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Background: Continuous-flow left ventricular assist devices (LVADs) produces supraphysiologic shear stress that causes von Willebrand factor (VWF) degradation and a bleeding diathesis. Reduction of revolutions per minute (RPM) with axial-flow LVADs does not decrease shear stress enough to reduce VWF degradation and bleeding. However, it is unknown if RPM reduction with centrifugal flow LVADs may minimize VWF degradation. We tested the hypothesis that RPM reduction preserves VWF multimers in the centrifugal-flow EVAHEART left ventricular assist system (LVAS), which is designed to minimize shear stress and blood trauma.Methods: Whole blood samples were collected from humans (n = 28). Blood was circulated in ex vivo mock circulatory loops for 6 hours with an EVAHEART LVAS at 2300 (n = 12), 2100 (n = 8), or 1800 RPM (n = 8). Immunoblotting was used to resolve and quantify VWF multimers and degradation fragments.Results: RPM reduction from 2300 to 2100 to 1800 RPM significantly decreased EVAHEART blood flow from 5.8 ± 0.4 to 4.3 ± 0.6 to 4.1 ± 0.5 L/min (analysis of variance [ANOVA], P = .03). RPM reduction protected VWF from pathologic degradation. At lower RPMs, significantly greater levels of VWF multimers were observed (ANOVA, P = .001). Similarly, at lower RPMs, significantly fewer VWF fragments, a product of VWF degradation, were observed (ANOVA, P = .007).Conclusions: RPM reduction significantly reduced VWF degradation with the centrifugal-flow EVAHEART LVAS, an LVAD specifically designed with low shear stress. Different LVADs have unique hematologic footprints and should be managed with device-specific protocols. Adjustment of RPM to minimize blood trauma while still maintaining physiologic hemodynamics has the potential to decrease complications related to LVAD-associated von Willebrand's disease, such as gastrointestinal bleeding and hemorrhagic stroke. [ABSTRACT FROM AUTHOR]

Background Left ventricular assist device (LVAD) thrombosis is a life-threatening complication that remains a major clinical problem. Consensus diagnostic criteria do not exist. We investigated whether hematologic, echocardiographic, or pump parameters reliably change during LVAD thrombosis. Methods A retrospective analysis of 20 consecutive cases of continuous-flow LVAD thrombosis (Thoratec HeartMate II n = 16, HeartWare HVAD n = 4) was performed. Hematologic markers (lactate dehydrogenase, plasma-free hemoglobin, hemoglobin, creatinine), echocardiographic parameters (left ventricular end-systolic and end-diastolic diameter, mitral regurgitation, aortic insufficiency, inflow-cannula velocity), and pump characteristics (speed, power, estimated flow, pulsatility index) were analyzed with one-way repeated measures ANOVA with Tukey post-test or paired Student t-tests. Results Lactate dehydrogenase and plasma-free hemoglobin were significantly (p < 0.05) elevated at admission for LVAD thrombosis. Hemoglobin and creatinine were not significantly different at admission but changed significantly after admission. Left ventricular end-systolic and end-diastolic diameter, mitral regurgitation, aortic insufficiency, inflow-cannula velocity, LVAD speed, power consumption, estimated flow, and pulsatility index were not significantly different at admission for LVAD thrombosis. Conclusion Hematological markers of hemolysis, but not echocardiographic or pump parameters, reliably changed during LVAD thrombosis. Markers of hemolysis are the best early predictors of LVAD thrombosis. [ABSTRACT FROM AUTHOR]

Left ventricular assist device (LVAD) thrombosis is a life-threatening complication. Multiple case reports describe successful nonsurgical management with thrombolytics, aggressive antiplatelet therapy, or percutaneous catheter-directed thrombectomy. However, consensus management of LVAD thrombosis has not been established and guidelines are urgently needed. In order to raise awareness of nonsurgical treatment options, we review the current strategies for the clinical diagnosis, management, and prevention of LVAD thrombosis. doi: 10.1111/jocs.12238 (J Card Surg 2014;29:83-94) [ABSTRACT FROM AUTHOR]

Ventricular assist devices ( VADs) have emerged as a successful treatment option for advanced heart failure. The objective of this study was to develop a clinically relevant model of chronic ischemic cardiomyopathy to investigate functional, histological, and molecular changes during mechanical circulatory support. In calves ( n = 17, 94 ± 7 kg), 90 μm microspheres were injected percutaneously into the left coronary artery. Serial echocardiography was performed weekly to evaluate cardiac function. Sixty days after coronary microembolization, a terminal study was performed via thoracotomy to measure hemodynamics. Regional myocardial and end-organ blood flows were quantified with 15-μm fluorescent-labeled microspheres. Myocardial fibrosis, myocyte size, and myocardial apoptosis were quantified with histological stains. Eleven animals survived coronary microembolization and exhibited clinical and statistically significant echocardiographic and hemodynamic signs of severe systolic dysfunction. Statistically significant decreases in regional myocardial blood flow and increases in myocardial fibrosis, myocyte size, total myocardial apoptosis, and cardiac myocyte-specific apoptosis were observed. End-organ hypoperfusion was observed. Coronary microembolization induced stable and reproducible chronic left ventricular failure in calves. The anatomical size and physiology of the bovine heart and thorax are appropriate to study novel interventions for the clinical management of heart failure. This model is an appropriate physiological substrate in which to test VAD and adjunctive biological therapies. [ABSTRACT FROM AUTHOR]

Left ventricular assist device (LVAD) pocket infection is a serious and potentially fatal complication. Not infrequently, the device erodes externally through the thoracoabdominal wall or internally into the peritoneum. In this article, we report two cases to illustrate the presentation and challenges associated with management of LVAD-pocket infection and wound necrosis. Afterward, we review the current therapeutic strategies for LVAD erosion. doi: 10.1111/jocs.12207 (J Card Surg 2013;28:776-782) [ABSTRACT FROM AUTHOR]

