A Critical Period of Ventricular Fibrillation More Susceptible to Defibrillation: Real-Time Waveform Analysis Using a Single ECG Lead

Previous studies have suggested that variations in the underlying ventricular fibrillation (VF) waveform may be one of the factors responsible for the probabilistic nature of defibrillation. The heart appeared to be more susceptible to defibrillation at higher absolute VF voltages (AVFV). This study investigated in an open-chest canine model (n = 8), a newly developed system that analyzed the VF waveform in real-time, instantaneously determined the time to shock, and immediately delivered a fixed low energy DC shock. A two parameter tracking technique using a running long-term and short-term AVFV average was devised to automatically identify a high voltage peak area of the VF waveform, which has been hypothesized to represent a critical period susceptible to defibrillation. Using a DC shock estimated at the 50% success level, the performance using this technique in 58 defibrillation trials was compared to the performance of the conventional method of shocking at a fixed time (random shock method) in 62 trials. Patch size, electrode location, and discharge voltage were kept constant while VF duration, transmyocardial resistance (TMR), energy delivered, and AVFV at the point of shock were measured. Shock energy and current, TMR, and VF duration were similar with both shock methods. A significantly higher AVFV was observed for trials performed with the peak shock method (0.66 ± 0.02 mV) as compared to trials performed with the random shock method (0.25 ± 0.09 mV) (P < 0.003). Using lead II as the only sensing lead, the success rate was increased in 6 of 8 dogs (75%) with the new method. One animal showed identical performance, and one animal a worse performance. The overall increase in success rate was 24% using a single ECG lead (range 0%-100%; P < 0.04). Our data document that using this algorithm a period of high VF voltage can be detected in realtime. The improved success in the majority of animals supports the hypothesis that a critical period susceptible to defibrillation exists during VF. However, the high AVFV detected using a single ECG lead did not translate to an improved success rate in all animals. This suggests that other factors in addition to the VF voltage measured on a single lead of the ECG are important in characterizing this critical period.     

Acceptability and potential effectiveness of a foot drop stimulator in children and adolescents with cerebral palsy

Aim Ankle–foot orthoses are the standard of care for foot drop in cerebral palsy (CP), but may overly constrain ankle movement and limit function in those with mild CP. Functional electrical stimulation (FES) may be a less restrictive and more effective alternative, but has rarely been used in CP. The primary objective of this study was to conduct the first trial in CP examining the acceptability and clinical effectiveness of a novel, commercially available device that delivers FES to stimulate ankle dorsiflexion. Method Twenty‐one individuals were enrolled (Gross Motor Function Classification System [GMFCS] levels I and II, mean age 13y 2mo). Gait analyses in FES and non‐FES conditions were performed at two walking speeds over a 4 month period of device use. Measures included ankle kinematics and spatiotemporal variables. Differences between conditions were revealed using repeated measures multivariate analyses of variance. Results Nineteen individuals (nine females, 10 males; mean age 12y 11mo, range 7y 5mo to 19y 11mo; 11 at GMFCS level I, eight at level II) completed the FES intervention, with all but one choosing to continue using FES beyond that phase. Average daily use was 5.6 hours (SD 2.3). Improved dorsiflexion was observed during swing (mean and peak) and at foot–floor contact, with partial preservation of ankle plantarflexion at toe‐off when using the FES at self‐selected and fast walking speeds. Gait speed was unchanged. Interpretation This FES device was well accepted and effective for foot drop in those with mild gait impairments from CP.     

The Effect of Left Ventricular Intracavitary Volume on the Unipolar Electrogram

In order to examine the effects of ventricular distention on the unipolar electrogram (UEG), an isolated rabbit heart modified Langendorff preparation was utilized. Left ventricular (LV) volume was adjusted using ionically permeable (PB = 9 hearts) or ionically impermeable balloons (IB = 4 hearts). LV UEGs, LV end-diastolic pressure (EDP), and LV minor axis dimension (MAD), as measured by ultrasonic transducers, were recorded. Three hundred twenty-five eiectrograms were digitized and analyzed with customdesigned software, In the PB group, a significant inverse linear relationship was found between UEG amplitude and changes in MAD (P < 0.0001). For each animal, this relationship had an R value > 0.8 and a P value < 0.0001. There was also a significant inverse linear relationship between UEG slope and changes in MAD (P < 0.01). UEG amplitude and slope also exhibited a significant inverse relationship to changes in LV EDP, which were best described by a third order polynomial function. In the IB group, no significont relationship was found between either UEG amplitude or slope and MAD or EDP. In this study, intracavitary volume exerted a profound and significant influence on UEG amplitude and slope. This effect was due to increases in conductive intraventricular volume and not to myocardial stretch     

Interpolating Unipolar Epicardial Potentials from Electrodes Separated by Increasing Distances

