Key Points
- To determine how muscarinic receptor stimulation influences basal and beta-adrenergic-stimulated left ventricular function in patients with heart failure.
- Studied 21 patients with heart failure and 14 subjects with normal ventricular function using intracoronary infusions of acetylcholine, dobutamine, and atropine.
- Assessed contractility via left ventricular +dP/dt and evaluated lusitropy by measuring the time constant of isovolumic relaxation (Tau) across three pharmacological protocols.
- Intracoronary acetylcholine inhibited the dobutamine-induced +dP/dt response by 60±8% in normal subjects and 70±13% in heart failure patients, while attenuating dobutamine-mediated shortening of Tau in both groups.
- Acetylcholine alone significantly prolonged Tau in heart failure patients but had no effect on Tau in normal controls, demonstrating an independent negative lusitropic effect.
- Intracoronary atropine augmented the inotropic response to dobutamine by 35±10% in normal subjects versus a non-significant 12±15% in heart failure, and atropine reversed both acetylcholine-mediated relaxation delay and adrenergic blunting in 6 heart failure patients.
Structured PICO
Does muscarinic receptor modulation affect basal and beta-adrenergic stimulated left ventricular function in patients with heart failure?
PPopulation35 subjects (21 patients with heart failure and 14 subjects with normal ventricular function)
IInterventionIntracoronary acetylcholine and/or intracoronary atropine, administered with intracoronary dobutamine
CComparatorSubjects with normal ventricular function, and baseline measurements
OOutcomeLeft ventricular +dP/dt response to intracoronary dobutamine and isovolumic relaxation (Tau)surrogate
In the failing human left ventricle, muscarinic stimulation has an independent negative lusitropic effect and antagonizes the effects of beta-adrenergic stimulation.