Effect of thromboxane receptor blockade on oxygen supply/consumption variables during reperfusion in the anesthetized dog.
The thromboxane A2/PGH2 receptor antagonist SQ 30,741 has been previously shown to reduce infarct size and to improve subendocardial reflow. The purpose of this study was to determine the effect of SQ 30,741 on reperfusion O2 supply/consumption variables. Anesthetized open-chest dogs treated with vehicle or 1 mg/kg + 1 mg/kg/hr SQ 30,741, i.v. (starting 10 min after the onset of ischemia) were subjected to 90 min left circumflex coronary occlusion and 3 hr reperfusion. Regional myocardial blood flow (radioactive microspheres) and arterial and venous O2 saturations (microspectrophotometry) were determined. Animals treated with SQ 30,741 had significantly higher subendocardial reflow at 3 hr (48 +/- 6 ml/min/100 g) compared with vehicle (27 +/- 10 ml/min/100 g). At 3 hr postreperfusion, O2 extraction was significantly higher in the reperfused region compared with the nonischemic region, although extraction was not at maximal values. O2 extraction was similar in vehicle- and SQ 30,741-treated animals despite the near doubling of reflow into the subendocardial region with SQ 30,741. O2 consumption was significantly reduced in the reperfused subendocardial region (1.65 +/- 0.9 ml O2/min/100 g) in vehicle controls compared with the nonischemic subendocardial region (10.2 +/- 2.6 ml O2/min/100 g). SQ 30,741 significantly improved subendocardial reperfused regional O2 consumption (4.03 +/- 0.41 ml O2/min/100 g) compared with vehicle and this increase was proportional to the flow increment (no change in the O2 supply/consumption ratio). SQ 30,741 is thus increasing subendocardial reflow secondary to an increase in O2 consumption and the increased O2 consumption may be due to preservation of myocardial tissue.
Grover
G J
GJ
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, New Jersey.
Sleph
P G
PG
Weiss
H R
HR
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control*; D010101:Oxygen Consumption / Q000187:drug effects*; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D017482:Receptors, Thromboxane; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; C054215:SQ 30741; D013928:Thromboxane A2