title: Intranasal nicotine spray does not augment the adverse effects of cigarette smoking on myocardial oxygen demand or coronary arterial dimensions.
abstract: OBJECTIVE
  Nicotine replacement therapy has become a popular therapy for smokers attempting to stop smoking. Unfortunately, some subjects continue to smoke while receiving it. Since nicotine is believed to be the primary constituent of cigarette smoke responsible for its acute adverse effects on myocardial oxygen supply and demand, concomitant nicotine replacement therapy and smoking theoretically could provoke a marked decrease in myocardial oxygen supply and increase in demand. This study was performed to assess the effects of cigarette smoking with and without concomitant intranasal nicotine spray on: (a) myocardial oxygen demand, (b) coronary arterial dimensions, and (c) the development of acute cardiovascular tolerance.
  
  
  METHODS
  In 19 smokers referred for cardiac catheterization for the evaluation of chest pain, we assessed the effects of cigarette smoking with and without concomitant intranasal nicotine spray on: (a) heart rate-systolic arterial pressure product (an estimate of myocardial oxygen demand), (b) coronary arterial dimensions (measured with computer-assisted quantitative arteriography), and (c) the development of acute cardiovascular tolerance.
  
  
  RESULTS
  Smoking a first cigarette increased rate pressure product (P < 0.001) and decreased coronary arterial dimensions (P < 0.0001). Subsequently, neither variable was altered by intranasal nicotine spray or a second cigarette. Despite a substantial increase in serum nicotine concentration with nicotine spray and smoking, acute cardiovascular tolerance appears to develop.
  
  
  CONCLUSIONS
  Cigarette smoking causes an increase in myocardial oxygen demand and concomitant coronary arterial vasoconstriction. However, further increases in the serum nicotine concentration do not cause a greater increase in demand or decrease in coronary arterial dimensions. These data suggest that humans acutely develop tolerance to an increasing nicotine concentration, thereby helping to explain the apparent lack of a potential synergistic adverse effect associated with continued smoking during nicotine replacement therapy.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Keeley
authors.forename: M J
authors.initials: MJ
authors.lastname: Pirwitz
authors.forename: C
authors.initials: C
authors.lastname: Landau
authors.forename: R A
authors.initials: RA
authors.lastname: Lange
authors.forename: L D
authors.initials: LD
authors.lastname: Hillis
authors.forename: E H
authors.initials: EH
authors.lastname: Foerster
authors.forename: K
authors.initials: K
authors.lastname: Conrad
authors.forename: J E
authors.initials: JE
authors.lastname: Willard
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D006328:Cardiac Catheterization; D002932:Cineangiography; D017023:Coronary Angiography; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009538:Nicotine / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D010101:Oxygen Consumption / Q000187:drug effects*; D012907:Smoking / Q000009:adverse effects*; D016540:Smoking Cessation; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D009538:Nicotine