Biomedical subjects

Robert A Malkin

Publications and source records attributed to Robert A Malkin.

9 recordsLinked to original sources

PubMed2006

Experimental verification of theoretical predictions concerning the optimum defibrillation waveform.

The efficacy of electrical therapy at terminating ventricular fibrillation is highly dependent on the waveform used. We present experimental results which test one theory for defibrillation waveform dependence. Forty-four defibrillation waveforms (22 monophasic, 22 biphasic) were designed according to the theoretical construct of Fishier (2000). The waveforms were then tested on 67 male guinea pigs (46 for monophasic, 21 for biphasic waveforms) using a custom designed defibrillator and 12-mm subcutaneous disc electrodes. There was considerable agreement between the theoretical and experimental results. For example, as predicted, the ascending exponential waveform of 1 ms proved to be the most effective (86.4%) monophasic waveform, where efficacy is the number of successful shocks divided by the total number delivered. In addition, the efficacy decrease with duration increase was accurately predicted by the model for monophasic waveforms. For biphasic waveforms, as predicted by the model, when the first phase was optimized, an increase in second phase duration caused an increase in defibrillation efficacy (10 of 11 tested duration pairs). We conclude that the theoretical framework adequately explains the mechanism by which the defibrillation waveform affects efficacy for monophasic waveforms and, in at least one aspect, biphasic waveforms.

Animals↗

PubMed2006

Experimental evidence of improved transthoracic defibrillation with electroporation-enhancing pulses.

There is considerable work on defibrillation wave form optimization. This paper determines the impedance changes during defibrillation, then uses that information to derive the optimum defibrillation wave form. METHODS PART I: Twelve guinea pigs and six swine were used to measure the current wave form for square voltage pulses of a strength which would defibrillate about 50% of the time. In guinea pigs, electrodes were placed thoracically, abdominally and subcutaneously using two electrode materials (zinc and steel) and two electrode pastes (Core-gel and metallic paste). RESULTS PART I: The measured current wave form indicated an exponentially increasing conductance over the first 3 ms, consistent with enhanced electroporation or another mechanism of time-dependent conductance. We fit this current with a parallel conductance composed of a time-independent component (g0 = 1.22 +/- 0.28 mS) and a time-dependent component described by g delta (1-e(-t/tau)), where g delta = 0.95 +/- 0.20 mS and tau = 0.82 +/- 0.17 ms in guinea pigs using zinc and Cor-gel. Different electrode placements and materials had no significant effect on this fit. From our fit, we determined the stimulating wave form that would theoretically charge the myocardial membrane to a given threshold using the least energy from the defibrillator. The solution was a very short, high voltage pulse followed immediately by a truncated ascending exponential tail. METHODS PART II: The optimized wave forms and similar nonoptimized wave forms were tested for efficacy in 25 additional guinea pigs and six additional swine using methods similar to Part I. RESULTS PART II: Optimized wave forms were significantly more efficacious than similar nonoptimized wave forms. In swine, a wave form with the short pulse was 41% effective while the same wave form without the short pulse was 8.3% effective (p < 0.03) despite there being only a small difference in energy (111 J versus 116 CONCLUSIONS: We conclude that a short pulse preceding a defibrillation pulse significantly improves efficacy, perhaps by enhancing electroporation.

Animals↗

PubMed2005

Advances in electrical and mechanical cardiac mapping.

Cardiac mapping--recording cardiac activity during electrophysiological testing--has evolved into an indispensable tool in studying the cardiac excitation process, analysing activation patterns, and identifying arrhythmogenic tissue. Cardiac mapping is a broad term that is used here to encompass applications that record electrical or mechanical activity of the heart or both. In recent years, simultaneous and sequential electrical mapping methods have been combined with direct mechanical measurements or imaging techniques to acquire information regarding both the electrical and mechanical activity of the heart (electromechanical mapping) during normal and irregular cardiac behavior. This paper reviews the emerging area of electromechanical mapping from the point of view of the applicable technology, including its history and application.

