title: Myocardial oxygen supply:demand ratio as reference for coronary vasodilatory drug effects in humans.
abstract: OBJECTIVE
  Introduction and measurement of human myocardial oxygen supply:demand ratio as a reference for quantification of coronary microvascular vasodilating drug effects in clinical studies. Myocardial oxygen consumption is the major determinant of coronary blood flow; therefore, the true vasodilating properties of coronary vasodilating drugs that may have an effect on oxygen consumption cannot be correctly assessed from blood flow changes alone.
  
  
  METHODS
  Prospective, controlled trial.
  
  
  METHODS
  Academic hospital.
  
  
  METHODS
  12 patients with multivessel coronary artery disease (CAD) undergoing coronary artery bypass grafting.
  
  
  METHODS
  Cardiac pacing at 30 beats/min above sinus rhythm in awake and anaesthetised patients (fentanyl/pancuronium bromide).
  
  
  METHODS
  Myocardial oxygen supply, defined as coronary sinus blood flow multiplied by arterial oxygen content; myocardial oxygen demand, defined as coronary sinus blood flow multiplied by arteriovenous oxygen content difference. The change in oxygen demand induced by pacing was related to the change in myocardial oxygen supply in awake and anaesthetised patients. This myocardial oxygen supply:demand ratio determined in the reference study was compared with that induced by intravenous and intracoronary drugs (nifedipine, felodipine, urapidil, and sodium nitroprusside) in two pharmacological studies: patients with CAD undergoing cardiac surgery (45 treated with sodium nitroprusside, 27 with nifedipine, and 27 with urapidil to manage arterial blood pressure); and patients with unstable angina (and a similar degree of CAD) undergoing cardiac catheterisation for diagnostic purposes (10 treated with intracoronary nifedipine and 10 with intracoronary felodipine).
  
  
  RESULTS
  When awake, the ratio of pacing induced oxygen supply:demand changes in the 12 reference study patients was 1.50 (95% confidence intervals (CI), 1.41-1.58), similar to the 1.45 (1.35-1.56) measured in the same patients after induction of anaesthesia. Anaesthesia per se did not increase coronary oxygen supply above the expected increase related to demand changes. The only significant change in the oxygen supply:demand ratio was induced by intracoronary bolus administration of nifedipine and felodipine (10.6 (SE 1.9) and 13.9 (1.9) ml/min, respectively, above the demand related supply).
  
  
  CONCLUSIONS
  Quantification of coronary vasoactive properties in relation to the physiological reference ratio between myocardial oxygen supply and demand may be a powerful tool to differentiate between true and apparent coronary vasoactive drugs.
authors.affiliation: Department of Medical Physics, University of Amsterdam, The Netherlands. I.Vergroesen@amc.uva.nl
authors.forename: I
authors.initials: I
authors.lastname: Vergroesen
authors.forename: J E
authors.initials: JE
authors.lastname: Kal
authors.forename: J A
authors.initials: JA
authors.lastname: Spaan
authors.forename: H B
authors.initials: HB
authors.lastname: Van Wezel
mesh_terms: D000368:Aged; D006328:Cardiac Catheterization; D002304:Cardiac Pacing, Artificial; D001026:Coronary Artery Bypass; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy / Q000601:surgery; D015736:Felodipine / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000627:therapeutic use; D009599:Nitroprusside / Q000627:therapeutic use; D010101:Oxygen Consumption / Q000187:drug effects*; D010879:Piperazines / Q000627:therapeutic use; D011446:Prospective Studies; D012016:Reference Values; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D010879:Piperazines; D014665:Vasodilator Agents; D009599:Nitroprusside; C015568:urapidil; D009543:Nifedipine; D015736:Felodipine