Oct 21, 2016 - Bachmann's Bundle. Fibrosis, %. CD3+ count. CD45+ count. Fibrosis, %. CD3+ count. CD45+ count. Fibrosis, %. CD3+ count. CD45+ count.
indistinguishable whether we perturbed CSP or AVNS indicating that they share the common central and peripheral neural mechanism.
Conclusions: AVNS resets the baroreflex neural arc and induces sympathoinhibition just like the native baroreflex. The AVNS induced sympathoinhibition may in part attribute to the beneficial impacts of VNS on heart failure.
I.A. Andersen, S. Mangiafico, B.K. Huntley, G. Boerrigter, G. Harty, A. Cataliotti, J.C. Burnett Jr. Mayo Clinic, Cardiorenal Research Laboratory, Rochester, MN, United States of America Purpose: While renal donation is safe and widely employed for the treatment of endstage chronic kidney disease, recent experimental and human studies suggest complex cardiovascular adaptation that may impact long-term cardiovascular homeostasis. Indeed, in a large animal model of acute uninephrectomy (UNX) we observed reduced CO and increased SVR. Here we define chronic cardiovascular, renal and humoral adaptation in a large animal model 12 weeks after UNX with the goal of understanding integrative adaptations so as to advance possible cardiorenal protective strategies in the setting of mild renal insufficiency and UNX commonly associated with renal donation. Methods: Dogs were assigned to UNX (n=6) or sham operation (n=6). Echocardiography was performed at baseline and after 12 weeks. At 12 weeks cardiovascular, renal and humoral functions were assessed invasively. Fibrosis was assessed by Picrosirius red staining, and microarray analyses were performed on tissue from the left atrium (LA) and left ventricle (LV). Data are presented as mean±SD, * indicates p 2 fold significant changes in the expression of 10 genes in the LA and 7 genes in the LV, associated with cardiac remodeling. Conclusion: UNX in a large animal is characterized by compensatory renal hypertrophy and preserved cardiovascular homeostasis after 12 weeks. Importantly however, the cardiorenal protective cGMP system is activated which may reflect triggering of endogenous vasodilating pathways mediating the preserved cardiovascular and renal function. Furthermore, our model is characterized by subclinical atrial fibrosis and altered remodeling-related gene expressions in the LA and LV. These studies provide insights into the complex responses to UNX and possible cGMP therapeutic strategies for cardioprotection in the setting of reduced renal mass.
P5036 | SPOTLIGHT 2013 Role of muscarinic and nitric oxide dependent mechanisms in cardioprotection established by remote ischaemic preconditioning S. Mastitskaya 1 , N. Marina 1 , A. Gourine 2 , A.V. Gourine 1 . 1 University College London, London, United Kingdom; 2 Karolinska University Hospital, Department of Cardiology, Stockholm, Sweden Purpose: The role of the parasympathetic innervation of the ventricle remains controversial, although there is evidence that stimulation of the vagus nerve protects against ventricular fibrillation and reduces myocardial ischaemia/reperfusion injury. We recently demonstrated that cardioprotection established by remote ischaemic preconditioning (RPc) is crucially dependent upon the activity of a distinct population of parasympathetic pre-ganglionic neurones residing in the dorsal motor nucleus of the vagus nerve. In this study we determined the role of muscarinic and nitric oxide dependent mechanisms in mediating RPc cardioprotection.
Methods: Experiments were performed in accordance with the UK Animals (Scientific Procedures) Act 1986 and associated guidelines. Sprague-Dawley rats were subjected to 30 min LCA occlusion followed by 2 h reperfusion. RPc was induced by 15 min occlusion of both femoral arteries, followed by 10 min reperfusion before onset of myocardial ischaemia/reperfusion. The sham-RPc procedure involved exposure of both femoral arteries without occlusion. To eliminate parasympathetic influences to the heart, animals underwent complete bilateral vagotomy 15 min prior to RPc or sham-RPc procedure. Systemic muscarinic receptor blockade was achieved with atropine methyl nitrate infusion commencing 15 min prior to RPc or sham-RPc (2mg/kg induction dose, 1mg/kg/h supporting dose). Neuronal nitric oxide synthase inhibitor 7-nitro-indazole (7-NI; 30 mg/kg) was administered i.p. 30 min prior to RPc. Results: There were no significant differences in haemodynamic parameters between the groups of animals. RPc induced by ischaemia/reperfusion of the limbs limited myocardial ischaemia/reperfusion injury as evident from a significant reduction in infarct size (38.5±3.3% [n=10] vs 51.0±1.8 [n=10] in sham-RPc group, p