Thromboxane contributes to submaximal coronary dilation during myocardial ischemia.
OBJECTIVE
Thromboxane has been shown to contribute to coronary constriction in conduit coronary arteries during platelet aggregation at the site of a critical stenosis. Previous studies from our laboratory suggest that following a critical coronary stenosis, persistent vasomotor tone occurs. We tested the hypothesis that thromboxane is responsible for that increased tone.


METHODS
To test this hypothesis, 14 mongrel dogs of either sex were anesthetized and subjected to a critical coronary stenosis where distal coronary perfusion pressure was reduced to 36 +/- 2 mm Hg. During the coronary stenosis, SQ 29,548 (thromboxane/endoperoxide receptor antagonist) was administered intravenously (0.2 mg/kg and 2.0 mg/kg). Coronary microvascular responses were observed by directly visualizing the epicardial microcirculation. Diameters were measured using intravital microscopy coupled to stroboscopic epi-illumination and jet ventilation to compensate for cardiac and respiratory-induced motion.


RESULTS
Coronary microvessels were divided into small (< 150 microns) and large (> 150 microns) arterioles. During SQ 29,548 administration, small coronary arterioles demonstrated no additional dilation during a critical coronary stenosis. In contrast, coronary microvessels > 150 microns demonstrated a dose-dependent vasodilation to SQ 29,548 (0.2 mg/kg: 6 +/- 2%; 2.0 mg/kg: 11 +/- 4%; P < 0.05 vs. no change). A time control study in six additional animals demonstrated no significant microvascular diameter changes following a critical stenosis over the time course of SQ 29,548 administration.


CONCLUSIONS
Endoperoxides contribute to poststenotic microvascular vasoconstriction in vessels 150-300 microns.
D000818:Animals; D001784:Blood Gas Analysis; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D005231:Fatty Acids, Unsaturated; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006834:Hydrazines / Q000627:therapeutic use*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D009129:Muscle Tonus / Q000502:physiology*; D013931:Thromboxanes / Q000037:antagonists & inhibitors / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*; D014741:Video Recording
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D013931:Thromboxanes; C045749:SQ 29548