A novel toolkit to improve percutaneous subxiphoid needle access to the healthy pericardial sac.

INTRODUCTION: The current practice of percutaneous subxiphoid needle access to the "healthy" pericardial sac has significant limitations. We sought to examine the feasibility of a novel toolkit designed to improve this procedure. METHODS AND RESULTS: The toolkit included a pericardial access needle and a virtual imaging platform. The needle had a 0.036 inch outer diameter, abbreviated 25° bevel, and was electrically insulated except for two small surfaces recessed from the tip. Radiofrequency energy was delivered via these surfaces to facilitate pericardial perforation. The virtual imaging system demonstrated the needle in real time and in its entirety within the thoracic anatomy of the individual animal, which was reconstructed from computed tomographic images obtained preoperatively and registered to the operative field. In five large (40-60 kg) healthy pigs, percutaneous subxiphoid access to the sac using both anterior and posterior approaches was performed. Spatial inaccuracy was measured as the distance between the pericardial puncture site and the anterior or posterior descending coronary artery, the pericardium contiguous to which had been targeted by the needle. In each animal, pericardial access was gained at 4 discrete sites (2 anterior, 2 posterior). Inaccuracy was 4.2 ± 2.2 millimeters (range 0-8 millimeters) and did not differ significantly between anterior and posterior approaches. No damage to the epicardium or coronary arteries was observed. CONCLUSIONS: Percutaneous subxiphoid access to the pericardial sac utilizing this toolkit was feasible, including safety and reasonable accuracy.

The National Heart, Lung, and Blood Institute Pediatric Circulatory Support Program.

Options for the circulatory support of pediatric patients under the age of 5 years are currently limited to short-term extracorporeal devices, the use of which is often complicated by infection, bleeding, and thromboembolism. Recognizing this void, the National Heart, Lung, and Blood Institute solicited proposals for the development of novel circulatory support systems for infants and children from 2 to 25 kg with congenital or acquired cardiovascular disease. Five contracts were awarded to develop a family of devices that includes (1) an implantable mixed-flow ventricular assist device designed specifically for patients up to 2 years of age, (2) another mixed-flow ventricular assist device that can be implanted intravascularly or extravascularly depending on patient size, (3) compact integrated pediatric cardiopulmonary assist systems, (4) apically implanted axial-flow ventricular assist devices, and (5) pulsatile-flow ventricular assist devices. The common objective for these devices is to reliably provide circulatory support for infants and children while minimizing risks related to infection, bleeding, and thromboembolism. The devices are expected to be ready for clinical studies at the conclusion of the awards in 2009.

Development and in vitro evaluation of infection resistant materials: A novel surface modification process for silicone and Dacron.

Silicone and Dacron are used in a wide spectrum of implantable and indwelling medical products. They elicit a foreign body response, which results in a chronic inflammatory environment and collagenous encapsulation of the medical device that compromises the immune system's ability to effectively fight infections at the biomaterial surface. The objective of this work is to evaluate a novel process to modify silicone and Dacron with a bioactive collagen surface coupled to a gentamicin impregnated hydrogel graft and assess the surface's cytocompatibility and infection resistance properties. Samples of silicone and polyethylene terephthalate (Dacron velour) were modified by plasma deposition and activation followed by a co-polymer acrylic acid (AA)/acrylamide (AAm) hydrogel graft and covalent immobilization of a bioactive collagen surface. The modified surfaces were characterized using FTIR, contact angle, staining, SEM, and XPS. The poly (AA-AAm) hydrogel was impregnated with gentamicin and tested for controlled release characteristics. Each modified surface was evaluated for its ability to resist infection and to promote normal healing as measured by bacterial growth inhibition (Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa) in both broth and agar conditions as well as using fluorescence microscopy to observe adherence of 3T3-NIH fibroblasts. The addition of the poly (AA-AAm) hydrogel with gentamicin inhibited bacterial growth and the subsequent addition of the collagen surface promoted robust fibroblast adhesion on both silicone and Dacron materials. Thorough surface characterization and in vitro bacterial and fibroblast evaluation results suggest that this novel surface bioengineering process generated a highly effective surface on silicone and Dacron with the potential to reduce infection and promote healing.

In vitro assessment of blood compatibility: residual and dynamic markers of cellular activation.

The blood compatibility of materials and surfaces used for medical device fabrication is a crucial factor in their function and effectiveness. Expansion of device use into more sensitive and longer term applications warrants increasingly detailed evaluations of blood compatibility that reach beyond the customary measures mandated by regulatory requirements. A panel of tests that assess both deposition on the surface and activation of circulating blood in contact with the surface has been developed. Specifically, the ability of a surface to modulate the biological response of blood is assessed by measuring: (1) dynamic thrombin generation; (2) surface-bound thrombin activity after exposure to blood; (3) activation of monocytes, polymorphonuclear leukocytes, lymphocytes, and platelets; (4) activation of complement; and (5) adherent monocytes, polymorphonuclear leukocytes, lymphocytes, and platelets on blood-contacting surfaces. The tests were used to evaluate surfaces modified with immobilized heparin (Ension's proprietary bioactive surface) and demonstrated that the modified surfaces reduced platelet activation, leukocyte activation, and complement activation in flowing human blood. Perfusion of the surfaces with human platelet-rich plasma showed that the immobilized heparin surfaces also reduce both dynamic thrombin levels in the circulating plasma and residual thrombin generated at the material surface.

