Brain structural change associated with Cognitive Behavioral Therapy in maltreated children.

BACKGROUND: Severely maltreatment child is a harmful social factor that can disrupt normal neurodevelopment. Two commonly reported effects of maltreatment are post-traumatic stress disorder (PTSD) symptoms and brain structural and functional alteration. While Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) is effectively used to reduce PTSD symptoms in maltreated children, yet, its impact on brain structural alterations has not been fully explored. This study investigated whether TF-CBT can attenuate alterations in brain structures associated with PTSD in middle childhood. METHODS: The study evaluated the longitudinal effects of Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) on post-traumatic stress disorder (PTSD) symptoms and gray matter volume (GMV) in two groups of children under 12 years old: maltreated children (MC) and healthy non- maltreatmentd children (HC). Structural magnetic resonance images T1 were obtained before and after TF-CBT in the MC group, while the HC group was scanned twice within the same time interval. Voxel-based morphometry (VBM) was used to analyze GMV changes over time. RESULTS: After TF-CBT, maltreated children showed significantly reduced PTSD symptoms. Furthermore, a significant group-by-time interaction effect was observed in certain areas of the Left Temporal, Left Occipital, and bilateral Frontal Cortex, the Basal Ganglia and Cerebellum. These interaction effects were driven by a GMV decrease in the MC group compared to the HC group. GMV changes can be predicted with clinical improvement in the left Middle Temporal gyrus, left Precuneus, and Cerebellum. CONCLUSIONS: Our results suggest that TF-CBT intervention in very young maltreated children may have an effect on gray matter. This evidence demonstrates the importance of timely intervention when neuroplasticity mechanisms may be activated.

Can psychopathy be prevented? Clinical, neuroimaging, and genetic data: an exploratory study.

The aim of the study was to explore the relationship among brain functional activations elicited by an emotional paradigm, clinical scores (PTSD, anxiety, and depression), psychopathic traits, and genetic characteristics (5-HTTLPR) in a group of severely maltreated children compared to a healthy control group before and after the implementation of a Trauma Focused-Cognitive Behavioral Therapy. The final sample consisted of an experimental group of 14 maltreated children (mean age = 8.77 years old, S.D. = 1.83) recruited from a non-governmental shelter in Mexico City for children who had experienced child abuse and a control group of 10 children from the general population (mean age = 9.57 years old, S.D. = 1.91). Both groups were matched according to age and gender and were assessed before and after the implementation of the aforementioned therapy by means of clinical scales and an emotional paradigm that elicited brain activations which were recorded through functional magnetic resonance imaging. Genotyping of the 5-HTTLPR polymorphism was made at first assessment. A region of interest analysis showed amygdala hyperactivation during exposure to fear and anger stimuli in the maltreated children before treatment. Following therapy, a decrease in brain activity as well as a decrease in clinical symptoms were also observed. 5-HTTLPR polymorphism did not show any effect on the severity of clinical symptoms in maltreated children. Trauma-Focused Behavioral Therapy may help reorganize the brain's processing of emotional stimuli. These observations reveal the importance of an early intervention when the mechanisms of neuroplasticity may be still recruited.

Longitudinal magnetic resonance evaluation of the schizophrenia model of neonatal lesion in the ventral hippocampus.

OBJECTIVE: To evaluate the progression by means of nuclear magnetic resonance of the lesion in the schizophrenia model of lesion of the ventral hippocampal nucleus (LVNH). METHOD: Magnetic resonance imaging (MRI) were performed in male Wistar rats, from 8 days postnatal to 139 days, in animals with LNHV and without lesion (sham). The MRI were carried out on a Variant 7 T equipment. The data were analyzed with the Amira software, for a voxel-based morphometric analysis. RESULTS: We observed the presence of hypersignals with a significant enhancement in the structures analyzed in the group with LVNH, and greater volume in the lateral ventricles, presenting a larger size of the lesion on day PD96 and significantly reducing on day PD139. CONCLUSIONS: We found a cell rearrangement during the progression of the lesion, which could be the effect of the activation of immune cells.