Abstract: Experimental data about the heat transfer from a heated 0.25mm in diameter nickel wire to a submerged upward flow slot jet of distilled water are reported. The tests are carried on in forced convection regime, in sub-cooled and saturated boiling conditions. The influence on the heat transfer rate of different parameters is investigated, such as the jet exit velocity, the distance between the slot exit and the wire and the heat transfer regime, in particular the sub-cooling degree. The choice of the nickel is due to the opportunity to operate in a wide range of the jet exit velocity, thanks to its mechanical and thermometric characteristics. The main aim of this research was to find out the optimal conditions, in order to maximize the heat transfer coefficient enhancement, and moreover, to make a comparison between other results obtained in the 1990s by the same authors on horizontal circular cylinders, with the diameter one size order bigger than the present wire. [Copyright &y& Elsevier]

A counterpulsation device (Symphony) is being developed to provide long-term circulatory support for advanced heart failure (HF) patients. In acute animal experiments, flow waveform patterns in the aortic, carotid, and coronary arteries were compared during Symphony and intra-aortic balloon pump (IABP) support. Human data were examined for similarities. The 30-mL Symphony was compared to a 40-mL IABP in calves with cardiac dysfunction (80-100 kg, n = 8). Aortic pressures and aortic, carotid, and coronary artery flows were simultaneously recorded at baseline (devices off) and during 1:1 and 1:2 support. Forward, retrograde, and mean flows were calculated and compared for each test condition. Findings were also compared to aortic flow measurements recorded in HF patients ( n = 21) supported by 40-mL IABP. IABP caused significant retrograde flows in the aorta, coronary (IABP: −24 ± 8 mL/min, Symphony: −6 ± 2 mL/min, baseline: −2 ± 1 mL/min, P < 0.05), and carotid arteries (IABP: −30 ± 5 mL/min, Symphony: −0 ± 0 mL/min, baseline: −0 ± 0 L/min, P < 0.05) during ventricular systole compared to the Symphony. IABP support produced higher diastolic pressure and flow augmentation compared to Symphony. Due to retrograde flows during IABP support, Symphony provided higher overall coronary, carotid, and aortic flows. Similar reduction in total aortic flows due to retrograde flow was observed in HF patients during IABP support. Counterpulsation with an IABP via aortic volume displacement produces retrograde flows during rapid balloon deflation that reduces total flow. Counterpulsation with Symphony via volume removal eliminates retrograde flow and improves total flow more than that achieved with IABP. The Symphony may provide long-term hemodynamic benefits in HF patients. [ABSTRACT FROM AUTHOR]

Abstract: This paper collects the experimental results obtained in the Thermal Fluid Dynamics Lab at the Department of Energy and Engineering Systems at the University of Pisa, concerning the influence of ultrasounds in single phase free convection and in pool saturated boiling, at atmospheric pressure. The authors have just reported in previous papers their results about the enhancement induced by the presence of ultrasonic waves in subcooled boiling conditions. The ultrasounds are applied at the set frequency of 40kHz, with a transducer output changing from 300 to 500W, on a circular horizontal cylinder heated by Joule effect, immersed in distilled water. The tests in single phase free convection, without ultrasonic waves, are validated by means of the classical correlations reported in literature. Moreover, the authors managed to correlate the data also in presence of ultrasounds. The enhancement of the heat transfer coefficient is lower than the one obtained in subcooled boiling and with regards to the saturated pool boiling conditions, as far as for subcooling degrees very close to the saturation, the ultrasounds cause a decrease of the heat transfer. At the same time, the ultrasounds induce the critical heat flux (CHF) at higher heat flux compared with the case without ultrasounds. Also in saturated pool boiling, without ultrasonic waves, the experimental value of the CHF is compared with the one obtained by equations reported in the literature. This paper, joined to the others published by the authors, makes clear systematically the effects of ultrasounds on the heat transfer and shows as they could be very useful in the last generation electronic components cooling. [Copyright &y& Elsevier]

Abstract: This work represents an experimental basic research aimed to investigate the influence on the heat transfer rate of the ultrasounds, in free convection and in presence of liquid. In fact the ultrasonic waves induce, thanks to vibrations, turbulence on the dynamic field, and so an increase of the convection coefficient. The heater is a circular cylinder, immersed in distilled water, and warmed up by Joule effect. This study has carried on for 1year at Energetics Department “L. Poggi”. The effect was observed since 1960s: different authors had studied the cooling effect due to the ultrasonic waves at different heat transfer regimes, especially from a thin platinum wire to water. We have chosen to investigate the subcooled boiling regime, because this one is the best condition for the heat transfer enhancement, according to the scientific literature. We have carried out a wide experimental study, varying the different water subcooling degrees, the ultrasonic generator power, the ultrasound frequency and the placement of the heater inside the ultrasonic tank, in function of the range of the values of heat flux per unit surface needed dissipating. These values were supplied us by a possible practical application of the ultrasonic streaming: the cooling of 3D highly integrated electronic components. These packaging systems should have to provide all future devices, such as electronics, actuators, sensors and antenna. In fact, for these systems the thermal problem is a critical challenge, because they do not have to overtake critical temperature, after that they could damage irreversibly. Moreover, the traditional cooling systems used in electronic do not seem to be useful for them. On the contrary, the results obtained with ultrasounds, allow heat transfer coefficient enhancement of about 50% to be reached. The purpose is to find out the set of optimal conditions, in order to apply successively all the results to a real packaging system. [ABSTRACT FROM AUTHOR]

Abstract: This paper aims to determine the heat transfer enhancement in natural convection between a downward-facing inclined wall, heated by Joule effect, and air in the presence of small air pulsating expired jets, in conditions of medium temperature difference between wall and air, namely 40K. Experimental measurements have been taken both with and without pulsating expired jets. The wall is kept in condition of uniform temperature. The expired jets blow out perpendicularly from the wall surface. An infrared thermo-camera was used to check the wall temperature uniformity. Hot-wire anemometer and visualization with smoke were used to find information on the air velocity field. The wall inclination angle which maximizes the convective heat exchange near the leading edge has been investigated too. [Copyright &y& Elsevier]

