Itamar Ilsar

Vagus nerve stimulation in experimental heart failure.

Chronic heart failure (HF) is associated with autonomic dysregulation characterized by a sustained increase in sympathetic drive and by withdrawal of parasympathetic activity. Sympathetic overdrive and increased heart rate are predictors of poor long-term outcome in patients with HF. Considerable evidence exists that supports the use of pharmacologic agents that partially inhibit sympathetic activity as effective long-term therapy for patients with HF; the classic example is the wide use of selective and non-selective beta-adrenergic receptor blockers. In contrast, modulation of parasympathetic activation as potential therapy for HF has received only limited attention over the years given its complex cardiovascular effects. In this article, we review the results of recent experimental animal studies that provide support for the possible use of electrical Vagus nerve stimulation (VNS) as a long-term therapy for the treatment of chronic HF. In addition to exploring the effects of chronic VNS on left ventricular (LV) function, the review will also address the effects of VNS on potential modifiers of the HF state that include cytokine production and nitric oxide elaboration. Finally, we will briefly review other nerve stimulation approaches which is also currently under investigation as potential therapeutic modalities for treating chronic HF.

Acute vagal stimulation attenuates cardiac metabolic response to β-adrenergic stress

•  Whereas the effects of catecholamines on myocardial metabolism are well characterized, the potential role of the parasympathetic system is generally considered minor or absent. •  We tested the hypothesis that acute stimulation of the right vagus nerve alters the balance between cardiac free fatty acid and carbohydrate oxidation and opposes the metabolic effects of beta‐adrenergic stimulation. •  Using a clinical‐type selective stimulator of the vagal efferent fibers in dogs, we found that vagal stimulation did not significantly affect baseline cardiac performance, haemodynamics and myocardial metabolism. •  During dobutamine stress, vagal stimulation attenuated the increase in left ventricular mechanical performance, cardiac oxygen consumption and myocardial glucose oxidation, while free fatty acid oxidation was affected only at low catecholamine dose. •  Our results elucidate a previously unexplored parasympathetic function, indicating that selective vagal efferent stimulation antagonizes the effects of beta‐adrenergic activation on myocardial metabolism.

Acute Left Ventricular Unloading in Dogs With Chronic Heart Failure: Continuous Aortic Flow Augmentation Versus Intra-Aortic Balloon Pumping

BACKGROUND Continuous aortic flow augmentation (CAFA) therapy with the Cancion System (Orqis Medical, Inc) was shown to effectively unload the left ventricle in dogs with chronic heart failure (HF). This study compared the extent of acute left ventricular (LV) unloading elicited by CAFA to that elicited by intra-aortic balloon counterpulsation (IABP) in normotensive dogs with coronary microembolization-induced HF. METHODS AND RESULTS Seven HF dogs were studied with both CAFA and IABP in random order and 1 week apart. In both instances, active therapy was maintained for 4 hours. The Cancion system was positioned using a dual femoral approach configuration with a constant pump flow of 250 mL/min. In all dogs and with both devices, LV end-diastolic pressure (EDP), LV end-systolic volume (ESV), and LV ejection fraction (EF) were measured at baseline and at 2 and 4 hours after instituting CAFA or IABP. Plasma samples obtained at the end of 4 hours of therapy were used to measure a host of circulating biomarkers that included neurohormones, cytokines, and A-type and B-type natriuretic peptides. IABP had no significant effects on LVEDP, LVESV, and LVEF. In contrast, CAFA significantly decreased LVEDP and LVESV and increased LVEF. Compared with IABP, CAFA was accompanied by significant improvements in circulating levels of neurohormones, cytokines, and natriuretic peptides. CONCLUSIONS The results indicate that CAFA is more effective than IABP in achieving acute global LV unloading in dogs with chronic HF not complicated by ongoing myocardial ischemia or cardiogenic shock.