An adenosinergic positive feedback loop extends pharmacological cardioprotection duration.

Background And Purpose: Adenosine receptor activation induces delayed, sustained cardioprotection against ischaemia-reperfusion (IR) injury (24-72 h), but the mechanisms underlying extended cardioprotection duration remain unresolved. We hypothesized that a positive feedback loop involving adenosine receptor-induced proteasomal degradation of adenosine kinase (ADK) and decreased myocardial adenosine metabolism extends the duration of cardioprotection.

Experimental Approach: Mice were administered an ADK inhibitor, ABT-702, to induce endogenous adenosine signalling.