In vitro characterization and performance testing of the ension pediatric cardiopulmonary assist system.

In the last 40 years, mechanical circulatory support devices have become an effective option for the treatment of end-stage heart failure in adults. Few possibilities, however, are available for pediatric cardiopulmonary support. Ension Inc. (Pittsburgh, PA) is developing a pediatric cardiopulmonary assist system (pCAS) intended to address the limitations of existing devices used for this patient population. The pCAS device is an integrated unit containing an oxygenator and pump within a single casing, significantly reducing the size and blood-contacting surface area in comparison to current devices. Prototype pCAS devices produce appropriate flows and pressures while minimizing priming volume and preparation time. The pCAS was tested on a mock circulation designed to approximate the hemodynamic parameters of a small infant using a 10-Fr. extracorporeal membrane oxygenation inflow cannula and an 8-Fr. extracorporeal membrane oxygenation outflow cannula. Revision 4 of the device provided a flow rate of 0.42 L/min at 6,500 RPM. Revision 5, featuring improved impeller and diffuser designs, provided a flow rate of 0.57 L/min at 5,000 RPM. The performance tests indicate that for this cannulae combination, the pCAS pump is capable of delivering sufficient flows for patients <5 kg.

A regional system for delivery of primary percutaneous coronary intervention in ST-elevation myocardial infarction: STEMI-St. Cloud.

BACKGROUND: Strategies of emergency care in the treatment of ST-segment elevation myocardial infarction (STEMI) have evolved rapidly over the past two decades to include primary percutaneous coronary intervention (PPCI) when possible. Most U.S.-based transfer programs still use complicated protocols that include fibrinolytic therapy often resulting in transfer delays, inappropriately applied therapy (wrong diagnosis) and bleeding and stroke complications. These protocols are often emphasized in low-volume centers. We implemented a program absent fibrinolytic therapy and applied it to a network of 25 participating hospitals over a 100-mile radius in central Minnesota. METHODS AND RESULTS: One-thousand consecutive patients ages 21 to 90 who presented within 12 hours of the onset of symptoms consistent with MI from April, 2004 to January, 2008 were included in this registry. Prior to transfer to the cardiac catheterization laboratory, patients received aspirin and heparin. Clopidogrel was added to the protocol in January, 2007. Glycoprotein (GP) IIb/IIIa inhibitors were typically utilized after diagnostic catheterization and prior to PPCI. Median door-to-balloon time was 56 minutes at the PCI Center and 110 minutes from referral sites (RS). Of the transfer patients, 71% underwent helicopter transfer. The success rate for PPCI was 99.4%. Despite inherent transfer delays, there was no difference in mortality between the PCI Center and RS. Overall mortality rates in-hospital, at 30 days, at 6 months, and 1 year were 2.1%, 2.9%, 3.8% and 4.5%, respectively, with follow up on 998 of 1,000 patients. In-hospital stroke, reinfarction and major bleeding were 0.7%, 2.0% and 2.7%, respectively. CONCLUSIONS: Despite increasing trends toward a pharmacoinvasive approach in transfer patients with STEMI, a protocol which stresses rapid transfer and PPCI results in excellent outcomes, with very low complication rates without fibrinolytic therapy.

Computational fluid flow and mass transfer of a functionally integrated pediatric pump-oxygenator configuration.

Ension, Inc., under a contract with the National Heart, Lung, and Blood Institute (HHSN268200448189C), is currently developing a pediatric cardiopulmonary assist system (pCAS). This work reports on the utilization of computational fluid dynamics to predict the performance of the first of two device iterations before physical fabrication and in vitro testing. Fluent, Inc. was consulted to assist with key technical aspects of model development. Activities included porous model development and verification, generation of predictive fluid velocity fields, and incorporation of postprocessing subroutines for calculating oxygenation, decarbonation, and hemolytic blood damage. Experimental validation was conducted using bovine blood and good quantitative agreement with computational predictions was demonstrated. The success of this work suggests that the generated models and subroutines can be used as a practical tool for design and analysis of subsequent candidate pCAS design configurations.

A computer model of the pediatric circulatory system for testing pediatric assist devices.

