Intracoronary administration of streptokinase in a canine model. Disturbance in thromboxane A2-prostacyclin balance.
The potential impact of local intracoronary infusion of streptokinase (SK) on vascular prostaglandin synthetic pathways was studied in a canine model. Control animals (n = 10) underwent left coronary artery (LCA) infusion of 50,000 units SK for 90 minutes; experimental animals (n = 10) underwent LCA infusion of normal saline. Plasma samples for radioimmunoassay (RIA) of prostacyclin (PGI-2) and thromboxane (TXA-2) were obtained from the coronary sinus (CS) as follows: one sample preinfusion, six samples during infusion, and three samples postinfusion in each animal. Comparisons between control and experimental plasma levels of PGI-2 and TXA-2 were made for each sampling time. The PGI-2 levels remained at or below the lower limits of detectability by RIA (the most sensitive assay available) in both control and experimental animals. TXA-2 levels were higher in experimental than in control animals at all sampling times, with the most significant differences occurring in samples 3 (after 30 minutes of infusion, .001 less than P less than .01), 4 (after 45 minutes of infusion, .05 less than P less than .10), and 5 (after 60 minutes of infusion, .02 less than P less than .05). We suggest (1) it is unlikely that any of the beneficial effects of coronary streptokinase infusions are PGI-2-mediated, (2) that the TXA-2 increases in our model may represent a pathophysiologic-biochemical correlate of previously identified morphologic evidence of endothelial damage in animals infused with fibrinolytic agents, and (3) that our findings may indicate that fibrinolytic infusions produce competing effects: lysis of thrombi and endothelial injury with TXA-2 production.(ABSTRACT TRUNCATED AT 250 WORDS)
Becker
G J
GJ
Kreipke
D L
DL
Holden
R W
RW
Dreesen
R G
RG
Ryder
K
K
Petersen
B
B
Evan
A P
AP
Bendick
P J
PJ
Franklin
T D
TD
Klatte
E C
EC
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D015232:Dinoprostone; D004285:Dogs; D011458:Prostaglandins E / Q000097:blood*; D011863:Radioimmunoassay; D013300:Streptokinase / Q000008:administration & dosage / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000097:blood*; D013997:Time Factors
D001095:Arachidonic Acids; D011458:Prostaglandins E; D016718:Arachidonic Acid; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D013300:Streptokinase; D015232:Dinoprostone