The Concerted Action 'Heart' European registry on clinical application of mechanical circulatory support systems: bridge to transplant. The Registry Scientific Committee.

OBJECTIVE: The goal of this paper is to identify in the field of mechanical support as bridge to transplant, by statistical analysis, variables influencing survival during support (transplanted patients) and the overall survival (discharged after transplant). METHODS: Clinical factors are analysed in 258 patients in the period 1986-1993. All variables were analyzed by a univariate and multivariate analysis. RESULTS: The indications for mechanically circulatory support were hemodynamic deterioration before transplantation in 177 (69%), post acute myocardial infarction in 40 (15%), postcardiotomy cardiogenic shock in 20 (8%), graft failure in 12 (5%) and cardiac rejection 9 (3%). The devices implanted have been: pneumatic VAD in 145 cases (56%), electromechanical LVAS in 15 cases (6%), TAH in 78 cases (30%) and centrifugal pumps in 20 cases (8%). The patients were supported for period ranging from 2 h to 623 days (mean 18.3 days +/- 43.2). The type of support was: LVAD 50 cases (20%), RVAD 3 cases (1%), BVAD 127 cases (49%), and TAH 78 cases (30%). Bleeding occurred in 84 patients (32.5%), infections in 83 patients (32.1%); 21 embolic complications were reported in 16 patients (6%). Renal failure occurred in 64 cases (25%) requiring dialysis in 33 (13%); respiratory failure in 47 cases (18%); neurological impairment was noted in 22 patients (9%). One hundred-sixty patients were transplanted (62%) and 104 ultimately discharged (40% out of total 258 patients and 65% out of 160 transplanted patients). Among postoperative parameters, renal failure, TAH, neurological impairment and infection shown statistical power. Some pre- and post-operative variables were identified as independent risk factors for overall mortality: age, indication for graft failure, all indications different from cardiomyopathy, neurological impairment, renal insufficiency, infection, bleeding and any type of support different from LVAD. The improvement in the success rate in the last 2 years is statistically significant (P = 0.0282) considering both the percentage of transplanted patients and of discharged patients. CONCLUSIONS: The results are encouraging if mechanical support is performed in patients with deterioration while awaiting transplant, when LVAD is feasible and effective, when an ideal timing of transplant during support period is identified.

The artificial heart: device and concept evolution.

In the artificial heart area, device evolution and evolution of application criteria have been synergetic in promoting advancement in the entire sector. In fact, limitations of conventional therapies prompted the short-term use of devices for supporting patients until heart transplantation or until recovery of natural heart function. This in turn stimulated device diversification. A first class of new intraventricular blood pumps, allowing simplified application procedures, but with limitation in blood flow, have been developed for short term mechanical support. Another class of devices, with more implantable components, have been developed for longer duration applications, and higher quality of patient life during the implant period. These temporary but progressively longer duration clinical applications in patients waiting for heart transplantation, demonstrated the clinical feasibility of permanent support or substitution of a failing heart; an application intended as an alternative to heart transplantation that is greatly limited by donor's organ availability. Research efforts are now focused on establishing readiness for permanent clinical use of totally implantable heart replacing systems, or of implantable devices for assisting left ventricular function.

The Italian Artificial Heart Program.

In Italy, artificial heart development was promoted by virtue of a special program on technological and industrial development in areas related to cardiology and cardiosurgery. A first prototype series of electromechanical total artificial hearts (TAHs) and ventricular assist devices (VADs), with ball-screw-based actuation technology, has been developed, and preliminary bench tests and short-term animal implant experiments were performed. The project started with analysis and development of existing TAH and VAD models, and it included a fill-sensor-free control scheme and anatomical fitting studies using a three-dimensional computer model of the chest cavity. Second-generation prototypes are currently being developed, and they are scheduled for medium-term bench and in vivo testing by early 1994.

Comparative biological tests on segmented polyurethanes for cardio-vascular applications.

In order to select a candidate segmented polyurethane (SPU) elastomer for the preparation of cardio-vascular prostheses, a series of biological tests (namely haemolysis, aPTT and PT coagulation tests, cytotoxicity, human endothelial cells seeding) was carried out on five commercially available biomedical polyurethanes. The tests were performed on solvent cast samples, from THF (Cardiothane 51, Pellethane 2363 80A, Estane 5714 F1, and Estane 58810), or DMAC (Biomer). All the materials were sterilized by gamma-irradiation before being tested. From the results obtained all the polyurethanes used in this study were shown to be devoid of toxicity towards blood (as proved by haemolysis and coagulation time tests) or blood cells (as proved by cytotoxicity and cell adhesion assays). A clear difference among the tested copolymers didn't stand out under our test conditions, although Cardiothane, possibly due to its physico-chemical characteristics, was less effective in promoting endothelial cell adhesion.

Comparative physical tests on segmented polyurethanes for cardiovascular applications.

