Epicardial Shocks Research Articles

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

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. 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. 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. NO contributes to free radical generation and nitrosative injury after epicardial shocks; NOS inhibitors decrease radical generation by inhibiting the production of O = NOO-.

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 determine the 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 (O 2 −) radical to form 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% from 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. Conclusions: NO contributes to free radical generation and nitrosative injury after epicardial shocks; NOS inhibitors decrease radical generation by inhibiting the production of ONOO −.

Magnesium reduces free radical concentration and preserves left ventricular function after direct current shocks

Objective: Our objective was to determine if magnesium reduces free radicals generated by direct current countershock and preserves left ventricular contractile function. Background: We have previously shown that magnesium reduces free radicals in a coronary occlusion-reperfusion model, and therefore also might reduce free radical generation by direct current shocks. Methods: In eight swine weighing 18–27 kg (mean: 22 kg), using electron paramagnetic resonance, we monitored continuously the coronary sinus concentration of ascorbate free radical, a measure of free radical generation (total oxidative flux). Epicardial shocks (30 J) using a truncated exponential biphasic waveform (5/5 ms) were administered. Each animal received two shocks, one without and one with magnesium, 80 mg/min IV, beginning 10 min before the shock and continuing to 15 min after the shock. Percent fractional area shortening of the left ventricular cavity was determined by 2-dimensional echocardiography. Results: Magnesium shocks resulted in a significantly lower increase in the ascorbate free radical concentration (0.6±4.6%) than no-magnesium shocks (16±3.3%, P<0.05) at 12 min after the shock. Total radical flux was reduced 72% ( P<0.05), and left ventricular fractional area shortening was preserved: baseline: 69±2.6%, no-magnesium shocks: 41±2.8% ( P<0.05, versus baseline) and magnesium shocks 61±3.7%. Conclusions: Magnesium pre-treatment reduced oxygen free radicals generated by direct current shocks; post-shock left ventricular contractile function was not impaired. Magnesium may be cardioprotective during epicardial (‘surgical’) defibrillation.

Myocardial effects of repeated electrical defibrillations in the isolated fibrillating rat heart.

Although substantial myocardial cell injury has been reported after high-energy electrical defibrillation, only minimal injury with transient functional defects seems to develop at energy levels not exceeding those required to reverse ventricular fibrillation. Because multiple electrical shocks are often delivered in clinical settings during attempts to reverse ventricular fibrillation, we investigated the effects of repetitive shocks on postresuscitation myocardial dysfunction by using an isolated rat heart model of ventricular fibrillation. Prospective and randomized. Cardiopulmonary resuscitation research laboratory. Twenty-seven Sprague-Dawley rats. Hearts were harvested and perfused at a constant flow of 10 mL/min by using a modified Krebs-Henseleit solution equilibrated with 95% oxygen and 5% CO2. Ventricular fibrillation (VF) was induced by a 0.05-mA current delivered to the right ventricular endocardium and the perfusate flow was stopped. After 10 mins, the perfusate flow was resumed at 20% of baseline flow and maintained for 15 additional minutes before returning to baseline flow after 25 mins of VF (VF25 mins). Twenty-seven hearts were randomized to receive from VF22 mins to VF25 mins either 0 epicardial shocks, 6 epicardial shocks, or 12 epicardial shocks. Isovolumic indices of left ventricular function were obtained by using a latex balloon advanced through the mitral valve into the ventricular cavity. After defibrillation, indices of contractile function rapidly returned to baseline without differences among groups. The isovolumic end-diastolic pressure, however, remained elevated throughout the postresuscitation interval. A left shift of the diastolic pressure-volume curves without changes in their slope was observed at 10 mins after resuscitation with partial return to baseline by 30 mins postresuscitation. The shifts were significantly greater in hearts that received 12 shocks. These findings indicate that repetitive low-energy electrical shocks do not accentuate postischemic systolic dysfunction in the isolated fibrillating rat heart but adversely affect postischemic diastolic dysfunction by reducing the unstressed left ventricular end-diastolic volume.

