title: Effect of N(G)-nitro-L-arginine methyl ester on autonomic modulation of heart rate variability during hypovolemic shock.
abstract: OBJECTIVE
  To study the changes in neuroautonomic regulation of heart rate and the effects of N(G)-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of nitric oxide synthase, on efferent sympathetic cardiac activity and blood pressure during hypovolemic shock. Hypotension during hypovolemic shock may be attributable, in part, to the failure of neuroautonomic regulation of heart rate and blood pressure. In addition, the release of nitric oxide may contribute to hypotension through vasodilation and inhibition of efferent sympathetic activity.
  
  
  METHODS
  Prospective, controlled trial.
  
  
  METHODS
  Experimental laboratory in a university hospital.
  
  
  METHODS
  Seventeen anesthetized adult male New Zealand White rabbits.
  
  
  METHODS
  The rabbits were divided into four groups: control (n = 3), control plus L-NAME (n = 5), hypovolemic (n = 4), and hypovolemic plus L-NAME (n = 5). Hypovolemic rabbits were bled of 10% of their circulating blood volume (85 mL/kg) every 10 mins until 30% cumulative hypovolemia was reached. Rabbits received either three doses of saline 1 mL/kg every 10 mins or L-NAME 10 mg/kg in 1 mL/kg of saline solution administered after each hemorrhage for a total of three doses. Changes in heart rate, respiratory rate, mean arterial pressure, plasma catecholamine levels, and heart rate power spectra were recorded every 10 mins during serial hypovolemia and during a 30-min recovery period.
  
  
  RESULTS
  During hypovolemic shock there was a decrease in log low-frequency heart rate power (p = .001) and in systolic (p = .003), diastolic (p < .001), and mean (p < .001) blood pressures compared with control rabbits. Treatment with L-NAME during hypovolemia resulted in increased log low-frequency heart rate power (p = .03) and systolic (p = .01), diastolic (p = .007), and mean (p = .009) blood pressures compared with hypovolemic rabbits who received saline placebo.
  
  
  CONCLUSIONS
  We found that treatment with L-NAME increased efferent sympathetic cardiac activity and mean arterial pressure during hypovolemic shock compared with control rabbits. We conclude that L-NAME may blunt hypotension during hypovolemic shock by inhibiting nitric oxide synthase and may act to restore neuroautonomic cardiovascular reactivity. Spectral analysis of heart rate variability may allow for insights into the pathophysiology of shock and provide a means of monitoring the neuroautonomic cardiovascular response to therapy.
authors.affiliation: Department of Pediatrics, University of Rochester School of Medicine and Dentistry, NY, USA.
authors.forename: B
authors.initials: B
authors.lastname: Goldstein
authors.forename: D
authors.initials: D
authors.lastname: Mickelsen
authors.forename: A
authors.initials: A
authors.lastname: Want
authors.forename: R
authors.initials: R
authors.lastname: Tipton
authors.forename: C
authors.initials: C
authors.lastname: Cox
authors.forename: P D
authors.initials: PD
authors.lastname: Woolf
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001810:Blood Volume; D002395:Catecholamines / Q000097:blood; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D011817:Rabbits; D012769:Shock / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002395:Catecholamines; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester