1. We tested the hypothesis that increasing myocardial cyclic GMP levels would reduce myocardial O2 consumption and areas of low O2 supply/consumption balance, using zaprinast, a selective cyclic GMP-phosphodiesterase inhibitor.2. The...
more1. We tested the hypothesis that increasing myocardial cyclic GMP levels would reduce myocardial O2 consumption and areas of low O2 supply/consumption balance, using zaprinast, a selective cyclic GMP-phosphodiesterase inhibitor.2. The study was conducted in three groups (vehicle, 10−-3 and 3×10−-3 mol/L zaprinast) of anaesthetized open-chest New Zealand white rabbits (n = 24). Coronary blood flow (radioactive microspheres), arterial and venous O2 saturation (microspectrophotometry), O2 consumption, cyclic GMP content (competitive binding) and cyclic GMP-phosphodiesterase activity (conversion of 3H-cyclic GMP to 3H-GMP) were determined.3. Agents were applied to a patch on the myocardial surface and did not cause significant haemodynamic changes, except for bradycardia in the vehicle and low dose group.4. The total myocardial cyclic GMP-phosphodiesterase activity was 148 ± 14 while the zaprinast (10 μmol/L) inhibitable activity averaged 63 ± 8 pmol/mg protein per min. Cyclic GMP content was increased with increasing doses of zaprinast (vehicle, 4.308 ± 0.349 pmol/g; low dose zaprinast, 4.803 ± 0.279 and high dose zaprinast, 7.938 ± 1.304 pmol/g).5. Coronary blood flow was not different after treatment (198 ±11, 209 ± 10 and 153 ± 9 mL/min per 100 g for the vehicle, low and high dose zaprinast, respectively).6. Under control conditions, 48% of the small veins had O2 saturations below 50%. With zaprinast, this value was reduced to 19% for the low and 24% for the high dose.7. Average venous O2 saturation increased with zaprinast (49 ± 2%, 61 ± 3% and 59 ± 1%). Myocardial O2 consumption was decreased with increasing doses of zaprinast (15.0 ± 1.9, 11.2 ± 1.0 and 7.7 ± 0.7 mL O2/min per 100 g for the vehicle, low and high dose zaprinast, respectively.8. Thus, increasing the myocardial level of cyclic GMP with zaprinast was correlated with reduced cardiac O2 consumption and a reduced number of veins with low O2 saturations.