Left ventricular assist devices (LVADs) constitute a recent advance in heart failure (HF) therapeutics. As the rigorous experimental assessment of LVADs in HF requires large animal models, our objective was to develop a bovine model of cardiomyopathy. Male calves (n = 8) were used. Four animals received 1.2 mg/kg intravenous doxorubicin weekly for seven weeks and four separate animals were studied as controls. Doxorubicin-treated animals were followed with weekly echocardiography. Target LV dysfunction was defined as an ejection fraction ≤35%. Sixty days after initiating doxorubicin, a terminal study was performed to determine hemodynamic, histological, biochemical, and molecular parameters. All four doxorubicin-treated animals exhibited significant (P < 0.05) contractile dysfunction, with target LV dysfunction achieved in three animals. Doxorubicin-treated hearts exhibited significantly reduced coronary blood flow and interstitial fibrosis and significantly increased apoptosis and myocyte size. Gene expression of atrial natriuretic factor increased more than 3-fold. Plasma norepinephrine and epinephrine levels were significantly increased early and late during the development of cardiomyopathy, respectively. We conclude that sequential administration of intravenous doxorubicin in calves induces a cardiomyopathy with many phenotypic hallmarks of the failing human heart. This clinically-relevant model may be useful for testing pathophysiologic responses to LVADs in the context of HF. [ABSTRACT FROM AUTHOR]

Medical devices implanted in subcutaneous tissue elicit wound-healing events that encapsulate the device. To investigate the foreign-body response to devices of clinically relevant size, we studied the relationship between capsule thickness, vascular density, and blood flow within the capsule. In nine canines, we implanted 40 subcutaneous devices (polysulfone n = 14, titanium n = 17, silicone-coated n = 9). Devices and surrounding tissue structures were harvested at 208 ± 142 (mean ± standard deviation) days after implantation. Tissues were processed for histological analysis with light microscopy. Foreign-body capsule (FBC) thickness and vascular density were determined. A subset of five animals was instrumented via thoracotomy for microsphere injections and reference blood sampling. In these animals, regional blood flow was determined in mL/min/g of tissue in the FBC to examine the relationship between capsule thickness and blood flow. One-way analysis of variance and linear regression analyses were performed. The FBC thickness was 0.92 ± 0.67 mm for all devices studied and was not influenced by device material. Capsule thickness correlated with vascular density for all devices ( R = 0.85, P < 0.0001) and for each device material (polysulfone R = 0.85, P < 0.0001; silicone R = 0.95, P < 0.0001; titanium R = 0.87, P < 0.0001). Capsule thickness correlated modestly with blood flow for all devices studied ( R = 0.59, P < 0.0001) and for each device material (polysulfone R = 0.77, P < 0.001; silicone R = 0.65, P = 0.10; titanium R = 0.52, P = 0.03). Capsule thickness, vascular density, and blood flow were similar within individual animals but variable across animals. Material type did not influence the thickness of FBCs surrounding devices of clinically relevant size. Capsule thickness correlated strongly with vascular density and modestly with blood flow within the capsule. Individual animals exhibited variable foreign-body responses. [ABSTRACT FROM AUTHOR]

Abstract: In this paper are reported the results of an experimental investigation about the heat transfer enhancement from vertical and downward inclined wall to air, in natural convection, by means of expired jets. The air was maintained at room temperature and the wall is heated by Joule effect. The temperature difference between the wall and the air was prefixed at 25K and the wall placement had been varied from the vertical to different downward inclined positions (5°, 10°, 15°, 20°, 25° and 30°). The experimental results had shown an increase in the heat transfer coefficient, at the different wall inclinations, due to the jets; actually they had induced turbulence in the dynamic field, by interrupting the laminar flow. Our aim was to optimize the variables involved in the phenomenon, in order to find out the highest enhancement of the heat transfer coefficient values, caused by the jets. The variables were the number of active horizontal lines of jets, their activity and the inactivity time and their velocity. We had also investigated the conditions without jets and we found out that the heat transfer coefficient trend versus the downward inclination angles, could not be described by correlations present in literature. In fact, in the investigated range of the downward wall inclinations, the heat transfer coefficient did not may be simply correlated with the cosine of the angle, but it increased up to a maximum value, reached at 15°, and then decreased. The visualization by smoke had confirmed these results: the boundary layer thickness had followed this trend. In correspondence to the wall inclination equal to 15°, it reached its minimum value. Finally, to the purpose to link the experimental data, we had proposed a numerical correlation. The values calculated thanks to this one reported differences much lower than the computed experimental error. [Copyright &y& Elsevier]

The miniaturization of mechanical assist devices and less invasive implantation techniques may lead to earlier intervention in patients with heart failure. As such, we evaluated the effectiveness of a novel, minimally invasive, implantable counterpulsation device (CPD) in augmenting cardiac function during impaired hemodynamics. We compared the efficacy of a 32-mL stroke volume CPD with a standard 40-mL intra-aortic balloon pump (IABP) over a range of clinically relevant pathophysiological conditions. Male calves were instrumented via thoracotomy, the CPD was anastomosed to the left carotid artery, and the IABP was positioned in the descending aorta. Hemodynamic conditions of hypertension, hypotension, and heart failure were pharmacologically simulated and data were recorded during CPD and IABP support (off, 1:2, 1:1 modes) for each condition. In all three pathophysiological conditions, the CPD and IABP produced similar and statistically significant ( P < 0.05) increases in coronary artery blood flow normalized to the left ventricular (LV) workload. During hypotension and heart failure conditions, however, the CPD produced significantly greater reductions in LV workload and myocardial oxygen consumption as compared with the IABP. A novel 32-mL CPD connected to a peripheral artery produced equivalent or greater hemodynamic benefits than a standard 40-mL IABP during pharmacologically induced hypertension, hypotension, and heart failure conditions. [ABSTRACT FROM AUTHOR]

