blood clot into soluble fibrin degradation products (see Fig. 4). As a result, the blood clot is dissolved and the blood flow into the infracted area is restored (Widmaier, Raff & Strang 2006; Bonow et al. 2012). However, it is the length of time between the onset of myocardial infarction and the start of the treatment that determines the probability of survival of a myocardial infarction patient. The earlier the therapy is given, the higher the chance of survival of the patient (Luellmann, Mohr & Hein 2011).

Generally, a patient recovered from myocardial infarction can lead a normal active life. Although their heart pumping capability usually becomes comparatively lower than normal healthy heart, the blood supplied is enough for them to carry out their normal activities (Hall 2011).


Myocardial infarction occurs when cardiac muscle cells deprive of oxygen and start to die, which is usually due to coronary artery occlusion. One of the possible treatments is tissue plasminogen activator (tPA). It acts as an effective fibrinolytic agent by converting plasma proezyme plasminogen into active plasmin. Subsequently, the plasmin formed degrades the fibrins and lyses the blood clot. As a result, blood flow is restored.

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