Carbocyclic thromboxane A2: aggrevation of myocardial ischemia by a new synthetic thromboxane A2 analog.
In vitro experiments indicate that thromboxane A2 (TA2) is a potent platelet aggregator and vascular constrictor. However, it is unclear what roles these specific actions may contribute in the pathophysiology of myocardial ischemia. Carbocyclic thromboxane A2 (CTA2), a TA2 analog, constrict isolated perfused cat coronary arteries, but does not aggregate platelets, and thus appeared useful to clarify these separate actions of TA2. In anesthetized cats, radioactive labeled microspheres were injected into the left atrium for measurement of cardiac output and tissue blood flows. Compared to control measurements, CTA2 infusion (4.8 microgram.kg-1.min-1 for 10 min) significantly decreased cardiac output from 347 to 16 ml.min-1 to 248 +/- 16 ml.min-1 (p less than 0.025). Furthermore, CTA2 also significantly reduced blood flow to the left ventricle by 33 +/- 7%, but did not alter heart rate or MABP in the intact cat. In cats subjected to left anterior descending coronary artery occlusion, infusion of CTA2 (1 microgram.min-1 for 120 minutes) 30 min after ligation resulted in a significantly reduced myocardial cellular integrity as measured by myocardial creatine kinase activity (p less than 0.01) or percent bound myocardial cathepsin D (p less than 0.01). Thus, these data suggest that activation of vascular thromboxane receptors as well as direct cellular damage may play a role in the pathophysiology of myocardial ischemia.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002402:Cathepsin D; D002403:Cathepsins / Q000378:metabolism; D002415:Cats; D003327:Coronary Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D012039:Regional Blood Flow / Q000187:drug effects; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D013931:Thromboxanes / Q000494:pharmacology*; D014662:Vasoconstrictor Agents
D013931:Thromboxanes; D014662:Vasoconstrictor Agents; C024587:thromboxane A2, carbocyclic; D013928:Thromboxane A2; D003402:Creatine Kinase; D002403:Cathepsins; D002402:Cathepsin D