Key result
Zaprinast increased myocardial cGMP content and reduced the proportion of small veins with O2 saturation <50% from 48% to 19% (low dose) and 24% (high dose).
Why the study?
This study tested the hypothesis that increasing myocardial cyclic GMP levels with the selective cyclic GMP-phosphodiesterase inhibitor zaprinast would reduce myocardial O2 consumption and areas of low O2 supply/consumption balance.
Does epicardial application of zaprinast increase myocardial cyclic GMP levels and reduce areas of low oxygen supply/consumption balance in rabbit hearts?
Does epicardial application of zaprinast increase myocardial cyclic GMP levels and reduce areas of low oxygen supply/consumption balance in rabbit hearts?
Selective cyclic GMP-phosphodiesterase inhibition with epicardial zaprinast increases myocardial cyclic GMP levels and improves microvascular oxygenation in rabbit hearts without significantly altering coronary blood flow.
Answers are grounded in this paper and cite their sources.
Should not change practice; hypothesis-generating for cGMP modulation of myocardial energetics in animals.
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 x 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 mumol/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%).(ABSTRACT TRUNCATED AT 250 WORDS)
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Weiss et al. (1994) studied Myocardial oxygen consumption and supply balance (n=24). Zaprinast vs. Vehicle applied to a patch on the myocardial surface was evaluated on Percentage of small myocardial veins with O2 saturations below 50%. Zaprinast increased myocardial cGMP content and reduced the proportion of small veins with O2 saturation <50% from 48% to 19% (low dose) and 24% (high dose).
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