Biomechanical Phenomena↗

PubMed2004

Design of an integrated sensor for in vivo simultaneous electrocontractile cardiac mapping.

While there is extensive mapping of the spread of electrical activity in the heart, there have been no measurements of electrical and localized mechanical, or contractile, activity. Yet the development of effective treatments for diseases like chronic heart failure and cardiac hypertrophy depend on the ability to quantify improvements in electrocontractile function. In this paper, we present a sensor that is capable of making simultaneous, electrocontractile measurements. Its small size facilitates placement in multiple myocardial sites for multichannel studies. Semiconductor strain gages are used for force sensing, and Ag/AgCl-plated tungsten electrodes act as electrogram sensors. The sensor contains electronics on-board, including instrumentation amplifiers and a microprocessor for data sampling and analog-to-digital conversion. Each sensor can accurately detect 0-245+/-5 mV in two electrogram channels with a sensitivity of 0.96+/-0.2 mV/step and less than 2% error, and 0-144+/-29 g of contractile force with a sensitivity of 0.56+/-0.11 g/step in the analog-to-digital conversion and less than 6% error. The sensor has been tested in vivo in open-chest rabbit and pig mapping studies. These studies indicated that the average peak-to-peak contractile force at the apex is smaller in the rabbit than the pig (13.3 versus 40.3 g), that the average peak-to-peak contractile force in the pig is smaller near the base than near the apex (31.3 versus 40.3 g), and that contractile force is visibly decreased during ventricular fibrillation compared to normal sinus rhythm.

Animals↗

PubMed2003

Very-long-chain acyl-coenzyme a dehydrogenase deficiency in mice.

Fatty acid oxidation (FAO) defects are inborn errors of metabolism clinically associated with cardiomyopathy and sudden infant death syndrome (SIDS). FAO disorders often present in infancy with myocardial dysfunction and arrhythmias after exposure to stresses such as fasting, exercise, or intercurrent viral illness. It is uncertain whether the heart, in the absence of stress, is normal. We generated very-long-chain acyl-coenzyme A dehydrogenase (VLCAD)-deficient mice by homologous recombination to define the onset and molecular mechanism of myocardial disease. We found that VLCAD-deficient hearts have microvesicular lipid accumulation, marked mitochondrial proliferation, and demonstrated facilitated induction of polymorphic ventricular tachycardia, without antecedent stress. The expression of acyl-CoA synthase (ACS1), adipophilin, activator protein 2, cytochrome c, and the peroxisome proliferator activated receptor gamma coactivator-1 were increased immediately after birth, preceding overt histological lipidosis, whereas ACS1 expression was markedly downregulated in the adult heart. We conclude that mice with VLCAD deficiency have altered expression of a variety of genes in the fatty acid metabolic pathway from birth, reflecting metabolic feedback circuits, with progression to ultrastructural and physiological correlates of the associated human disease in the absence of stress.

Acyl-CoA Dehydrogenase, Long-Chain↗

PubMed2003

Two-dimensional analysis of ventricular fibrillation in the guinea pig.

Cardiac arrhythmias are undesirable electrical activity in the heart. Ventricular fibrillation (VF) is a fatal cardiac arrhythmia and is characterized by the breakdown of organized electrical activity in the ventricular myocardium. However, little is known about VF, partially because it is difficult to study and understand an apparently disorganized activity. One method for discovering the nature of VF is processing the epicardial electrical signals by using cardiac mapping techniques. These techniques involve the study of propagation patterns seen in VF. In this project, we used guinea pigs to study the spatial organization of the epicardial electrical activity during VF. VF was induced in 9 open chest guinea pigs and epicardial electrode data were acquired by using a square array of 192 electrodes for 4 seconds every minute. The mean correlation length and dominant frequency were measured in each recorded segment. Correlation length is a measure of the spatial order in a system and dominant frequency is the frequency corresponding to the spectral maximum. The mean correlation length was found to vary between 1-7 mm and the dominant frequency was in the range of 1-14 Hz. This study suggests that guinea pig VF exhibits a level of organization equivalent to or greater than that seen in previous studies.

