Time course of delayed myocardial protection after transient adenosine A1-receptor activation in the rabbit.

Ischaemic preconditioning of myocardium enhances tolerance to infarction in a biphasic manner. Adenosine A1-receptor activation has been implicated as a trigger of both the early the late phases of protection in rabbit myocardium. Delayed protection against myocardial infarction in vivo was previously shown to occur 24 h after transient adenosine A1-receptor activation with the selective agonist 2-chloro-N6-cyclopentyladenosine (CCPA). Our studies examined the time course of CCPA-induced delayed myocardial protection and a possible mechanism of protection, the elevation of the cytoprotective inducible 72-kDa heat-shock protein (hsp70i). Rabbits were pretreated with a single dose of CCPA 100 micrograms/kg or saline i.v. Twenty-four, 48, 72, or 96 h after treatment, they were anaesthetised, and a left branch of the circumflex coronary artery was reversibly occluded for 30 min, followed by 120 min reperfusion. Infarct size was determined as a percentage of the myocardial risk volume by using triphenyltetrazolium staining. Approximately 50% reduction in infarct-to-risk volume ratio was observed 24, 48, and 72 h after CCPA pretreatment, compared with time-matched saline-pretreated controls. No infarct limitation was observed 96 h after CCPA pretreatment. Differences in infarct size were not related to differences in myocardial risk zone size or systemic haemodynamic parameters during the infarct protocol. Left ventricular tissue harvested from a separate cohort of animals pretreated with CCPA, 100 micrograms/kg, was assessed for content of hsp70i by Western blot analysis. The protein was not induced by CCPA treatment at any time point during the period in which cardioprotection was observed. We conclude that transient adenosine A1-receptor activation produces a delayed and prolonged period of enhanced resilience to ischaemia in rabbit myocardium. This is probably the result of an adaptive mechanism but does not involve elevation of hsp70i.