title: Multiple endothelial injury in epicardial coronary artery induces downstream microvascular spasm as well as remodeling partly via thromboxane A2.
abstract: OBJECTIVE
  The study was undertaken to develop a coronary microvascular spasm model in pigs by repeated epicardial coronary artery endothelial injury.
  
  
  BACKGROUND
  The pathophysiologic mechanisms responsible for coronary microvascular spasm remain unclear, in large part because a suitable animal model has yet to be found.
  
  
  METHODS
  Balloon endothelial denudation was done just distal to the site of an implanted Doppler flowmeter in the left anterior descending coronary artery (LAD) every two weeks for a total of four times. Changes in LAD blood flow by intracoronary administration of vasoactive agents were assessed before each denudation.
  
  
  RESULTS
  In the epicardial LAD endothelial denudation pigs, decreases in LAD blood flow caused by acetylcholine were augmented. Before denudation, it was - 15 +/- 4%, and at week 8 (i.e., two weeks after the fourth denudation) it was -100% (i.e., zero flow [p < 0.01]). The LAD flow changes in response to 5-hydroxytryptamine (5-HT) changed from an increase to a decrease, accompanied by medial thickening of microvessels in the LAD perfusion area. These flow responses were observed without significant changes in LAD diameter. In contrast, the LAD blood flow responses to acetylcholine and 5-HT did not change throughout the experiment in pigs given aspirin and a thromboxane A2 (TXA2) synthase inhibitor orally.
  
  
  CONCLUSIONS
  This microvascular spasm model indicates that hypersensitivity to vasoactive substances in the microvascular beds as well as microvascular remodeling are brought about partly through TXA2. This model should be useful for examining the pathophysiology and treatment of microvascular angina.
authors.affiliation: Fukushima Medical University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Saitoh
authors.forename: F
authors.initials: F
authors.lastname: Onogi
authors.forename: K
authors.initials: K
authors.lastname: Aikawa
authors.forename: M
authors.initials: M
authors.lastname: Muto
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Maehara
authors.forename: Y
authors.initials: Y
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D003329:Coronary Vasospasm / Q000473:pathology / Q000503:physiopathology*; D003331:Coronary Vessels / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004699:Endocardium / Q000473:pathology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000293:injuries* / Q000473:pathology / Q000503:physiopathology; D008833:Microcirculation / Q000473:pathology / Q000503:physiopathology; D013552:Swine; D013928:Thromboxane A2 / Q000502:physiology*
chemical_list: D013928:Thromboxane A2