Objective: In this article, the presentation, pathophysiology, diagnosis, treatment, and complications of lipomas of the hand are reviewed and evaluated. Methods: A thorough review of the literature is completed, and a series of 13 patients are summarized and briefly examined. Results: Lipomas may present as asymptomatic tumors or produce concerning signs and symptoms such as muscular atrophy and paralysis. Some lipomas may be identified by physical examination alone. However, magnetic resonance imaging best facilitates definitive diagnosis. Conclusions: In the absence of mechanical impairment or cosmetic concern, observation remains the clinical standard of care. When pain, compression neuropathy, disfigurement, or decreased function affect the patient, surgical resection is typically curative. Malignant transformation rarely occurs. [ABSTRACT FROM AUTHOR]

Background: Surgically implanted devices initiate inflammatory mechanisms and wound healing events and result in the formation of a thick fibrotic capsule that surrounds the device. To investigate the foreign-body response to devices of clinically relevant size, we used microspheres to determine regional blood flow patterns in the foreign-body capsule (FBC) and surrounding subcutaneous tissue after device implantation. Materials and Methods: In 10 canines, we implanted 40 subcutaneous devices (polysulfone n = 20, silicone-coated n = 10, titanium n = 10). Via thoracotomy, animals were instrumented with left atrial and aortic vascular access catheters for serial microsphere injections and reference blood sampling. Regional blood flow was repeatedly determined in the FBC, subcutaneous fascia surrounding the FBC, and subcutaneous fascia distal to the surgical site up to 19 wk after device implantation (n = 55 determinations). Results: Compared with normal blood flow in subcutaneous fascia distal to the surgical site, blood flow increased in FBCs surrounding each device material (polysulfone P = 0.0035, silicone-coated P < 0.0001, titanium P < 0.0001). Additionally, blood flow increased in the subcutaneous fascia within half a centimeter of fibrous capsules encasing polysulfone (P = 0.0081) but not silicone (P = 0.3706) or titanium (P = 0.8160) devices. The time-course of measured blood flow changes within FBCs were similar for polysulfone and silicone but not for titanium. Conclusions: Surgically implanted subcutaneous devices of clinically relevant size elicit increases in blood flow in the FBC as well as surrounding fascia. Device material may influence regional blood flow patterns. [Copyright &y& Elsevier]

BACKGROUND: Epidemiologic studies suggest a positive association between fine particulate matter and arterial blood pressure, but the results have been inconsistent. OBJECTIVES: We investigated the effect of ambient particles on systemic hemodynamics during a 5-hr exposure to concentrated ambient air particles (CAPs) or filtered air (FA) in conscious canines. METHODS: Thirteen dogs were repeatedly exposed via permanent tracheostomy to CAPs (358.1 ± 306.7 µg/m3, mean ± SD) or FA in a crossover protocol (55 CAPs days, 63 FA days). Femoral artery blood pressure was monitored continuously via implanted telemetry devices. We measured baroreceptor reflex sensitivity before and after exposure in a subset of these experiments (n = 10 dogs, 19 CAPs days, 20 FA days). In additional experiments, we administered α-adrenergic blockade before exposure (n = 8 dogs, 16 CAPs days, 15 FA days). Blood pressure, heart rate, rate--pressure product, and baroreceptor reflex sensitivity responses were compared using linear mixed-effects models. RESULTS: CAPs exposure increased systolic blood pressure (2.7 ± 1.0 mmHg, p = 0.006), diastolic blood pressure (4.1 ± 0.8 mmHg; p < 0.001), mean arterial pressure (3.7 ± 0.8 mmHg; p < 0.001) heart rate (1.6 ± 0.5 bpm; p < 0.001) and rate--pressure product (539 ± 110 bpm × mmHg; p < 0.001) and decreased pulse pressure (--1.7 ± 0.7 mmHg, p = 0.02). These changes were accompanied by a 20 ± 6 msec/mmHg (p = 0.005) increase in baroreceptor reflex sensitivity after CAPs versus FA. After α-adrenergic blockade, responses to CAPs and FA no longer differed significantly. CONCLUSIONS: Controlled exposure to ambient particles elevates arterial blood pressure. Increased peripheral vascular resistance may mediate these changes, whereas increased baroreceptor reflex sensitivity may compensate for particle-induced alterations in blood pressure. [ABSTRACT FROM AUTHOR]

BACKGROUND: Experimental and observational studies have demonstrated that short-term exposure to ambient particulate matter (PM) exacerbates myocardial ischemia. OBJECTIVES: We conducted this study to investigate the effects of concentrated ambient particles (CAPs) on myocardial blood flow during myocardial ischemia in chronically instrumented conscious canines. METHODS: Eleven canines were instrumented with a balloon occluder around the left anterior descending coronary artery and catheters for determination of myocardial blood flow using fluorescent microspheres. Telemetric electrocardiographic and blood pressure monitoring was available for four of these animals. After recovery, we exposed animals by inhalation to 5 hr of either filtered air or CAPs (mean concentration ± SD, 349.0 ± 282.6 µg/m3) in a crossover protocol. We determined myocardial blood flow during a 5-min coronary artery occlusion immediately after each exposure. Data were analyzed using mixed models for repeated measures. The primary analysis was based on four canines that completed the protocol. RESULTS: CAPs exposure decreased total myocardial blood flow during coronary artery occlusion by 0.12 mL/min/g (p < 0.001) and was accompanied by a 13% (p < 0.001) increase in coronary vascular resistance. Rate--pressure product, an index of myocardial oxygen demand, did not differ by exposure (p = 0.90). CAPs effects on myocardial blood flow were significantly more pronounced in myocardium within or near the ischemic zone versus more remote myocardium (p interaction < 0.001). CONCLUSIONS: These results suggest that PM exacerbates myocardial ischemia by increased coronary vascular resistance and decreased myocardial perfusion. Further studies are needed to elucidate the mechanism of these effects. [ABSTRACT FROM AUTHOR]

