title: The thromboxane A2 mimetic U46619 worsens canine myocardial hypoperfusion during exercise in the presence of a coronary artery stenosis.
abstract: OBJECTIVE
  The aim was to test the hypothesis that thromboxane A2 can cause vasoconstriction of coronary resistance vessels during exercise in hypoperfused regions of myocardium distal to an arterial stenosis.
  
  
  METHODS
  Eight adult mongrel dogs were studied. Chronically instrumented animals with a left circumflex coronary artery Doppler flow meter, hydraulic occluder, and indwelling catheter underwent treadmill exercise at heart rates of 190-200 beats.min-1. Myocardial blood flow was measured with microspheres during unimpeded arterial inflow and in the presence of a coronary stenosis which decreased distal pressure to 42-45 mm Hg. Measurements were repeated during infusion of the thromboxane A2 analogue, U46619.
  
  
  RESULTS
  When the occluder was partially inflated to produce a stenosis, blood flow in the region perfused by the stenotic artery was 58 (SEM 6)% of flow in the normally perfused region (p less than 0.01). U46619 (0.01 microgram.kg-1.min-1) caused a further 21 (7)% decrease in blood flow in the region perfused by the stenotic artery (p less than 0.05). The vasoconstriction produced by U46619 was uniform across the left ventricular wall from epicardium to endocardium. U46619 did not significantly decrease myocardial blood flow in the absence of a coronary stenosis.
  
  
  CONCLUSIONS
  Even during hypoperfusion produced by a flow limiting arterial stenosis, the coronary resistance vessels remain responsive to the vasoconstrictor effect of thromboxane A2. Liberation of thromboxane A2 during platelet activation at the site of a proximal coronary stenosis may worsen myocardial hypoperfusion by causing vasoconstriction of the distal resistance vessels.
authors.affiliation: Department of Internal Medicine, University of Minnesota Medical School, Minneapolis.
authors.forename: R J
authors.initials: RJ
authors.lastname: Bache
authors.forename: X Z
authors.initials: XZ
authors.lastname: Dai
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D003327:Coronary Disease / Q000503:physiopathology*; D004285:Dogs; D006339:Heart Rate / Q000502:physiology; D008863:Microspheres; D005082:Physical Exertion / Q000502:physiology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D013928:Thromboxane A2
chemical_list: D011450:Prostaglandin Endoperoxides, Synthetic; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid