The nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) increases free radical generation and degrades left ventricular function after myocardial ischemia-reperfusion.

BACKGROUND: During reperfusion of ischemic myocardium nitric oxide (NO) reacts with superoxide radicals to form cardiotoxic peroxynitrite, which causes lipid peroxidation. Our hypothesis was that infusion of a NO donor S-nitroso-N-acetylpenicillamine (SNAP) during ischemia-reperfusion would exacerbate the oxidative damage to the myocardium by increased formation of nitrogen radicals. METHODS AND RESULTS: In 19 open-chest dogs, left anterior descending (LAD) coronary occlusion (15 min)-reperfusion (15 min) sequences were created. Using electron paramagnetic resonance (EPR), we monitored the coronary sinus concentration of ascorbate free radical (Ascz*-), a measure of free radical generation (total oxidative flux). Seven control dogs (Group 1) received intravenous saline infusion during occlusion-reperfusion, while 12 dogs received SNAP infusion (Group 2: 2.5 microg/min per kg SNAP, and Group 3: 5 microg/min per kg SNAP). Left ventricular fractional area shortening was determined by echocardiography. Dogs in Group 3 receiving a high dose of SNAP (5 microg/min per kg) demonstrated a higher Ascz*- concentration increase than the control group. Percent fractional area shortening in Group 1 declined from 77+/-4.0 (baseline) to 54+/-9.0% during ischemia (P<0.05), and then fully recovered to 74+/-3.7% with reperfusion. In the SNAP-treated dogs, the percent fractional area shortening during reperfusion was significantly lower than baseline in Group 2 (55+/-3.9 vs. baseline 74+/-4.4%, P<0.05) and in Group 3 (49+/-5.0 vs. baseline 71+/-4.5%, P<0.01). In five additional dogs, nitrotyrosine immunohistochemistry showed heavy staining of the ischemic-reperfused myocardium. CONCLUSIONS: The NO donor SNAP increased free radical concentration and exacerbated myocardial oxidative damage after ischemia-reperfusion.

Open-chest epicardial "surgical" defibrillation: biphasic versus monophasic waveform shocks.

The aim of the study was to compare biphasic versus monophasic shocks for open-chest epicardial defibrillation. Transthoracic biphasic waveform shocks require less energy to terminate ventricular fibrillation compared to monophasic waveform shocks. However, if biphasic shocks are effective for open-chest epicardial ("surgical") defibrillation has not been established. Twenty-eight anesthetized adult swine (15-25 kg) underwent a midline sternotomy. Ventricular fibrillation was electrically induced. After 15 seconds of ventricular fibrillation, each pig in group 1 (n = 16) randomly received damped sinusoidal monophasic epicardial shocks and truncated exponential biphasic epicardial shocks from large (44.2 cm2) paddle electrodes at eight energy levels (2-50 J). Pigs in group 2 (n = 12) received monophasic and truncated exponential biphasic shocks from small (15.9 cm2) paddle electrodes. In group 1 (large paddle electrodes), the overall percent shock success rose from 15 +/- 9% at 2 J to 97 +/- 3% at 50 J. In this group there was no significant difference in percent of shock success between damped sinusoidal monophasic and biphasic waveform shocks. In group 2 (small paddle electrodes), biphasic shocks yielded a significantly higher percent of shock success than monophasic shocks at mid-energy levels from 7 to 20 J (all P < 0.01). With small surgical paddle electrodes, biphasic waveform shocks demonstrated a significantly higher percent of shock success rate compared to monophasic waveform shocks. With large paddle electrodes, the two waveforms were equally effective.