Circulation. Heart failure
-
Autonomic dysfunction, characterized by sympathetic activation and vagal withdrawal, contributes to the progression of heart failure (HF). Although the therapeutic benefits of sympathetic inhibition with beta-blockers in HF are clear, the role of increased vagal tone in this setting has been less studied. We have investigated the impact of enhancing vagal tone (achieved through chronic cervical vagus nerve stimulation, [VNS]) on HF development in a canine high-rate ventricular pacing model. ⋯ Chronic VNS improves cardiac autonomic control and significantly attenuates HF development in the canine high-rate ventricular pacing model. The therapeutic benefit of VNS is associated with pronounced anti-inflammatory effects. VNS is a novel and potentially useful therapy for treating HF.
-
Urocortin 2 (Ucn2), a novel peptide with therapeutic potential in heart failure, and diuretics have opposing effects on renal function and the renin-angiotensin-aldosterone system. Because any prospective new treatment is likely to be used in conjunction with standard diuretic therapy, it is necessary to investigate the combined effects of these agents. ⋯ Ucn2 cotreatment with furosemide enhanced hemodynamic and renal function and diuretic responsiveness (without additional potassium depletion) in experimental heart failure. Furthermore, Ucn2 reversed furosemide-induced increases in plasma renin activity and induced greater decreases in plasma aldosterone and vasopressin. These data indicate that adjunct Ucn2 therapy with diuretics in heart failure is beneficial.
-
Inflammation has been implicated in the pathogenesis of heart failure (HF), but knowledge about the production and role of inflammatory actors remains incomplete. On the basis of its role in vascular inflammation, vascular proliferation, and matrix degradation, we hypothesized a role for the chemokine CXCL16 in the pathogenesis of myocardial remodeling and development of HF. ⋯ We show enhanced myocardial CXCL16 expression in experimental and clinical HF. The effect of CXCL16 on cardiomyocytes and fibroblasts suggests a role for CXCL16 in matrix remodeling and ultimately in the development of HF.