Simulated interactions between a Class III antiarrhythmic drug and a figure 8 reentry.

Ventricular Fibrillation is responsible for a majority of sudden cardiac death, but little is known about how ventricular tachycardia (VT) degenerates into ventricular fibrillation. Several clinical studies focused only on preventing VT with a class III antiarrhythmic drug resulted in many deaths. Our simulations investigate the interactions between an antiarrhythmic drug likely to suppress a VT and a Figure 8 reentry. A parameter AAR is introduced to increase the action potential duration and therefore simulate various Class III drugs. Simulations are ran under several conditions (phases of the reentry, values of AAR, durations). They show that a VT can be suppressed whatever the phase of the reentry but it strongly depends on the duration of the effect. It confirms that a drug which can suppress a reentry can also worsen it. It also shows a great variety of activation patterns and thus the complexity of antiarrhythmic drugs effects. Simulations also demonstrate that suppressing VT is an increasing function of AAR.

[Feasibility of prosthesis insertion by laparotomy as palliative treatment for malignant duodenal stenosis]. / Faisabilité de l'insertion des prothèses par laparotomie comme traitement palliatif des sténoses duodénales malignes.

The authors report a preliminary series assessing the feasibility of duodenal stenting using a surgical approach. The study included 16 patients with a malignant duodenal outlet obstruction for whom a biliaryobstruction necessitated a laparotomyor following an endoscopic stenting failure. The stent was efficient in 15 patients with a complete relieve of obstruction. These patients could have oral intake at the end of the first postoperative week. No stent obstruction occurred. The duodenal stenting by laparotomy could be a good alternative to palliative gastroenteral anasotomosis.

Numerically solving physiological models based on a polynomial approach.

Much research effort has been directed in different physiological contexts towards describing realistic behaviors with differential equations. One observes obviously that more state-variables give the model more accuracy. Unfortunately, the computational cost involved is higher. A new algorithm is presented for simulating a model described by a system of differential equations in which efficiency may not be altered by its size. In order to do this, the method is based on a polynomial description of the state-variables' evolution and on a computation distributed control. Evaluations and results performed with classical models like Fitzhugh Nagumo or Hodgkin Huxley, allow validation of the method and exhibits its potential to decrease the computational costs.

Overview of CARMEM: a new dynamic quantitative cardiac model for ECG monitoring and its adaptation to observed signals.

Different approaches have been proposed in order to achieve knowledge integration for coronary care monitoring applications, usually in the form of expert systems. The clinical impact of these expert systems, which are based only on "shallow" knowledge, has not been remarkable due to the difficulties associated with the construction and maintenance of a complete knowledge base. Model-based systems represent an alternative to these problems because they allow efficient integration of the "deep" knowledge on the underlying physiological phenomena being monitored. In this work, a brief review of existing model-based systems for cardiac rhythm interpretation is presented, followed by the description of a new system for Cardiac Arrhythmia Recognition by Model-Based ECG Matching (CARMEM). Fundamental characteristics of CARMEM are presented; in particular, its ability to provide online parameter adaptation to simulate complex rhythms and to match observed ECG signals. The proposed model can be useful for the explanation of the origin of cardiac arrhythmias and contribute towards their robust characterization in the context of coronary care units.

Role of the dispersion of refractoriness on cardiac reentries.

We used computer simulation to study the possible role of the dispersion of cellular coupling, refractoriness or both, in the mechanisms underlying cardiac arrhythmias. Local ischemia was first assumed to induce cell to cell dispersion of the coupling resistance (case 1), refractory period (case 2), or both (case 3). Our numerical experiments based on the van Capelle and Durrer model showed that vortices could not be induced. On the other hand, with cellular properties dispersed in a patchy way within the ischemic zone, a single activation wave could give rise to abnormal activities. This demonstrates the stability of the wave front under small inhomogeneities. Probabilities of reentry, estimated for the three cases cited above showed that a severe alteration of the coupling resistance may be an important factor in the genesis of reentry. Moreover, use of isochronal maps revealed that vortices were both stable and sustained with an alteration of the coupling alone or along with a reduction of the action potential duration. Conversely, simulations with reduction of the refractoriness alone, inducing only transient patterns, could exhibit functionally determined reentries.

Incidence of dispersion of refractoriness and cellular coupling resistance on cardiac reentries and ventricular fibrillation.

