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 +/- 11.5%) 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 (1 IU mL) 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 (A1 selective, 3 x 10 M) impaired left atrial recovery (5 minutes, 38.1 +/- 5.0%), through direct negative inotropy, but did not affect papillary muscles.
CGS21680 (A2A selective, 3 x 10 M) did not affect recovery.
APNEA (A1/A3 receptor agonist, 10 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 A3 receptor antagonist,
MRS-1220 (10 M).
IB-MECA (A3 selective, 3 x 10 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, A3 receptor stimulation reverses
myocardial stunning of isolated atria and papillary muscles.