Background: Direct measurement of blood flow output has been incorporated into ventricular assist devices (VADs), but long-term reliability of the additional device components has raised concerns regarding sensor drift and failure. As an alternative approach, the HeartMate II axial VAD (Thoratec Corp, Pleasanton, CA) estimates device flow output from power consumption and rotational speed of the device motor. This study evaluated the accuracy of HeartMate II flow estimation at the time of implantation. Methods: In 20 patients, intraoperative blood flow measurement of the HeartMate II flow estimator was compared with flow values obtained with an ultrasonic flow probe placed around the device outflow graft. Estimated and measured VAD flow data were simultaneously recorded and digitally stored while the device motor speed varied from 7,800 to 11,000 rpm and while achieving device flow outputs of 2 to 7 liters/min. Estimated and measured flows were compared using linear regression analyses and root mean square error. Results: HeartMate II flow estimation (FE) demonstrated a linear correlation with ultrasonic flow probe (FP) measurements: FE = 0.74 FP + 0.99 (R 2 = 0.56, p = 0.0001). A root mean square error of 0.8 liters/min was observed between flow estimation and direct flow measurement and suggests a 15% to 20% difference at flows of 4 of 6 liters/min. Conclusions: These results suggest that HeartMate II flow estimation may be used to provide directional information for trend purposes rather than absolute values of device blood flow output. Patient management should include but not be limited to this information. [Copyright &y& Elsevier]

Introduction: For chronic, repeat hemodynamic studies in conscious dogs, we designed and tested a chronically instrumented canine microsphere delivery model. The goals of this study were (1) to investigate the accuracy of repeated estimations of blood perfusion using fluorescent-labeled microspheres and (2) to develop and validate a chronic preparation that permits consecutive estimations in the same conscious animal over an extended protocol. Methods: Via thoracotomy, nine dogs were instrumented with left atrial appendage and aortic vascular access catheters connected to subcutaneous vascular access ports. Four animals received seven serial injections of 1.6 million 15 μm microspheres (total: 11.2 million), and five animals received 8 serial injections of 2.25 million microspheres (total: 18 million) over the course of 11 or 18 wk. Results: All catheters have remained bidirectionally patent during protocol for 14.9 ± 0.8 (mean ± SEM) wk. Sphere accumulation did not significantly alter global myocardial (P = 0.69, P = 0.25), renal (P = 0.92, P = 0.12), hepatic (P = 0.84, P = 0.32), or splenic (P = 0.33, P = 0.70) blood perfusion in either set of animals. Conclusions: Catheters remained bidirectionally patent for months, did not interfere with the hemodynamic responses of the preparation, and allowed repeat percutaneous injection of microspheres and withdrawal of reference arterial blood from within conscious canines. Eight serial injections totaling 18 million microspheres over 18 weeks did not alter regional myocardial, hepatic, renal, or splenic blood flow. This dependable, chronic, percutaneous arterial access preparation provides a means for examining acute and long-term effects of pathophysiological, pharmaceutical, and environmental influences on regional arterial blood flow in conscious, large animals. [Copyright &y& Elsevier]

Background: We describe a modified surgical technique for permanent, anterior tracheal-wall stoma for chronic, repeat respiratory studies in trained, conscious dogs. These cannula-free tracheostomies require minimal daily maintenance, permit repeat intubation with endotracheal tubes modified for airflow respiratory measurement, and facilitate up to 6 h continuous administration of aerosol agents during long-term or repeat respiratory studies. Methods: In 20 dogs, during a 30 to 40 min procedure, portions of tracheal rings 2–4 were removed to create an oval stoma, approximately 2 × 1 cm. The dermis was secured to the transected cartilage and tracheal mucosa in such a manner that skin covered the sternohyoid muscles and grew-in flush with the tracheal mucosa at the stomal opening. Stomas were cleaned daily, and fur was clipped weekly around the stomal site. No other maintenance procedures or environmental modifications were needed. Animals breathed through both the stoma and the upper airway and barked normally. Results: Stomas remained viable in long-term animals (n = 4) ongoing for 70.3 ± 32.2 mo (mean ± SEM), with an ongoing maximum of 126 mo. Postmortem examinations were performed on shorter-term animals (n = 16) sacrificed at 16.7 ± 7.3 mo. Thirteen showed no appreciable tracheal stenosis and three showed <10% stenosis at the level of the stoma. Histopathological examination of the stomal opening and surrounding tissue revealed minimal chronic inflammation and no evidence of necrosis or infection. Conclusions: During long-term respiratory studies, this practical and dependable tracheal stoma provides a means for examining acute and chronic effects of environmental and pathophysiological influences on the respiratory system of conscious dogs. [Copyright &y& Elsevier]

Abstract: The present communication deals with the tests for the validation of the DJOSER steady-state thermal simulation program, purposely designed for power electronic assembling structures and which is based on the resolution of analytical relationships. The validation experiments were carried out theoretically by comparing the thermal maps with those obtained using standard finite-elements programs and yielding temperature accuracy below 1%. Experimental tests were also performed on purposely built multi-layer structures and industrial circuits with power diodes mounted in naked-chip configuration. The simulated maps were compared with accurate thermo-graphic recordings and showed a good agreement, testifying the validity of the mathematical model. [Copyright &y& Elsevier]

Introduction For chronic, repeated cardiovascular studies in trained, conscious dogs, we describe a technique for implantation of an arterial vascular access catheter in the aorta. In comparison to previous techniques, our technique enables arterial catheter implantation without interrupting the systemic circulation or compromising peripheral arterial flow, requires only a single penetration of the aortic wall, and results in a catheter facing downstream in the aorta. The catheter is usable for both arterial blood sampling and intra-arterial injection of pharmacologic agents.Methods After thoracotomy, two purse-string sutures were set in the aortic wall at the catheter entry-site. A Debakey–Satinsky vena cava clamp was used to partially clamp and isolate a 3-cm portion of aorta surrounding the pursestring sutures. The catheter was prepared by inserting a 0.35 mm guide wire, curve tip end first, into a 7 French silicone Access Technologies catheter. This caused a slight bend at the tip of the catheter, which later facilitated entry into the aorta and prevented damage to the intima of the aortic wall. Catheters were tunneled from the thorax to the nape of the neck, attached to a subcutaneous vascular access port (VAP), and buried in the fascia. Catheters were locked with 2 mL heparinized saline (20 IU/mL). With this technique, we implanted 16 aortic vascular access catheters in 16 dogs.Results Of the 16 animals, 8 are being maintained for long-term study, 7 were sacrificed for histopathological examination, and 1 died due to improper catheter implantation without the aid of the curved-tip guide-wire technique. VAPs have remained bidirectionally patent in all long-term animals (n = 8) ongoing for 7.5 ± 1.4 months (mean ± SEM), with an ongoing maximum of 14 months. In these long-term animals, VAPs were used 5.88 ± 1.34 times. Postmortem examinations were performed on short-term animals (n = 8) sacrificed at 2.85 ± 1.29 months. The catheters have remained bidirectionally patent in all but the one animal that died. In the short-term animals, the 7 patent VAPs were used 12.71 ± 1.64 times. Histopathological examination of hematoxylin and eosin (H&E) slides from the catheter entry site revealed only minimal chronic inflammation. No evidence of tissue overgrowth around any of the intravascular segments of these silicone catheters was noted in any animal.Conclusions Thus, this dependable subcutaneous arterial access system provides a means for examining acute and long-term effects of environmental and pathophysiological influences in conscious dogs. These catheters have remained bidirectionally patent ongoing for more than 1 year and allowed infusion of agents and withdrawal of central arterial blood samples. [ABSTRACT FROM AUTHOR]

