Effects of Bretschneider cardioplegic fluid on the lysosomal cathepsins D and L of myocardium of coronary patients during coronary-aortal bypass graft operation

摘要

We evaluated the effects of replacing the standard St. Thomas Hospital (ST) cardioplegic fluid with Bretschneider (BR) fluid during coronary-aortal bypass graft operation (CABG) in patients with coronary disease. BR fluid contains enormous concentration of histidine (~ 0.2 mole L-1): thus increased levels of histamine or other metabolites might exert some cardiovascular effects. Therefore, the changes in the level of two lysosomal proteases: cathepsin D and L of myocardium were evaluated. Small fragments of right atrium (SFRA) were taken out during CABG: just before the injection of cold cardioplegia (control), at the peak of ischaemia and after reperfusion. Cathepsin D and L were assayed in SFRA homogenates at pH 3.6 (with haemoglobin as a substrate and pepstatin as cathepsin D inhibitor). The values of parameters Ai and Ae: being the indexes of intralysosomal (Ai) and extralysosomal (Ae) activation or inactivation of cathepsins were calculated.Results/Conclusions: With BR cardioplegia - unlikely ST fluid - there is a significant increase in total activity (T) of both cathepsins but free (F) only for cathepsin L during ischaemia with come back (to the control level) during reperfusion period. T for both cathepsins and F for cathepsin L with BR are much greater than those with ST fluid both in ischaemia and reperfusion period. BR cardioplegia results in distinct, extralysosomal activation of cathepsin L during ischaemia instead of the inhibition found with ST fluid.