Effects of intracoronary acetylcholine and atropine on basal and dobutamine-stimulated left ventricular contractility.
BACKGROUND
The role of cholinergic pathways in modulating left ventricular contractile function in humans is not known. This study evaluated the effect of a cholinergic agonist (acetylcholine) and antagonist (atropine) on basal and beta-adrenergically stimulated left ventricular contractile function in normal subjects and subjects with denervated hearts after cardiac transplantation.


RESULTS
Six subjects with normal left ventricular function and seven subjects who were 1 to 3 years after cardiac transplantation were studied. Acetylcholine, atropine, and the beta-adrenergic agonist dobutamine were infused via the left main coronary artery, and changes in left ventricular contractile function were assessed by measurement of peak +dP/dt. Intracoronary dobutamine increased +dP/dt by 70 +/- 15% and 66 +/- 20% in the normal subjects and transplant recipients, respectively. Intracoronary acetylcholine and atropine alone each had no effect on left ventricular +dP/dt in either normal subjects or transplant recipients. The concurrent infusion of acetylcholine with dobutamine reduced the response to dobutamine by 66 +/- 10% and 79 +/- 9% in normal subjects and transplant recipients, respectively. The concurrent infusion of atropine with dobutamine potentiated the response to dobutamine by 25 +/- 7% in normal subjects but had no effect in transplant recipients.


CONCLUSIONS
Stimulation and inhibition of cholinergic receptors in the human heart can modulate the positive inotropic response to beta-adrenergic stimulation.
Landzberg
J S
JS
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Parker
J D
JD
Gauthier
D F
DF
Colucci
W S
WS
D000109:Acetylcholine / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000294:innervation; D016027:Heart Transplantation / Q000502:physiology; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical; D016277:Ventricular Function, Left / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D011950:Receptors, Cholinergic; D004280:Dobutamine; D001285:Atropine; D000109:Acetylcholine