We used computer simulations to study the possible role of the dispersion of cellular coupling, refractoriness or both, in the mechanisms underlying cardiac arrhythmias. Local ischemia was first assumed to induce cell to cell dispersion of the coupling resistance (Case 1), refractory period (Case 2), or both of them (Case 3). Our numerical experiments based on the van Capelle and Durrer model showed that vortices could not be induced by cell to cell variations. With cellular properties dispersed in a patchy way within the ischemic zone, a single activation wave could give rise to abnormal activities. This demonstrates the stability of the wave front under small inhomogeneities. Probabilities of reentry, estimated for the three cases cited above showed that a severe alteration of the coupling resistance may be an important factor in the genesis of reentry. Moreover, use of isochronal maps revealed that vortices were both stable and sustained with an alteration of the coupling alone or combined with a reduction of the action potential duration. Conversely, simulations with reduction of the refractoriness alone, inducing only transient patterns, could exhibit functionally determined reentries.

Theoretical study of cardiac transient conduction blocks on reentries induction. Applications to antiarrhythmic drugs.

Limitations of antiarrhythmic drugs on cardiac sudden death prevention appeared since the early 80's. The "Cardiac Arrhythmia Suppression Trial" (CAST) showed more recently that mortality was significantly higher in patients treated with some particular antiarrhythmic drugs than in non-treated patients. In this field, our group recently demonstrated that a bolus of a Class 1 B antiarrhythmic drug was able to trigger a ventricular fibrillation due to transient blocks induction. The aim of the present work was to systematically study, by use of the van Capelle and Durrer (VCD) model which allows to simulate ventricular activation wave propagation, the link between arrhythmogenic effects and the ability of transient blocks to possibly degenerate in severe arrhythmias. A fragment of the ventricular wall is represented by an array of 16384 elements electrically coupled. Effects of induction of one or several transient blocks, as the effects of their size and duration on possible induction of reentries have been studied. Results obtained show that various combinations between these different parameters may trigger reentries, ventricular tachycardia and/or more complex patterns assimilable to ventricular fibrillation. These results clearly evidence the fact that possible induction of transient blocks may directly be related to risk factor associated to arrhythmogenic effects of antiarrhythmic drugs.

Modeling of cardiac electrophysiological mechanisms: from action potential genesis to its propagation in myocardium.

The aim of the present paper is to describe the different attempts at modeling cardiac electrophysiological mechanisms, mainly at the membrane and cellular level, from action potential genesis to its propagation in myocardium. The Hodgkin and Huxley model describing the nervous action potential's theoretical reconstruction is first recalled, for it represents the basic model for a large part of cardiac action potential models. These models (Beeler and Reuter, Van Capelle and Durrer, Luo and Rudy) are then successively studied as their main applications by diverse authors. Varied approaches, like the Fitzhugh-Nagumo model (derived from the Bonhoeffer-Van der Pol model of oscillatory systems) or cellular automata models applied to the study of ventricular activation wave propagation and diseases associated with its perturbation, are then presented and discussed. Other, different approaches, such as general studies of excitable media, are evoked. This paper concludes with a critical evaluation of these different methods of electrophysiological cardiac modeling and of the main domains in which they led to significant results and in which they appear able to generate future perspectives.

Effect of myocardial infarction and ischemia on induction of cardiac reentries and ventricular fibrillation.

The present work is aimed at investigating the effects of myocardial infarction and ischemia on induction of ventricular fibrillation. Electrophysiologic effects of global and local ischemia (variation of the dispersion of refractory periods as well as conduction velocity) on initiation of reentry mechanisms was studied by means of computer simulations based on a cellular automata model of propagation of activation wave through a ventricular surface element. A local area of ischemia where effects of the dispersion of refractory periods are investigated is then simulated. This is made using a Gaussian distribution characterized by its mean and standard deviation. These simulations show that ischemia is capable of initiating reentry phenomena which propagate through the whole ventricle; they are responsible for ventricular fibrillation which causes sudden cardiac death, even when ischemia only involves limited parts of the myocardium. Statistical study of the probability of reentries as a function of both of the size of ischemic zones and the rate of dispersion of refractory periods shows that the latter parameter is of primary importance in triggering cardiac reentries.

Interpretation of epicardial mapping by means of computer simulations: applications to calcium, lidocaine and to BRL 34915.

