Correlation of electrophysiological activation patterns to tension generation in stimulated latissimus dorsi muscle.

Skeletal muscle has been used for biomechanical assist in experimental and clinical studies. Central to the success of these procedures is the generation of sufficient muscle force for the lifetime of the subject. Burst (tetanic) stimulation results in summation of individual twitches and generates higher power output. However, the superiority of paraneural versus intramuscular as well as proximal versus middle and distal intramuscular stimulations remains unclear. Electrophysiological mapping and mechanical performance of seven canine latissimus dorsi muscles were analyzed. The mechanism of higher tension generation produced by: (1) increased temporal summation; (2) greater motor units activated; or (3) result of both were determined. The parameters primarily dependent on the number of activated motor units are significantly greater following paraneural and proximal intramuscular stimulations. The parameters mainly related to temporal summation are not different between various electrode configurations. For intramuscular stimulation, it is the location of interelectrode field rather than the location of the cathode per se that determines the mechanical performance of the skeletal muscle. Furthermore, tension development of skeletal muscle is primary nerve activation rather than direct muscle stimulation. The higher tension generation that resulted from different electrode configurations is produced by activating a higher number of muscle fibers through the neuromuscular junctions.

Reproducibility of successful drug trials in patients with inducible sustained ventricular tachycardia.

Patients whose inducible sustained ventricular tachycardia is suppressed during serial electrophysiological testing have a small but gradually increasing actuarial incidence of recurrent arrhythmias despite therapy with the "successful" drug. In an effort to improve the predictive value of a drug response, in 1990 we began to require that our full stimulation protocol be repeated successfully several times before considering a drug to be effective. In 23 consecutive patients who had inducible sustained ventricular tachycardia which was suppressed by at least one drug during invasive serial drug testing using a standard stimulation protocol, the identical stimulation protocol was performed six times during therapy with the initially successful drug (three trials on Day 1 and three trials on Day 2). Repeat trials were completed (i.e., either all six trials were successfully finished or sustained tachycardia was induced) for 29 initially successful drugs in these 23 patients. With 18 of these 29 initially successful drugs (62%), sustained ventricular tachycardia was eventually induced during repeat trials. The eventual drug failures could not be correlated with specific drugs tested, subtherapeutic or falling serum drug levels, marked fluctuations in autonomic tone, or changes in anatomic substrate. The proportion of patients failing each repeat trial was relatively constant: 4/29 (14%) failed Trial 2, 2/25 (8%) failed Trial 3, 7/23 (30%) failed Trial 4, 2/16 (13%) failed Trial 5, and 3/14 (21%) failed Trial 6. The increase in the cumulative incidence of drug failure during repeat trials was nearly linear. Inducibility of ventricular tachycardia appears to be a probability function; a successful drug study should not be regarded as an absolute phenomenon.

Long-term outcome of survivors of cardiac arrest whose therapy is guided by electrophysiologic testing.

The long-term outcome of 217 consecutive survivors of cardiac arrest whose therapy was guided by electrophysiologic testing was analyzed. After electrophysiologic testing, 81 patients (37%) were classified as having no inducible arrhythmia and were treated without antiarrhythmic drugs; 23 received an implantable defibrillator. Of the 136 patients with inducible arrhythmia, the 51 (38%) who responded to serial drug testing were treated with the successful drug and the 85 (62%) with unsuccessful drug testing were treated with an implantable defibrillator (47 patients), amiodarone (36 patients) or drugs that were unsuccessful during testing (2 patients). The mean follow-up interval for all patients was 35 +/- 23 months. The actuarial incidence of sudden death and overall death was similar for patients whose arrhythmias were not inducible, drug responders and nonresponders. The actuarial incidence rate of recurrent arrhythmic events in nonresponders was 35 +/- 5% and 53 +/- 7% at 2 and 5 years, respectively. These values were significantly lower (and statistically similar to each other) in the other two patient groups: patients with noninducible arrhythmia (19 +/- 5% and 31 +/- 7%, respectively, p less than 0.05) and drug responders (13 +/- 5% and 23 +/- 8%, respectively, p less than 0.01). Patients with an implantable defibrillator who had recurrent arrhythmic events were significantly less likely to die suddenly than were patients without a defibrillator who had recurrent events (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term efficacy of an antitachycardia pacemaker and implantable defibrillator combination.

