© 2002 by European Society of Cardiology
Copyright © 2002, European Society of Cardiology
Noradrenaline, infused locally, reduces arrhythmia severity during coronary artery occlusion in anaesthetised dogs
Department of Pharmacology and Pharmacotherapy, University of Szeged, Albert Szent-Györgyi Faculty of Medicine, Dóm tér 12, P.O. Box 427, Szeged H-6701, Hungary
* Corresponding author. Department of Physiology and Pharmacology, University of Strathclyde, Strathclyde Institute for Biomedical Sciences, 27 Taylor Street, Glasgow G4 0NR, UK. Tel.: +44-141-548-2859; fax: +44-141-552-2562 j.r.parratt{at}strath.ac.uk
Objective: To contribute to the debate, discussed in an earlier issue, regarding the role of adrenoceptors in the genesis of early, coronary artery occlusion-induced ventricular arrhythmias. Methods: Mongrel dogs anaesthetised with chloralose and urethane were given either noradrenaline (NA, 100 ng kg–1 min–1), phenylephrine (PHE, 200 ng kg–1 min–1) or isoprenaline (ISO 12.5 ng kg–1 min–1) by intracoronary infusion into a side branch of the left anterior descending coronary artery (LAD), commencing 10 min prior to the occlusion and then throughout the 25-min occlusion period. Control dogs were infused for the same period with saline. In another group of dogs noradrenaline was infused intravenously in a dose of 1 and then 2 µg kg–1 min–1 over a period of 60 min, 24 h prior to coronary artery occlusion. Haemodynamic and coronary blood flow changes, as well as changes in the epicardial ST-segment and in the degree of inhomogeneity were continuously recorded. Ventricular arrhythmias were evaluated as ventricular premature beats (VPBs), tachycardiac (VT) episodes and the incidences of VT and ventricular fibrillation (VF) during occlusion and following reperfusion. Results: Compared to the controls, NA markedly reduced the severity of ventricular arrhythmias resulted from coronary artery occlusion and increased survival (to 40%) following reperfusion; there were no survivors in the control group. Noradrenaline released endogenously following guanethidine administration was also protective. Protection was also seen, although to a lesser extent with intracoronary PHE (occlusion VF 20% cp 80% in controls; survival 42%). In contrast, ISO enhanced arrhythmia severity; five out of seven dogs infused with ISO fibrillated within 10 min of the commencement of occlusion and no dog survived reperfusion. Other indices of ischaemia severity (epicardial ST-segment and inhomogeneity) were also reduced by NA and by PHE. NA, infused 24 h prior to occlusion was also protective against ischaemia and reperfusion-induced arrhythmias and ischaemia-induced changes in inhomogeneity. Conclusion: We conclude that exogenously administered NA, or released endogenously by chemical means, reduces the severity of ischaemia and reperfusion-induced ventricular arrhythmias and that this is mediated by 
-adrenoceptors, perhaps through presynaptic inhibition of local NA release or by a ‘preconditioning’ effect presumably mediated by PKC.
KEYWORDS Arrhythmia (mechanisms); Ischemia