In cardiac mapping, potentials for unexplored areas are estimated by interpolating values from nearest neighbor electrodes regardless of distances between these sites or wave front orientation. The effects of these variables on interpolated unipolar electrograms were analyzed two ways: with a computer model and with electrograms recorded 9.9 and 14.1 mm apart. For the model, wave fronts (n = 39) were generated from electrograms recorded during right ventricular (RV) activation in five dogs following the RV isolation procedure. Each wave front was assumed to propagate radially at 0.5 m/sec from a site 30 mm from the center of a square array with electrodes located at the center and corners. Each wave front crossed the array with its tangent at an angle of 0 degrees, 45 degrees, or 90 degrees to the diagonal line connecting opposite corner electrodes. Potentials for all five sites were generated from each wave front and were interpolated for the center site from the generated corner potentials. Generated and interpolated center site potentials were compared using correlation coefficients (r) and percent root mean square differences (%RMSD). Mean r values fell below 0.90 for interelectrode distances of 15.6 mm, 2.8 mm, and 1.4 mm at 0 degrees, 45 degrees, and 90 degrees wave front orientations, respectively. For experimentally measured potentials recorded 9.9 mm apart, results from interpolated electrograms were similar to results from the model at 0 degrees propagation. Electrograms interpolated from potentials measured 14.1 mm apart had poorer r and %RMS values than those from the computer model. Thus, with linear interpolation unipolar electrograms can be inaccurately interpolated from electrodes less than 3 mm apart or correctly interpolated from electrodes more than 14 mm apart depending upon wave front orientation.     

Can Amiodarone Pulmonary Toxicity Be Predicted in Patients Undergoing Implantable Cardioverter Defibrillator Implantation?

Implantable cardioverter defibrillator (ICD)implantation is rapidly becoming accepted as primary therapy for malignant ventricular arrhythmias. Many patients undergoing ICD implantation are on concomitant antiarrhythmic drugs to decrease shock frequency, slow tachycardia rate, and suppress supraventricular arrhythmias. Amiodarone is a potent antiarrhythmic agent that is also frequently used in the treatment of patients with refractory ventricular arrhythmias. Ten to forty percent of patients undergoing ICD implantation will also be taking amiodarone. It has been reported to cause pulmonary toxicity in about 5% of patients per year. Acute amiodarone toxicity presenting as adult respiratory distress syndrome has been reported much less frequently. Although perioperative morbidity due to amiodarone has been described, the risk, predictability, and consequences of acute pulmonary toxicity from amiodarone in patients undergoing ICD implantation have not been previously described. We reviewed the records of 99 consecutive patients undergoing ICD implantation at our institution from October 1987 to April 1992. Thirty-nine patients were taking 480 ± 230 mg of amiodarone (median 400 mg, lower 20th percentile 400 mg, upper 80th percentile 800 mg)for 291 ± 554 days prior to ICD implantation. Ten patients taking amiodarone developed acute pulmonary toxicity clinically manifesting as diffuse pulmonary infiltrates on chest radiography and adult respiratory distress syndrome with hypoxia (arterial pO₂ < 60 mmHg)without evidence of pneumonia or elevated pulmonary capillary wedge pressure (PCW ±15 mmHg). Of the 60 patients not taking amiodarone none developed adult respiratory distress syndrome. There was no relationship between the clinical variables of age, type of anesthesia, ejection fraction, dose or duration of amiodarone use, number of intraoperative ICD test shocks, operative time, or intraoperative FI_O2. Compared to patients on amiodarone who did not develop toxicity, patients with amiodarone pulmonary toxicity had prolonged intensive care unit stays (17.1 ± 16.9 days vs 3.5 ± 1.5 days, P < 0.001), as well as prolonged ventilator dependence (9.1 ± 18.7 days vs 0.9 ± 1.1 days. P = 0.02). Acute amiodarone pulmonary toxicity resulted in a widely variable clinical syndrome that occurred 1–5 days after surgery. In conclusion, pulmonary toxicity was not predicted by clinical orhemodynamic variables, results in markedly prolonged ventilator dependence and intensive care unit stays, and may result in death.     

URODYNAMIC AND CLINICAL EVIDENCE OF ACUTE INHIBITORY EFFECTS OF INTRAVESICAL NOCICEPTIN/ORPHANIN FQ ON DETRUSOR OVERACTIVITY IN HUMANS: A PILOT STUDY

