Interference with the prostaglandin system as a therapeutical concept to protect the myocardium during ischemic stress: experimental studies with inhibition of thromboxane synthesis.
The characterization of thromboxane A2 as vasoconstrictor and potent stimulus of platelet aggregation has led to attempts to overcome these effects obviously unfavourable in ischemia. As an attractive approach, we examined potentially protective results of thromboxane synthetase inhibition on canine myocardium stressed by transient ischemia, using as inhibitor the imidazole derivative UK 38.485. On anaesthetized open-chest mongrel-dogs (n = 5) repeated ischemia (3 min) was produced by proximal, intermittent occlusion of the LAD artery. In each experiment 3-4 control occlusions were compared to 3-4 occlusions under therapy. The efficiency of the drug (5 mg/kg body weight, i.v., 30 min before therapy occlusion) was examined (a) by quantification of the energy deficit occurring as the difference between oxygen demand and uptake during occlusion, (b) by the amounts of potassium, inorganic phosphate, and lactate released in the postischemic reperfusion and (c) by changes of the regional myocardial wall function in the central- and peripheral ischemic zone. Compared to control, premedication with UK 38.485 led to a reduced energy deficit (-39.1%; p less than 0.01) combined with a significant decrease in the release of potassium (-15.7%; p less than 0.001), inorganic phosphate (-20.2%; p less than 0.002), and lactate (-20.7%; p less than 0.01). Regional myocardial wall function was improved in the central and peripheral ischemic region as demonstrated by a significantly reduced systolic bulging. The protective effects seem to be mainly due to enhanced flow to ischemic areas.(ABSTRACT TRUNCATED AT 250 WORDS)
Korb
H
H
Clinic for Thoracic, Heart and Vascular Surgery, University of Göttingen, FRG.
Hoeft
A
A
Borowski
A
A
de Vivie
E R
ER
Hellige
G
G
D000818:Animals; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007093:Imidazoles / Q000627:therapeutic use*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011448:Prostaglandin Antagonists / Q000627:therapeutic use*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D011448:Prostaglandin Antagonists; C039242:dazmegrel; D013930:Thromboxane-A Synthase