OBJETIVO: Evaluar mediante resonancia magnética (RM) la progresión de la lesión en el modelo de esquizofrenia de lesión del núcleo del hipocampo ventral (LNHV). MÉTODO: Se realizaron RM en ratas Wistar macho, desde los 8 días posnatales hasta los 139 días, en animales con LNHV y sin lesión (sham). Las RM se realizaron con un equipo Variant de 7 T. Los datos se analizaron con el software Amira para un análisis de morfometría basada en vóxels. RESULTADOS: Observamos hiperseñales con un realce significativo en las estructuras analizadas en el grupo con LNHV, y mayor volumen en los ventrículos laterales, presentando un mayor tamaño de la lesión el día PD96 y significativamente reducido en el día PD139. CONCLUSIONES: Encontramos un reacomodo celular durante la progresión de la lesión, lo cual podría ser efecto de la activación de las células inmunitarias.

Neuroanatomical features and its usefulness in classification of patients with PANDAS.

OBJECTIVE: An obsessive-compulsive disorder (OCD) subtype has been associated with streptococcal infections and is called pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS). The neuroanatomical characterization of subjects with this disorder is crucial for the better understanding of its pathophysiology; also, evaluation of these features as classifiers between patients and controls is relevant to determine potential biomarkers and useful in clinical diagnosis. This was the first multivariate pattern analysis (MVPA) study on an early-onset OCD subtype. METHODS: Fourteen pediatric patients with PANDAS were paired with 14 healthy subjects and were scanned to obtain structural magnetic resonance images (MRI). We identified neuroanatomical differences between subjects with PANDAS and healthy controls using voxel-based morphometry, diffusion tensor imaging (DTI), and surface analysis. We investigated the usefulness of these neuroanatomical differences to classify patients with PANDAS using MVPA. RESULTS: The pattern for the gray and white matter was significantly different between subjects with PANDAS and controls. Alterations emerged in the cortex, subcortex, and cerebellum. There were no significant group differences in DTI measures (fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) or cortical features (thickness, sulci, volume, curvature, and gyrification). The overall accuracy of 75% was achieved using the gray matter features to classify patients with PANDAS and healthy controls. CONCLUSION: The results of this integrative study allow a better understanding of the neural substrates in this OCD subtype, suggesting that the anatomical gray matter characteristics could have an immune origin that might be helpful in patient classification.

A Pilot Study of Facial Nerve Stimulation on Cerebral Artery Vasospasm in Subarachnoid Hemorrhage Patients.

BACKGROUND: The objective of this pilot study was to assess the safety and efficacy of VitalFlow stimulation in aneurysmal subarachnoid hemorrhage (aSAH) patients with vasospasm for the purpose of guiding the design of larger, controlled studies in vasospasm patients, a largely untreated condition [1]. METHODS: Six patients with angiographic vasospasm developing post-aSAH were treated with VitalFlow stimulation. Digital subtraction angiograms were obtained at the time of diagnosis (baseline) and then 30 minutes post-stimulation. A single 2-minute period of stimulation was delivered to the patients using parameters previously shown to be safe, tolerable, and effective at increasing cerebral blood flow (CBF) in healthy volunteers. RESULTS: VitalFlow stimulation improved tissue perfusion as assessed by parenchymography and reversed the constriction of vasospastic arteries. Two patients had only partial improvement and so were treated with intraarterial nimodipine after VitalFlow stimulation, whereas four patients had complete resolution of the vasospasm after VitalFlow stimulation per the treating neuroendovascular surgeon's evaluation. Clinical examination showed improvement in Hunt and Hess Scale scores assessed post-stimulation. CONCLUSIONS: Non-invasive magnetic stimulation of the facial nerve with the VitalFlow stimulator appears to be a safe and effective means to reverse angiographic vasospasm in aSAH patients. Clinical Impact: This study provides Class IV evidence that non-invasive magnetic stimulation of the facial nerves reduce angiographic vasospasm in aSAH patients.

Facial nerve stimulation in normal pigs and healthy human volunteers: transitional development of a medical device for the emergency treatment of ischemic stroke.

