Direct Blood Contact Research Articles

Closed-loop control of extracorporeal oxygen and carbon dioxide gas transfer

Additional extracorporeal gas transfer facilitates ultra-protective mechanical ventilation during treatment of severe lung disease. The proposed automation contributes to both patient safety and therapeutic success. A decentralized control system set the oxygen and carbon dioxide gas transfer rates. The controlled variables are estimated using standard measurement devices without direct blood contact. To reduce patient stress, an outer-loop integral controller adjusts the extracorporeal blood flow. The control system was first evaluated in silico and then in vivo using an animal model. Finally, the method is shown to be feasible and its response time is sufficient to meet patients' clinical needs.

New dextran coated activated carbons for medical use

Activated carbon (AC) can be used for blood purification (hemoperfusion) to treat a range of conditions by direct perfusion of blood through an adsorbent column. The clinical effects of hemoperfusion relate to the AC adsorptive capacity, and any inflammatory response generated by direct blood contact. The use of a biocompatible coating minimizes side-effects but at the same time significantly reduces AC adsorption capacity in particular towards substances with large molecular mass. We investigated the adsorption capacity for biological molecules in a wide range of molecular masses and biocompatibility of a dextran (Dx) coated mesoporous AC (HSGD) produced from a polymer precursor. The hemocompatibility of the Dx-coated beads was investigated according to the ISO guidelines. Coating the HSGD with a Dx coating (5–30% weight of AC) decreased the specific surface area and pore volume of the materials and reduced adsorption capacity for methylene blue, vitamin B12, bilirubin and albumin, while minimizing fines production. Even the partially coated materials did not activate the inflammatory response and thus could be considered hemocompatible, with the Dx coating reducing fibrinogen adsorption and complement generation, suggesting the material warrants continued development for hemoperfusion applications.

Blood Accessibility to Fibrin in Venous Thrombosis is Thrombus Age-Dependent and Predicts Fibrinolytic Efficacy: An In Vivo Fibrin Molecular Imaging Study.

Fibrinolytic therapy of venous thromboembolism (VTE) is increasingly utilized, yet limited knowledge is available regarding in vivo mechanisms that govern fibrinolytic efficacy. In particular, it is unknown how age-dependent thrombus organization limits direct blood contact with fibrin, the target of blood-based fibrinolytic agents. Utilizing high-resolution in vivo optical molecular imaging with FTP11, a near-infrared fluorescence (NIRF) fibrin-specific reporter, here we investigated the in vivo interrelationships of blood accessibility to fibrin, thrombus age, thrombus neoendothelialization, and fibrinolysis in murine venous thrombosis (VT). In both stasis VT and non-stasis VT, NIRF microscopy showed that FTP11 fibrin binding was thrombus age-dependent. FTP11 localized to the luminal surface of early-stage VT, but only minimally to subacute VT (p<0.001). Transmission electron microscopy of early stage VT revealed direct blood cell contact with luminal fibrin-rich surfaces. In contrast, subacute VT exhibited an encasing CD31+ neoendothelial layer that limited blood cell contact with thrombus fibrin in both VT models. Next we developed a theranostic strategy to predict fibrinolytic efficacy based on the in vivo fibrin accessibility to blood NIRF signal. Mice with variably aged VT underwent FTP11 injection and intravital microscopy (IVM), followed by tissue plasminogen activator infusion to induce VT fibrinolysis. Fibrin molecular IVM revealed that early stage VT, but not subacute VT, bound FTP11 (p<0.05), and experienced higher rates of fibrinolysis and total fibrinolysis (p<0.05 vs. subacute VT). Before fibrinolysis, the baseline FTP11 NIRF signal predicted the net fibrinolysis at 60 minutes (p<0.001). Taken together, these data provide novel insights into the temporal evolution of VT and its susceptibility to therapeutic fibrinolysis. Fibrin molecular imaging may provide a theranostic strategy to identify venous thrombi amenable to fibrinolytic therapies.

