Dazoxiben, UK 38,485 and aspirin: Duration of effect for preventing thrombotic sudden death in rabbits

Lindsay, Linda; Olson, Richard W.; Sakane, Y.; Ghai, Rajendra D.; Smith, Edward F.

doi:10.1016/0049-3848(86)90058-7

Cited by 5 publications

(3 citation statements)

References 19 publications

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“…Although other studies have demon strated that thromboxane synthetase inhibi tors can protect in some models of sudden cardiac death [9,10], results of the present study showed no significant protection. The concept of protecting against sudden coronary death by inhibiting the effects of thromboxane A2 assumes that the latter has a significant role in mediating coronary va sospasm and/or platelet aggregation and in travascular thrombosis.…”

Section: Discussioncontrasting

confidence: 54%

“…Increased concentrations of thromboxane have been reported in both humans and experimental animals during the development of myocardial ischemic in jury and infarction [3,4]. Thromboxane has been shown to exert vasoconstrictor effects on the coronary vasculature [5,6] and has been suggested as a possible mediator of cor onary vasospasm [7] and sudden cardiac death [8][9][10], A number of studies have presented evi dence which suggests a role for thromboxane in the genesis of occlusion/reperfusion ar rhythmias in experimental animals [11][12][13]. Inhibition of the physiologic effects of thromboxane either by reducing its biosyn thesis with a thromboxane synthetase inhibi tor, or by blocking its actions on effector cells with thromboxane receptor antagonists, have been reported to reduce the incidence and severity of ventricular arrhythmias in response to coronary artery occlusion and reperfusion [14,15].…”

Section: Introductionmentioning

confidence: 99%

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Failure of Thromboxane Synthetase Inhibition to Protect the Postinfarcted Heart against the Induction of Ventricular Tachycardia and Ventricular Fibrillation in a Conscious Canine Model of Sudden Coronary Death

et al. 1988

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The role of thromboxane as a contributor to the genesis of ventricular tachycardia and fibrillation was examined in conscious dogs which had been subjected to myocardial infarction. CGS 12970, a thromboxane synthetase inhibitor was administered in a dose of 10 mg/kg (i.v.) every 12 h. Ex vivo thrombin-activated thromboxane synthesis, as determined by assay for thromboxane B₂, was reduced to 15 % of baseline 2 h after administration of CGS 12970. Drug administration was found to inhibit ex vivo platelet aggregation significantly in response to arachidonic acid, while aggregation to ADP and collagen was unaffected. CGS 12970 did not protect against the induction of ventricular tachycardia by programmed electrical stimulation of the postinfarcted heart. During provocative electrical stimulation, 9 of 11 (82 %) animals continued to respond in the post-treatment period with the development of VT. Pretreatment with CGS 12970 failed to prevent the spontaneous development of ventricular fibrillation which occurred in 7 of 10 (70%) animals when a secondary ischemic event was superimposed in the region of the noninfarct-related circumflex coronary artery. The results suggest that the thromboxane synthetase inhibitor, CGS 12970, when administered in the subacute phase of recovery from myocardial infarction, does not protect against the induction of ventricular tachycardia by programmed electrical stimulation or the spontaneous development of ventricular fibrillation in the postinfarcted canine heart. The findings suggest that thromboxane may not serve a critical role in the genesis of ventricular tachyarrhythmias and ventricular fibrillation in the postinfarcted canine heart.

