Effects of endogenous adenosine and adenosine receptor agonists on hypoxia-induced myocardial stunning in guinea-pig atria and papillary muscles

The effects of endogenous adenosine and adenosine receptor agonists were examined on hypoxia-induced myocardial stunning of guinea-pig isolated paced left atria and papillary muscles. Hypoxia (30 minutes) reduced developed tension and increased diastolic tension (contracture) of left atria (41.8 +/- 1.5%) and papillary muscles (17.7 +/- 6.2%). Developed tension recovered to 80.8 +/- 3.15 and 77.2 +/- 5.3% 15 minutes after reoxygenation (stunning). Recovery of left atria was unaffected by adenosine deaminase (l IU mL(-1)) but was depressed in papillary muscles (15 minutes, 48.6 +/- 4.3%) and contracture (46.1 +/- 7.5%) increased. Endogenous adenosine therefore protects from ventricular but not atrial stunning. Adenosine receptor agonists were introduced at 10 minutes into hypoxia. CPA (A(1) selective, 3 x 10(-8) M) impaired left atrial recovery (5 minutes, 38.1 +/- 5.0%), through direct negative inotropy, but did not affect papillary muscles. CGS21680 (A(2A) selective, 3 x 10(-7) M) did not affect recovery. APNEA (A(1)/A(3) receptor agonist, 10(-8) M), increased recovery rate of left atria. Improved rate and extent of recovery of papillary muscles by APNEA (15 minutes, 94.8 +/- 3.1%) was prevented by the A(3) receptor antagonist, MRS-1220 ( 10(-7) M). IB-MECA (A(3) selective, 3 x 10(-7) M) increased atrial recovery rate but not the maximum developed tension reached in either tissue. However, when added at reoxygenation, IB-MECA caused complete recovery of both tissues, in the absence or presence of adenosine deaminase. Thus, A(3) receptor stimulation reverses myocardial stunning of isolated atria and papillary muscles.