Antitachycardia pacemakers and implantable cardioverter defibrillators (ICD) were implanted in 14 patients to control recurrent hemodynamically stable ventricular tachycardia (VT). All patients underwent extensive preimplant testing in the electrophysiology laboratory documenting that in each patient at least 50 episodes of VT could be reliably terminated by an external model of the antitachycardia pacemaker. The burst scanning mode of antitachycardia pacing was used in all patients. ICDs were implanted solely as a back up should acceleration of VT occur, and all had high nonprogrammable rate cutoffs (mean 191 +/- 12 beats/min). During a mean follow-up of 25 +/- 6 months, 6,029 episodes of VT were treated in the 14 patients. Only 103 ICD discharges were required (approximately one discharge per 60 episodes of VT). Ten of the 14 patients received discharges from their ICDs. No deaths have occurred. All devices remain active and in the automatic mode. Thus, an antitachycardia pacemaker and ICD combination can safely and effectively terminate VT in highly selected patients who are subjected to extensive preimplant testing. In such patients, the vast majority of episodes of VT can be terminated with antitachycardia pacing, and only rarely is a discharge required from the ICD.

Efficacy of the automatic implantable cardioverter-defibrillator in prolonging survival in patients with severe underlying cardiac disease.

The ability of the automatic implantable cardioverter-defibrillator to prolong overall survival, particularly in patients with significantly depressed cardiac function, has not been well documented. Of 119 patients who received the implantable defibrillator in this institution, 40 had a left ventricular ejection fraction less than 30% (Group A) and 79 had an ejection fraction greater than or equal to 30% (Group B). For each group, cumulative survival was compared with the projected survival if the implantable defibrillator had not been used. Projected survival was based on the assumption that the first appropriate shock would have resulted in death without the defibrillator. For Group A, the 3 year cumulative survival rate was 67 +/- 12% versus a projected survival rate of 6 +/- 15% (p less than 0.001). For Group B, the 3 year cumulative survival rate was 96 +/- 3% versus a projected survival rate of 46 +/- 8% (p less than 0.001). Both the cumulative and projected survival rates for patients in Group A were significantly worse than for patients in Group B (p less than 0.01). The projected survival rates for both Groups A and B were comparable with the observed survival rate in similar patients treated without the implantable defibrillator. In summary, the implantable cardioverter-defibrillator significantly prolonged overall survival, even in patients with poor cardiac function. The technique of estimating projected survival appears to allow a realistic estimate of the reduction in mortality achieved by the defibrillator.

Actuarial incidence and pattern of occurrence of shocks following implantation of the automatic implantable cardioverter defibrillator.

The actuarial incidence and pattern of occurrence of shocks were analyzed in 65 patients after implantation of the automatic implantable cardioverter defibrillator. During a mean follow-up of 25 +/- 21 months only one patient died suddenly, and this patient had a nonfunctioning device at the time of death. The long-term actuarial risk of death from any cause in the patients who received appropriate shocks was not significantly different than for the entire group. The 1- and 4-year cumulative risk of receiving any shock was 51 +/- 7% and 81 +/- 11%; of receiving an appropriate shock was 33 +/- 7% and 64 +/- 10%; of receiving a spurious shock was 17 +/- 5% and 21 +/- 6%; and of receiving an "indeterminate" shock was 19 +/- 6% and 52 +/- 10%. In 14 patients who were followed for 24 months without receiving an appropriate shock, the actuarial risk of receiving an appropriate shock was 29 +/- 14% during the next 24 months. The mean number of shocks delivered during appropriate episodes was 1.6 +/- 0.9, which was significantly lower than the mean of 4.0 +/- 2.0 shocks during spurious episodes (P less than 0.02). The mean number of shocks during indeterminate episodes was 1.7 +/- 1.5. Our data confirms the efficacy of the implantable defibrillator in preventing sudden death. The majority of patients with this device receive appropriate shocks during long-term follow-up, and the cumulative incidence of appropriate shocks increases steadily for at least 4 years. In contrast, the cumulative incidence of spurious shocks plateaus at about 12 months. Our data suggests that many "indeterminate" shocks actually appear to be appropriate.

