title: Cold stress provokes sympathoinhibitory presyncope in healthy subjects and hemodialysis patients with low cardiac output.
abstract: BACKGROUND
  Sudden hypotension in progressive hypovolemia or during hemodialysis is attributed to sudden inhibition of sympathetic activity. Critical ventricular underfilling seems responsible for this paradox, but it is unknown why the transition from sympathoactivation accompanying hypovolemia to sympathoinhibition is so abrupt. We studied whether brief fluctuation of sympathetic activity induced by cold pressor test (CPT) evokes sympathoinhibition if applied during low cardiac output.
  
  
  RESULTS
  Fourteen healthy subjects underwent CPT, lower-body negative pressure (LBNP; -45 mm Hg for 60 minutes), or the combination thereof. CPT alone caused vasoconstriction and increased muscle sympathetic nerve activity, followed by uneventful relaxation. When applied during reduced cardiac output, tachycardia, and vasoconstriction induced by prior LBNP for 6 minutes, CPT again caused vasoconstriction, now followed by acute hypotension in 10 subjects, and was associated with vasorelaxation, relative bradycardia, and fall in muscle sympathetic nerve activity. Eight subjects also experienced acute LBNP-induced hypotension in the absence of CPT, but not until 17 +/- 6 minutes of LBNP. We also performed CPT before and in the final phase of hemodialysis in 8 patients. Before dialysis, the patients tolerated CPT uneventfully, but during hemodialysis, CPT provoked acute hypotension in 5 cases, showing similar withdrawal of vasoconstriction.
  
  
  CONCLUSIONS
  This is the first study showing that brief cold stress, tolerated well in normal circulatory conditions, can provoke sudden sympathoinhibition and hypotension when applied during decreased cardiac output induced by LBNP or hemodialysis. We suggest that during conditions of a decreased cardiac output, subtle sympathetic relaxation such as follows cold stress triggers self-enhancing relaxation that cannot be controlled.
authors.affiliation: Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Ligtenberg
authors.forename: P J
authors.initials: PJ
authors.lastname: Blankestijn
authors.forename: P L
authors.initials: PL
authors.lastname: Oey
authors.forename: G H
authors.initials: GH
authors.lastname: Wieneke
authors.forename: A C
authors.initials: AC
authors.lastname: van Huffelen
authors.forename: H A
authors.initials: HA
authors.lastname: Koomans
mesh_terms: D000328:Adult; D002303:Cardiac Output, Low / Q000150:complications*; D003080:Cold Temperature; D006801:Humans; D008150:Lower Body Negative Pressure; D008875:Middle Aged; D009433:Neural Inhibition; D012016:Reference Values; D006435:Renal Dialysis / Q000009:adverse effects*; D013312:Stress, Physiological; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013575:Syncope / Q000209:etiology*