Acadesine lowers temporal threshold for the myocardial infarct size limiting effect of preconditioning.

Abstract

OBJECTIVE:

The aim was to test the hypothesis that adenosine A1 receptor activation triggers the cardioprotective effects of ischaemic preconditioning, by determining whether pretreatment with acadesine (5-amino-4-imidazolecarboxamide riboside), an agent which increases cardiac adenosine level during ischaemia, could alter the threshold for preconditioning.

METHODS:

A branch of the left coronary artery of rabbit hearts was occluded for 30 min and reperfused for 3 h. Infarct size and risk zone size were determined with tetrazolium and fluorescent particles, respectively. Four groups were studied: untreated controls, a group which was pretreated with acadesine (2.5 mg.kg-1.min-1 for 5 min followed by 0.5 mg.kg-1.min-1 for 30 min ending 10 min prior to ischaemia), a group which was preconditioned with 2 min coronary branch occlusion + 10 min reperfusion, and a group which received pretreatment with acadesine prior to 2 min ischaemic preconditioning.

RESULTS:

Percent infarction, normalised as a percentage of the ischaemic zone, in the 2 min preconditioning group was 43.2(SEM 5.1)% which was not different from control [40.2(3.5)%]. Two minutes of preconditioning was not long enough to confer the cardioprotective effect of preconditioning. Acadesine alone had no protective effect on infarct size [38.5(4.5)%], but acadesine + 2 min preconditioning significantly limited infarction [18.1(2.7)%; p < 0.01].

CONCLUSIONS:

Acadesine lowered the threshold for preconditioning in the rabbit to below 2 min of ischaemia. This observation supports the theory that endogenous adenosine which accumulates during the preconditioning ischaemia mediates the protective effects, and that this response can be augmented by acadesine.

• Authors: A Tsuchida, G S Liu, K Mullane, J M Downey
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 27 Issue 1 Pg. 116-20 (Jan 1993) ISSN: 0008-6363 [Print] England
• PMID: 8458021 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Purinergic
• Ribonucleosides
• Aminoimidazole Carboxamide
• acadesine
• Adenosine

Topics

• Adenosine (metabolism)
• Aminoimidazole Carboxamide (analogs & derivatives, pharmacology)
• Animals
• Female
• Male
• Myocardial Infarction (prevention & control)
• Myocardial Ischemia (metabolism)
• Myocardium (metabolism)
• Rabbits
• Receptors, Purinergic (drug effects)
• Ribonucleosides (pharmacology)
• Time Factors