Nicholas Jackson1, Sigfús Gizurarson1, Mohammed Ali Azam1, Benjamin King1, Andrew Ramadeen1, Nima Zamiri1, Andreu Porta-Sánchez1, Abdul Al-Hesayen1, John Graham1, Marjan Kusha1, Stéphane Massé1, Patrick F H Lai1, John Parker1, Rohan John1, Tim-Rasmus Kiehl1, Govind Krishna Kumar Nair1, Paul Dorian1, Kumaraswamy Nanthakumar2. 1. From the Hull Family Cardiac Fibrillation Management Laboratory, Division of Cardiology (N.J., S.G., M.A.A., B.K., N.Z., A.P.-S., M.K., S.M., P.F.H.L., G.K.K.N., K.N.) and Department of Pathology (R.J., T.-R.K.), University Health Network, Toronto, Ontario, Canada; St Michael's Hospital, Toronto, Ontario, Canada (A.R., A.A.-H., J.G., P.D.); University of Newcastle, Australia (N.J.); and Mount Sinai Hospital, Toronto, Ontario, Canada (J.P.). 2. From the Hull Family Cardiac Fibrillation Management Laboratory, Division of Cardiology (N.J., S.G., M.A.A., B.K., N.Z., A.P.-S., M.K., S.M., P.F.H.L., G.K.K.N., K.N.) and Department of Pathology (R.J., T.-R.K.), University Health Network, Toronto, Ontario, Canada; St Michael's Hospital, Toronto, Ontario, Canada (A.R., A.A.-H., J.G., P.D.); University of Newcastle, Australia (N.J.); and Mount Sinai Hospital, Toronto, Ontario, Canada (J.P.). kumar.nanthakumar@uhn.ca.
Abstract
BACKGROUND: The therapeutic potential of renal denervation (RDN) for arrhythmias has not been fully explored. Detailed mechanistic evaluation is in order. The objective of the present study was to determine the antiarrhythmic potential of RDN in a postinfarct animal model and to determine whether any benefits relate to RDN-induced reduction of sympathetic effectors on the myocardium. METHODS AND RESULTS: Pigs implanted with single-chamber implantable cardioverter defibrillators to record ventricular arrhythmias (VAs) were subjected to percutaneous coronary occlusion to induce myocardial infarction. Two weeks later, a sham or real RDN treatment was performed bilaterally using the St Jude EnligHTN basket catheter. Parameters of ventricular remodeling and modulation of cardio-renal sympathetic axis were monitored for 3 weeks after myocardial infarction. Histological analysis of renal arteries yielded a mean neurofilament score of healthy nerves that was significantly lower in the real RDN group than in sham controls; damaged nerves were found only in the real RDN group. There was a 100% reduction in the rate of spontaneous VAs after real RDN and a 75% increase in the rate of spontaneous VAs after sham RDN (P=0.03). In the infarcted myocardium, presence of sympathetic nerves and tissue abundance of neuropeptide-Y, an indicator of sympathetic nerve activities, were significantly lower in the RDN group. Peak and mean sinus tachycardia rates were significantly reduced after RDN. CONCLUSIONS: RDN in the infarcted pig model leads to reduction of postinfarction VAs and myocardial sympathetic effectors. This may form the basis for a potential therapeutic role of RDN in postinfarct VAs.
BACKGROUND: The therapeutic potential of renal denervation (RDN) for arrhythmias has not been fully explored. Detailed mechanistic evaluation is in order. The objective of the present study was to determine the antiarrhythmic potential of RDN in a postinfarct animal model and to determine whether any benefits relate to RDN-induced reduction of sympathetic effectors on the myocardium. METHODS AND RESULTS:Pigs implanted with single-chamber implantable cardioverter defibrillators to record ventricular arrhythmias (VAs) were subjected to percutaneous coronary occlusion to induce myocardial infarction. Two weeks later, a sham or real RDN treatment was performed bilaterally using the St Jude EnligHTN basket catheter. Parameters of ventricular remodeling and modulation of cardio-renal sympathetic axis were monitored for 3 weeks after myocardial infarction. Histological analysis of renal arteries yielded a mean neurofilament score of healthy nerves that was significantly lower in the real RDN group than in sham controls; damaged nerves were found only in the real RDN group. There was a 100% reduction in the rate of spontaneous VAs after real RDN and a 75% increase in the rate of spontaneous VAs after sham RDN (P=0.03). In the infarcted myocardium, presence of sympathetic nerves and tissue abundance of neuropeptide-Y, an indicator of sympathetic nerve activities, were significantly lower in the RDN group. Peak and mean sinus tachycardia rates were significantly reduced after RDN. CONCLUSIONS: RDN in the infarctedpig model leads to reduction of postinfarction VAs and myocardial sympathetic effectors. This may form the basis for a potential therapeutic role of RDN in postinfarct VAs.
Authors: Dominik Linz; Mathias Hohl; Adrian D Elliott; Dennis H Lau; Felix Mahfoud; Murray D Esler; Prashanthan Sanders; Michael Böhm Journal: Clin Auton Res Date: 2018-02-10 Impact factor: 4.435
Authors: Derek J Hausenloy; Hans Erik Bøtker; Peter Ferdinandy; Gerd Heusch; G André Ng; Andrew Redington; David Garcia-Dorado Journal: Cardiovasc Res Date: 2019-06-01 Impact factor: 10.787