Ischaemic pre-conditioning means an increased adenosine metabolism with decreased glycolytic flow in ischaemic pig myocardium

Abstract

Ischaemic pre-conditioning (IP) is a potent protective mechanism for limiting the myocardial damage due to ischaemia. It is not fully known as to how IP protects. The metabolism of adenosine may be an important mechanistic component. We study the role of adenosine turnover together with glycolytic flow in ischaemic myocardium subjected to IP. An acute myocardial ischaemia pig model was used, with microdialysis sampling of some metabolites (lactate, adenosine, glucose, glycerol, taurine) of ischaemic myocardium. An IP group was compared with a control group before and during a prolonged ischaemia. ¹⁴C-labelled adenosine and glucose were infused through microdialysis probes, and lactate, ¹⁴C-labelled lactate, glucose, taurine and glycerol were analysed in the effluent. The glycogen content in myocardial biopsies was determined. The ¹⁴C-adenosine metabolism was higher as there was a higher production of ¹⁴C-lactate in IP animals compared with the controls. The glycolytic flow, measured as myocardial lactate formation, was retarded during prolonged ischaemia in IP animals. Myocardial free glucose and glycogen content decreased during the prolonged ischaemia in both groups, with higher free glucose in the IP group. We confirmed the protective effects of IP with lower myocardial concentrations of markers for cellular damage (glycerol). This association between increased adenosine turnover and decreased glycolytic flow during prolonged ischaemia in response to IP can possibly be explained by the competitive effect for the metabolites from both glucose and adenosine metabolism for entering glycolysis. We conclude that this study provides support for an energy-metabolic explanation for the protective mechanisms of IP.