An adsorbent monolith device to augment the removal of uraemic toxins during haemodialysis

Adsorbents designed with porosity which allows the removal of protein bound and high molecular weight uraemic toxins may improve the effectiveness of haemodialysis treatment of chronic kidney disease (CKD). A nanoporous activated carbon monolith prototype designed for direct blood contact was first assessed for its capacity to remove albumin bound marker toxins indoxyl sulphate (IS), p-cresyl sulphate (p-CS) and high molecular weight cytokine interleukin-6 in spiked healthy donor studies. Haemodialysis patient blood samples were then used to measure the presence of these markers in pre- and post-dialysis blood and their removal by adsorbent recirculation of post-dialysis blood samples. Nanopores (20–100 nm) were necessary for marker uraemic toxin removal during in vitro studies. Limited removal of IS and p-CS occurred during haemodialysis, whereas almost complete removal occurred following perfusion through the carbon monoliths suggesting a key role for such adsorbent therapies in CKD patient care.

膜および膜以外の除去素材を組み合わせた溶質除去－災害時にも対応可能な携帯型血液浄化システム

Hemodialysis is by far the most popular treatment modality for kidney disease patients in which blood and washingsolution (called dialysate)are separating flowing on either side of the separation membrane in order to remove wastesubstances mainly due to concentration gradient. This treatment, however, requires not only membrane devices (dialyzers)but also electric power source, computer-controlled high-tech dialysis machine, more than 120 L ofdialysate, and cannot be performed when the crisis occurs. We have been developing a wearable blood purificationsystem by combining membrane and other devices. The first system included particles of adsorbent dispersed inagar gel and it removed toxic substances as long as 1 week; however, the direct contact of blood with agar mayinduce bioincompatible reactions. The second and third systems included an ultrafilter and an adsorbent that connected to the outside loop of the ultrafilter with various returning points of ultrafiltrate. Ultrafiltration naturallyoccurs due to pressure gradient from blood compartment to the outer lumen of the membrane and the ultrafiltratereturns back to the main blood stream by virtue of the connection. Both systems showed the solute removal performances with satisfactory results. Moreover, this system may be further developed to the system with no electricpower source, water, or pump that can be available even under the crisis.

Current situation of Crimean Congo hemorrhagic fever (CCHF) in Anatolia and Balkan Peninsula

Current situation of Crimean Congo hemorrhagic fever (CCHF) in Anatolia and Balkan Peninsula

Midterm Results of Valve Repair With a Biodegradable Annuloplasty Ring for Acute Endocarditis

Conventional annuloplasty rings consist of woven, nondegradable prosthetic material. Their use should theoretically be limited in acute infective endocarditis. Novel biodegradable annuloplasty rings, which are implanted into the annulus, carry theoretical advantages, but have never been evaluated for feasibility and mid-term outcome in such patients. Between 2004 and 2009, 17 consecutive patients with acute infective endocarditis (age, 34.5+/-21.6 years; range, 11-82 years; 8 men) had mitral (n=13), tricuspid (n=3), and mitral and tricuspid (n=1) annuloplasty to conclude valve repair. Repair was performed by complete excision of the infected tissue, valvar reconstruction, and biodegradable ring annuloplasty. Prospectively collected clinical and echocardiographic data were analyzed retrospectively. Indications for surgery were heart failure (n=9; 52.9%), hemodynamic instability (n=8; 47%), and persistent infection or sepsis despite antibiotics (n=6; 35.3%). Staphylococci (n=7) and Streptococci (n=4) were the most common causes. Three patients died on postoperative days 1, 2, and 34 because of massive gastrointestinal bleeding; heart failure and pneumonia; and sepsis and acute renal failure, respectively. During a median follow-up of survivors at 29.6 months (range, 2.0 to 51.0 months), no mortality, recurrence, or reoperation occurred. At follow-up, transthoracic echocardiography revealed no or trivial regurgitation in 11 and mild in 3 patients. Left ventricular dimensions regressed significantly after mitral repair. Valve repair using a biodegradable ring showed good structural and functional properties up to 4 years after repair. Implantation of the biodegradable ring is feasible and effective in patients with acute infective endocarditis. Its intraannular implantation, hindering direct blood contact and associated risk of colonization, represents a theoretical advantage in such patients. Larger comparative studies are needed for further conclusions.