Captopril Lowers Coronary Venous Free Radical Concentration After Direct Current Cardiac Shocks

Direct current (DC) shocks to the heart cause morphologic and functional myocardial damage. Previous studies have suggested that acute DC shock injury is free radical mediated and that the administration of antioxidant enzymes superoxide dismutase and catalase can reduce the level of DC shock-induced free radicals. Angiotensin-converting enzyme (ACE) inhibitors are clinically used drugs that may scavenge free radicals or reduce free radical generation. The objective of our study was to determine whether the ACE inhibitor captopril lowers free radicals after DC shocks. In six open-chest dogs, we administered 100-J DC shocks to the epicardium, before and after administration of captopril, 3 mg/kg. We used electron paramagnetic resonance measurements of arterial and coronary venous ascorbate free radical (AFR) as a real-time marker of free radical generation (total oxidative flux). Captopril resulted in a significant lowering of coronary venous AFR concentration: the peak rise in AFR after 100-J shocks was 17.3+/-3.4% (mean +/- SEM before captopril vs. 3.2+/-4.0% after captopril; p<0.05). Captopril lowers coronary venous AFR concentration after high-energy epicardial shocks.

Direct current shocks to the heart generate free radicals: An electron paramagnetic resonance study

Objectives. We sought to demonstrate that direct current (DC) shocks to the heart generate free radicals.Background. Although it is a lifesaving maneuver, defibrillation is known to have myocardial toxicity. The mechanism of this toxicity is unknown. If DC shocks generate free radicals, free radicals could be a mechanism of myocardial injury.Methods. In a canine model, DC shocks of 10 to 100 J were delivered to the epicardium of both beating and fibrillating hearts, and 200-J transthoracic shocks were administered in dogs with beating hearts. Ascorbate free radical (AFR) concentration was measured in arterial blood and blood continuously withdrawn from the coronary sinus. In some dogs, the antioxidant enzymes superoxide dismutase (15,000 U/Kg) and catalase (55,000 U/kg) (SOD/Cat) were administered before shocks.Results. Ascorbate free radicals were generated by DC shocks. A peak AFR increase of 14 ± 2% (mean ± SEM) was seen 5 to 6 min after 100-J epicardial shocks. A peak AFR increase of 7 ± 5% occurred after transthoracic shocks. There was a significant linear relation between the shock energy and peak percent AFR increase: %AFR increase = 0.18 (Shock energy) + 2.9 (r = 0.73, p < 0.0001). Shocks delivered to hearts in ventricular fibrillation (30s) resulted in generation of AFR equal to but not greater than that observed during similar shocks delivered to beating hearts in sinus rhythm. Multiple successive shocks (100 J delivered twice or five times) did not result in a greater AFR increase than single 100-J shocks, indicating that peak, not cumulative, energy is the principal determinant of AFR increase. Animals receiving SOD/Cat before shock administration, showed significant attenuation of the AFR increase.Conclusions. Direct current epicardial and transthoracic shocks generate free radicals; antioxidant enzymes reduce the free radical generation by shocks.

959-101 Antioxidant Enzymes Attenuate Free Radical Generation After Direct Current Countershocks

Previous work in our lab has shown that direct current (DC) shocks generate free radicals, which may be toxic to the myocardium. We hypothesized that administration of free radical scavenging enzymes prior to shock delivery would attenuate the generation of free radicals. We used a newly developed and validated technique for real time quantitation of free radical production: ascorbyl free radical (AFR) concentration in coronary sinus blood, measured by electron paramagnetic resonance. In 10 open-chest dogs, 75J and 100J epicardial shocks were administered during NSR. Then superoxide dismutase (SOD, 15,000 μ/kg).and catalase (CAT. 55,000 u/kg) were given as a continuous infusion. Ten mins. after initiating the SOD/CAT infusion, 75J and 100J shocks were repeated. Four control dogs received normal saline instead of SOD/CAT. % Δ AFR Area AFR Energy Pre SOD Post SOD Pre SOD Post SOD 75 J 17 ± 4 5 ± 2 * 150 ± 39 37 ± 8 * 100 J 20 ± 5 6 ± 2 * 184 ± 26 53 ± 17 * x ± SO. * p &lt; 0,05 post vs. pre. Area = integrated area under AFR concentration vs. time curve The 4 control dogs showed no significant differences in AFR generation when comparing shocks administered before and after saline infusion rather than SOD/CAT. antioxidant enzymes markedly attenuate free radical generation by DC shocks. If free radicals are a mechanism of defibrillation injury in patients, drugs with free radical inhibiting or scavenging properties may prevent such injury.

