No further improvement of ischaemic myocardial metabolism by combining preconditioning with β‐blockade: an in vivo experimental study in the pig heart using a microdialysis technique

Adenine nucleotides, lactate and pyruvate were monitored by microdialysis in pig hearts, comprising four experimental groups. Two preconditioned groups, one beta-blocked by metoprolol (0.3 mg kg-1 body wt; n = 6) and the other (n = 7) without beta-blockade. Two groups were not preconditioned, one beta-blocked (n = 6) and one without beta-blockade (n = 7). Probes were inserted into ischaemic and non-ischaemic myocardium. Preconditioning consisted of four consecutive 10 min periods of ischaemia each separated by 20 min of reperfusion. All animals were subjected to 40 min of index ischaemia followed by 25 min of reperfusion. Myocardial cAMP content was determined in biopsies after the final reperfusion and was found low in the beta-blocked groups. Lactate levels during index ischaemia exceeded the basal level 4-6 fold in dialysate. Adenosine concentration reached 12 mumol L-1 during the first preconditioning period while an attenuation was typical for the following three preconditioning periods. The sum of the concentrations of adenosine inosine and hypoxanthine was significantly lower during index ischaemia in the preconditioned groups displaying a peak value of 115 mumol L-1. The corresponding value for unpreconditioned hearts was 230 mumol L-1. The part of adenosine was 5% and less than 1%, respectively. Pyruvate concentration decreased during each brief ischaemic period of preconditioning rising to a higher level of reperfusion. The decrease in pyruvate was smaller in the controls during index ischaemia. The effects of beta-blockade and preconditioning on ischaemic metabolism were comparable and the results of the two treatments were not additive in this respect.