Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151814 (coronary occlusion)
 3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A previous study indicated that 5 mg/kg aspirin can reverse the cardioprotective effects of thromboxane A2 synthetase inhibitors. We determined in the present study if this dose of aspirin can also reverse the protective effects of the thromboxane A2/PGH2 receptor antagonist SQ 30,741 in the same model of coronary occlusion and reperfusion. Anesthetized dogs were subjected to 90 min of coronary occlusion and 5 h of reperfusion and were treated with vehicle or SQ 30,741 (1 mg/kg + 1 mg/kg/h) 10 min after the onset of coronary occlusion. SQ 30,741 was given to dogs pretreated with aspirin (5 mg/kg, 24 h presurgery) or vehicle. SQ 30,741 significantly reduced infarct size compared to vehicle treatment (58% vs 35% of the left ventricular area at risk for vehicle and SQ 30,741 groups respectively) and aspirin did not reverse this. These anti-ischemic effects occurred despite a lack of change in collateral flow. Thus, important differences in mechanism of action between thromboxane synthesis inhibitors and receptor antagonists seem to exist and further work in this area is warranted.
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PMID:The cardioprotective effects of the thromboxane receptor antagonist SQ 30,741 are not reversed by aspirin. 183 10

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.
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PMID:Effect of thromboxane receptor blockade on oxygen supply/consumption variables during reperfusion in the anesthetized dog. 214 35

Platelets are suggested to exacerbate ischemia-induced myocardial injury, which has led to the study of various antiplatelet therapies including thromboxane synthetase inhibitors (TXSI). Two such agents, benzylimidazole and OKY-046, reduce infarct size commensurate with a diminution in serum thromboxane B2 formation in anesthetized dogs subjected to 90 minutes of coronary artery occlusion followed by 5 hours of reperfusion. In contrast, platelet depletion with specific antiserum does not reduce infarct size but prevents the cardioprotection afforded by the TXSI. Platelet-derived prostaglandin endoperoxides (PGG2 and PGH2), which cannot be converted to thromboxane A2 in the inhibited platelet, can be transformed to PGE2 and PGD2 in plasma and to PGI2 by the blood vessel wall. These prostaglandins are considered "cardioprotective." Consequently, a low dose of aspirin (3-5 mg/kg) given 24 hours before coronary occlusion was used to selectively block the platelet cyclooxygenase enzyme. Aspirin, by itself, does not reduce infarct size, but it suppresses the myocardial salvage induced by OKY-046. Thus, TXSI reduce infarct size by platelet-dependent, aspirin-sensitive mechanism that depends on the redirection of platelet-derived PGG2 and PGH2 to protective metabolites, rather than inhibition of thromboxane A2 per se. Moreover, myocardial salvage induced by the TXSI is accompanied by a reduction in neutrophil accumulation in the myocardium, as indicated by the levels of the neutrophil-specific myeloperoxidase enzyme. Platelet depletion or pretreatment with aspirin prevents the TXSI-induced suppression of neutrophil accumulation. Consequently, it is proposed that the prostaglandin-mediated protective effects of TXSI can be resolved, at least in part, in terms of a braking action on neutrophil activation to prevent leukocyte-dependent tissue injury.
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PMID:Thromboxane synthetase inhibitors reduce infarct size by a platelet-dependent, aspirin-sensitive mechanism. 312 73