Emergency simultaneous transthoracic and epicardial defibrillation for refractory ventricular fibrillation during routine implantable cardioverter-defibrillator testing in the operating room

Ventricular fibrillation (VF) induced during routine implantable cardioverter-defibrillator placement in the operating room almost always responds to the prompt application of direct-current epicardial shocks (≤40 J), and in some cases, high-energy transthoracic shocks or internal paddle defibrillation is needed to terminate VF. In rare cases, VF that is unresponsive to the standard methods occurs. Recently, a method of emergency intracardiac defibrillation was described for treatment of refractory VF during routine electrophysiologic study. 1 This method uses a standard right ventricular pacing catheter and a posterior skin patch. Defibrillation is performed from the distal pole of the right ventricular catheter to the posterior patch. This method has been successful in 9 of 9 patients at our institution in the electrophysiology laboratory. However, no such rescue procedure has been described for refractory VF induced in the operating room. In this report, we describe 2 patients who received emergency simultaneous transthoracic and epicardial defibrillation for the management of refractory VF during implantable cardioverter-defibrillator placement and testing.

Multiple epicardial shocks during a fibrillation episode do not alter characteristics of defibrillation probability curves

Multiple epicardial shocks during a fibrillation episode do not alter characteristics of defibrillation probability curves

Comparison of activation during ventricular fibrillation and following unsuccessful defibrillation shocks in open-chest dogs.

The purpose of this study was to map in detail the spread of activation away from sites of early postshock excitation following unsuccessful defibrillation to determine whether these activation fronts are the unaltered continuation of activation fronts present just before the shock. We recorded simultaneously from 120 bipolar electrodes on 40 plunge needles in a 20 x 35 x 5-mm volume of tissue of the right ventricular outflow tract immediately before and after shocks of 190-350 V were given via electrodes on the right atrium and left ventricular apex to six open-chest dogs with electrically induced ventricular fibrillation. For 20 shocks approximately 100 V below the defibrillation threshold, the site of earliest recorded activation following the shock was near the center of the mapped region. At the earliest recorded activation sites, there was an isoelectric window in the immediate postshock period lasting 42 +/- 15 msec after which activation fronts either spread away from a site in all directions in a focal pattern (12 episodes) or else spread away in only one direction (eight episodes). Comparison of activation patterns immediately before and after the shock revealed that in 18 of the 20 episodes, the location and pathway of activation fronts after the shock were markedly different from those before the shock. The preshock intervals at the sites of earliest activation following the shock, that is, the interval between the last activation at the site and the time of the shock, were not randomly distributed but were similar, averaging 64 +/- 11 msec, and were negatively correlated with the isoelectric postshock window (r = -0.70, p = 0.0001). These findings indicate that the presence and the site of origin of activation fronts after the shock are influenced by at least two factors: the shock itself and the electrophysiological state of the myocardium at the time of the shock. Thus, epicardial shocks approximately 100 V below the defibrillation threshold markedly alter the activation sequences of fibrillation but are unsuccessful because the activation fronts following the shock reinitiate fibrillation.