BACKGROUND: Magnetic stimulation of the facial nerve has been tested in preclinical studies as a new, non-invasive emergency treatment of ischemic stroke that acts by increasing cerebral blood flow (CBF). The objective of the studies reported herein was to identify minimal stimulation parameters that increase CBF in large animals and then test those stimulation parameters in healthy volunteers for safety, tolerability, and effectiveness at increasing CBF. This translational research is necessary preparation for clinical studies in ischemic stroke patients. METHODS: Initial experiments in anesthetized Yorkshire pigs were undertaken in order to identify the lowest stimulus power and duration that increase CBF. A full 3 × 3 factorial design was used to evaluate magnetic stimulation of the facial nerve at various stimulation powers (1.3, 1.6, and 1.9 Tesla field strength at coil surface) and for various durations (2, 3.5, and 5 min). CBF was measured with contrast MRI perfusion imaging and the internal carotid arteries were assessed with MR angiography. Magnetic facial nerve stimulation with parameters identified in the pig study was then applied to 35 healthy volunteers. Safety was assessed with adverse event reports and by medical examination. Tolerability was defined as each volunteer's ability to withstand at least 2 min of stimulation. Volunteers could determine the maximum power of stimulation they received during a ramp-up period. RESULTS: In pigs, unilateral facial nerve stimulation increased CBF by as much as 77% over pre-stimulation baseline when administered across a range of 1.3-1.9 Tesla power and for 2- to 5-min duration. No clear dose-response relationship could be observed across this range, but lower powers and durations than these were markedly less effective. The effect of a single stimulation lasted 90 min. A second stimulation delivered 100 min after the first stimulation sustained the increased CBF without evidence of tachyphylaxis. In human, bilateral facial nerve stimulation caused only non-serious adverse events that were limited to the 2-min stimulation period. Tolerability was greatly improved by gentle encouragement from the study staff, which enabled most volunteers to tolerate 1.6-1.8 Tesla of stimulation power. CBF measures taken approximately 10 min after stimulation demonstrated on average a 32 ± 6% increase in CBF, with ≥ 25% increases in CBF occurring in 10 of the 31 volunteers who had adequate CBF measurements. CONCLUSIONS: The minimal effective stimulation parameters defined by increased CBF, as identified in the pig study, translated into safe, tolerable, and effective stimulation of healthy volunteers. These results support the future development and evaluation of non-invasive facial nerve stimulation for the emergency treatment of ischemic stroke. Trial Registration retrospectively registered with clinicaltrials.gov NRV_P1_01_15 on June 6, 2017.

Magnetic facial nerve stimulation in animal models of active seizure.

PURPOSE: As part of our efforts to develop a non-invasive facial nerve stimulator as an emergency treatment for ischemic stroke, we considered possible safety consequences if the technology was misapplied to stroke mimics, e.g., seizure. We hypothesized that magnetic facial nerve stimulation would worsen epileptiform activity in two animal models of active seizures. The rat intraperitoneal kainate model and pig intracortical penicillin model were employed. Magnetic facial nerve stimulation was delivered unilaterally at a variety of stimulation parameters, and the effect on ictal epileptiform activity measured by electroencephalography was determined according to an established categorical scale. PRINCIPAL RESULTS: In 6 rats and 3 pigs evaluated with 83 stimulation trials, only a single stimulation trial was associated with worsening epileptiform activity according to a standard categorization scheme. Surprisingly, a reduction in the severity of the epileptiform activity was observed in 20 of 50 stimulation trials using patterned stimulation (3 pulses at 30Hz repeated at 0.5-10Hz) versus 2 of 33 stimulation trials using simple monotonic patterns (P<0.005, chi-squared test). The reduction of epileptiform activity after stimulation lasted a few minutes and was reproducible. Major Conclusions Epileptiform activity measured by electroencephalography was not reliably worsened by repetitive facial nerve stimulation with pulsed magnetic energy, even when significant brain exposure to the magnetic field occurred as in the rat model. To the contrary, a temporary reduction in epileptiform activity was often, but not invariably, observed with certain stimulation parameters.

Facial nerve stimulation as a future treatment for ischemic stroke.

Stimulation of the autonomic parasympathetic fibers of the facial nerve system (hereafter simply "facial nerve") rapidly dilates the cerebral arteries and increases cerebral blood flow whether that stimulation is delivered at the facial nerve trunk or at distal points such as the sphenopalatine ganglion. Facial nerve stimulation thus could be used as an emergency treatment of conditions of brain ischemia such as ischemic stroke. A rich history of scientific research has examined this property of the facial nerve, and various means of activating the facial nerve can be employed including noninvasive means. Herein, we review the anatomical and physiological research behind facial nerve stimulation and the facial nerve stimulation devices that are in development for the treatment of ischemic stroke.

Effect of Feeding and Suction on Gastric Impedance Spectroscopy Measurements.