Sorbent Augmented Hemodialysis Systems

Recent publications have reintroduced the concept of using sorbent systems to augment the efficiency of the dialysis process, either by making stationary or compact wearable devices to regenerate dialysis fluid or to target larger molecules for removal by direct blood or plasma contact with sorbent particles. Many of the inherent problems associated with older sorbents have been overcome by designing sorbents with improved biocompatibility and potential for removing molecules beyond the limits of conventional dialysis membranes. One system is approved for use in acute renal failure in the United States, but other devices are not approved for use in humans and continue to be tested in animals and humans. A prototype wearable sorbent device under investigation is not yet able to meet acceptable small molecular weight solute removal, and the other sorbent devices that possess the ability to remove unconventional uremic toxins have not been studied sufficiently in dialysis patients to define their role as augmentation devices. That there is a renewal of interest in sorbents in augmentation of dialysis points to the dissatisfaction with current dialysis technology.

Hemocompatibility of high strength oxide ceramic materials: An in vitro study

High strength oxide ceramic materials like alumina and zirconia are frequently used for artificial joints because of their biocompatibility and high wear resistance. Their suitability as materials for implants and biomedical devices with direct blood contact, such as cardiovascular implants or components for blood pumps and dialyzers, has not been confirmed to date. The objective of this study was to investigate whether oxide ceramics show sufficient hemocompatibility. Dense specimens were made out of alumina, zirconia, titanium oxide, and aluminum titanate. Polyvinylchloride and silicone were additionally tested as reference materials. Interactions of human blood with the surfaces were studied by investigating partial thromboplastin time (PTT), thrombin antithrombin III complex (TAT), free plasma hemoglobin concentration, complete blood count, complement factor 5a, and protein adsorption. The results from the PTT and TAT tests clearly indicated higher blood activation by the ceramic materials when compared to the two polymer materials. However, alumina and zirconia showed lower C5a concentrations and less protein adsorption than the reference materials. Our results revealed that oxide ceramic materials alone cannot be used for implants in direct blood contact without modification of the ceramic surface, for example, by made-to-measure inert nanocoatings.

