The nitric oxide synthase inhibitor N(G)-nitro-L-arginine decreases defibrillation-induced free radical generation.

OBJECTIVES: to demonstrate that nitric oxide (NO) contributes to free radical generation after epicardial shocks and to determinethe effect of a nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine (L-NNA), on free radical generation. BACKGROUND: Free radicals are generated by direct current shocks for defibrillation. NO reacts with the superoxide (O2*-) radical to for peroxynitrite (O = NOO-), which is toxic and initiates additional free radical generation. The contribution of NO to free radical generation after defibrillation is not fully defined. METHODS AND RESULTS: Fourteen open chest dogs were studied. In the initial eight dogs, 40 J damped sinusoidal monophasic epicardial shocks was administered. Using electron paramagnetic resonance, we monitored the coronary sinus concentration of ascorbate free radical (Asc*-), a measure of free radical generation (total oxidative flux). Epicardial shocks were repeated after L-NNA, 5 mg/kg IV. In six additional dogs, immunohistochemical staining was done to identify nitrotyrosine, a marker of reactive nitrogen species-mediated injury, in post-shock myocardial tissue. Three of these dogs received L-NNA pre-shock. After the initial 40 J shock, Asc*- rose 39 +/- 2.5% from baseline. After L-NNA infusion, a similar 40 J shock caused Asc*- to increase only 2 +/- 3% form baseline (P < 0.05, post-L-NNA shock versus initial shock). Nitrotyrosine staining was more prominent in control animals than dogs receiving L-NNA, suggesting prevention of O = NOO- formation. CONCLUSION: NO contributes to free radical generation and nitrosative injury after epicardial shocks; NOS inhibitors decrease radical generation by inhibiting the production of O = NOO-.

Body weight is a predictor of biphasic shock success for low energy transthoracic defibrillation.

BACKGROUND: Transthoracic impedance and current flow are determinants of defibrillation success with monophasic shocks. Whether transthoracic impedance, either independently or via its association with body weight, is a determinant of biphasic waveform shock success has not been determined. METHODS AND RESULTS: We studied 22 swine, weighing 18-41 kg. After 15 s of ventricular fibrillation, each pig received transthoracic truncated exponential biphasic shocks (5/5 ms), 70-360 J. Shock success was strongly associated individually with body weight, leading-edge transthoracic impedance and current at low energy levels (70 and 100 J, all P<0.001). Multiple logistic regression analysis showed a significant association of body weight with shock success after adjusting for the effect of leading-edge impedance (odds ratio of success for 1 kg decrease in weight at 70 J was 1.29, 95% CI: 1.05-1.59, P=0.02; and at 100 J was 1.30, 95% CI: 1.14-1.49, P<0.0001). The same result was observed after adjusting for the effect of leading-edge current. At 150 J or higher energy levels, no significant association was observed. CONCLUSIONS: Body weight is a determinant of shock success with biphasic waveforms at low energy levels in this swine model.

Transthoracic biphasic waveform defibrillation at very high and very low energies: a comparison with monophasic waveforms in an animal model of ventricular fibrillation.

The purpose of this study was to compare truncated exponential biphasic waveform versus truncated exponential monophasic waveform shocks for transthoracic defibrillation over a wide range of energies. Biphasic waveforms are more effective than monophasic shocks for defibrillation at energies of 150-200 Joules (J) but there are few data available comparing efficacy and safety of biphasic versus monophasic defibrillation at energies of <150 J or >200 J. Thirteen adult swine (weighing 18-26 kg, mean 20 kg) were deeply anesthetized and intubated. After 15 s of electrically-induced ventricular fibrillation (VF), each pig received truncated exponential monophasic shocks (10 ms) and truncated exponential biphasic shocks (5/5 ms) in random order. Energy doses ranged from 70 to 360 J. Success was defined as termination of VF at 5 s post-shock. For both biphasic and monophasic waveforms success rate rose as energy was increased. Biphasic waveform shocks (5/5 ms) were superior to 10 ms monophasic waveform shocks at the very low energy levels (at 70 J, biphasic: 80+/-9%, monophasic; 32+/-11% and at 100 J, biphasic; 96+/-3% and monophasic 39+/-11%, both P < 0.01). No significant differences in shock success were seen between biphasic and monophasic waveform shocks at 200 J or higher energy levels. Shock success of > 75% was achieved with 200 J (10 J/kg) for both waveforms. Pulseless electrical activity (PEA) or ventricular asystole occurred in 4 animals receiving monophasic shocks and 1 animal receiving biphasic shocks. Biphasic waveform shocks (5/5 ms) for transthoracic defibrillation were superior to monophasic shocks (10 ms) at low energy levels. Percent success increased with increasing energies. PEA occurred infrequently with either waveform.