Focused very high-energy electron beams as a novel radiotherapy modality for producing high-dose volumetric elements.

The increased inertia of very high-energy electrons (VHEEs) due to relativistic effects reduces scattering and enables irradiation of deep-seated tumours. However, entrance and exit doses are high for collimated or diverging beams. Here, we perform a study based on Monte Carlo simulations of focused VHEE beams in a water phantom, showing that dose can be concentrated into a small, well-defined volumetric element, which can be shaped or scanned to treat deep-seated tumours. The dose to surrounding tissue is distributed over a larger volume, which reduces peak surface and exit doses for a single beam by more than one order of magnitude compared with a collimated beam.

Dosimetry of very high energy electrons (VHEE) for radiotherapy applications: using radiochromic film measurements and Monte Carlo simulations.

Very high energy electrons (VHEE) in the range from 100-250 MeV have the potential of becoming an alternative modality in radiotherapy because of their improved dosimetry properties compared with MV photons from contemporary medical linear accelerators. Due to the need for accurate dosimetry of small field size VHEE beams we have performed dose measurements using EBT2 Gafchromic® film. Calibration of the film has been carried out for beams of two different energy ranges: 20 MeV and 165 MeV from conventional radio frequency linear accelerators. In addition, EBT2 film has been used for dose measurements with 135 MeV electron beams produced by a laser-plasma wakefield accelerator. The dose response measurements and percentage depth dose profiles have been compared with calculations carried out using the general-purpose FLUKA Monte Carlo (MC) radiation transport code. The impact of induced radioactivity on film response for VHEEs has been evaluated using the MC simulations. A neutron yield of the order of 10(-5) neutrons cm(-2) per incident electron has been estimated and induced activity due to radionuclide production is found to have a negligible effect on total dose deposition and film response. Neutron and proton contribution to the equivalent doses are negligible for VHEE. The study demonstrates that EBT2 Gafchromic film is a reliable dosimeter that can be used for dosimetry of VHEE. The results indicate an energy-independent response of the dosimeter for 20 MeV and 165 MeV electron beams and has been found to be suitable for dosimetry of VHEE.

SU-E-J-170: Clinical Evaluation of Positioning Accuracy of Two Immobilization Devices for Stereotactic Body Radiotherapy Using Cone Beam CT.

PURPOSE: To evaluate the patient positioning accuracy and reproducibility of two commercially available immobilization systems for Stereotactic Body Radiotherapy (SBRT) treatment. METHODS: Forty one patients with lung (n=21) or liver (n=20) malignancies were assigned to one of the two immobilization devices: Elekta stereotactic body frame (SBF) with built-in stereotactic coordinate system and Civco modular indexing based frame (MIF) without stereotactic reference. All patients underwent the same simulation and planning procedure followed by cone beam CT (CBCT) guided treatment setup. A total of 151 CBCT images were analyzed. The systematic and random isocenter setup errors of the two systems were calculated and compared based on the daily setup corrections under CBCT guidance. RESULTS: There was not statistically significant difference between the two systems in terms of systematic setup errors in all three translational directions, for both lung and liver patients. The random errors for the lung patients under SBF setup were 1.8mm, 2.0mm and 2.9mm for the vertical, longitudinal and lateral directions, respectively compared to 3.6mm, 4.1mm, and 4.2mm for MIF. A similar trend was also observed for liver patients. The random errors of liver MIF setup reached 3.5mm, 6.1mm and 5.7mm for the vertical, longitudinal and lateral directions, respectively, with relatively smaller errors 1.7mm, 3.4mm and 2.6mm with SBF setup. Repeated CBCTs occurred for MIF system in 42.4% and 40.7% of the lung and liver treatment to verify couch corrections based on the institutional tolerance, resulting in prolonged setup time. Only 25% and 13.6% of the lung and liver treatment with SBF required with repeated CBCT. CONCLUSIONS: Without stereotactic coordinate reference, the body frame system tended to have larger random setup errors and patient positioning accuracy inevitably relies on the volumetric imaging guidance. Patient comfort and reproducibility should be clearly considered for selecting a system.

