Role of NADPH oxidase and xanthine oxidase in mediating inducible VT/VF and triggered activity in a canine model of myocardial ischemia.

Published online

Journal Article

BACKGROUND: Ventricular tachycardia or fibrillation (VT/VF) of focal origin due to triggered activity (TA) from delayed afterdepolarizations (DADs) is reproducibly inducible after anterior coronary artery occlusion. Both VT/VF and TA can be blocked by reducing reactive oxygen species (ROS). We tested the hypothesis that inhibition of NADPH oxidase and xanthine oxidase would block VT/VF. METHODS: 69 dogs received apocynin (APO), 4 mg/kg intraveneously (IV), oxypurinol (OXY), 4 mg/kg IV, or both APO and OXY (BOTH) agents, or saline 3 h after coronary occlusion. Endocardium from ischemic sites (3-D mapping) was sampled for Rac1 (GTP-binding protein in membrane NADPH oxidase) activation or standard microelectrode techniques. Results (mean±SE, * p<0.05): VT/VF originating from ischemic zones was blocked by APO in 6/10 *, OXY in 4/9 *, BOTH in 5/8 * or saline in 1/27; 11/16 VT/VFs blocked were focal. In isolated myocardium, TA was blocked by APO (10(-6) M) or OXY (10(-8) M). Rac1 levels in ischemic endocardium were decreased by APO or OXY. CONCLUSION: APO and OXY suppressed focal VT/VF due to DADs, but the combination of the drugs was not more effective than either alone. Both drugs inhibited ischemic Rac1 with inhibition by OXY suggesting ROS-induced ROS. The inability to totally prevent VT/VF suggests that other mechanisms also contribute to ischemic VT.

Full Text

Duke Authors

Cited Authors

  • Martins, JB; Chaudhary, AK; Jiang, S; Kwofie, M; Mackie, P; Miller, FJ

Published Date

  • November 4, 2014

Published In

Volume / Issue

  • 15 / 11

Start / End Page

  • 20079 - 20100

PubMed ID

  • 25375191

Pubmed Central ID

  • 25375191

Electronic International Standard Serial Number (EISSN)

  • 1422-0067

Digital Object Identifier (DOI)

  • 10.3390/ijms151120079

Language

  • eng

Conference Location

  • Switzerland