Abstract: This research study focuses its attention on the local and temporal distribution of the entropy production generated by thermal irreversibilities as well as on the fact that they contribute, together with the entropy flow through the frontier, towards raising the solid entropy, under situations of thermal transient. For simplicity, a simple unidimensional model, the semi-infinite solid, for which several solutions depending on the Fourier equation time are well known, is investigated; they are here discussed with respect to their aspects of second principle. Moreover, it should be noticed that both entropy and entropy production are not linear in temperature. The principle of superposition is, therefore, not valid for them; this gets the remarks expounded in this paper to be considered as an exemplification of the entropic problems in simple cases, rather than a method for working out entropic solutions in more complex cases. [Copyright &y& Elsevier]

The paper provides a methodology for the optimal control of heating, ventilation, and air conditioning (HVAC) systems used in public buildings, with the purpose of obtaining high comfort and safety standards along with energy efficiency. The combination of the two concurrent objectives of minimizing energy use and guaranteeing high standards of occupant comfort is obtained by means of multi-objective optimization, in which a comfort model is combined along with a dynamic energy model of the building. The use of dynamic setpoints for the HVAC and the inclusion of comfort indicators represent a step forward, compared to the current design and operation procedures suggested by technical standards. The utilization of the proposed methodology is tested with reference to a case study, represented by an academic building used by the University of Pisa for educational purposes, whose extensive and variable occupancy can help to emphasize the importance of comfort in the operation of HVAC systems in different climatic conditions and with different occupancy profiles. We show how this optimization brings interesting results in terms of energy-saving (up to 30%), obtaining an increased comfort level (of more than 25%) compared to the operating conditions suggested by technical standards. [ABSTRACT FROM AUTHOR]

Worldwide increasing awareness of energy sustainability issues has been the main driver in developing the concepts of (Nearly) Zero Energy Buildings, where the reduced energy consumptions are (nearly) fully covered by power locally generated by renewable sources. At the same time, recent advances in Internet of Things technologies are among the main enablers of Smart Homes and Buildings. The transition of conventional buildings into active environments that process, elaborate and react to online measured environmental quantities is being accelerated by the aspects related to COVID-19, most notably in terms of air exchange and the monitoring of the density of occupants. In this paper, we address the problem of maximizing the energy efficiency and comfort perceived by occupants, defined in terms of thermal comfort, visual comfort and air quality. The case study of the University of Pisa is considered as a practical example to show preliminary results of the aggregation of environmental data. [ABSTRACT FROM AUTHOR]

We describe a 36-year-old male with a HeartWare LVAD and a Medtronic Virtuoso DR pacemaker in whom increased intrathoracic impedance preceded suction events, low LVAD flows, symptoms of a heart failure exacerbation, and hospitalization. Measurement of intrathoracic impedance may identify fluid shifts prior to symptoms and predict adverse events in patients with an LVAD. doi: 10.1111/jocs.12191 (J Card Surg 2013;28:616-618) [ABSTRACT FROM AUTHOR]

A response by Carlo R. Bartoli and colleagues to a letter to the editor about their article "A Novel Subcutaneous Counterpulsation Device: Acute Hemodynamic Efficacy During Pharmacologically Induced Hypertension, Hypotension, and Heart Failure," in the 2010 issue is presented.

Two and a half million Americans with atrial fibrillation are at an elevated risk for embolic stroke. Warfarin therapy is standard treatment for high-risk patients, yet 40–65% of elderly patients do not receive anticoagulation therapy due to bleeding complications. To address this clinical need, we are evaluating a minimally invasive stent-based stroke prevention device to divert emboli from entering the arterial supply of the brain. The feasibility of a J-shaped stroke prevention device was tested in a mock circulatory loop. Sixteen sets of 100 simulated emboli (1–5 mm3) were injected into the left atrium with and without J stents protecting the aortic arch vessels. To determine efficacy, emboli were trapped in filters in the aortic arch vessels and distal aorta for manual counting. J stents decreased the number of emboli that entered the brachiocephalic trunk by 93.7% ( p < 0.0001), left common carotid artery by 79.8% ( p < 0.0001), and left subclavian artery by 89.7% ( p < 0.0001). In a mock circulation, J stents positioned in the aortic arch vessels and oriented downstream of aortic flow significantly decreased the number of emboli that entered the aortic arch vessels. These results warrant further investigation to determine the safety and efficacy of this prophylactic intervention to reduce embolic events, and chronic large animal studies are underway. [ABSTRACT FROM AUTHOR]