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Section: Discussioncontrasting

confidence: 54%

Section: Introductionmentioning

confidence: 99%

Failure of Thromboxane Synthetase Inhibition to Protect the Postinfarcted Heart against the Induction of Ventricular Tachycardia and Ventricular Fibrillation in a Conscious Canine Model of Sudden Coronary Death

et al. 1988

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“…In contrast, dazoxiben and dazmegrel, both short-term inhibitors of thromboxane synthetase, had only shortlasting protective effects. 49 Other investigators have compared the effects of a variety of thromboxane receptor antagonists (for example, the Squibb compound SQ 29548) and the thromboxane synthetase inhibitor, pirmagrel. These compounds were also beneficial in preventing sudden death induced by arachidonic acid infusion into mice.…”

Section: Inhibition Of Platelet Aggregationmentioning

confidence: 99%

Mechanisms of Pathogenesis of Arterial Thrombosis: Potential Sites of Inhibition by Therapeutic Compounds

Buchanan

1988

Semin Thromb Hemost

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Preventive effect of the thromboxane A₂ receptor antagonist S‐1452 (d‐s‐145 Ca) on arachidonate‐induced sudden death and cerebral infarction in rabbits

Jyoy¹,

Kurosawa²

1993

Drug Development Research

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The thromboxane A, (TXA,) receptor antagonist S-1452, d-S-145 Ca, calcium 5(Z)- 1R,2S,3S,4S-7-[3-phenylsulfonylaminobicyclo[2.2.llhept-2-yll-5-heptenoate dihydrate, prevented sudden death induced by arachidonate or U46619 in rabbits when given in a dose range between 0.1 mg/kg and 1 mg/kg, p.0. OKY-046 and aspirin were also effective in this thromboembolism model, but 10 to 30 times larger doses were needed. Orally administered S-1452 successfully prevented the incidence of cerebral infarction in the rabbit, which was elicited by infusion of 10 mg/ml sodium arachidonate at a rate of 0.1 m h i n for 30 min via a left internal carotid artery. Significant reduction of the infarction grade was observed in dosing above 3 mg/kg of this compound 1 to 4 h before the arachidonate infusion. OKY-046 was effective similarly, but less active than S-1452 (the minimum effective dose: 10 mg/kg). Ticlopidine and aspirin were entirely inactive in this model even after much larger doses. 5-1452 IS a useful compound for prevention of TXA,-mediated thrombosis in the brain. o 1993 Wiley-Liss, Inc

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Dazoxiben, UK 38,485 and aspirin: Duration of effect for preventing thrombotic sudden death in rabbits

Cited by 5 publications

References 19 publications

Failure of Thromboxane Synthetase Inhibition to Protect the Postinfarcted Heart against the Induction of Ventricular Tachycardia and Ventricular Fibrillation in a Conscious Canine Model of Sudden Coronary Death

Failure of Thromboxane Synthetase Inhibition to Protect the Postinfarcted Heart against the Induction of Ventricular Tachycardia and Ventricular Fibrillation in a Conscious Canine Model of Sudden Coronary Death

Mechanisms of Pathogenesis of Arterial Thrombosis: Potential Sites of Inhibition by Therapeutic Compounds

Preventive effect of the thromboxane A₂ receptor antagonist S‐1452 (d‐s‐145 Ca) on arachidonate‐induced sudden death and cerebral infarction in rabbits

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Dazoxiben, UK 38,485 and aspirin: Duration of effect for preventing thrombotic sudden death in rabbits

Cited by 5 publications

References 19 publications

Failure of Thromboxane Synthetase Inhibition to Protect the Postinfarcted Heart against the Induction of Ventricular Tachycardia and Ventricular Fibrillation in a Conscious Canine Model of Sudden Coronary Death

Failure of Thromboxane Synthetase Inhibition to Protect the Postinfarcted Heart against the Induction of Ventricular Tachycardia and Ventricular Fibrillation in a Conscious Canine Model of Sudden Coronary Death

Mechanisms of Pathogenesis of Arterial Thrombosis: Potential Sites of Inhibition by Therapeutic Compounds

Preventive effect of the thromboxane A2 receptor antagonist S‐1452 (d‐s‐145 Ca) on arachidonate‐induced sudden death and cerebral infarction in rabbits

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Preventive effect of the thromboxane A₂ receptor antagonist S‐1452 (d‐s‐145 Ca) on arachidonate‐induced sudden death and cerebral infarction in rabbits