Sympathetic nervous response to ischemia-reperfusion injury in humans is altered with remote ischemic preconditioning.
Sympathetic neural activation may be detrimentally involved in tissue injury caused by ischemia-reperfusion (IR). We examined the effects of experimental IR in the forearm on sympathetic nerve response, finger reactive hyperemia, and oxidative stress, and the protection afforded by applying remote ischemic preconditioning (RIPC). Ischemia was induced in the forearm for 20 min in healthy volunteers. RIPC was induced by applying two cycles, 5 min each, of ischemia and reperfusion to the upper leg immediately before IR. We examined muscle sympathetic nerve activity (MSNA) in the contralateral leg using microneurography, finger reactive hyperemia [ischemic reactive hyperemia index (RHI)], erythrocyte production of reduced gluthathione (GSH), and plasma nitric oxide (NO) concentration. In controls (no RIPC; n = 15), IR increased MSNA in the early and late phase of ischemia (70% at 5 min; 101% at 15 min). In subjects who underwent RIPC (n = 15), the increase in MSNA was delayed to the late phase of ischemia and increased only by 40%. GSH increased during ischemia in the control group (P = 0.05), but not in those who underwent RIPC. Nitrate and nitrite concentration, taken as an index of NO availability, decreased during the reperfusion period in control individuals (P < 0.05), while no change was observed in those who underwent RIPC. Experimental IR did not affect RHI in the control condition, but a significant vasodilatory response occurred in the RIPC group (P < 0.05). RIPC attenuated ischemia-induced sympathetic activation, prevented the production of an erythrocyte marker of oxidative stress and the reduction of NO availability, and ameliorated RHI.
Human Neurotransmitters Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; Department of Physiology, Monash University, Clayton, Victoria, Australia; and elisabeth.lambert@bakeridi.edu.au.
Elisabeth A
EA
Lambert
Department of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, Melbourne, Victoria, Australia;
Colleen J
CJ
Thomas
Human Neurotransmitters Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia;
Robyn
R
Hemmes
Human Neurotransmitters Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia;
Nina
N
Eikelis
Centre de Recherche Clinique Cardiovasculaire Pasteur, Centre Hospitalier Universitaire, Toulouse, France;
Atul
A
Pathak
School of Medicine and Pharmacology, Royal Perth Hospital Unit, Faculty of Medicine, Dentistry & Health Sciences, The University of Western Australia, Perth, Western Australia, Australia;
Markus P
MP
Schlaich
Human Neurotransmitters Laboratory, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia.
Gavin W
GW
Lambert
D000293:Adolescent; D000328:Adult; D005260:Female; D005385:Fingers / Q000098:blood supply*; D005542:Forearm; D005978:Glutathione / Q000097:blood; D064368:Healthy Volunteers; D006801:Humans; D006940:Hyperemia / Q000097:blood* / Q000503:physiopathology; D019194:Ischemic Preconditioning; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation*; D009569:Nitric Oxide / Q000097:blood; D018384:Oxidative Stress; D010991:Plethysmography; D015427:Reperfusion Injury / Q000097:blood* / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D055815:Young Adult
D009569:Nitric Oxide; D005978:Glutathione
endothelial function; ischemia-reperfusion injury; oxidative stress; remote conditioning; sympathetic nervous system