title: Moderate, Short-Term, Local Hyperglycemia Attenuates Forearm Endothelium-Dependent Vasodilation After Transient Ischemia-Reperfusion in Human Volunteers.
abstract: OBJECTIVE
  Acute hyperglycemia causes endothelial dysfunction in diabetic patients, abolishes ischemic pre- and postconditioning, and is an independent predictor of adverse outcome after myocardial infarction in nondiabetic patients. Its effects on endothelial-dependent vasodilation are controversial in healthy subjects. The authors studied the effect of moderate short-term local hyperglycemia on forearm endothelium-dependent vasodilation in healthy volunteers.
  
  
  METHODS
  Randomized, crossover, blinded, 2-visit, pilot design.
  
  
  METHODS
  Veterans Affairs Medical Center.
  
  
  METHODS
  Five male and 3 female healthy adult volunteers (23±4 years; height 171±13 cm; weight 66±9 kg; [mean±standard error of the mean]).
  
  
  METHODS
  At each visit, volunteers received an infusion through a brachial artery catheter of either 0.9% saline or dextrose in the experimental, non-dominant arm, to establish mild forearm hyperglycemia. Hemodynamics and forearm blood flow (FBF; plethysmography) were measured at baseline, during brachial artery infusions of acetylcholine in consecutive increments (5, 10, and 15 μg/min), before ischemia (20 min, blood pressure cuff at 200 mmHg), and after 15 minutes of reperfusion. Blood glucose and insulin concentrations were determined from venous samples. The effect of duration of intra-arterial dextrose on FBF was examined.
  
  
  RESULTS
  Dextrose increased steady-state blood glucose concentration in the experimental but not the control arm (dominant arm). Dextrose increased FBF compared with saline (4.5±0.5 v 2.6±0.4 mL/min/100 g of tissue, respectively). Acetylcholine caused similar increases in FBF in the absence and presence of dextrose (+239±90% v+203±75%, respectively, during 15 μg/min). The duration of dextrose did not affect this acetylcholine-induced vasodilation. Acetylcholine-stimulated increases in FBF were attenuated in dextrose-treated versus saline after reperfusion (+180±18% v+257±53%, respectively, during 10 μg/min). Interventions in the experimental arm did not affect FBF in the control arm.
  
  
  CONCLUSIONS
  These results indicated that moderate, short-term, local hyperglycemia induced by intra-arterial administration of dextrose attenuated forearm endothelial-dependent vasodilation after ischemia-reperfusion injury in healthy volunteers.
authors.affiliation: Anesthesia Service, the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI. Electronic address: tjebert@mcw.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Ebert
authors.affiliation: Anesthesia Service, the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI.
authors.forename: Jutta
authors.initials: J
authors.lastname: Novalija
authors.affiliation: Anesthesia Service, the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Barney
authors.affiliation: Anesthesia Service, the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI.
authors.forename: Toni D
authors.initials: TD
authors.lastname: Uhrich
authors.affiliation: Anesthesia Service, the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI.
authors.forename: Shahbaz R
authors.initials: SR
authors.lastname: Arain
authors.affiliation: Anesthesia Service, the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI.
authors.forename: Julie K
authors.initials: JK
authors.lastname: Freed
authors.affiliation: Anesthesia Service, the Clement J. Zablocki Veterans Affairs Medical Center, Milwaukee, WI.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Pagel
mesh_terms: D000208:Acute Disease; D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005542:Forearm / Q000098:blood supply / Q000502:physiology*; D005947:Glucose / Q000008:administration & dosage / Q000009:adverse effects; D064368:Healthy Volunteers; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology*; D007261:Infusions, Intra-Arterial; D008297:Male; D010865:Pilot Projects; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*; D015427:Reperfusion Injury / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D016037:Single-Blind Method; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
chemical_list: D005947:Glucose
keywords: acetylcholine; endothelium; forearm blood flow; hyperglycemia; ischemia-reperfusion injury; vascular reactivity