In order to select a candidate segmented polyurethane (SPU) elastomer for cardiovascular prostheses, a series of physical tests was carried out on five commercially available biomedical polyurethanes. The tests were performed on uniformly thick sheets (0.2-0.3 mm), obtained by solvent casting from THF (Cardiothane 51, Pellethane 2363 80A, Estane 5714 F1, and Estane 58810) or DMAC (Biomer). Tensile mechanical tests at 23 and 37 degrees C showed for all the copolymers typical stress/strain behaviour of elastomeric materials, with small individual differences. Hydrolytic stability was investigated at 85, 60, and 37 degrees C, at increasing times of exposure (96-168 h), in water or alkaline buffer (pH = 10). As indicated by gel permeation chromatography, in almost all cases a degradation of the molecular weight (particularly the M w) was noticed after the hydrolytic tests, but tensile, thermal (by DSC) and dynamic mechanical properties were substantially not affected. SEM was also performed on the materials, before and after the hydrolytic tests. Changes in the morphology of the materials (related to degradation effects) was observed only in the case of Biomer, as shown also by the thermomechanical analyses. After this first series of physical tests, a clear choice of a particular SPU among the five investigated was not found.

Voluntary control of motor units in human antagonist muscles: coactivation and reciprocal activation.

1. Myoelectric (ME) activity of several motor units was detected simultaneously from the human flexor pollicis longus and extensor pollicis longus muscles, the only two muscles that control the interphalangeal joint of the thumb. The ME signals were detected while the subjects produced isometric force outputs to track three different paradigms: triangular trajectories, random-force trajectories requiring both flexion and extension contractions, and net zero force resulting from stiffening the joint by voluntarily coactivating both muscles. 2. The ME signals were decomposed into their constituent motor-unit action potential trains. The firing rate behavior of the concurrently active motor units was studied using cross-correlation techniques. 3. During isometric contractions, the firing rates of motor units within a muscle were greatly cross-correlated with essentially zero time shift with respect to each other. This observation confirms our previous report of this behavior, which has been called common drive. Common drive was also found among the motor units of the agonist and antagonist muscles during voluntary coactivation to stiffen the interphalangeal joint. This observation suggests two interesting points: 1) that the common drive mechanism has a component of central origin, and 2) that the central nervous system may control the motoneuron pools of an agonist-antagonist muscle pair as if they were one pool when both are performing the same task. 4. During force reversals, the firing rates of motor units reverse in an orderly manner: earlier recruited motor units decrease their firing rate before later recruited motor units. This orderly reversal of firing rates is consistent with the concept of orderly recruitment and derecruitment. 5. A control scheme is suggested to explain the behavior of the motor units in both muscles during force reversal. It consists of centrally mediated reciprocally organized flexion and extension commands along with a common coactivation command to both muscles. This control scheme allows for coactivation and reciprocal activation of an agonist-antagonist set. 6. The agonist-antagonist pair was observed to generate a net force in two control modalities: proportional activation and reciprocal activation. In proportional activation, the agonist-antagonist set is coactivated during either of two states: when uncertainty exists in the required task or when a compensatory force contraction is perceived to be required.(ABSTRACT TRUNCATED AT 400 WORDS)

Motor unit recruitment and firing rates interaction in the control of human muscles.

Muscle contractions are modulated by the number of motor units recruited and their respective firing rates. The work described in this report documents an interplay between recruitment and firing rates of motor units. The recruitment of a new motor unit appears to have a disfacilitatory influence on the firing rates of previously activated motor units. It is speculated that this effect is likely to be mediated, at least partially, via the stretch reflex loop and possibly by the recurrent inhibition of the Renshaw circuit. Such a mechanism would be functionally useful in providing smooth control of muscle output via peripheral circuitry (consisting of proprioceptive reflexes and recurrent inhibition), thus lessening the amount of detailed supervision of the alpha-motoneuron pool required by the central nervous system.

A technique for the detection, decomposition and analysis of the EMG signal.

In the present paper we have described a system for acquiring, processing and decomposing EMG signals for the purpose of extracting as many motor unit action potential trains as possible with the greatest level of accuracy. This system consists of 4 main sections. The first section consists of methodologies for signal acquisition and quality verification. Three channels of EMG signals are acquired using a quadripolar needle electrode designed to enhance discrimination among different MUAPs. An automated experiment control system is devised to free the experimenter from the burden of experiment detailed surveillance and bookkeeping; and to allow on-line assessment of the EMG signal quality in terms of decomposition suitability. The second section consists of methodologies for signal sampling and conditioning. The EMG signal is bandpass filtered (between 1 kHz and 10 kHz), sampled and compressed by eliminating parts of the signal under a preset threshold level. The third section consists of a signal decomposition technique where motor unit action potential trains are extracted from the EMG signal using a highly computer assisted interactive algorithm. The algorithm uses a continuously updated template matching routine and firing statistics to identify MUAPs in the EMG signal. The templates of the MUAPs are continuously updated to enable the algorithm to function even when the shape of a specific MUAP undergoes slow variations. The fourth section deals with ways in which to analyze and display the results. The more frequently used representation formats are: (1) display of MUAP wave shapes; (2) impulse trains representing motor unit firings; (3) IPI plots where time interval between successive firings of the same motor unit is plotted vs. time of the muscle contraction; (4) firing rate plots where the estimated time-varying mean firing rate of the detected motor units is plotted vs. time of the muscle contraction. The performance of the system has been tested in terms of: (1) consistency among results obtained by different operators; (2) accuracy evaluated on synthetic EMG signal; (3) indirect measure of accuracy on real EMG signal by comparing results pertaining the same motor unit action potential trains derived by two EMG signals, independently and simultaneously recorded from two different electrodes.