No abstract

A microdialysis technique was used to measure myocardial catabolism of adenine nucleotides during preconditioning. Following thoracotomy in domestic pigs, a probe was inserted into the ischaemic myocardium and two probes into normal myocardium. Preconditioning was instituted by occluding a diagonal branch of the left anterior descending coronary artery four times over a 10 min period (interspersed with 20 min of reperfusion each time), followed by index ischaemia for 40 min and terminated by 20 min of reperfusion. Non-preconditioned animals, which had been subjected to 40 min ischaemia and 20 min of reperfusion were used as controls. Sham operated animals were additional controls. Following equilibration, the dialysis fluid was continuously pumped and the microdialysate analysed at 5 min intervals. In the dialysate, the amount of lactate, pyruvate, adenosine, inosine, hypoxanthine and guanosine was measured. Circulatory parameters were: rate pressure product, pulmonary artery pressures, cardiac output and pulmonary wedge pressure. There was no significant statistical difference in cardiac work between preconditioned pigs and controls. A sharp rise in adenosine was observed during the first short ischaemic period with attenuation during the following three short ischaemic periods. In the microdialysate, lactate, adenosine, inosine, hypoxanthine and guanosine were significantly lower during index ischaemia in the preconditioned group than in the non-preconditioned group. Pyruvate levels decreased during preconditioning and rose to a higher level after each brief ischaemic period, followed by a decrease, which was proportionally similar in the preconditioned and unpreconditioned animals during index ischaemia. The effect of preconditioning on lactate and catabolite levels indicated a powerful inhibition of adenine nucleotide catabolic processes due to ischaemia.

Endotoxemia induced a myocardial COX-mediated inflammation without signs of ischemia. In parallel, a depletion of myocardial energy substrates and a deterioration in myocardial performance were seen.

No abstract

The concentrations of lactate, pyruvate, and adenosine, together with some of their derivatives, were determined in microdialysates from 12 pig hearts, 6 of which were subjected to preconditioning and 40 min of ischemia (index ischemia) and 6 of which were subjected to only 40 min of index ischemia. Two microdialysis probes were inserted in ischemic myocardium. Glyburide (10 mu M) in a modified isotonic Krebs-Ringer phosphate buffer was administered through one of the probes and plain isotonic phosphate buffer was administered through the other. Accordingly, the experimental setup permitted us to study the metabolic effects of glyburide on ischemic myocardium constituting two groups that were either preconditioned or unpreconditioned. The preconditioning effect was validated with area at risk and infarction area measurements in 12 other pigs. We noted no functional differences between the groups. In the unpreconditioned group glyburide infusion resulted in enhanced 60% lactate production during index ischemia. However, preconditioning attenuated the enhancing effect of glyburide on lactate production. The interplay between the effects of glyburide and preconditioning on ischemic myocardium is suggested to be dependent on the different modes of action on the K(+)(ATP) channel.