SU-E-T-288: Skin Dose Measurement of Whole Brain with GAFCHROMIC EBT2 Films.

PURPOSE: To measure skin dose of whole brain irradiation of a humanoid unsliced phantom treated by standard lateral fields with GAFCHROMIC EBT2 films. METHODS: The head and neck of the whole body phantom was scanned at the slice thickness of 2mm. A whole brain plan using 6MV beam was created with standard parallel opposed lateral fields. The isocenter was placed at the outer canthus to avoid divergence to orbital structures. The plan was normalized to the calculation point and with = 95% of brain volume covered by = 95% of prescription dose. The EBT2 films were carefully cut and labeled with same orientation in the film calibration and skin dose measurement. EBT2 film was calibrated in the reference condition with various dose (0-10Gy). After the phantom was positioned for treatment and correct setup was verified by kV-kV imaging and CBCT, the films were placed at various sites and irradiated. An Epson flatbed color scanner was utilized and the scanner response from the red channel of the RGB image was used as the density value for the estimation of dose. The comparison was made between the measured dose and the planned dose for different head locations. RESULTS: Our preliminary results indicated that the measured skin dose agrees with the planned dose within 10% for the sites centered in the treatment fields such as mid right/left sphenoid bones. For the sites outside or near the edge of the treatment fields, such as the right/left orbits and low chin, the measured dose is significantly different from the planned dose (>15%). CONCLUSIONS: Skin dose of whole brain irradiation could be measured by GAFCHROMIC EBT2 films. The difference between the measured dose and the planned dose varies significantly depending on the location of interest relative to the treatment field. Further investigation is needed.

SU-E-T-230: Field Factor Verification in Small Fields.

PURPOSE: Small field is being commonly used in radiosurgery and IMRT, however dosimetry is challenging due to source size, electronic disequilibrium and detector size. Correction factor, K, has been published for a limited set of detectors and beam energies. Validity of K for several detectors is investigated. Also extrapolation ion chamber could be used using reciprocity theorem for small fields which is attempted in this study. METHODS: Various small volume detectors: IBA SFD, PTW TN60012 diode, and PTW Pinpoint N31006, Standard Imaging A16, along with Nuclear Associate N2339IT extrapolation chamber were used to measure output of square fields from 1×1 to 10×10 cm2 for Varian 6 and 16 MV beams. Measurements were made in a water phantom at 1.5cm depth for 6MV photon and 3.0cm depth for 15MV photon with SSD 100cm. Extrapolation chamber was used in solid water. Published correction factors (Francescon et al, MP, 2011)1, K were used for the detectors used in this study. The K value was derived for extrapolation chamber by modeling based on the difference between its detector output and the average output factor from the diodes and pinpoints. RESULTS: The variation in output as measured from different detector is significant (±7.0%) for field sizes = 3×3 cm2 and converges after large field sizes for both energies. The output factor for the extrapolation chamber was out of range from diodes/pinpoints in both 6MV and 16 MV beams. After applying detector K, the field size factors agree each other within ±2.2% for all field sizes. CONCLUSIONS: The value of K provides reasonably good data for field factors irrespective of detector and the field factors can be matched within 2.2%. A mathematical function for extrapolation chamber also provides field factors comparable to the other detectors.

SU-E-T-472: Characterization of the Very High Energy Electrons, ISO - 250 MeV (VHEE) Beam Generated by ALPHA-X Laser Wakefield Accelerator Beam Line for Utilization in Monte Carlo Simulation for Biomedical Experiment Planning.

