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Activity of cathepsin D and L in the heart muscle of coronary patients during coronary-aortal bypass graft operation

Wojciech A. Turski, Janusz Zasłonka

Med Sci Monit 2000; 6(5): BR853-860

ID: 507810

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During coronary - aortal bypass graft operation (CABG) the period of ischaemia with cardioplegia in coronaries, is followed by the phase of reperfusion. The role of lysosomal proteases in both ischaemic and reperfusion injuries of myocardium is not very well understood. Therefore, we decided to evaluate the changes in the activity of two lysosomal proteases: cathepsin D and L taking place in the heart muscle of the coronary sufferers during CABG. Small fragments of right atrium (SFRA) were taken out during CABG: 1) just before the injection of standard St. Thomas Hospital cold cardioplegic fluid (control) 2) just after completion of artificial circulation (peak of ischaemia) and 3) after 30-40 min. of reperfusion. Cathepsins were assayed in homogenates of SFRA at pH 3.6 with haemoglobin in the absence and presence of pepstatin (cathepsin D inhibitor). Some simple calculations allow for a better insight into what is going on with lysosomal enzymes of myocardium during CABG. Essentially, total and free activity of both cathepsin D and L in the myocardium of coronary patients did not undergo significant changes during CABG. However, the values of A expressing activation (A>1) or inactivation (A<1) of enzymes in intralysosomal (Ai) and extralysosomal (Ae) compartment varied to a large extent (regardless of the damage of lysosomes in vivo). During ischaemia Ai for both enzymes was 2.0-2.7 while Ae for cathepsin L was about 0.7. During reperfusion Ae and Ai values ranged between 0.5 and 0.7. During CABG ischaemia period the prominent activation of both cathepsin D and L in intralysosomal compartment and inactivation, especially of cathepsin L, outside the lysosomes (outside cells) takes place probably
reflecting more intensive endocytosis into cardiomyocytes. During reperfusion, the inactivation of both enzymes in both compartments takes place. Some changes seem to be irreversible, especially for cathepsin L.

Keywords: Reperfusion, ischaemia, cardioplegic fluid(s), CABG, cathepsins (D and L), lysosomal proteases