PURPOSE: Management of neurogenic incontinence is complex and available treatments are not satisfactory. Nociceptin/orphanin FQ, a recently discovered neuropeptide, has been reported to inhibit the voiding reflex in the rat. These experimental results prompted us to investigate the urodynamic and clinical effects of intravesical instillation of nociceptin/orphanin FQ in humans. MATERIAL AND METHODS: Our study involved 5 normal subjects (group 1) with a mean age of 40.4 years (range 21 to 54) and 9 patients (group 2) 40.4 years (24 to 54). All patients in group 2 presented with detrusor hyperreflexia refractory to standard therapy. They were invited to undergo a filling cystometrogram with saline solution and after 30 minutes, a new one with a solution containing 1 microM. nociceptin/orphanin FQ. The urodynamic parameters that were recorded included bladder capacity, volume threshold for the appearance of detrusor hyperreflexia and maximum bladder pressure. Clinical and urodynamic followup was performed after 15 days. The data were statistically analyzed with 1-way analysis of variance followed by the Dunnett test for multiple comparison considered statistically significant with p <0.05. RESULTS: Intravesical instillation of 1 microM. nociceptin/orphanin FQ in group 1 did not produce significant functional changes. This infusion in group 2 produced a statistically significant increase in mean bladder capacity and volume threshold for the appearance of detrusor hyperreflexia from 164 plus or minus standard deviation (SD) 84 to 301 +/- 118 and 93 plus or minus SD 41 to 231 +/- 104 ml. (p <0.05, respectively). Mean maximum bladder pressure decreased from 79 plus or minus SD 25 to 54 +/- 44 cm. water but was not statistically significant (p = 0.19). After 15 days an absence of clinical improvement was noticed in group 2, and the urodynamic control did not show any significant changes compared to the values before nociceptin/orphanin FQ treatment. No severe symptomatic reactions were observed during infusion of 1 microM. nociceptin/orphanin FQ. CONCLUSIONS: Our results demonstrate that nociceptin/orphanin FQ is able to elicit a robust inhibitory effect on voiding reflex in group 2 but not 1. The ideal dosage, route of administration of nociceptin/orphanin FQ and treatment interval are not yet established.     

Improved Nonthoracotomy Defibrillation Based on Ventricular Fibrillation Waveform Characteristics

The heart has been shown to be more susceptible to defibrillation at a higher absolute ventricular fibrillation voltage (AVFV) measured on the surface ECG. This study evaluated in a closed-chest canine model (n = 7) the clinical applicability of using a real-time VF waveform analysis system using an electrogram defined between the generator can and an RV endocardial electrode. Under fluoroscopic guidance, superior vena cava and RV spring coil catheter electrodes were inserted through the external jugular vein. A subcutaneous patch was placed on the left chest. A two-parameter tracking algorithm was used to dynamically identify the high AVFV area, and a biphasic shock was triggered synchronously at the next peak. The performance of this new peak shock method (PSM) was compared to the conventional method of shocking at a fixed time in 175 paired trials. Five shocks per voltage and five voltages per animal were randomized between the two methods to permit the generation of sigmoidal dose response curves for the estimation of 50% (E50), 75% (E75), and 100% (E100) success energies. Induction of VF and discharge voltage were kept constant while energy delivered, impedance (R), and AVFV at the point of shock were measured. Energy (8.63 ± 0.40 vs 8.64 ± 0.40 J), R (48.60 ± 0.30 vs 48.59 ± 0.30 Ω), and current (7.50 ± 0.18 vs 7.51 ± 0.16 A) were not significantly different between trials for either the conventional or the PSM. The time from the onset of VF until the defibrillation shock was 7.98 ± 1.44 seconds. Higher overall successes (46.3% vs 33.1%; P < 0.01) and lower E50, E75, and E100 were observed for the PSM. Finally, the significantly higher AVFV (9.12 ± 0.32 vs 4.73 ± 0.34 mV; P < 0.0001) with the peak method suggests that the high VF voltage could be detected as it occurred in real-time. The improved defibrillation success supports the use of this method for nonthoracotomy defibrillation.     

Prevalence and risk factors associated with decreased bone mineral density in patients with haemophilia

Summary.  Osteoporosis in adult males is an under-recognized problem. Patients with haemophilia have several predisposing factors for developing decreased bone mineral density (BMD) including prolonged periods of immobility, reduced weight bearing and co-morbidities associated with bone loss. To establish prevalence and risk factors associated with decreased BMD in patients with haemophilia. Adults with moderate or severe haemophilia A or B underwent dual-energy X-ray absorptiometry (DXA). BMD was correlated to laboratory values, joint mobility measurements and physical activity questionnaires. Thirty patients completed evaluations. The median age was 41.5 years (range 18–61). Median lowest T-score by DXA was −1.7 (range: −5.8 to +0.6), with the femoral neck being the site of the lowest T-scores. Based on World Health Organization criteria, 70% of patients had decreased BMD. Twenty-seven per cent of the participants ( n  = 8) had osteoporosis and 43% ( n  = 13) had osteopenia. Variables associated with increased bone loss included lower serum 25-hydroxyvitamin D levels ( P  = 0.03), lower body mass index ( P  = 0.047), lower activity scores ( P  = 0.02), decreased joint range of motion ( P  = 0.046), HIV ( P  = 0.03), HCV ( P  = 0.02), history of inhibitor ( P  = 0.01) and age ( P  = 0.03). Adults with haemophilia are at increased risk for developing osteoporosis. A history of HCV and HIV infections, decreased joint range-of-motion, decreased activity levels, history of an inhibitor and low body weight predict bone loss and suggest a population to target for screening. A high prevalence of vitamin D insufficiency was observed. Future studies should investigate interventions, including vitamin D supplementation, to prevent bone loss and fractures for this at-risk population.