Estimating and optimizing the dynamic performance of a heat pump system coupled to a building is a paramount yet complex task, especially under intermittent conditions. This paper presents the "hardware-in-the-loop" experimental campaign of an air-source heat pump serving a typical dwelling in Pisa (Italy). The experimental apparatus uses real pieces of equipment, together with a thermal load emulator controlled by a full energy dynamic simulation of the considered building. Real weather data are continuously collected and used to run the simulation. The experimental campaign was performed from November 2019 to February 2020, measuring the system performances under real climate and load dynamics. With a water set point equal to 40 °C, the average heat pump coefficient of performance was about 3, while the overall building-plant performance was around 2. The deviation between the two performance indexes can be ascribed to the continuous on-off signals given by the zone thermostat due to the oversized capacity of the heat emission system. The overall performance raised to 2.5 thanks to a smoother operation obtained with reduced supply temperature (35 °C) and fan coil speed. The paper demonstrates the relevance of a dynamic analysis of the building-HVAC system and the potential of the "hardware-in-the-loop" approach in assessing actual part-load heat pump performances with respect to the standard stationary methodology. [ABSTRACT FROM AUTHOR]

Background: The Matrigel assay provides a versatile platform to examine vessel growth. Similarly, the microsphere method is used extensively in laboratory animals to measure tissue-specific blood flow. However, microsphere models have not been used with Matrigel to study angiogenesis in live animals. The goal of this study was to develop a novel technique to directly measure blood flow with microspheres in vessels grown in Matrigel in vivo. Methods: In calves (n = 10, 110 ± 5 kg), 5 mL of Matrigel was injected subcutaneously. After 10 d, a percutaneous cardiac catheterization was performed. Fluorescent-labeled 15 μm microspheres were injected into the left ventricular chamber to distribute throughout the body based on systemic blood flow patterns. Afterwards, Matrigel plugs were removed, and animals were recovered. Flow cytometry was used to count microspheres and quantify blood flow within the plug. FITC-conjugated isolectin-B4 staining was performed to quantify Matrigel capillary density. Flow cytometry was performed to quantify circulating plasma CD34+ cells. Linear regressions were used to determine relationships between Matrigel blood flow, Matrigel capillary density, and plasma CD34+ cells. Results: Over 10 d, small-caliber vessels grew into subcutaneous Matrigel plugs. Microspheres lodged throughout the plug and indicated that newly grown vessels in the Matrigel were functional and able to accommodate blood flow. Modest associations between Matrigel blood flow, Matrigel capillary density, and circulating plasma CD34+ cells were noted. Conclusion: This method provides a novel and cost-effective technique to measure blood flow within vessels grown in Matrigel in vivo. [Copyright &y& Elsevier]

Left ventricular assist devices (LVADs) constitute a recent advance in heart failure (HF) therapeutics. As the rigorous experimental assessment of LVADs in HF requires large animal models, our objective was to develop a bovine model of cardiomyopathy. Male calves (n = 8) were used. Four animals received 1.2 mg/kg intravenous doxorubicin weekly for seven weeks and four separate animals were studied as controls. Doxorubicin-treated animals were followed with weekly echocardiography. Target LV dysfunction was defined as an ejection fraction <= 35%. Sixty days after initiating doxorubicin, a terminal study was performed to determine hemodynamic, histological, biochemical, and molecular parameters. All four doxorubicin-treated animals exhibited significant (P < 0.05) contractile dysfunction, with target LV dysfunction achieved in three animals. Doxorubicin-treated hearts exhibited significantly reduced coronary blood flow and interstitial fibrosis and significantly increased apoptosis and myocyte size. Gene expression of atrial natriuretic factor increased more than 3-fold. Plasma norepinephrine and epinephrine levels were significantly increased early and late during the development of cardiomyopathy, respectively. We conclude that sequential administration of intravenous doxorubicin in calves induces a cardiomyopathy with many phenotypic hallmarks of the failing human heart. This clinically-relevant model may be useful for testing pathophysiologic responses to LVADs in the context of HF. [ABSTRACT FROM AUTHOR]

Continuous flow left ventricular assist devices have improved outcomes in patients with end-stage heart failure that require mechanical circulatory support. Current devices have an adverse event profile that has hindered widespread application. The EVAHEART®2 left ventricular assist device (EVA2) has design features such as large blood gaps, lower pump speeds and an inflow cannula that does not protrude into the left ventricle that may mitigate the adverse events currently seen with other continuous flow devices. A prospective, multi-center randomized non-inferiority study, COMPETENCE Trial, is underway to assess non-inferiority of the EVA2 to the HeartMate 3 LVAS when used for the treatment of refractory advanced heart failure. The primary end-point is a composite of the individual primary outcomes: Survival to cardiac transplant or device explant for recovery; Free from disabling stroke; Free from severe Right Heart Failure after implantation of original device. Randomization is in a 2:1 (EVA2:HM3) ratio. The first patient was enrolled into the COMPETENCE Trial in December of 2020, and 25 subjects (16 EVA2 and 9 HM3) are currently enrolled. Enrollment of a safety cohort is projected to be completed by third quarter of 2022 at which time an interim analysis will be performed. Short-term cohort (92 EVA2 subjects) and long-term cohort is expected to be completed by the end of 2023 and 2024, respectively. The design features of the EVA2 such as a novel inflow cannula and large blood gaps may improve clinical outcomes but require further study. The ongoing COMPETENCE trial is designed to determine if the EVA2 is non-inferior to the HM3. [ABSTRACT FROM AUTHOR]