Long-term prognosis of patients undergoing electrophysiologic studies for syncope of unknown origin.

Long-term prognosis was determined in 70 patients with unexplained syncope who underwent electrophysiologic testing between April 1981 and April 1986. The electrophysiologic study had positive results in 37 patients--31 with ventricular tachycardia, 3 with supraventricular tachycardia and 3 with abnormal conduction. There was no significant difference in the 3-year actuarial recurrence rate between the positive and negative outcomes (32 vs 24%, respectively). At 3 years, patients with positive outcomes had higher rates of sudden death than patients with negative results (48 vs 9%, respectively, p less than 0.002). The 3-year total mortality rate was also markedly higher in patients with positive results than among those with negative outcomes (61 vs 15%, respectively, p less than 0.001). Multivariate analyses showed mortality to be independently associated with unsustained ventricular tachycardia on prolonged electrocardiographic monitoring. It was concluded that patients with electrophysiologically positive results had high rates of sudden death and total mortality that have not been previously well recognized.

Efficacy of phenytoin in suppressing inducible ventricular tachyarrhythmias.

We examined the efficacy of phenytoin in 69 of 87 consecutive patients undergoing serial electrophysiologic studies for inducible sustained ventricular tachycardia or fibrillation (VT/VF). In general, during the initial session lidocaine and procainamide were tested immediately after baseline electrophysiologic evaluation, followed by phenytoin and quinidine during the next two sessions, and then by additional drugs as needed. Once a successful drug was identified, all testing was stopped. Drugs that had failed in prior empiric trials were not tested. Twenty-five of the 87 patients (28.7%) had success in 258 serial drug tests. Sixty-nine patients were tested on phenytoin (mean serum level 13.4 +/- 5.0 mg/L), 52 after oral loading, and 17 after intravenous loading; the remaining 18 had either had prior successful testing with other drugs (9 patients) or had prior empiric failures with phenytoin (9 patients) or had prior empiric failures with phenytoin (9 patients). Nine of the 69 phenytoin trials were successful (13.0%), compared to 8 of 57 trials (14.0%) with procainamide, 4 of 37 trials (10.8%) with quinidine, and 0 of 41 trials (0%) with lidocaine. All nine patients who had successful phenytoin trials tolerated chronic doses adequate to maintain serum phenytoin levels equivalent to those measured during successful drug testing. For the 25 patients with successful drug trials, the mean follow-up was 14.5 +/- 9.8 months, and the actuarial incidence or recurrent VT/VF was 7 +/- 5% at 12 months. For the nine patients who had success with phenytoin the mean follow-up was 18.4 +/- 11.7 months, and the 12-month actuarial recurrence was 0%. Phenytoin is a well tolerated drug whose efficacy appears similar to most standard antiarrhythmic agents. If our results are confirmed in a larger, randomized study, routine testing with phenytoin should be considered.

Empiric amiodarone versus "ineffective" drug therapy in patients with refractory ventricular tachyarrhythmias.