The aim of this work was to compare experimental investigations on effects of lidocaine, calcium and, BRL 34915 on reentries to simulated data obtained by use of a model of propagation based on the Huygens' construction method already described in previous works. Calcium and lidocaine effects are investigated on anisotropic conduction conditions. In both cases, reduction in conduction velocities are observed. In lidocaine case, a refractory area is located along the longitudinal axis. In agreement with experimental electrical mapping, the simulations show that the stabilization of reentrant excitation is mainly due to the existence of this refractory area around which the reentrant circuit can develop. The experimental study shows that BRL 34915 has both arrhythmogenic and antiarrhythmic effects. A detailed electrophysiological analysis has shown that drug infusion act on normal cardiac cells by decreasing the relative and absolute refractory period. BRL 34915 action is simulated by a decrease in the refractory period showing that the time frequency of the reentrant activity is increased and that the spatial size where the reentry is developing is becoming smaller. These two effects are arrhythmogenic, the simulated data being so in good agreement with the experimental ones.

Directional variability of stimulation threshold measurements in isolated guinea pig cardiomyocytes: relationship with orthogonal sequential defibrillating pulses.

Reports on delivery of separated orthogonal pulses markedly improving cardiac defibrillation have suggested that the stimulation threshold of heart fibers varies in accordance with their orientation within the electric field. The present work was aimed at investigating the directional variability of stimulation thresholds in isolated guinea pig cardiomyocytes. This variability was measured in 48 single myocytes by rotating each one through a theta (theta) angle between two-fixed parallel electrodes 1.1 cm apart, thus making theta vary between the electric field and the myocyte axis. For theta = 0 degrees, the mean longitudinal current stimulation threshold was 16.92 +/- 4.20 mA (n = 48). When theta was increased by increments of 10 degrees up to 90 degrees, the stimulation threshold increased in an exponential way. For theta = 90 degrees, the mean transverse stimulation threshold was 63.13 +/- 13.30 mA. These results clearly demonstrate the dependence of isolated cardiomyocyte stimulation thresholds on their orientation within the electric field and may account for the improved efficacy of defibrillation previously observed after delivery of orthogonal pulses.

Reduction of energy required for defibrillation by delivering shocks in orthogonal directions in the dog.

Reduction of energy required to defibrillate (ERD) seems to represent a necessary condition for intensive development of implantable defibrillator, so as for minimization of cardiac and pulmonary damages provoked by high energy transthoracic defibrillation electric shocks. The present work describes a defibrillation method using shocks delivered in orthogonal directions and separated by a 100 ms delay. Defibrillation threshold measured with classical unidirectional shocks on 30 dogs has been found to be 286.8 +/- 22.2 joules. In the same animals, defibrillation threshold measured by use of orthogonal shocks has been found to be 101.4 +/- 14.9 joules. We conclude that this crossed shocks method leads to a substantial reduction of ERD (64%).

Quantitative ascending aortic Doppler blood velocity in normal human subjects.

We have developed digital, Apple II microcomputer-based methods for the numerical analysis of pulsed, range-gated, ultrasonic Doppler blood velocity signals. These methods were then used to analyse Doppler data recorded every 5 ms from the ascending aorta via the suprasternal notch in normal subjects ranging in age from 3 to 62 years. Normal values for peak velocity, the integral of velocity over the time of systole, and the rate of change of velocity in early ejection are reported. It was found that, after an initial step increase, the velocity of blood flow in early ejection increased in a linear manner in more than two thirds of the individual beats analysed. The time for which the linear acceleration in the aorta was constant (circa 50 ms) was unrelated to the age or size of the subject.

Simultaneous Doppler blood velocity measurements from aorta and radial artery in normal human subjects.

We used two independent, pulsed, range-gated, ultrasonic, Doppler blood velocity meters to record blood velocities in the aorta and a peripheral artery in 32 normal subjects aged 8 to 62 years. Aortic signals were obtained from an unfocussed transducer in the suprasternal notch using a 2.25 MHz instrument. Simultaneous tracings were obtained from the radial or posterior tibial artery using an 8 MHz instrument. The audio Doppler signals were subjected to spectral analysis and mean velocity was calculated at 5 ms intervals during 11 successive heart beats at each site. The increase in mean velocity at the start of systole in the aorta followed a linear pattern for the first 45 ms of ejection in two thirds of the beats, irrespective of the age or size of the subject. A similar linear velocity increase in early systole was seen in the peripheral arterial signals after a delay due to the time taken for the flow wave to pass to the periphery. Thus the constant acceleration seen in aortic blood velocity tracings is transmitted to peripheral arteries in an attenuated and delayed but undistorted form.