Analysis of Variance↗

PubMed2002

Left ventricular geometry immediately following defibrillation: shock-induced relaxation.

A previous two-dimensional (2D) ultrasound study suggested that there is relaxation of the myocardium after defibrillation. The 2D study could not measure activity occurring within the first 33 ms after the shock, a period that may be critical for discriminating between shock- and excitation-induced relaxation. The objective of our study was to determine the left ventricular (LV) geometry during the first 33 ms after defibrillation. Biphasic defibrillation shocks were delivered 5-50 s after the induction of ventricular fibrillation in each of the seven dogs. One-dimensional, short-axis ultrasound images of the LV cavity were acquired at a rate of 250 samples/s. The LV cavity diameter was computed from 32 ms before to 32 ms after the shock. Preshock and postshock percent changes in LV diameter were analyzed as a function of time with the use of regression analysis. The normalized mean pre- and postshock slopes (0.2 +/- 2.2 and 3.3 +/- 7.9% per 10 ms) were significantly different (P < 0.01). The postshock slope was positive (P < 0.005). Our results confirm that the bulk of the myocardium is relaxing immediately after defibrillation.

Animals↗

PubMed2002

Large sample test of defibrillation waveform sensitivity.

INTRODUCTION: An unknown mechanism causes defibrillation efficacy to be sensitive to the temporal pattern (waveform) of the delivered energy. Using a guinea pig model, we tested hypotheses in 140 defibrillation waveforms. METHODS AND RESULTS: Two hundred seven male guinea pigs (950 +/- 100 g) were instrumented to continuously monitor the ECG and an optical plethysmographic signal from a forepaw. Two amplifiers served as a voltage-based defibrillator with a maximum output of 400 V at 2 A. Defibrillation electrodes (12-mm diameter) were placed 40 mm apart on the thorax. Thirty ventricular fibrillation episodes were induced where the first 10 episodes were used to estimate ED50 for a biphasic pulse (7/2 msec) and the remaining episodes were defibrillated with 18 test waveforms and two control waveforms all at the ED50 energy. Seven groups of 20 waveforms were tested. We directly tested hypotheses based on charge banking/burping, frequency concentration, and stimulus strength/duration. Of the hypotheses tested, nine are able to predict at least a 10% change in efficacy (P < 0.05): parabolic fit to duration; maximum, minimum, and remaining delivered charge; power at peak frequency; stimulus charge; and maximum, minimum, and maximum of the absolute value of stimulus strength. However, of these, only three are independent predictors of waveform efficacy (P < 0.05, near-minimum residual variance): power at peak frequency; parabolic fit to the stimulus duration; and minimum stimulus strength. CONCLUSION: Stimulus strength and duration are the main determinants of the efficacy of a defibrillation waveform.

Animals↗

PubMed2002

A novel ultrasound technique to estimate right ventricular geometry during fibrillation.

Finite element modelling of the heart for the purpose of studying the electric fields of defibrillation shocks requires knowledge of the geometry of the heart during fibrillation. However, the standard method of measuring this geometry, MRI. cannot be used during fibrillation because the heart geometry changes rapidly and perhaps unpredictably. We present a new ultrasound approach to measuring the right ventricular geometry during fibrillation and preliminary data using this technique. In six anaesthetized pigs, we find that a short axis cross-sectional area of the right ventricle increases by 38% during a 30 s episode of ventricular fibrillation. A long axis cross-sectional area increases by 19% during this same time. By fitting parameters of a simple geometric model to the experimental data, we estimate that the volume of blood in the right ventricular cavity increases by approximately 30% during the episode of ventricular fibrillation. We present the first study of the RV area during-fibrillation with the estimated volume. Our data suggest changes in defibrillation threshold may be linked to current shunting through the increased blood volume.

Animals↗