Invited commentary

In their well-written article, the authors [1Ota T. Sawa Y. Iwai S. et al.Fibronectin-hepatocyte growth factor enhances reendothelialization in tissue-engineered heart valve.Ann Thorac Surg. 2005; 80: 1794-1802Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar] describe the in-vivo re-endothelialization of decellularized tissue in a dog-model. The re-population of the implanted tissue was improved by introducing fibronectin-hepatocyte growth factor into the scaffold. The lack of endothelialization of foreign surfaces in humans is surely one of the most important issues of all biomaterials with direct blood contact. Whereas several animals, dogs included, still possess the ability to cover various implants with endothelial cells, only a short distance is covered with a kind of neointima in primates, leaving the remaining surface in direct blood contact. Lining these surfaces with autologous endothelial cells would surely improve biocompatibility. It would be the most elegant way to let it be done by the recipient himself after implantation. So far so good, but there are several limitations to the presented work and still a lot of questions to be asked.The dog model is far from being an ideal model for endothelialization, because dogs re-endothelialize various surfaces including polytetrafluoroethylene. Therefore the results achieved in this model are not transferable to humans. Introducing a growth factor obviously improved re-population. Today, several growth factors, including those attracting endothelial progenitor cells are tested in the labs. However, a clinical application would be very difficult and expensive, because the manufacturer of such pre-coated prostheses has to guarantee for the factor, its origin and purity, and its freedom from side effects. The decellularization process also requires further research to define hemodynamic stability, durability, and immunogenicity of these prostheses.The presented article can not answer all these questions; it shows an original way to achieve endothelialization after implantation of biological valve prostheses. This is a completely different approach compared with the more “classical” way of tissue engineering (ie, seeding of different cell types onto a matrix, letting them grow to confluence, and implanting the complete construct). In-vivo re-endothelialization seems to be closer to the physiological ways to repair endothelial defects but its efficacy has to be proven in long-term animal experiments. However, the article shows that the field of tissue engineering still creates new ideas and concepts. In their well-written article, the authors [1Ota T. Sawa Y. Iwai S. et al.Fibronectin-hepatocyte growth factor enhances reendothelialization in tissue-engineered heart valve.Ann Thorac Surg. 2005; 80: 1794-1802Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar] describe the in-vivo re-endothelialization of decellularized tissue in a dog-model. The re-population of the implanted tissue was improved by introducing fibronectin-hepatocyte growth factor into the scaffold. The lack of endothelialization of foreign surfaces in humans is surely one of the most important issues of all biomaterials with direct blood contact. Whereas several animals, dogs included, still possess the ability to cover various implants with endothelial cells, only a short distance is covered with a kind of neointima in primates, leaving the remaining surface in direct blood contact. Lining these surfaces with autologous endothelial cells would surely improve biocompatibility. It would be the most elegant way to let it be done by the recipient himself after implantation. So far so good, but there are several limitations to the presented work and still a lot of questions to be asked. The dog model is far from being an ideal model for endothelialization, because dogs re-endothelialize various surfaces including polytetrafluoroethylene. Therefore the results achieved in this model are not transferable to humans. Introducing a growth factor obviously improved re-population. Today, several growth factors, including those attracting endothelial progenitor cells are tested in the labs. However, a clinical application would be very difficult and expensive, because the manufacturer of such pre-coated prostheses has to guarantee for the factor, its origin and purity, and its freedom from side effects. The decellularization process also requires further research to define hemodynamic stability, durability, and immunogenicity of these prostheses. The presented article can not answer all these questions; it shows an original way to achieve endothelialization after implantation of biological valve prostheses. This is a completely different approach compared with the more “classical” way of tissue engineering (ie, seeding of different cell types onto a matrix, letting them grow to confluence, and implanting the complete construct). In-vivo re-endothelialization seems to be closer to the physiological ways to repair endothelial defects but its efficacy has to be proven in long-term animal experiments. However, the article shows that the field of tissue engineering still creates new ideas and concepts.

A new cardiopulmonary bypass circuit with reduced foreign surface (CorX™): initial clinical experience and implications for anaesthesia management

A new cardiopulmonary bypass circuit with reduced foreign surface (CorX™): initial clinical experience and implications for anaesthesia management

Heart Booster: a pericardial support device

Background. Congestive heart failure is a pervasive disease afflicting millions of people. For many, their quality of life can be significantly improved by a pericardial device that can enhance cardiac output without the added risk of thromboembolism associated with direct blood contact. Methods. A cardiac assist device with tubular elements is wrapped around the heart. Fluid is pumped into and out of the wrap causing contraction and dilation of its circumference. This contracting and relaxing action generates cardiac assistance without the need to contact blood. In vitro characterization and in vivo studies in calves were conducted to demonstrate the characteristics of the device. Results. In vitro characterization with the device wrapped around one-half of a ventricle to simulate left ventricular support demonstrated outputs of 6.5 L/min at physiological afterloads. In vivo studies in calves demonstrated both cardiac output and afterload enhancements when the device is activated. Conclusions. This study provides a first demonstration of a device that provides cardiac support by a contraction and relaxation scheme with the device wrapped around the epicardium of the heart. The main feature of this actuation method is the potential for building a small device for implantation without blood contact.