A specific device and system has been developed and tested for clinical monitoring of gastric mucosal reactance in the critically ill as an early warning of splanchnic hypoperfusion associated with shock and sepsis. This device has been proven effective in clinical trials and is expected to become commercially available next year. The system uses a combination nasogastric tube and impedance spectroscopy probe as a single catheter. Because this device has a double function, the question is: Does enteral feeding or suction affect the gastric reactance measurements? This study was designed to evaluate the effect of feeding and suction on the measurement of gastric impedance spectroscopy in healthy volunteers. Impedance spectra were obtained from the gastric wall epithelia of 18 subjects. The spectra were measured for each of the following conditions: postinsertion of gastric probe, during active suction, postactive suction, and during enteral feeding (236 ml of nutritional supplement). Impedance spectra were reproducible in all volunteers under all conditions tested. There was a slight increase in impedance parameters after suction, and a decrease in impedance after feeding; however, these observed differences were insignificant compared to patient-to-patient variability, and truly negligible compared with previously observed changes associated with splanchnic ischemia in critically ill patients. Our results demonstrate that suction or feeding when using the impedance spectro-metry probe/nasogastric tube does not significantly interfere with gastric impedance spectrometer measurements.

Gastrointestinal ischemia monitoring through impedance spectroscopy as a tool for the management of the critically ill.

Impedance spectroscopy (IS) has been proposed as a tool for monitoring mucosal tissue ischemia and damage in the gut of critically ill patients resulting from shock and hypoperfusion. A specific device and system have been developed and tested for this specific application over the past 12 years by our research group. This paper reviews previously published studies as well as unpublished experimental results, and puts the whole in context and perspective to help understand this technology. Results presented include summaries of gastric reactance measurement understanding, in vivo measurements in animal models, clinical significance of the measurement, and future perspectives of clinical use of this technology. All of the experimental work done to date has been designed to determine the evolving device prototypes' performance and limitations from an instrumentation point of view. Although there are still questions to be answered with regard to the IS measurement, we conclude that we have reached enough confidence in the measurement and the device's performance and safety to begin clinically oriented research to learn how this technology may be useful in the diagnosis and management of different populations of the critically ill.

Modeling the effects of biomass accumulation on the performance of a biotrickling filter packed with PUF support for the alkaline biotreatment of dimethyl disulfide vapors in air.

Excess biomass buildup in biotrickling filters leads to low performance. The effect of biomass accumulation in a biotrickling filter (BTF) packed with polyurethane foam (PUF) was assessed in terms of hydrodynamics and void space availability in a system treating dimethyl disulfide (DMDS) vapors with an alkaliphilic consortium. A sample of colonized support from a BTF having been operating for over a year was analyzed, and it was found that the BTF void bed fraction was reduced to almost half of that calculated initially without biomass. Liquid flow through the examined BTF yielded dispersion coefficient values of 0.30 and 0.72 m(2) h(-1), for clean or colonized PUF, respectively. 3D images of attached biomass obtained with magnetic resonance imaging allowed to calculate the superficial area and the biofilm volume percentage and depth as 650 m(2) m(-3), 35%, and 0.6 mm respectively. A simplified geometric approximation of the complex PUF structure was proposed using an orthogonal 3D mesh that predicted 600 m(2) m(-3) for the same biomass content. With this simplified model, it is suggested that the optimum biomass content would be around 20% of bed volume. The activity of the microorganisms was evaluated by respirometry and the kinetics represented with a Haldane equation type. Experimentally determined parameters were used in a mathematical model to simulate the DMDS elimination capacity (EC), and better description was found when the removal experimental data were matched with a model including liquid axial dispersion in contrast to an ideal plug flow model.

Effects of noninvasive facial nerve stimulation in the dog middle cerebral artery occlusion model of ischemic stroke.

BACKGROUND AND PURPOSE: Facial nerve stimulation has been proposed as a new treatment of ischemic stroke because autonomic components of the nerve dilate cerebral arteries and increase cerebral blood flow when activated. A noninvasive facial nerve stimulator device based on pulsed magnetic stimulation was tested in a dog middle cerebral artery occlusion model. METHODS: We used an ischemic stroke dog model involving injection of autologous blood clot into the internal carotid artery that reliably embolizes to the middle cerebral artery. Thirty minutes after middle cerebral artery occlusion, the geniculate ganglion region of the facial nerve was stimulated for 5 minutes. Brain perfusion was measured using gadolinium-enhanced contrast MRI, and ATP and total phosphate levels were measured using 31P spectroscopy. Separately, a dog model of brain hemorrhage involving puncture of the intracranial internal carotid artery served as an initial examination of facial nerve stimulation safety. RESULTS: Facial nerve stimulation caused a significant improvement in perfusion in the hemisphere affected by ischemic stroke and a reduction in ischemic core volume in comparison to sham stimulation control. The ATP/total phosphate ratio showed a large decrease poststroke in the control group versus a normal level in the stimulation group. The same stimulation administered to dogs with brain hemorrhage did not cause hematoma enlargement. CONCLUSIONS: These results support the development and evaluation of a noninvasive facial nerve stimulator device as a treatment of ischemic stroke.

