8′-Aminoguanosine Inclusion Results in Enhanced Efflux of Taurine in Preconditioned Ischemic Myocardium

Abstract

Attenuated purine levels are characteristic findings of ischemic preconditioning (PC). Lower energy demand in PC myocardium leading to less nucleotide decay is a reasonable explanation. However, experimental data suggest that the activities of the enzymes involved in purine metabolism are increased in PC myocardium. Recently it was suggested that PC favored degradation of exogenous adenosine to inosine successively ending up in enhanced lactate production. This was probably because of the involvement of the hexose monophosphate pathway in the PC ischemic myocardium. This route may therefore be supplementary in energy metabolism as a metabolic flow can be started by adenosine ending up in lactate without initial adenosine 5'-triphosphate (ATP) investment. Purine nucleoside phosphorylase (PNP) is a key enzyme in the proposed metabolic route. In the current study the effect of PNP inhibition (with 8'-aminoguanosine) on myocardial energy metabolism during PC was studied in an open chest porcine heart model using the microdialysis technique. A dose-dependent inhibition of PNP by 8'-aminoguanosine was observed in PC myocardium. This inhibition resulted in an enhanced exodus of taurine reflecting a disturbed energy economy of the cardiomyocytes. Addition of inosine being a true substrate of PNP reversed these changes, which indicated that 8'-aminoguanosine was a competitive inhibitor of PNP. It is concluded that the ischemic PC phenomenon at least partly involves the activated enzyme PNP.

Ischaemic preconditioning alters the energy metabolism and protects the ischaemic myocardium in a stepwise fashion

“…This line of reasoning was recently advertised as a potential mechanistic explanation of the protective effect of IP , Kavianipour et al 2003. These findings suggested a modified handling of adenine nucleotide breakdown products in the preconditioned myocardium.…”

“…These findings suggested a modified handling of adenine nucleotide breakdown products in the preconditioned myocardium. This line of reasoning was recently advertised as a potential mechanistic explanation of the protective effect of IP , Kavianipour et al 2003. According to this hypothesis IP (in presence of orthophosphate) enhances release of the phosphoribose moiety of adenosine (via inosine and subsequent hypoxanthine formation).…”

“…Components of the microdialysate were analysed with respect to lactate, taurine and hypoxanthine using high performance liquid chromatography (Hillered et al 1989, Kavianipour et al 2003. Components of the microdialysate were analysed with respect to lactate, taurine and hypoxanthine using high performance liquid chromatography (Hillered et al 1989, Kavianipour et al 2003.…”

“…Microdialysis data. Components of the microdialysate were analysed with respect to lactate, taurine and hypoxanthine using high performance liquid chromatography (Hillered et al 1989, Kavianipour et al 2003. All peaks were well separated from each other and the position of each metabolite in the chromatogram corresponded exactly with that of the standard.…”

Ischaemic preconditioning is related to decreasing levels of extracellular adenosine that may be metabolically useful in the at‐risk myocardium: an experimental study in the pig

“…We have studied key metabolites in pig myocardium subjected to preconditioning using a microdialysis technique well suited to study dynamics of energy metabolism (Wikstrom et al. 1995a,b, Kavianipour et al. 2003a,b,c).…”