title: The effect of thromboxane inhibition on vulnerability to ventricular fibrillation in the acute and chronic feline infarction models.
abstract: Inhibition of the enzyme that synthesizes thromboxanes may protect against the development of ventricular fibrillation (VF) during acute myocardial ischemia. This study was carried out to test this hypothesis with a new thromboxane synthetase inhibitor, and to extend the studies to alternative animal models of myocardial infarction. In a series of acute experiments, 19 cats were pretreated with 10 mg/kg of U-63557A (a dose that produced greater than 75% reduction in thromboxane B2 [TxB2] levels) or saline before abrupt left anterior descending coronary artery occlusion. Seven of the nine control animals suffered spontaneous VF associated with a 77% fall in VF threshold compared with the treated animals, of which 2 of 10 had spontaneous VF and in which VF threshold fell by only 45% (p less than 0.025). Despite a similar extent of TxB2 inhibition in another set of nine animals, U-63557A failed to protect against a fall in VF threshold during coronary reperfusion. Finally, chronic changes in VF threshold and inducibility of sustained ventricular tachycardia by programmed stimulation were assessed in a group of eight animals. The lowering of VF threshold and inducibility of ventricular tachycardia seen in the control state were not influenced by treatment with U-63557A. Thus protection against infarct-related VF by TxB2 inhibition is a property shared by more than one pharmacologic agent. Arrhythmias generated by reperfusion or induced in a more chronic setting may not be thromboxane-dependent. These results have important implications for the planning of studies designed to assess the antiarrhythmic potential of drugs that inhibit thromboxane synthesis.
authors.affiliation: Department of Medicine, Medical College of Pennsylvania, Philadelphia 19129.
authors.forename: K M
authors.initials: KM
authors.lastname: O'Connor
authors.forename: T D
authors.initials: TD
authors.lastname: Friehling
authors.forename: P R
authors.initials: PR
authors.lastname: Kowey
mesh_terms: D000208:Acute Disease; D000818:Animals; D001572:Benzofurans / Q000627:therapeutic use*; D002304:Cardiac Pacing, Artificial; D002415:Cats; D002908:Chronic Disease; D005260:Female; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014693:Ventricular Fibrillation / Q000209:etiology / Q000517:prevention & control*
chemical_list: D001572:Benzofurans; D013929:Thromboxane B2; D013930:Thromboxane-A Synthase; C039936:furegrelate