| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
CARDIOVASCULAR |
1 Department of Pharmacology, Division of Neuroscience, University of Birmingham, Birmingham, UK
2
Cardiology group, Department of Cardiovascular Sciences, University of Leicester, Leicester, UK
We have previously shown that direct vagus nerve stimulation (VNS) reduces the slope of action potential duration (APD) restitution while simultaneously protecting the heart against induction of ventricular fibrillation (VF) in the absence of any sympathetic activity or tone. In the current study we have examined the role of nitric oxide (NO) in the effect of VNS. Monophasic action potentials were recorded from a left ventricular epicardial site on innervated, isolated rabbit hearts (n = 7). Standard restitution, effective refractory period (ERP) and VF threshold (VFT) were measured at baseline and during VNS in the presence of the NO synthase inhibitor NG-nitro-L-arginine (L-NA, 200 µM) and during reversing NO blockade with L-arginine (L-Arg, 1 mM). Data represent the mean ± S.E.M. The restitution curve was shifted upwards and became less steep with VNS when compared to baseline. L-NA blocked the effect of VNS whereas L-Arg restored the effect of VNS. The maximum slope of restitution was reduced from 1.17 ± 0.14 to 0.60 ± 0.09 (50 ± 5%, P < 0.0001) during control, from 0.98 ± 0.14 to 0.93 ± 0.12 (2 ± 10%, P = NS) in the presence of L-NA and from 1.16 ± 0.17 to 0.50 ± 0.10 (41 ± 9%, P = 0.003) with L-Arg plus L-NA. ERP was increased by VNS in control from 119 ± 6 ms to 130 ± 6 ms (10 ± 5%, P = 0.045) and this increase was not affected by L-NA (120 ± 4 to 133 ± 4 ms, 11 ± 3%, P = 0.0019) or L-Arg with L-NA (114 ± 4 to 123 ± 4 ms, 8 ± 2%, P = 0.006). VFT was increased from 3.0 ± 0.3 to 5.8 ± 0.5 mA (98 ± 12%, P = 0.0017) in control, 3.4 ± 0.4 to 3.8 ± 0.5 mA (13 ± 12%, P = 0.6) during perfusion with L-NA and 2.5 ± 0.4 to 6.0 ± 0.7 mA (175 ± 50%, P = 0.0017) during perfusion with L-Arg plus L-NA. Direct VNS increased VFT and flattened the slope of APD restitution curve in this isolated rabbit heart preparation with intact autonomic nerves. These effects were blocked using L-NA and reversed by replenishing the substrate for NO production with L-Arg. This is the first study to demonstrate that NO plays an important role in the anti-fibrillatory effect of VNS on the rabbit ventricle, possibly via effects on APD restitution.
(Received 11 June 2007;
accepted after revision 5 July 2007;
first published online 12 July 2007)
Corresponding author G. A. Ng: Senior Lecturer/Honorary Consultant Cardiologist, Department of Cardiovascular Sciences, Cardiology group, University of Leicester, Clinical Sciences Wing, Glenfield Hospital, Leicester LE3 9QP, UK. Email: gan1{at}le.ac.uk
This article has been cited by other articles:
|
|
 |
|
  M. Said, R. Becerra, J. Palomeque, G. Rinaldi, M. A. Kaetzel, P. L. Diaz-Sylvester, J. A. Copello, J. R. Dedman, C. Mundina-Weilenmann, L. Vittone, et al. Increased intracellular Ca2+ and SR Ca2+ load contribute to arrhythmias after acidosis in rat heart. Role of Ca2+/calmodulin-dependent protein kinase II Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1669 - H1683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. del Rio, T. A. Dawson, B. D. Clymer, D. J. Paterson, and G. E. Billman Effects of acute vagal nerve stimulation on the early passive electrical changes induced by myocardial ischaemia in dogs: heart rate-mediated attenuation Exp Physiol, August 1, 2008; 93(8): 931 - 944. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
