Direct evidence of nitric oxide release from neuronal nitric oxide synthase activation in the left ventricle as a result of cervical vagus nerve stimulation

Abstract

Abnormal autonomic activity has been shown to be a strong prognostic indicator of mortality in patients with heart failure (Nolan et al. 1998) and those who have had a previous myocardial infarct (La Rovere et al. 1998). Depressed heart rate variability and baroreceptor sensitivity are surrogate markers of impaired vagal tone associated with mortality in these conditions in which most of the deaths are sudden and due to ventricular arrhythmias, especially ventricular fibrillation (VF). We have recently shown that electrical stimulation of the vagus nerve in the neck ) has a strong anti-arrhythmic effect in the rabbit ventricle against VF. These effects are blocked in the presence of a nitric oxide (NO) synthase inhibitor providing indirect evidence that NO is involved in this effect. The implication of NO in mediating vagal activity in the ventricle is novel although

Long-term prognostic value of cardiac autonomic nervous activity in postoperative patients with congenital heart disease

“…6, respectively. which is associated with the BRS, supports our results [15]. In addition, keeping an effective parasympathetic nerve stimulation through the preserved BRS may have a beneficial impact on the volume and/or pressure overloaded ventricular remodeling and/or oxidative stress modification [16][17][18] in postoperative CHD patients. However, the prognostic value may be limited in postoperative complex CHD patients because the parasympathetic nervous activity is originally much diminished in patients with severe heart failure [1,5,19] and postoperative complex CHD with severely denervated hearts.…”

Inflammatory cytokines and nitric oxide in heart failure and potential modulation by vagus nerve stimulation

“…NO-dependent fluorescence was increased in the ventricle in a stimulation frequency-dependent manner during vagus nerve stimulation. This was abolished with a nonspecific NOS inhibitor and an nNOS selective inhibitor [78]. These data suggest that nNOS mediates vagal stimulationinduced NO release.…”

“…Isolated innervated rabbit hearts were employed with the use of the NO fluorescent indicator 4, 5-diaminofluorescein diacetate (DAF-2 DA) during stimulation of the cervical vagus nerves [78]. NO-dependent fluorescence was increased in the ventricle in a stimulation frequency-dependent manner during vagus nerve stimulation.…”

Mechanisms underlying the autonomic modulation of ventricular fibrillation initiation—tentative prophylactic properties of vagus nerve stimulation on malignant arrhythmias in heart failure

“…Through the use of the NO-sensitive dye DAF-2 DA, we were able to provide direct evidence of VNS-mediated NO release [134]. NO-dependent fluorescence was found to increase during both left and right cervical VNS in relation to the intensity of stimulation (see Fig.…”

“…a Raw data from a single experiment illustrating the change in left ventricular pressure (LVP), aortic perfusion pressure (AP) and nitric oxide dependent florescence (F490) during low-, medium- and high-intensity VS. b and c Mean data demonstrating the change in F490 before, during and after individual left and right VS. * P  < 0.05, ** P  < 0.01, *** P  < 0.001; comparison with steady-state response or between intensities of stimulation. Reproduced with permission from Brack et al [134]…”