Restored brain perfusion after non-invasive stimulation of the facial nerve in a canine stroke model.

Ischemic stroke affects over 15 million patients per year and is a leading cause of death worldwide. Currently available treatments are indicated for less than 5% of patients. Stimulation of the facial nerve has been proposed as a possible new treatment of ischemic stroke that acts by increasing blood flow to the brain and thereby restoring perfusion through collateral vessels. The objective of this project was to evaluate the changes in brain perfusion, following facial nerve stimulation in an animal stroke model using MRI measures of cerebral blood flow. Autologous blood clot was injected in the internal carotid artery to occlude the middle cerebral artery (MCA) in 17 mongrel dogs. Occlusion in the MCA was verified using fluoroscopy and MRI angiography. Following baseline and post-stroke MRI images, the facial nerve at the site of the geniculate ganglion was located and then stimulated using a transcranial magnetic stimulator and a neuro-navigation system in 11 animals. Six animals followed the same procedure but were not stimulated (control group). The perfusion index of both sides of the brain was measured using gadolinium contrast MRI before and after stroke, and at 30 minute intervals after stimulation. Results show a significant and persistent increase in perfusion in the stroke side of the brain relative to the non-stroke / contralateral side, after stimulation, when compared to the control group. These results strongly support the future development and evaluation of a non-invasive facial nerve stimulator device for the early treatment of ischemic stroke.

Effect of pulsed magnetic stimulation of the facial nerve on cerebral blood flow.

In these experiments we define an effective means of pulsed magnetic stimulation of the facial nerve for the purpose of increasing cerebral blood flow (CBF). In normal anesthetized dog and sheep, a focal magnetic field was directed toward the facial nerve within the temporal bone by placing a 6.5 cm figure-8 stimulation coil over the ear. In an initial set of experiments, CBF was measured by laser Doppler flowmetry and the cerebral vasculature was visualized by angiography. The effect of facial nerve stimulation was found to be dependent on stimulation power, frequency, and the precise positioning of the stimulation coil. Furthermore, an increase in CBF was not observed after direct electrical stimulation in the middle ear space, indicating that non-specific stimulation of the tympanic plexus, an intervening neural structure with vasoactive effects, was not responsible for the increase in CBF after pulsed magnetic stimulation. Subsequent experiments using perfusion MRI demonstrated reproducible increases in CBF throughout the forebrain that manifested bilaterally, albeit with an ipsilateral predominance. These experiments support the development of a non-invasive pulsed magnetic facial nerve stimulator that will increase CBF as a treatment of ischemic stroke.

Incidence of gastric mucosal injury as measured by reactance in critically ill patients.

Gastric reactance has been proposed as a measure of mucosal ischemic injury in the critically ill. The purpose of this study was to evaluate the incidence of gastric mucosal injury as measured by gastric reactance in different subgroups of critical patients. We studied 100 adult patients admitted to 7 different hospital intensive care units, requiring a nasogastric tube. Gastric impedance measurements were continuously obtained from each patient for 24 hours. Patients were managed based on conventional protocols by hospital staff, blinded to the changes in gastric impedance parameters. The low-frequency central reactance (X L) reflects tissue edema caused by prolonged ischemia. The previously reported threshold of X L ≥ 13 - jΩ was used to classify injured mucosa; 80% of all patients had mean X L above this threshold. No significant differences were found in the incidence of mucosal ischemia between medical versus surgical, hemodynamic versus respiratory or neurological patients. Significant lower urine output was found in patients with X L above threshold (P < .01); also, there was a significant effect of fluid balance in those patients (P < .05). More complicated patients had higher average reactance. This study shows that gastric ischemia as estimated by gastric reactance has a very high incidence in the critically ill, independently of the reason for admission. High reactance is related with higher morbidity in agreement with other reports using different methods of assessing splanchnic hypoperfusion in this patient population.

In vivo performance evaluation of the innovamedica pneumatic ventricular assist device.