PURPOSE: Progress in the development of compact high-energy pulsed laser- plasma wakefield accelerators is opening up the potential for using Very High Energy Electron (VHEEs) beams in the range of 150 - 250 MeV for biomedical studies. Initial experiments using VHEE for this purpose have been carried out using the ALPHA-X laser-plasma wakefield accelerator beam line at the University of Strathclyde, Glasgow, UK. The purpose of this investigation is to use Monte Carlo simulations to plan experiments and compare with characterization of the interaction of the VHEE beam using a dosimeter. METHODS: An experiment using the VHEE beam to irradiate a muscle-equivalent BANG polymer gel dosimeter has been carried out. Simulations have been used to prepare for the experiments. These were undertaken using the expected average energy for a pulse set and an energy spread approximated by Gaussian distribution. The model was implemented in FLUKA Monte Carlo code with follow up modeling using the Geant4 toolkit. The results have been compared with 1mm̂3 voxel laser CT based measurements of the dose deposited in the BANG dosimeter and with measurement of the induced radioactivity. RESULTS: The results of the measured dose from induced radioactivity have been compared with data from the FLUKA simulations. The beam model based on an average energy of particles in irradiation gives an acceptable estimate of the induced radioactivity and the dose deposited in the BANG dosimeter. Comparison with the dosimeter scanned profiles shows that the structure of the spectra of VHEE beams in the experiment and secondary scattered particles in the beam line should be accounted for in any model. Such model description of the VHEE beam for the ALPHA-X beam line has been developed. CONCLUSIONS: Monte Carlo simulations using the FLUKA code is an efficient way to plan a VHEE experiment and analyze data from measurements.

The relation of environmental contaminants exposure to behavioral indicators in Inuit preschoolers in Arctic Quebec.

Although lead (Pb) exposure has been identified as an important risk factor in child behavioral development, less is known regarding the relation between child behavior and exposure to polychlorinated biphenyls (PCBs) and mercury (Hg). Inuit children are particularly exposed to these chemicals and the aim of this study was to investigate the association between prenatal and postnatal exposure to Pb, PCBs, Hg and several aspects of behavioral function in Inuit preschoolers. The sample consisted of one hundred and ten 5-year-old Inuit children from Arctic Quebec. An umbilical cord blood sample was used to document prenatal exposure to Pb, PCBs and Hg. Child blood samples were collected at age 5 and the same contaminants were measured. A modified version of the Infant Behavior Rating Scale from the Bayley Scales of Infant Development-II was used to assess child behavior through examiners' ratings. Furthermore, attention, activity and emotional outcomes were assessed through behavioral coding of video recordings taken during fine motor testing. Pb exposure during childhood was associated with examiners ratings of greater impulsivity, irritability and with coding of observed inattention. Prenatal exposure to PCB 153 correlated with the examiners ratings of increased state of unhappiness and anxiety during the testing session, which was corroborated from video coding since cord PCB 153 was related to fewer manifestations of positive affects. No association was found with Hg exposure. These data corroborated those from previous Pb cohort studies and revealed an association between prenatal PCBs exposure and emotional outcomes in preschoolers.

Ytterbium fiber laser based on first-order fiber Bragg gratings written with 400 nm femtosecond pulses and a phase-mask.

A Fiber Bragg grating of 369 nm pitch was inscribed in a germanium-free double-clad ytterbium doped silica fiber using a femto-second pulse train at 400 nm wavelength and a phase mask. The photo-induced refractive index modulation of higher than 4 x 10(-3) was obtained and the accompanying photo-induced losses were subsequently removed by thermal annealing, resulting in a low loss (<0.1 dB), stable and high reflectivity (>40 dB) FBG. Based on this FBG, a monolithic Ytterbium fiber laser operating at 1073 nm with slope efficiency of 71% and output power of 13 W was demonstrated.

Proteases involved in mammary tissue damage during endotoxin-induced mastitis in dairy cows.