Introduction: Extensive in vitro studies and clinical evidence (MERLIN trial) indicate an antiarrhythmic potential of ranolazine, a novel antianginal agent. Programmed electrophysiologic testing was performed to quantify ranolazine's effects on ventricular vulnerability and defibrillation thresholds and to gain insights into mechanisms. Methods and Results: Effects of ranolazine (9.2 ± 2.1 μM, plasma level) on surface ECG, right ventricular effective refractory period (ERP), and repetitive extrasystole (RE), ventricular fibrillation (VF), and defibrillation (DFT) thresholds were determined in 29 normal closed-chest anesthetized pigs. The single extrastimulus method was employed for ERP and for RE and VF thresholds. DFT50 was determined using an up-down testing protocol with an implantable cardioverter-defibrillator. Ranolazine increased rate-corrected QT interval from 490 ± 30 to 527 ± 24 ms (P < 0.05) but did not alter Tpeak-Tend interval (59 ± 8 to 62 ± 11, P = 0.65). ERP increased by 40 ± 6 ms (P < 0.001). Compared with baseline, ranolazine raised RE threshold from 20 ± 6 to 34 ± 9 mA (P < 0.001) and VF threshold from 38 ± 4 to 48 ± 10 mA (P < 0.05). DFT50 was unchanged (baseline: 14 ± 2 J; ranolazine: 14 ± 2 J; P = 0.6), whereas diastolic pacing threshold increased from baseline pulse width of 0.07 ± 0.03 to 0.17 ± 0.07 ms (P < 0.01) with 1V pulse amplitude. Conclusions: Ranolazine, at therapeutic concentrations, produces a mild increase in QT interval and a marked increase in both RE and VF thresholds. Thus, ranolazine does not augment and may improve dispersion of ventricular repolarization, suggesting a potential antiarrhythmic action. Ranolazine is unlikely to affect the margin of safety of defibrillation, given no significant effect on DFT, but could result in a mild increase in pacing threshold. [ABSTRACT FROM AUTHOR]

• Electrochemical reforming of ethanol to H 2 is achieved at 150 °C. • An autoclave electrochemical cell is constructed that allows the safe pressurization of the H 2 produced as no O 2 is evolved. • Highly active ethanol oxidation catalyst (PdCoNi foam) is stabilized by treatment with phosphorous vapors. • Self-pressurization of the H 2 produced by the electrochemical reaction is demonstrated. The electrochemical reforming of ethanol to H 2 is achieved at 150 °C in an autoclave electrochemical cell that allows the safe pressurization of the H 2 produced as no O 2 is evolved. The alkaline conditions are very aggressive to catalysts including noble metals like Pt and Pd. We report a highly active ethanol oxidation catalyst (PdCoNi foam) composed of Pd nanoparticles supported on nanostructured Co oxide structures grown on nickel foam. Treatment with phosphorous vapors at high temperature yields a thin coating of phosphate that confers enhanced stability to the electrode operating in an electrolysis cell at 150 °C. A combination of scanning electron microscopy (energy dispersive X-ray spectroscopy) and X-ray photoelectron spectroscopy reveal a 3D nano-flake surface with an external layer of phosphates that prevents Pd dissolution. The PdCoP@Ni foam catalyst was successfully used for ethanol electrochemical reforming at 150 °C with self-pressurization of the H 2 produced by the electrochemical reaction. [ABSTRACT FROM AUTHOR]

B Learning Objectives: b We present a case of percutaneous thrombectomy of a large in-transit right atrial (RA) thrombus. B Results: b Right heart thrombi in the absence of structural heart disease, atrial fibrillation, or intracardiac catheter are usually in-transit, migrating from the venous system, and potentially lead to life threatening pulmonary embolism. Preferred therapy for in-transit thrombi is controversial and includes systemic anticoagulation, tPA and operative removal. [Extracted from the article]

This article describes the development of a high power density Direct Formate Fuel Cell (DFFC) fed with potassium formate (KCOOH). The membrane electrode assembly (MEA) contains no platinum metal. The cathode catalyst is FeCo/C combined with a commercial anion exchange membrane (AEM). To enhance the power output and energy efficiency we have employed a nanostructured Pd/C-CeO2 anode catalyst. The activity for the formate oxidation reaction (FOR) is enhanced when compared to a Pd/C catalyst with the same Pd loading. Fuel cell tests at 60 °C show a peak power density of almost 250 mW cm-2. The discharge energy (14 kJ), faradic efficiency (89%) and energy efficiency (46%) were determined for a single fuel charge (30 mL of 4 M KCOOH and 4 M KOH). Energy analysis demonstrates that removal of the expensive KOH electrolyte is essential for the future development of these devices. To compensate we apply for the first time a polymeric ionomer in the catalyst layer of the anode electrode. A homopolymer is synthesized by the radical polymerization of vinyl benzene chloride followed by amination with 1,4-diazabicyclo[2.2.2]octane (DABCO). The energy delivered, energy efficiency and fuel consumption efficiency of DFFCs fed with 4 M KCOOH are doubled with the use of the ionomer. [ABSTRACT FROM AUTHOR]

Evidence suggests a major role for von Willebrand factor (vWF) in left ventricular assist device (LVAD)-associated bleeding. However, the mechanisms of vWF degradation during LVAD support are not well understood. We developed: (i) a simple and inexpensive vortexer model; and (ii) a translational LVAD mock circulatory loop to perform preclinical investigations of LVAD-associated vWF degradation. Whole blood was obtained from LVAD patients (n = 8) and normal humans (n = 15). Experimental groups included: (i) blood from continuous-flow LVAD patients (baseline vs. post-LVAD, n = 8); (ii) blood from normal humans (baseline vs. 4 h in vitro laboratory vortexer, ∼ 2400 rpm, shear stress ∼175 dyne/cm2, n = 8); and (iii) blood from normal humans (baseline vs. 12 h HeartMate II mock circulatory loop, 10 000 rpm, n = 7). vWF multimers and degradation fragments were characterized with electrophoresis and immunoblotting. Blood from LVAD patients, blood exposed to in vitro supraphysiologic shear stress, and blood circulated through an LVAD mock circulatory loop demonstrated a similar profile of decreased large vWF multimers and increased vWF degradation fragments. A laboratory vortexer and an LVAD mock circulatory loop reproduced the pathologic degradation of vWF that occurs during LVAD support. Both models are appropriate for preclinical studies of LVAD-associated vWF degradation. [ABSTRACT FROM AUTHOR]

The circadian rhythm of varying blood pressure and heart rate is attenuated or absent in patients with severe heart failure. In 28 patients supported by a left ventricular assist device (LVAD) for at least 30 days, a restoration of the circadian rhythm was demonstrated by a consistent nocturnal decrease, and then increase, of the LVAD flow while at a constant LVAD speed. The return of the circadian rhythm has implications for cardiac recovery, and the observation indicates that the continuous-flow LVAD has an intrinsic automatic response to physiologic demands. [Copyright &y& Elsevier]