Modulation of arachidonic acid metabolites and vulnerability to ventricular fibrillation during myocardial ischemia in the cat.
To determine the relative importance of arachidonic acid pathway products on vulnerability to ventricular fibrillation (VF), we examined the effects of synthesis inhibitors and a receptor blocker acting in the cyclooxygenase (C) and lipoxygenase (L) pathways on VF thresholds in a feline model of coronary occlusion. Thresholds for the induction of VF wer measured before and after a 5-minute coronary occlusion in drug-treated animals and control subjects. Animals were treated with BW755c, a dual L and C inhibitor, CGS-8515, and L inhibitor, FPL-55712, a leukotriene receptor blocker, or sulfinpyrazone, a C inhibitor. BW755c, CGS-8515, and FPL-55712 all prevented an otherwise significant fall in VF threshold during coronary occlusion (p less than 0.01) independent of an effect on effective refractory period, heart rate, or blood pressure. In contrast, sulfinpyrazone, the only compound devoid of an effect on the L pathway, did not protect against an occlusion-related fall in VF threshold. BW755c and CGS-8515 inhibited the synthesis of L and C metabolites coincident with their protection against VF (p less than 0.01). We conclude that agents that antagonize the effects of L products protect against enhanced ventricular vulnerability during acute ischemia, whereas C inhibition alone may not afford this protection.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D002304:Cardiac Pacing, Artificial; D002415:Cats; D002867:Chromones; D003327:Coronary Disease / Q000150:complications*; D005260:Female; D008297:Male; D009285:Naphthoquinones; D011720:Pyrazoles; D013189:SRS-A / Q000037:antagonists & inhibitors; D013442:Sulfinpyrazone; D014693:Ventricular Fibrillation / Q000209:etiology*; D062367:ortho-Aminobenzoates
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D002867:Chromones; D009285:Naphthoquinones; D011720:Pyrazoles; D013189:SRS-A; D062367:ortho-Aminobenzoates; C055523:methyl 2-((3,4-dihydro-3,4-dioxo-1-naphthalenyl)amino)benzoate; D016718:Arachidonic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; C006312:FPL 55712; D013442:Sulfinpyrazone