During and after diapedesis, milk polymorphonu-clear neutrophils (PMN) release many proteases that have the potential of degrading extracellular matrix proteins and milk proteins. However, the kinetics of milk proteolysis during inflammation and the underlying mechanisms are poorly defined. The enzymes involved in bovine mammary tissue destruction were investigated in this study using an endotoxin-induced mastitis model. Using zymography techniques, the proteolytic activity of milk and mammary tissue during mastitis was examined. Mastitic milk produced 6 caseolysis bands, 4 of which differed from the ones produced by plasmin. Peak proteolytic activity, bovine serum albumin contents, and mammary tissue damage occurred between 6 and 12 h postchallenge. Mastitic milk proteases hydrolyzed casein, gelatin, collagen, hemoglobin, mammary gland membrane proteins, and lactoferrin. These results confirm that mastitic milk proteases have a broad spectrum of activity. The hydrolytic activity of mastitic milk was partially inhibited by aprotinin, EDTA, 1,10-phenanthroline, leupeptin, and pefabloc. When cocultured with normal mammary tissue, mastitic milk, but not normal milk, caused mammary tissue degradation. In situ zymography of mammary gland showed increased proteolytic activity in mastitic tissue compared with normal tissue. The similarity of zymograms of mastitic milk, blood PMN, milk somatic cells, and PMN strongly suggests that proteases in mastitic milk mainly originate from milk PMN. These results suggest that proteases released by PMN are actively involved in udder tissue damage during mastitis.

Contamination dose from photoneutron processes in bodily tissues during therapeutic radiation delivery.

Dose to the total body from induced radiation resulting from primary exposure to radiotherapeutic beams is not detailed in routine treatment planning though this information is potentially important for better estimates of health risks including secondary cancers. This information can also allow better management of patient treatment logistics, suggesting better timing, sequencing, and conduct of treatment. Monte Carlo simulations capable of taking into account all interactions contributing to the dose to the total body, including neutron scattering and induced radioactivity, provide the most versatile and accurate tool for investigating these effects. MCNPX code version 2.2.6 with full IAEA library of photoneutron cross sections is particularly suited to trace not only photoneutrons but also protons and heavy ion particles that result from photoneutron interactions. Specifically, the MCNPX code is applied here to the problem of dose calculations in traditional (non-IMRT) photon beam therapy. Points of calculation are located in the head, where the primary irradiation has been directed, but also in the superior portion of the torso of the ORNL Mathematical Human Phantom. We calculated dose contributions from neutrons, protons, deutrons, tritons and He-3 that are produced at the time of photoneutron interactions in the body and that would not have been accounted for by conventional radiation oncology dosimetry.

150-250 meV electron beams in radiation therapy.

High-energy electron beams in the range 150-250 MeV are studied to evaluate the feasibility for radiotherapy. Monte Carlo simulation results from the PENELOPE code are presented and used to determine lateral spread and penetration of these beams. It is shown that the penumbra is comparable to photon beams at depths less than 10 cm and the practical range (Rp) of these beams is greater than 40 cm. The depth dose distribution of electron beams compares favourably with photon beams. Effects caused by nuclear reactions are evaluated, including increased dose due to neutron production and induced radioactivity resulting in an increased relative biological effectiveness (RBE) factor of < 1.03.

The clinical application of dynamic shielding and imaging in moving table total body irradiation.

The moving table technique for total body irradiation (MTT TBI) has some advantages in regard to dose homogeneity, patient positioning and comfort. However, divergence of the radiation field coupled with patient motion necessitates corresponding motion of the shielding blocks and verification film so that penumbra is minimized. MTT TBI system is presented, together with dose calculations, incorporating moving trays for shields and film to ensure dose delivery with minimal penumbra of the blocked field.

Nitric oxide production during endotoxin-induced mastitis in the cow.