Nonpharmacologic treatment of supraventricular tachycardia

During the last 2 decades, more than 1,000 patients have undergone surgical division of an accessory pathway; many refinements in epicardial mapping and surgical techniques have been made. In institutions where the procedure is routinely performed, the rate of successful accessory pathway interruption now approaches 98%. Concomitant risk of complete heart block among patients with posteroseptal pathways has declined to <5%. Among patients with other organic heart disease, myocardial preservation techniques result in mortality rates within 1 to 2%; among those with significant cardiac abnormalities, the mortality rate is 4 to 6%. Two techniques are generally used to ablate an accessory pathway: the endocardial and the epicardial. The aim of both approaches is to identify the site of the accessary pathway and disarticulate the atrioventricular groove or expose and ablate the atrioventricular junction to interrupt accessory pathway conduction. Although each technique has its advantages, the choice of technique is far less important than the skill of the surgeon and clinical electrophysiologist performing the procedure. Newer surgical techniques include application of external epicardial shocks in the area of the accessory pathway and use of a cryosurgical probe in the sinus to ablate accessory pathways. Whereas our current thought is that surgery should be limited to those adults who fail to respond to pharmacologie therapy, advances in atrial endocardial and epicardial mapping, as well as surgical techniques, may expand the role of surgery in the treatment of ectopic atrial tachycardia.

Activation during ventricular defibrillation in open-chest dogs. Evidence of complete cessation and regeneration of ventricular fibrillation after unsuccessful shocks.

To test the hypothesis that a defibrillation shock is unsuccessful because it fails to annihilate activation fronts within a critical mass of myocardium, we recorded epicardial and transmural activation in 11 open-chest dogs during electrically induced ventricular fibrillation (VF). Shocks of 1-30 J were delivered through defibrillation electrodes on the left ventricular apex and right atrium. Simultaneous recordings were made from septal, intramural, and epicardial electrodes in various combinations. Immediately after all 104 unsuccessful and 116 successful defibrillation shocks, an isoelectric interval much longer than that observed during preshock VF occurred. During this time no epicardial, septal, or intramural activations were observed. This isoelectric window averaged 64 +/- 22 ms after unsuccessful defibrillation and 339 +/- 292 ms after successful defibrillation (P less than 0.02). After the isoelectric window of unsuccessful shocks, earliest activation was recorded from the base of the ventricles, which was the area farthest from the apical defibrillation electrode. Activation was synchronized for one or two cycles following unsuccessful shocks, after which VF regenerated. Thus, after both successful and unsuccessful defibrillation with epicardial shocks of greater than or equal to 1 J, an isoelectric window occurs during which no activation fronts are present; the postshock isoelectric window is shorter for unsuccessful than for successful defibrillation; unsuccessful shocks transiently synchronize activation before fibrillation regenerates; activation leading to the regeneration of VF after the isoelectric window for unsuccessful shocks originates in areas away from the defibrillation electrodes. The isoelectric window does not support the hypothesis that defibrillation fails solely because activation fronts are not halted within a critical mass of myocardium. Rather, unsuccessful epicardial shocks of greater than or equal to 1 J halt all activation fronts after which VF regenerates.

Effect of direct-current countershocks on regional myocardial contractility and perfusion. Experimental studies.

Very high energy electrical countershocks can cause morphologic damage to the myocardium. In this study we searched for functional correlates of these shock-induced morphologic changes. We used ultrasonic sonomicrometers to measure myocardial contractility and radiolabeled microspheres to assess perfusion. Acute and chronic experiments were conducted in 45 dogs, assessing the effect of both direct (epicardial) and transthoracic shocks on beating and fibrillating hearts. High-energy or rapidly repeated epicardial shocks caused subepicardial contraction abnormalities. This indicates that electrical current delivered to the myocardium in sufficiently high amounts and concentration can cause functional damage. Thus, in open-chest defibrillation during cardiac surgery, low energies (10-20 J) should be used initially and higher energies resorted to only if lower-energy shocks fail. However, single and multiple transthoracic shocks up to 460 J delivered energy caused no detectable contraction abnormalities. Myocardial perfusion did not fall after shocks. Thus, high-energy transthoracic shocks may have no deleterious effects on the contraction and perfusion of normal myocardium.