Effect of vasopressin on phasic coronary blood flow.

The effects of vasopressin on the coronary circulation have been studied with regard to its general hemodynamic effects. Aortic blood pressure (BP), left ventricular pressure (LVP), aortic blood flow (AoBF), and circumflex blood flow (CBF), were measured in 12 open-chest dogs, under control conditions and during vasopressin infusion (25 mU/kg/min). During vasopressin infusion, the mean aortic blood pressure (MBP) was increased from 104 +/- 23 mm Hg to 161 +/- 23 mm diastolic blood pressure (DBP) was more increased (+55%) than the systolic blood pressure (SBP) (+40%). AoBF was decreased from 2.169 +/- 0.408 l/min to 1.118 +/- 0.303 l/min; and the heart rate was decreased by 18%. The total combined left ventricular power did not change significantly. The increase in total peripheral resistance (TPR) (+200%) was the main change in impedance spectrum. The mean circumflex coronary blood flow (MCBF) was decreased from 48 +/- 8.6 ml/min to 33.4 +/- 9.7 ml/min. This decrease was more important in the diastolic circumflex blood flow (DCBF) (-33%) than in the systolic one (-0.8%). The diastolic pressure time index (DPTI) was more increased than the systolic pressure time index (SPTI). The DPTI/SPTI ratio was increased from 0.91 to 1.3. Long diastoles, induced by vagus nerve stimulation, have permitted to characterise the relationship between pressure and coronary blood flow during diastole. This relationship was linear under basal condition, and during vasopressin perfusion. This made it possible to determine the critical closing pressure (Pf0), and the coronary conductance (the slope of the regression curve). Vasopressin induced an increase in Pf0, from 33.7 +/- 95 to 77.4 +/- 16.07 mm Hg (p less than 0.001), and a decrease in coronary conductance, from 0.8 +/- 0.32 to 0.5 +/- 0.1 ml/min/mm Hg. The effect of an acute change in perfusion pressure on the coronary flow, under control conditions and during vasopressin infusion was studied by opening a large arteriovenous fistula. Unclamping of the fistula, under control conditions, allowed to realize an acute fall in DBP from 82.5 +/- 6.36 to 35.5 +/- 9.19 mm Hg, and in DCBF, from 58.5 +/- 9.2 to 20 +/- 9.8 ml/min. During vasopressin infusion, a similar fall in perfusion pressure lead to a zero diastolic circumflex blood flow, for a diastolic aortic blood pressure of 56 +/- 12 mm Hg. However, vasopressin did not affect the delayed active coronary vasodilatation.

Effect of descending thoracic aorta clamping and unclamping on phasic coronary blood flow.

Myocardial infarctions during aortic surgery often occur after aortic clamping and unclamping. In order to investigate the aortic blood pressure (AoBP)-coronary blood flow (CBF) relationship, hemodynamic parameters and phasic circumflex CBF in 15 anesthetized and open-chest dogs during clamping and unclamping of the thoracic descending aorta have been recorded. During clamping, mean aortic blood pressure (MAoBP) rose from 97 + 17 to 150 + 42 mm Hg (P less than 0.001), and total combined left-ventricular power (Wtc) from 692 + 232 to 923 + 402 mW (P less than 0.001) while the ascending aortic blood flow (AoBF) and heart rate did not change significantly. The mean circumflex blood flow (MCBF) increased from 67 + 30 to 88 + 30 ml/min. The increase in systolic coronary blood flow (+73%) was larger than that in diastolic coronary blood flow (DCBF) (19%). The late coronary resistances were increased 39%. Conversely, after unclamping, MAoBP decreased while AoBF and Wtc increased. During the first cardiac cycles after aortic unclamping DCBF decreased 50% with a decrease in the diastolic blood pressure (DBP). Four cycles later, DCBF reincreased while DBP kept on decreasing. This may be related to an active coronary vasodilatation. A linear relationship between DCBF and DBP has been obtained during acute change in DBP due to clamping or unclamping. From these linear relationships, the change in diastolic zero flow pressure (PfO) has been found to be about + 40 mm Hg during clamping. This change in PfO may be responsible for the observed large fall in DCBF during unclamping. The decrease in DCBF associated with the increase in Wtc accounts for the delayed active vasodilatation.