Nitric oxide production was measured during endotoxin-induced mastitis. One hour after morning milking, the right hind quarters of 15 cows were infused with saline containing Escherichia coli endotoxin. Left hind control quarters were infused with saline only. At varying intervals before and after infusion, diagnostic markers of mastitis were recorded and nitric oxide production was evaluated by measuring nitrite plus nitrate levels in milk. In endotoxin-infused quarters, a significant increase in nitrite plus nitrate concentrations was observed 3 h postinfusion; concentrations decreased to preinfusion levels within 48 h. This change indicates that significant amounts of nitric oxide are released during endotoxin-induced mastitis. At 3 different time points, somatic cells were harvested from milk samples, plated, and maintained in culture for 24 h. The concentration of nitrite plus nitrate in medium from cells harvested 12 h postinfusion was increased, suggesting that nitric oxide is released, at least in part, by milk somatic cells. In a second set of experiments, we evaluated nitric oxide production when animals were infused with endotoxin and aminoguanidine, a specific inhibitor of the inducible form of nitric oxide synthase. In cows treated with aminoguanidine, the increase in nitrite plus nitrate observed after endotoxin infusion was prevented. These results suggest that nitric oxide production during endotoxin-induced mastitis resulted from the activity of the inducible form of nitric oxide synthase. They also support a possible involvement for nitric oxide in the inflammatory reaction observed during mastitis.

Dynamic cardiomyoplasty for hemodynamic support during acute pulmonary hypertension. An experimental study.

The efficacy of dynamic cardiomyoplasty for hemodynamic support during acute pulmonary hypertension was studied. Five dogs underwent a right latissimus dorsi cardiomyoplasty. Each dog was later studied in a short-term experiment. A graded acute pulmonary hypertension was induced by infusion of glass microspheres into the pulmonary artery. This resulted in decrease in pulmonary artery flow, systemic pressure, and systemic flow. The cardiomyoplasty was then stimulated with a new R wave synchronous rate-responsive pulse-train stimulator (Prometheus system). This pacemaker delivers a pulse train with the duration of stimulation determined as a proportion of the RR interval. At an optimal level of hemodynamic impairment, the dynamic cardiomyoplasty was able to immediately improve pulmonary artery flow 26.4% +/- 5.84% (standard error of the mean) (p less than 0.005, paired t test), mean systemic arterial pressure 11.6% +/- 3.7% (p less than 0.05), and thoracic aortic flow 15.7% +/- 6.3% (p less than 0.05). The degree of improvement in hemodynamic variables could be correlated with the magnitude of hemodynamic impairment present (e.g., r = 0.78; p less than 0.005 for pulmonary blood flow). We conclude that a significant beneficial effect of dynamic cardiomyoplasty on hemodynamics in short-term canine pulmonary hypertension is demonstrated in this study. Thus cardiomyoplasty may be useful in patients with right heart failure associated with increased pulmonary vascular resistance.

Cell transplantation for myocardial repair: an experimental approach.

Myocardium lacks the ability to regenerate following injury. This is in contrast to skeletal muscle (SKM), in which capacity for tissue repair is attributed to the presence of satellite cells. It was hypothesized that SKM satellite cells multiplied in vitro could be used to repair injured heart muscle. Fourteen dogs underwent explantation of the anterior tibialis muscle. Satellite cells were multiplied in vitro and their nuclei were labeled with tritiated thymidine 24 h prior to implantation. The same dogs were then subjected successfully to a myocardial injury by the application of a cryoprobe. The cells were suspended in serum-free growth medium and autotransplanted within the damaged muscle. Medium without cells was injected into an adjacent site to serve as a control. Endpoints comprised histology using standard stains as well as Masson trichrome (specific for connective tissue), and radioautography. In five dogs, satellite cell isolation, culture, and implantation were technically satisfactory. In three implanted dogs, specimens were taken within 6-8 wk. There were persistence of the implantation channels in the experimental sites when compared to the controls. Macroscopically, muscle tissue completely surrounded by scar tissue could be seen. Masson trichrome staining showed homogeneous scar in the control site, but not in the test site where a patch of muscle fibres containing intercalated discs (characteristic of myocardial tissue) was observed. In two other dogs, specimens were taken at 14 wk postimplantation. Muscle tissue could not be found. These preliminary results could be consistent with the hypothesis that SKM satellite cells can form neo-myocardium within an appropriate environment. Our specimens failed to demonstrate the presence of myocyte nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Hybrid biomechanical assist for acute biventricular failure.

