title: Dissociation between reflex sympathetic and forearm vascular responses to lower body negative pressure in heart failure patients with coronary artery disease.
abstract: Many heart failure (HF) patients exhibit paradoxical forearm vasodilation when central blood volume is reduced by lower body negative pressure (LBNP). We tested the hypothesis that this response results from reflex sympathetic withdrawal. We recorded simultaneously forearm blood flow, muscle sympathetic nerve activity (MSNA), and plasma norepinephrine (PNE) during four random applications of LBNP, -5, -10, -20, and -40 mmHg, in 12 men with HF (mean left ventricular ejection fraction = 24 + or - 2%) and 10 healthy, normal, age-matched men (N). Compared with N, MSNA burst frequency (P = 0.001) and PNE (P = 0.005) were significantly higher in the HF group, both at rest and during LBNP. As anticipated in N, LBNP -40 mmHg significantly increased MSNA (+14.2 + or - 2.5 bursts/min; P < 0.05) and PNE (+0.83 + or - 0.22 nmol/l; P < 0.05) and decreased forearm vascular conductance (FVC) (-11.7 + or - 3.2 ml.min(-1).mmHg(-1); P < 0.05). In the HF group, LBNP elicited similar increases in MSNA (+11.5 + or - 2.0; P < 0.05) and PNE (+0.85 + or - 0.12; P < 0.05), without affecting FVC significantly (-4.1 + or - 2.4; P = 0.01 vs. N, interaction P = 0.03). However, within the HF group, responses were bimodal: LBNP -40 mmHg increased MSNA in all subjects (P < 0.001), yet the six patients with nonischemic or dilated cardiomyopathy (DCM) exhibited significant vasoconstriction (decrease in FVC; P = 0.001), whereas the six patients with ischemic cardiomyopathy (ICM) exhibited significant vasodilation (increase in FVC; P < 0.02 vs. DCM and N; interaction P = 0.02). Cold pressor testing increased MSNA and decreased FVC in ICM (n = 4). Thus paradoxical forearm vasodilator responses to LBNP in HF are not mediated by reflex sympathetic withdrawal. ICM and DCM patients differ qualitatively in their vascular responses to hypotensive LBNP.
authors.affiliation: Division of Cardiology, University Health Network and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada. c.notarius@utoronto.ca
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Notarius
authors.forename: Beverley L
authors.initials: BL
authors.lastname: Morris
authors.forename: John S
authors.initials: JS
authors.lastname: Floras
mesh_terms: D000200:Action Potentials; D015415:Biomarkers / Q000097:blood; D001810:Blood Volume; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000503:physiopathology; D016022:Case-Control Studies; D003080:Cold Temperature; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D004562:Electrocardiography; D005542:Forearm / Q000098:blood supply*; D006333:Heart Failure / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D008150:Lower Body Negative Pressure; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation*; D009638:Norepinephrine / Q000097:blood; D010991:Plethysmography; D011897:Random Allocation; D012018:Reflex; D012039:Regional Blood Flow; D013318:Stroke Volume; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology*; D014661:Vasoconstriction; D014664:Vasodilation; D016277:Ventricular Function, Left
chemical_list: D015415:Biomarkers; D009638:Norepinephrine