Free radical scavenger specifically prevents ischemic focal ventricular tachycardia
Dezhi Xing1, Ashok K Chaudhary, Francis J Miller
1Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
Background:
Focal ventricular tachycardia (VT) in acute myocardial ischemia is closely related to triggered activity (TA), which may be blocked by scavenging reactive oxygen species (ROS).
Objective:
This study analyzed effects of acutely administered ROS scavenger-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) on VT in vivo and TA in vitro.
Methods:
Forty-three alpha chloralose anesthetized dogs with coronary artery occlusion were studied. Three-dimensional activation mapping helped to locate the origin of focal or reentrant VT. TEMPO (30 mg/kg intravenously) or vehicle was given. Endocardium excised from the site of origin of VT was studied using standard microelectrode techniques and measures of ROS.
Results:
Reentry and focal VT induction were both highly reproducible. TEMPO blocked focal VT in 6 of 11 dogs (P <.05), but 9 of 9 dogs with reentrant VT continued to have VT re-induced after TEMPO. TEMPO did not alter effective refractory period (168 +/- 3 to 171 +/- 3 ms), mean blood pressure (88 +/- 3 to 81 +/- 3 mm Hg), and size of ischemia (42% +/- 3% vs 40% +/- 4%). In vitro, TEMPO (10(-3) M, n = 14) produced no change in action potentials. Nevertheless, TA was reversibly attenuated from 5.3 +/- 1.1 to 0.4 +/- 0.4 complexes with TEMPO (n = 15, P <.05). Lucigenin-enhanced chemiluminescence and dihydroethidium staining showed increased ROS in ischemic endocardium; TEMPO dramatically reduced ROS in ischemic sites.
Conclusion:
TEMPO, a scavenger of ROS, prevented triggered activity associated with focal VT during myocardial ischemia in areas of increased ROS. Antioxidant therapy may play an important role in blockade of focal VT under the conditions of myocardial ischemia.
Insights
Reactive oxygen species (ROS) scavenger TEMPO blocked focal ventricular tachycardia (VT) by preventing triggered activity in myocardial ischemia. Antioxidant therapy shows promise for treating focal VT during ischemia.
Area of Science:
- Cardiology
- Electrophysiology
- Biochemistry
Background:
- Focal ventricular tachycardia (VT) during acute myocardial ischemia is linked to triggered activity (TA).
- Reactive oxygen species (ROS) may play a role in the development of TA and subsequent VT.
- Scavenging ROS presents a potential therapeutic strategy for blocking VT.
Purpose of the Study:
- To investigate the effects of the ROS scavenger 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) on focal VT in vivo.
- To assess the impact of TEMPO on triggered activity (TA) in vitro.
- To determine if TEMPO can attenuate ROS in ischemic cardiac tissue.
Main Methods:
- Studied 43 anesthetized dogs with induced coronary artery occlusion and VT.
- Utilized 3D activation mapping to pinpoint VT origins (focal or reentrant).
- Administered TEMPO intravenously and analyzed endocardial tissue for ROS and TA.
Main Results:
- TEMPO successfully blocked focal VT in 6 of 11 dogs, while reentrant VT remained unaffected.
- In vitro studies showed TEMPO significantly reduced TA from 5.3 to 0.4 complexes.
- TEMPO administration markedly decreased ROS levels in ischemic endocardial sites without altering hemodynamic parameters or refractory periods.
Conclusions:
- TEMPO, as a ROS scavenger, effectively prevented TA-associated focal VT in myocardial ischemia.
- These findings suggest that antioxidant therapy, specifically targeting ROS, could be a valuable approach for blocking focal VT in ischemic conditions.
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