Lumped parameter computer models of the pediatric circulatory systems for 1- and 4-year-olds were developed to predict hemodynamic responses to mechanical circulatory support devices. Model parameters, including resistance, compliance and volume, were adjusted to match hemodynamic pressure and flow waveforms, pressure-volume loops, percent systole, and heart rate of pediatric patients (n = 6) with normal ventricles. Left ventricular failure was modeled by adjusting the time-varying compliance curve of the left heart to produce aortic pressures and cardiac outputs consistent with those observed clinically. Models of pediatric continuous flow (CF) and pulsatile flow (PF) ventricular assist devices (VAD) and intraaortic balloon pump (IABP) were developed and integrated into the heart failure pediatric circulatory system models. Computer simulations were conducted to predict acute hemodynamic responses to PF and CF VAD operating at 50%, 75% and 100% support and 2.5 and 5 ml IABP operating at 1:1 and 1:2 support modes. The computer model of the pediatric circulation matched the human pediatric hemodynamic waveform morphology to within 90% and cardiac function parameters with 95% accuracy. The computer model predicted PF VAD and IABP restore aortic pressure pulsatility and variation in end-systolic and end-diastolic volume, but diminish with increasing CF VAD support.

Effect of continuous and pulsatile flow left ventricular assist on pulsatility in a pediatric animal model of left ventricular dysfunction: pilot observations.

Pediatric ventricular assist devices are being developed that can produce pulsatile flow (PF) or continuous flow (CF). An important aspect of choosing between these two modes is understanding the consequences of each mode on pediatric vascular pulsatility. Differences in vascular pulsatility generated by PF and CF operation of the 3-inch pediatric cardiopulmonary assist system (pCAS, Ension, Inc., Pittsburgh, PA) were investigated while providing left atrium-to-aorta left ventricular assist (LVA), using an infant animal model of left ventricular dysfunction. Hemodynamic data were digitally recorded with the pCAS providing LVA at incremental flow rates while operating in continuous mode, pulsatile mode at 100 bpm, and pulsatile mode at 140 bpm. These data were used to calculate vascular input impedance (Zart), energy equivalent pressure, and surplus hemodynamic energy as indices of pulsatility for partial (50% of maximum) and maximum LVA flow. Both CF and PF LVA by the pCAS resulted in favorable hemodynamic rectification of left ventricular dysfunction while generating equivalent flows. PF LVA maintained a greater degree of pulsatility compared with CF, as evidenced by increasing energy equivalent pressure and a lesser drop in surplus hemodynamic energy with increasing pCAS flow. Differences in Zart modulus and phase were indiscernible. The selection of flow mode may have long-term consequences on Zart and end-organ perfusion affecting clinical outcomes in pediatric patients.

Progress toward an ambulatory pump-lung.

OBJECTIVES: Currently available therapies for acute and chronic lung diseases have not been effective and have various problems associated with the technologies used. We present a novel active mixing pump-lung with the goal of providing total respiratory support to ambulatory patients. METHODS: The pump-lung is based on the concept of active mixing oxygenation within a constrained vortex. The rotation of hollow-fiber membranes disrupts the concentration boundary layer, increasing gas exchange efficiency, and simultaneously pumps the blood. Consequently, the amount of membranes required to achieve gas transfer sufficient for total respiratory support is considerably small. A series of studies, including computational design, experimental bench testing, and in vivo animal experiments, have been performed to implement this concept into a viable artificial pump-lung device. RESULTS: A series of pump-lung prototypes with a membrane surface area of 0.17 to 0.5 m2 were designed and characterized in vitro with bovine blood, demonstrating extremely high gas exchange efficiency. The prototype with a gas exchange surface area of 0.5 m2 was evaluated in calves. The device provided oxygen transfer of approximately 115 mL/min for respiratory support of an animal for up to 5 days. CONCLUSIONS: Progress to date suggests a high likelihood of success for an extracorporeal shorter-term lung that can be switched in and out like dialysis devices. Our device is unique in that it incorporates an integrated pumping and active mixing principle for excellent gas transfer and eliminates the need of the native right ventricle's ability to power blood through the artificial and natural lungs.

Predicting membrane oxygenator pressure drop using computational fluid dynamics.

Three-dimensional computational fluid dynamic (CFD) simulations of membrane oxygenators should allow prediction of spatially dependent variables and subsequent shape optimization. Fiber bed complexity and current computational limitations require the use of approximate models to predict fiber drag effects in complete device simulations. A membrane oxygenator was modified to allow pressure measurement along the fiber bundle in all cardinal axes. Experimental pressure drop information with water perfusion was used to calculate the permeability of the fiber bundle. A three-dimensional CFD model of a commercial membrane oxygenator was developed to predict pressure drops throughout the device. Darcy's Law was used to account for the viscous drag of the fibers and was incorporated as a momentum loss term in the conservation equations. Close agreement was shown between experimental and simulated pressure drops at lower flow rates, but the simulated pressure drops were lower than experimental results at higher flows. Alternate models of fiber drag effects and flow field visualization are suggested as means to potentially improve the accuracy of the flow simulation. Computational techniques coupled with experimental verification offer insight into model validity and show promise for the development of accurate three-dimensional simulations of membrane oxygenators.