Because of its presumed unique efficacy, amiodarone (AM) is often used to treat patients whose sustained ventricular tachyarrhythmias (VT/VF) appear to be drug-refractory. To examine the efficacy of AM in such patients, we performed a retrospective analysis of 77 patients with drug-refractory VT/VF treated with either empiric AM or with drugs predicted during electrophysiological (EP) testing to be ineffective (ID). To qualify for the study, patients had to have spontaneous, symptomatic VT/VF, and persistently inducible VT during serial EP testing with drugs. All 77 patients were offered therapy with AM. Those who refused were treated with ID, whenever possible, an ID was selected which "improved" the EP study compared to baseline. Originally, 68 patients elected AM and nine elected ID. Because of drug intolerance or inefficacy, 10 patients crossed over during the course of the study; a total of 71 patients were followed on AM for 15.7 +/- 11.0 months, and 16 on ID for 17.8 +/- 10.8 months (mean +/- SD). During follow-up, the cumulative recurrence of VT/VF at 6, 12, and 24 months for AM versus ID was 16 +/- 5% versus 44 + 12% (P less than 0.002), 32 +/- 6% versus 44 +/- 12% (NS), and 41 +/- 7% versus 44 +/- 12% (NS) (+/- SE). The recurrence of VT was significantly lower in the AM group only for the first 6 months of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The automatic implantable cardioverter-defibrillator in drug-refractory ventricular tachyarrhythmias.

STUDY OBJECTIVE: To assess the efficacy of the automatic implantable cardioverter-defibrillator in preventing sudden death in high-risk patients. DESIGN: Nonrandomized cohort study. SETTING: A university teaching hospital with 500 beds. PATIENTS: Consecutive sample of 78 patients with symptomatic, sustained ventricular tachyarrhythmias that were previously drug-refractory. INTERVENTIONS: Before February 1985, patients received treatment with the defibrillator and amiodarone if they presented with loss of consciousness (group A) and amiodarone alone if they did not lose consciousness (group C). After February 1985, because the availability of the defibrillator was severely curtailed, patients who lost consciousness received treatment with amiodarone alone (group B). MEASUREMENTS AND MAIN RESULTS: The risk for recurrent arrhythmias was similar between groups. The actuarial risk for sudden death in group B was 31% (95% confidence interval, 11% to 51%) at 1 and 2 years, a value that was significantly higher than that for group A (p less than 0.003) or group C (p less than 0.03). The risk for dying suddenly with the first recurrence was 0.78 in group B, a value that was significantly higher than that for group A (p less than 0.003) or group C (p less than 0.002). CONCLUSION: The defibrillator is highly effective in preventing sudden death in patients whose presenting arrhythmias caused loss of consciousness (group A). In patients whose presenting arrhythmias did not result in loss of consciousness (group C), initial treatment with the defibrillator appears unnecessary.

Autonomic nervous system and cellular injury from circumflex ligation in dogs.

The role of the autonomic nerves in the development of irreversible cellular injury (ICI) after circumflex coronary occlusion was examined in dogs with intact, acutely, or chronically decentralized cardiac nerves. Cardiac nerves were chronically decentralized 2 wk before ligation (CD) or acutely at the time of ligation (AD). In one group of AD dogs, the beta-blocker oxprenolol (0.3 mg/kg) was administered before ligation (AD + Ox). Hearts were paced at 160 beats/min to exclude any contribution of rate change secondary to autonomic intervention. The results are expressed in terms of percent of the cross-sectional area of the posterior papillary muscle (PPM) sustaining ICI after 40-min occlusion: intact 64 +/- 4% (SE), 6 +/- 4%, AD 39 +/- 10%, and AD + Ox 2 +/- 2%. Both acute and chronic denervation protect against ICI even in the absence of changes in heart rate. Furthermore, in dogs with intact cardiac nerves, reduction in pacing rate from 160 to 60 beats/min also decreased the extent of ICI from 64 +/- 4 to 34 +/- 10%. Experiments defining the time course of development of ICI in the PPM indicate that protection was only temporary, delaying the onset of injury by 25 min. These findings suggest that 1) neural activity in extrinsic cardiac sympathetic nerves activate beta-receptors, thereby influencing the development of ICI, and 2) differences in protection afforded by acute denervation with and without beta-blockade indicated that intrinsic postganglionic sympathetic nerve terminals can liberate transmitter in response to ischemia even in the absence of extrinsic neural activity.