Carbachol prolongs ventricular repolarisation through nitric oxide release in an intact heart.
OBJECTIVE
The primary ain of this study was to investigate the effect of carbachol on ventricular repolarisation in an intact animal heart.


METHODS
In five sheep, carbachol was administered to the left circumflex coronary artery (LCX) at 1.0 and 2.5 micromol/ml/min respectively for 3 min. Multiple unipolar ECGs were acquired from the epicardium of LCX territory. Administration of carbachol at 2.5 micromol/ml/min was also repeated after pre-treatment with nitro-L-arginine (20 mg/kg), a nitric oxide synthase inhibitor.


RESULTS
Carbachol at 1.0 or 2.5 micromol/ml/min resulted in a T wave inversion and ARI prolongation in the LCX territory. The increase in ARI at 1.0 and 2.5 micromol/ml/min was 38 +/- 17 and 58 +/- 14 ms respectively (p<0.05). T wave inversion and ARI prolongation at 2.5 micromol/ml/min was diminished by pre-treatment with nitro-L-arginine.


CONCLUSIONS
Carbachol results in a dose-dependent prolongation in ventricular repolarisation in this open-chest animal model. This effect is partially mediated by endogenous nitric oxide.
Wang
Lexin
L
School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW 2678, Australia. lwang@csu.edu.au
D000818:Animals; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects*; D008297:Male; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D019335:Nitroarginine / Q000494:pharmacology; D012756:Sheep; D017725:Ventricular Pressure / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D019335:Nitroarginine; D009569:Nitric Oxide; D002217:Carbachol