It is now clear dynamic cardiomyoplasty alone will not be able to support patients in severe cardiogenic shock. On the other hand, implantable univentricular electromechanically driven devices for permanent circulatory support are undergoing early clinical trials. Because of the potential for existing or subsequent biventricular failure and to avoid the need to implant two space-occupying mechanical devices, hybrid biomechanical assist devices could have certain advantages. To evaluate the feasibility of supporting profound biventricular failure, utilizing the combination of dynamic cardiomyoplasty and mechanical ventricular assistance, six dogs underwent simultaneous right latissimus dorsi cardiomyoplasty and left heart bypass. Microspheres were embolized into the pulmonary artery resulting in pulmonary hypertension and acutely impairing the right ventricle. The left ventricle was unloaded via a centrifugal Biomedicus pump. To create severe biventricular failure, the aorta was cross-clamped and potassium cardioplegia was infused into the aortic root to achieve a flaccid diastolic arrest of the heart. Infusion of microspheres into the pulmonary artery resulted in a dose-dependent increase in pulmonary artery pressure. Stimulation of the cardiomyoplasty under these conditions showed a 25.9 +/- 7.9% (S.E.M.) (p less than 0.05, paired t-test) increase in mean pulmonary artery flow. There was a corresponding increase of 6.75 +/- 10.6% in the centrifugal pump flow. Following diastolic arrest, the mean pulmonary artery and centrifugal pump flows increased 90.8 +/- 11.5% (p less than 0.001) and 16.4 +/- 12.1%, respectively. These preliminary results suggest this approach could be a useful alternative to patients who require long-term biventricular support.

The remodelling of skeletal muscle for indefatigable hemodynamic work.

Skeletal muscle possesses inherent plasticity of gene expression. Low frequency pulse-train stimulation can remodel the biochemical machinery that confers physiological expression and fatigue resistance approaching that of the myocardium. This fatigue-resistant muscle can generate sufficient force to meet the power requirements for useful cardiac work. This ultimate goal is currently being pursued in models of cardiomyoplasty and muscle-powered cardiac assist devices. In this article, we review the three major subcellular systems subserving canine skeletal muscle transformation and compare them to those of cardiac muscle. The magnitude of the problem of clinical heart failure and the feasibility of fatigue-resistant skeletal muscle joining the therapeutic armamentarium are addressed. The adaptation and transformation of fast-twitch skeletal muscle in response to chronic electrical stimulation augers therapeutic potential as an endogenous, readily available power source for myocardial assistance. The basis mechanisms of skeletal muscle fatigue require elucidation to gain a complete and thorough understanding of how to manipulate this property to provide continuous hemodynamic work.

Pulmonary artery counterpulsation with a skeletal muscle power source.

We evaluated the feasibility of using skeletal muscle (SM) to provide pulmonary artery (PA) counterpulsation in an acute pulmonary hypertension (PHT) model. PA counterpulsation was achieved in six dogs with a dual chambered pump powered by the latissimus dorsi muscle. A rate-responsive stimulator was used to make the muscle contract in counterpulsation. Graded PHT was induced by infusing 150 microns glass beads into the PA, while RV and PA pressures were monitored. With PA pressures ranging from 19/10 to 115/62 mmHg, effective counterpulsation was observed. The degree of counterpulsation was influenced by the extent of PHT induced, with the amount of RV tension-time index (TTI) unloading correlated with the level of PA systole (r = 0.92). Therefore, results were divided into two groups (Group 1: PA systole less than or equal to 40 mmHg, and Group 2: PA systole greater than 40 mmHg). In Group 1, RV TTI decreased from 11.29 +/- 0.76 to 9.99 +/- 0.72 mmHg.sec, PA diastole increased from 20 +/- 2.3 to 31 +/- 3.0 mmHg, and PA mean increased from 24 +/- 2.2 to 2.9 +/- 2.2 mmHg (all p less than 0.05). In Group 2, RV TT1 decreased from 15.12 +/- 1.83 to 10.99 +/- 0.90 mmHg.sec, PA diastole increased from 41 +/- 3.5 to 64 +/- 6.2 mmHg, and PA mean increased from 49 +/- 4.8 to 55 +/- 5.7 mmHg (all p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Biochemical transformation of canine skeletal muscle for use in cardiac-assist devices.

