Role of NADPH Oxidase and Xanthine Oxidase in Mediating Inducible VT/VF and Triggered Activity in a Canine Model of Myocardial Ischemia

Abstract

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.

Protective potential of royal jelly against cadmium‐induced infertility in male rats

“…ROS directly affects the biological macromolecules of the cell including proteins, nucleic acids and lipids and finally can result in cell death (Dewanjee et al., ; Khanra et al., ). Moreover, ROS induces nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity (Martins et al., ) and mitochondrial dysfunction; both take part in the cell apoptosis (Xu, Li, & Jiang, ). With regard to Cd toxicity mechanisms, it would be of value to think about its oxidative activity.…”

The effects of two common edible herbs, Ipomoea aquatica and Enhydra fluctuans, on cadmium-induced pathophysiology: a focus on oxidative defence and anti-apoptotic mechanism

“…The reactive oxygen species (ROS) directly react with cellular macromolecules mainly lipids, proteins and nucleic acids and that can ultimately lead to cell death [ 5 , 6 ]. Besides, ROS activates NADPH oxidase [ 7 ] and mitochondrial dysfunction, both participate in the apoptotic events within the tissues [ 8 ]. Considering the mechanisms of Cd toxicity, it would be important to consider antioxidants to counteract with these toxic manifestations.…”