Key Points
- To evaluate how acetylcholine, ischemia, and anoxia influence myocardial cyclic GMP, cyclic AMP, and contractile function in isolated perfused rat hearts.
- Perfused isolated rat hearts under constant flow (14 ml/min) or constant pressure (100 cm H2O) using oxygenated or nitrogenated physiological saline.
- Assessed myocardial contractility (dP/dt), coronary flow, cyclic GMP, cyclic AMP, and lactate under exposure to 1 µM acetylcholine, reduced flow, ischemia, or anoxia.
- Tested the modulating effects of atropine (10 µM), indomethacin (10 µM), and calcium-free perfusion conditions.
- In constant-flow hearts, 1 µM acetylcholine elevated cyclic GMP from 35 to 62 fmol/mg protein while contractility decreased transiently from 2,650 to 1,750 mm Hg/sec before returning toward control.
- Reduced coronary flow and total ischemia raised cyclic GMP from 43 to 85 and 127 fmol/mg protein, an effect not blocked by atropine or indomethacin but partially blocked by calcium-free perfusion.
- Anoxia increased cyclic AMP from 3.8 to 6.0 pmol/mg protein without altering cyclic GMP, whereas acetylcholine and ischemia did not affect cyclic AMP levels.
Structured PICO
What are the effects of acetylcholine, ischemia, and anoxia on myocardial cyclic nucleotides and contractility in isolated rat hearts?
PPopulationisolated rat hearts perfused under either constant flow (14 ml/min) or constant pressure (100 cm H2O) conditions
IInterventionacetylcholine (1 µM), ischemia (termination of perfusion or reduction to one-half), and anoxia (perfusion with 95% N2-5% CO2)
CComparatorcontrol perfusion with physiological saline gassed with 95% O2-5% CO2
OOutcomemyocardial cyclic GMP, cyclic AMP, and contractility (dP/dt)surrogate
Limitation of coronary perfusion augments cardiac cyclic GMP by a mechanism independent of acetylcholine but largely dependent on external calcium, and there is not always an inverse relationship between myocardial cyclic GMP and contractility.