Markus Amann1, Massimo Venturelli2, Stephen J Ives3, David E Morgan4, Benjamin Gmelch4, Melissa A H Witman3, H Jonathan Groot3, D Walter Wray5, Josef Stehlik2, Russell S Richardson5. 1. Department of Medicine, University of Utah, Salt Lake City, UT, USA; Department of Anesthesiology, University of Utah, Salt Lake City, UT, USA; Geriatric Research, Education, and Clinical Center, VAMC Salt Lake City, UT, USA. Electronic address: markus.amann@hsc.utah.edu. 2. Department of Medicine, University of Utah, Salt Lake City, UT, USA. 3. Geriatric Research, Education, and Clinical Center, VAMC Salt Lake City, UT, USA. 4. Department of Anesthesiology, University of Utah, Salt Lake City, UT, USA. 5. Department of Medicine, University of Utah, Salt Lake City, UT, USA; Geriatric Research, Education, and Clinical Center, VAMC Salt Lake City, UT, USA.
Abstract
OBJECTIVE: To better understand the hemodynamic and autonomic reflex abnormalities in heart-failure patients (HF), we investigated the influence of group III/IV muscle afferents on their cardiovascular response to rhythmic exercise. METHODS: Nine HF-patients (NYHA class-II, mean left ventricular ejection-fraction: 27 ± 3%) performed single leg knee-extensor exercise (25/50/80% peak-workload) under control conditions and with lumbar intrathecal fentanyl impairing μ-opioid receptor-sensitive muscle afferents. RESULTS: Cardiac-output (Q) and femoral blood-flow (QL) were determined, and arterial/venous blood samples collected at each workload. Exercise-induced fatigue was estimated via pre/post-exercise changes in quadriceps strength. There were no hemodynamic differences between conditions at rest. During exercise, Q was 8-13% lower with Fentanyl-blockade, secondary to significant reductions in stroke volume and heart rate. Lower norepinephrine spillover during exercise with Fentanyl revealed an attenuated sympathetic outflow that likely contributed to the 25% increase in leg vascular conductance (p<0.05). Despite a concomitant 4% reduction in blood pressure, QL was 10-14% higher and end-exercise fatigue attenuated by 30% with Fentanyl-blockade (p<0.05). CONCLUSION/PRACTICE/IMPLICATIONS: Although group III/IV muscle afferents play a critical role for central hemodynamics in HF-patients, it also appears that these sensory neurons cause excessive sympatho-excitation impairing QL which likely contributes to the exercise intolerance in this population.
OBJECTIVE: To better understand the hemodynamic and autonomic reflex abnormalities in heart-failurepatients (HF), we investigated the influence of group III/IV muscle afferents on their cardiovascular response to rhythmic exercise. METHODS: Nine HF-patients (NYHA class-II, mean left ventricular ejection-fraction: 27 ± 3%) performed single leg knee-extensor exercise (25/50/80% peak-workload) under control conditions and with lumbar intrathecal fentanyl impairing μ-opioid receptor-sensitive muscle afferents. RESULTS: Cardiac-output (Q) and femoral blood-flow (QL) were determined, and arterial/venous blood samples collected at each workload. Exercise-induced fatigue was estimated via pre/post-exercise changes in quadriceps strength. There were no hemodynamic differences between conditions at rest. During exercise, Q was 8-13% lower with Fentanyl-blockade, secondary to significant reductions in stroke volume and heart rate. Lower norepinephrine spillover during exercise with Fentanyl revealed an attenuated sympathetic outflow that likely contributed to the 25% increase in leg vascular conductance (p<0.05). Despite a concomitant 4% reduction in blood pressure, QL was 10-14% higher and end-exercise fatigue attenuated by 30% with Fentanyl-blockade (p<0.05). CONCLUSION/PRACTICE/IMPLICATIONS: Although group III/IV muscle afferents play a critical role for central hemodynamics in HF-patients, it also appears that these sensory neurons cause excessive sympatho-excitation impairing QL which likely contributes to the exercise intolerance in this population.
Authors: C Indolfi; A Maione; M Volpe; A Rapacciuolo; G Esposito; R Ceravolo; V Rendina; M Condorelli; M Chiariello Journal: Circulation Date: 1994-07 Impact factor: 29.690
Authors: Erik H Van Iterson; Eric M Snyder; Michael J Joyner; Bruce D Johnson; Thomas P Olson Journal: Int J Cardiol Date: 2015-08-14 Impact factor: 4.164
Authors: Catherine F Notarius; Philip J Millar; Daniel A Keir; Hisayoshi Murai; Nobuhiko Haruki; Emma O'Donnell; Susan Marzolini; Paul Oh; John S Floras Journal: Am J Physiol Regul Integr Comp Physiol Date: 2019-07-31 Impact factor: 3.619
Authors: Jasdeep Kaur; Abhinav C Krishnan; Danielle Senador; Alberto Alvarez; Hanna W Hanna; Donal S O'Leary Journal: Am J Physiol Heart Circ Physiol Date: 2018-08-03 Impact factor: 4.733
Authors: Manda L Keller-Ross; Andrielle L Sarkinen; Troy Cross; Bruce D Johnson; Thomas P Olson Journal: Med Sci Sports Exerc Date: 2016-03 Impact factor: 5.411
Authors: J C Weavil; T S Thurston; T J Hureau; J R Gifford; P A Kithas; R M Broxterman; A D Bledsoe; J N Nativi; R S Richardson; M Amann Journal: Am J Physiol Heart Circ Physiol Date: 2020-11-08 Impact factor: 4.733
Authors: Joshua R Smith; Corey R Hart; Paola A Ramos; Joshua G Akinsanya; Ian R Lanza; Michael J Joyner; Timothy B Curry; Thomas P Olson Journal: Exp Physiol Date: 2020-03-29 Impact factor: 2.969
Authors: Thales C Barbosa; Lauro C Vianna; Igor A Fernandes; Eliza Prodel; Helena N M Rocha; Vinicius P Garcia; Natalia G Rocha; Niels H Secher; Antonio C L Nobrega Journal: J Physiol Date: 2016-01-15 Impact factor: 5.182
Authors: Joshua F Lee; Zachary Barrett-O'Keefe; Ashley D Nelson; Ryan S Garten; John J Ryan; Jose N Nativi-Nicolau; Russell S Richardson; D Walter Wray Journal: Int J Cardiol Date: 2016-03-02 Impact factor: 4.164