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METALYSE® - THE PRODUCT

Substance

Principle of Lysis

Action of Metalyse®

The use of Metalyse® is now established as a major advance in the management of acute myocardial infarction, and can give a 12–50% reduction in short-term mortality, and up to 47% in long-term mortality.
Thrombolytics activate the natural endogenous lytic pathways in the circulation, and dissolve blood clots. The precursor of this pathway is plasminogen, which is converted into the active enzyme plasmin. Plasmin is a protease enzyme (i.e. it breaks down proteins) which breaks down the fibrin matrix of the thrombus, thus dissolving the clot itself. Thrombolytics have no effect on the underlying atheromatous disease.

Plasmin is non-specific and can attack other proteins including fibrinogen, the precursor to fibrin. This may increase the risk of bleeding as it can dissolve other clots in the body, and prevent new clotting taking place.
Alteplase and its derivatives (for example, reteplase and tenecteplase) are more specific than streptokinase, targeting plasminogen in the presence of a fibrin clot as opposed to circulating fibrinogen. Therefore, these agents attain higher early patency rates. Heparin inhibits clotting by affecting fibrin formation and modifying platelet aggregation. A better clinical effect, notably improved angiographic patency, has been achieved in studies when thrombolytics have been administered in conjunction with heparin.

Given early enough, thrombolytic treatment will remove the thrombus, re-establish the blood flow, limit myocardial damage and consequently improve prognosis by preserving left ventricular function.

Concept of coronary patency and recanalisation

Recanalisation is the process of reopening a blocked artery to allow blood to flow through it. Patency is the state of being wide open. Therefore recanalisation restores the patency of the blocked artery and thus allows resumption of blood flow through this artery. The goal of thrombolysis is recanalisation.

Restoring the patency of a coronary blood vessel, and reintroducing the blood flow to the tissue, enables reperfusion. The muscle is then receiving oxygen and can respire aerobically. This means anaerobic respiration is halted, and so is cell death. It is not possible to reverse cell death, but by restoring the blood flow and availability of oxygen, jeopardised muscle can be salvaged. This preserves the left ventricular function, increasing the survival.

Outcomes - what to expect

Early reperfusion:

• prompt relief of pain,
• reduction in ST elevation.

Late reperfusion:

• less likely to produce resolution of ECG,
• reduced mortality,
• improved morbidity.

Thrombolysis has been shown to significantly reduce the risk of mortality of patients suffering an acute myocardial infarction. Early treatment, within 2 hours of symptom onset, is even more beneficial with large reductions in risk of mortality. Reperfusion usually occurs within 1 hour of thrombolysis. This results in a prompt relief of pain and a reduction in the ST elevation can be seen on the ECG. However, late reperfusion due to delayed administration of a thrombolytic or a slow acting thrombolytic, is less likely to produce resolution of the ECG changes. It is quite common to get reperfusion arrhythmias due to atrial or ventricular ectopys, but they are usually short-lived and rarely require treatment. Early treatment can therefore minimalise the damage to the myocardium, salvaging some muscle. This results in improvements in left ventricular function, increasing both short-term and long-term survival.