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Chronic vagal nerve stimulation for the treatment of human heart failure : progress in translating a vision into reality
| Content Provider | Semantic Scholar |
|---|---|
| Author | Nkoulou, René N. Wolfrum, Mathias Kaufmann, Philipp A. |
| Copyright Year | 2011 |
| Abstract | Heart failure resulting from cardiac ischaemia and/or tachycardia is accompanied by changes in autonomic tone that typically result in increased heart rate and a reduction in heart rate variability. In this setting, autonomic dysfunction is often accompanied by evidence of neurohormonal activation (increased plasma levels of norepinephrine, angiotensin II, and endothelin-1) as well as inflammatory biomarkers and cytokines (tumor necrosis factor-a and C-reactive protein), metabolic changes, and increased systemic and cardiac oxidant stress. As illustrated in Figure 1, these processes promote cardiovascular structural and electrical remodelling, leading to dilation of the cardiac chambers, increased interstitial fibrosis, pump failure, and an increased susceptibility to lethal ventricular arrhythmia. Preclinical studies have been crucial to the elucidation of the role of the autonomic nervous system in cardiac function, and the dysfunction that accompanies ischaemia, infarction, and tachycardia-mediated cardiomyopathy. In 1984, Schwartz and colleagues showed that the autonomic nervous system had a critical role in the induction of ischaemia-induced lethal ventricular arrhythmias [ventricular tachycardia (VT)/ventricular fibrillation (VF)] in dogs with a healed myocardial infarction. This group showed that the sympathetic nervous system had a critical role in arrhythmogenesis, and that left stellectomy (which removes sympathetic input to the heart) essentially eliminated arrhythmogenesis in their model. Left stellectomy slows heart rate, but the authors showed that it was the combination of tachycardia plus acute ischaemia that was essential for arrhythmia induction. Recognition that pharmacological addition of b-adrenergic receptor blockers was able to slow heart rate, improve cardiac pump function, and reduce mortality in heart failure patients constitutes one of the major paradigm shifts in 20th century medicine. In the same canine model, Schwartz et al. demonstrated that the animals surviving acute ischaemia following exercise had a slower heart rate than those that did not survive. In follow-up studies, Billman et al. demonstrated that daily exercise could reduce the risk of arrhythmia in dogs previously vulnerable to ischaemic VT/VF. They inferred that either activation of the parasympathetic nervous system (mediated by the vagus) or deactivation of the sympathetic nervous system was likely to account for the heart rate slowing and enhanced survival. These studies suggested that daily exercise might improve function and reduce mortality in heart failure patients at risk for sudden cardiac death. Anginal pain is a sign of acute cardiac ischaemia. b-Adrenergic receptor blockers and calcium channel blockers were originally developed as anti-anginal agents. In a bold and impressive study reported in 1967, Braunwald et al. demonstrated that vagal nerve stimulation (VNS; in the carotid sinus) could reproducibly attenuate angina symptoms and improve exercise capacity in two patients following myocardial infarction. For reasons that are unclear but probably related to the technical challenges of creating an implantable device at that time, further development of VNS paused until the supporting technology evolved. With the development of pacemaker and defibrillator technology, the essential elements needed to package and deliver VNS became feasible, and devices capable of delivering this treatment were commercially developed in the 1990s. Chronic VNS has been clinically approved for the treatment of epilepsy since 1997, and more recently approved for the treatment of depression. In recent preclinical studies, chronic VNS has been shown to be effective in the treatment of both ischaemic and tachycardiamediated heart failure. In a ventricular tachypacing model, our group showed that this intervention improved baroreflex sensitivity and cardiac function, and reduced chamber dimensions. Chronic VNS decreased circulating plasma catecholamine levels, |
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| Alternate Webpage(s) | https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/eurheartj/32/7/10.1093_eurheartj_ehq424/2/ehq424.pdf?Expires=1492561548&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q&Signature=gNnH8qlmf4Xg7eXYNsrh12s9iW8~gJo22ih5euS-BxSZPnUlgBFV5CLUVsSvtVuxy26VmheLV2LtaLyZ-EYi8r5arSrQqaHKT0E0RIxXNtR8e~0D-knDe3Xk-TU7X7vhwOmi8CxjTii3dZnEYjifFhzgwyfBNAA8VG6HpvD9~Y6DdCNN8dPAbxzlwgfqvi1B6qzGHFUU2xd7mIDfl-YDpeFXmwA6vifGg8qL2J8Km1qt0PyE0xNDeqd-w-8D4iLn4CCIMPlPV7VXytF~t7j9CzLuT4MFP73ULscphDgBsvCRQNtkLkPphkh5mL3HIinWYbnFlrbv4FOJRPZLq~E5pA__ |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