Skeletal muscle has an inherent biochemical phenotypic plasticity that provides the possibility for it to be remodeled into a "heart-like" muscle for use in cardiac-assist devices. The purpose of this study was to chronically stimulate skeletal muscle electrically to transform the biochemical capacities of the three major subcellular systems (i.e., metabolic, calcium regulating, and contractile) to resemble those of heart muscle. The latissimus dorsi muscle (LDM) of mongrel dogs weighing 22-27 kg was stimulated via the thoracodorsal nerve at 2 Hz for 6-8 wk. This stimulation protocol reduced the phosphorylase (glycogenolytic) and phosphofructokinase (glycolytic) activities by 70%. The aerobic (citrate synthase activity) and fatty acid oxidative (3-hydroxyacyl-CoA dehydrogenase activity) capacities were not significantly increased by chronic stimulation and remained at about one-fourth those in the canine heart. The calcium-dependent sarcoplasmic reticulum adenosinetriphosphatase (ATPase) activity in the microsomal fraction, which was sixfold greater in the nonstimulated LDM than in the heart, was reduced by electrical stimulation to a level similar to that of the dog heart. The contractile capacity was evaluated by determining the percentage of types I and II fibers, the myofibrillar ATPase activity, and the proportion of myosin isoforms. The transformed muscle was comprised of 93 +/- 2% type I fibers, a myofibrillar ATPase activity similar to that in heart with primarily a slow-twitch muscle myosin isoform. In conclusion, electrical stimulation of canine LDM at 2 Hz for 6-8 wk resulted in two of the three biochemical systems, which confer physiological expression and fatigue resistance to muscle being transformed to resemble those of the myocardium.

Implantable rate-responsive counterpulsation assist system.

To apply the potential energy source available from skeletal muscle in cardiac assistance, we developed an implantable counterpulsation assist system. This study reports the results using this implantable counterpulsation assist system in an acute in vivo animal model. Twelve dogs had a dual-chambered, extraaortic counter-pulsation pump anastomosed in parallel to the thoracic aorta. The left latissimus dorsi muscle was used to power the pump. A newly developed implantable stimulator was used to make the muscle contract in synchrony with the diastolic phase. The unique feature of this stimulator is its ability to adjust timing of muscle contraction according to changing heart rates. The stimulator is also able to detect arrhythmias, and as a safety measure, shuts down until a normal rhythm is resumed. During counterpulsation assist with the implantable counterpulsation assist system, diastolic pressure increased an average of 34 mm Hg from baseline, equivalent to a 69% augmentation. Systolic peak pressure decreased an average of 10 mm Hg, equivalent to an 11% unloading. With induced heart rate changes, the implantable counterpulsation assist system readjusted its timing, maintaining optimal counterpulsation without systolic interference. Induced ventricular tachycardia resulted in immediate shutdown of the stimulator until resumption of a normal rhythm. The feasibility of using an intraaortic balloon pump console as back-up was also demonstrated. Excellent counterpulsation was obtained with either muscle power or balloon pump console. We conclude that the implantable counterpulsation assist system can provide effective counterpulsation assist and has the potential for continuous cardiac support.