We evaluated the short- and mid-term in vivo performance of the Innovamedica ventricular assist device (VAD), a new, low-cost, paracorporeal, pneumatically actuated, pulsatile blood pump. We implanted the VAD in six healthy sheep by inserting the stainless-steel inflow cannula into the left ventricular apex and suturing the outflow graft to the descending thoracic aorta. The anesthetized animals were supported for 6 hours, and pump performance, hemodynamic parameters, and hemolysis were monitored. The pump maintained a blood flow of 4.4 ± 0.8 L/min and an arterial blood pressure of 76 ± 15 mm Hg. At 6 hours, the plasma free hemoglobin concentration was 5.11 ± 0.6 mg/dl (baseline value, 4.52 ± 0.7 mg/dl). The VAD was easy to implant and deair and performed well during the 6 hour period. After successful short-term results, we similarly implanted the VAD in two healthy sheep for 30 days. The animals reached the scheduled end point without device-related problems. Postmortem examination of the explanted organs revealed small infarcted areas in the kidneys of one animal, but renal function was unaffected; the animal also had two thrombi (3 and 7 mm) on the outlet valve. This device may offer a simple, economical alternative to currently available VADs.

In vivo performance evaluation of the Innovamedica pneumatic ventricular assist device.

We evaluated the in vivo performance of the Innovamedica pneumatic ventricular assist device (VAD), a new prototype of a simple, low-cost device for hospital circulatory support programs. We implanted the Innovamedica VAD in 6 sheep (weighing 55 to 91 kg). The inflow cannula was placed in the left ventricle, and the outflow cannula was anastomosed to the descending thoracic aorta. After heparinization (3mg/kg), we initiated the pump and monitored its hemodynamic performance for 6 hours. In a subsequent study we implanted the device for left ventricular support in two sheep for a 30-day period. We evaluated device performance based on implantation procedure, hemodynamic performance, and hematological impact. We monitored hematological and biochemical variables, and we assessed hemolysis. In the short-term experiments, the pumps maintained a mean blood flow of 4.4 ± 0.8 L/min. During support, mean arterial blood pressure was 76 ± 15 mmHg. The overall average concentration of plasma free hemoglobin was 5.11 ± 0.6 mg/dl compared with a baseline value of 4.52 ± 0.7 mg/dl. In the 30 day trials, mean blood output was 4 l/min ± 0.2, plasma free hemoglobin was 5.9 ± 4 mg/dl for the 30 day period excluding the first 48 hours. Warfarin/Aspirin anticoagulation was used after the first 72 hours with an average INR of 2.9 for the entire test period. Post-mortem showed no blood clots or any significant tissue damage to brain, lungs or kidneys. The devices operated without any significant adverse events in all of the experiments. The Innovamedica VAD was easy to implant and de-air and was found to be effective, reliable and biocompatible.

In vivo assessment of hemocompatibility of a ventricular assist device in healthy swine.

OBJECTIVE: To assess the hemocompatible performance of a novel implantable pneumatic ventricular assist device (VAD, Innovamédica, México) in healthy swine. The aim of this pilot study was first, to determine if short-term VAD implantation elicited remarkable inflammatory response above that expected from surgical trauma; and second, to assess if heparinized or passivated VAD coatings, in combination with systemic anticoagulant or antiaggregant therapies, modified the VAD's hemocompatible performance. METHODS: Hemodynamic, physicologic, inflammatory and histological parameters were measured in 27 pigs receiving VAD support for six hours, testing combinations of heparinized or passivated VAD coatings and systemic anticoagulant/ antiaggregant therapies. Mean concentrations of interleukin -1 B (IL-1B), interleukin -6 (IL-6), C-reactive protein (CRP), or thrombin-antithrombin III (TAT) complexes (coagulation indicator) were measured from blood. ANOVA statistics were employed. RESULTS: No substantial increases in mean IL -1B, IL-6, CRP, or TAT were obtained during VAD support. Hemodynamic ans physiologic parameters were normal. We found no evidence of thromboembolisms or micro-infarctions in heart and lung samples. No major coaguli/deposits were found in VAD compartments. Overall, no remarkable differences in measurements were found using heparinized, passivated, or uncoated VAD, or with systemic anticoagulation, antiaggregant therapy, or no treatment. CONCLUSIONS: Our findings demonstrate, firstly, that during the time-period tested, the VAD elicited negligible inflammation above the effects of surgical trauma; and secondly, that little coagulation was observed upon VAD support in any of the cases tested. Contemplating further validation studies, our data indicate that the Innovamédica VAD is a highly hemocompatible system.