Comparison of the incision and aspiration methods for the diagnosis of placental malaria infection

SummaryA safe and efficient method for obtaining blood smears for the diagnosis of placental malaria infection is required in order to reduce the risks associated with direct blood contact. We describe a simple and safe method of needle aspiration of the placenta for the diagnosis of placental malaria infection. The method was compared with the conventional incision method in 60 consecutive placentae obtained at term. The quality of the blood smear prepared with the methods were similar. There was a significant correlation between parasite counts from samples prepared with both the incision and aspiration methods. Altman-Bland analysis of the counts revealed narrow limits of agreement with an insignificant bias. The method is useful for obtaining blood smears from the placenta for the diagnosis of placental malaria infection and reducing contact with potential pathogens in blood.

First successful bridge to cardiac transplantation using direct mechanical ventricular actuation

Currently available ventricular assist devices are technically difficult to implant, require continuous anticoagulation, and are associated with hemorrhagic and thromboembolic complications. Direct mechanical ventricular actuation is a biventricular assist device that can be applied in 3 to 5 minutes through a left anterior thoracotomy and has no direct blood contact or need for anticoagulation. The present study was designed to determine the effects of direct mechanical ventricular actuation in total biventricular circulatory support. Cardiogenic shock refractory to standard therapy developed in 2 patients awaiting cardiac transplantation. Direct mechanical ventricular actuation was applied and provided immediate hemodynamic stabilization in both. All inotropic agents and intraaortic balloon support were then discontinued. Fifty-six hours of circulatory support bridged the first patient to successful cardiac transplantation without complication. The patient is alive and well more than 1 year later without incident of infection or rejection. The second patient suffered cardiac arrest and required closed chest cardiopulmonary resuscitation before device application. After 45 hours of support, it was determined that irreversible neurologic injury had occurred and direct mechanical ventricular actuation was discontinued. Neither patient's native heart exhibited any histologic evidence of device-related trauma. Direct mechanical ventricular actuation has undergone limited clinical investigation since its original description 25 years ago, but in these initial trials, the device has proved effective. The concept of mechanically actuating the ventricles appears to be a valuable, yet under-utilized method of total circulatory support.

Fluorocarbon-encapsulated oxygen bubbles for blood oxygenation use: An experimental study

This paper is concerned with a novel class of oxygenators which Li and Asher first proposed and called "liquid membrane oxygenators." They are different from usual bubble blood oxygenators in that oxygen bubbles are individually encapsulated by a liquid fluorocarbon membrane and dispersed in blood, instead of bare oxygen bubbles normally used. The fluorocarbon membrane's role is to prevent direct contact of blood with oxygen gas which can cause a rupture of red blood cells and denaturation of proteins in blood. We have attempted to produce encapsulated bubbles by use of a fine double-tube nozzle where oxygen is supplied through the inner tube of the nozzle while a liquid fluorocarbon is supplied through the annular space between the outer and the inner tubes. This device has been found to enable steady formation, both in pure water and in an aqueous solution of bovine serum albumin, of encapsulated bubbles of about 2 mm in diameter, which are far smaller than those produced by Li and Asher's original device. A comparative study of oxygenation of water (a substitute for blood) by encapsulated bubbles and by nonencapsulated bubbles indicates that the former is only slightly inferior to the latter.

HIV Infection in Women

Acquired immunodeficiency syndrome (AIDS) cripples the immune system, making the patient susceptible to a variety of infections and disorders. AIDS is caused by direct blood contact with a transmissible agent, now known as the human immunodeficiency virus (HIV). The pathophysiology, clinical disease, and treatment of HIV infection in women are discussed.

Biocompatibility tests of components of an implantable cardiac assist device.

