Increased production of thromboxane A2 by coronary arteries after thrombolysis.
The coronary artery produces large amounts of prostacyclin (PGI2) and a small amount of thromboxane A2 (TXA2); this high PGI2/TXA2 ratio contributes to the antithrombotic properties of the coronary artery. This study was designed to determine whether this ratio changes after coronary artery thrombosis and thrombolysis and accounts for coronary artery reocclusion. Anesthetized dogs (N = 12) were subjected to electrically induced coronary artery thrombosis and tissue plasminogen activator-induced thrombolysis. Thrombolysis was achieved in 11 dogs, and the coronary artery reoccluded in five of these dogs after the initial reperfusion. Spontaneous and ionophore A23,187-stimulated PGI2 and TXA2 synthesis in normal circumflex and ischemic-reperfused left anterior descending coronary artery segments was measured by radioimmunoassay of thromboxane B2 and 6-keto-prostaglandin F1 alpha, respectively. Production of TXA2 was 413% to 656% greater in left anterior descending segments (from the region of thrombosis and sites proximal and distal to the thrombus) compared with normal circumflex segments (p < 0.001). Production of PGI2 was also increased but only by 46% to 80% in the left anterior descending segments compared with normal circumflex segments (p < 0.05). TXA2 production was greater in coronary artery segments that reocculded compared with segments that stayed open (p < 0.02). Scanning electron microscopy revealed platelet deposition in thrombosed left anterior descending segments but not in segments proximal or distal to the thrombus site, indicating that the vascular wall per se may be a source of increased production of TXA2.(ABSTRACT TRUNCATED AT 250 WORDS)
Saldeen
T G
TG
Department of Medicine, University of Florida College of Medicine, Gainesville.
Saldeen
P
P
Nichols
W W
WW
Lawson
D L
DL
Nicolini
F A
FA
Mehta
J L
JL
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D003328:Coronary Thrombosis / Q000188:drug therapy / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004285:Dogs; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008855:Microscopy, Electron, Scanning; D012008:Recurrence; D015912:Thrombolytic Therapy; D013928:Thromboxane A2 / Q000096:biosynthesis*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use
D000001:Calcimycin; D013928:Thromboxane A2; D011464:Epoprostenol; D010959:Tissue Plasminogen Activator; D007213:Indomethacin