A permanently implantable in-series left ventricular assist device, the dynamic aortic patch (DAP), has been tested in chronic animal experiments. The DAP replaces a section of the intrathoracic aortic wall. Hemothorax and hematocele at the implantation site have been complications in recent experiments. Primary postoperative hemorrhage was ruled out, and the biocompatibility of all components was therefore examined. Dacron velour, Teflon felt, conductive polyurethane, segmented polyether polyurethane, and Teflon-coated polyester fiber sutures were implanted in the pleural cavities of dogs and tested in vitro by culturing canine saphenous vein explants on them. In vivo experiments demonstrated that all components elicited mild to moderate inflammatory reactions, but hematocele occurred only when the components were implanted in the aorta with direct blood contact and exposed to arterial blood pressures. In vitro, cells were cultured on all components with no signs of toxic reactions. These results indicated that the host tolerated all implant components without major inflammatory responses. However, histological data indicated that chronic slow bleeding into or through the Dacron velour in contact with the arterial blood serum could account for hemothorax or hematocele formation. Therefore, a configuration of the assist device using materials impermeable to blood may obviate these difficulties.

A Nonpulsatile Artificial Heart

The concept of a nonpulsatile artificial heart is discussed. The approach used in this investigation embodies the principle of a constrained force vortex to propel the blood. This novel approach eliminates the need for the direct contact of blood with impellers and also alleviates the constrictive and mechanical forces on blood cells resulting from high levels of shear and turbulence as well as direct impaction. By eliminating the direct contact of blood with these mechanical forces and with the use of atraumatic and nonthrombogenic low temperature isotropic carbon as the material of construction, a largely atraumatic pump is made possible. The use of force vortices enables the investigators to retain the high efficiency of a centrifugal impeller pump without encountering the traumatic effects of direct impeller contact. The result is a highly efficient, atraumatic, non pulsatile blood pump. The possible effects of nonpulsatile flow in the body are reviewed. Pump optimization is discussed. Finally, implantation of the artificial heart pump into animals on an experimental basis is discussed briefly.

A Nonpulsatile Artificial Heart

The concept of a nonpulsatile artificial heart is discussed. The approach used in this investigation embodies the principle of a constrained force vortex to propel the blood. This novel approach eliminates the need for the direct contact of blood with impellers and also alleviates the constrictive and mechanical forces on blood cells resulting from high levels of shear and turbulence as well as direct impaction. By eliminating the direct contact of blood with these mechanical forces and with the use of atraumatic and nonthrombogenic low temperature isotropic carbon as the material of construction, a largely atraumatic pump is made possible. The use of force vortices enables the investigators to retain the high efficiency of a centrifugal impeller pump without encountering the traumatic effects of direct impeller contact. The result is a high efficient, atraumatic, nonpulsatile blood pump. The possible effects of nonpulsatile flow in the body are reviewed. Pump optimization is discussed. Finally, implantation of the artificial heart pump into animals on an experimental basis is discussed briefly.

A Long-term Partial Bypass Oxygenation System

n adequate membrane blood oxygenator should aid in the clinical support of infants suffering from respiratory distress, congenital A heart disease, and respiratory burns. An oxygenator designed for such use must allow for minimal priming volume, extracorporeal transit time, exposed surface area, and trauma to the body and blood. The first and last criteria preclude the use of oxygenators that rely on the direct contact of blood with the oxygen gas phase (bubble, disc, screen, or centrifugal). Existing membrane oxygenators are designed primarily for adult heart-lung bypass [l, 21. They have not achieved clinical prominence, partly because of their complexity and their early stage of development. Although membrane oxygenators have proved to be much less damaging to the blood [3], the large models available cannot be adapted easily to patients who are in their first two years of life (1 to 16 kg. body weight). In addition, certain basic designs, such as individually stacked flat membranes, do not have the potential for low priming volume or transit time necessary for neonatal use. Several research groups have concentrated on developing a miniature oxygenator for infant use, and in general, new design concepts have been employed to achieve this goal. Typical reported priming volumes within the oxygenator have been between 40 ml. for partial bypass [6] and 75 ml. for total bypass [8]. The present design effort has concentrated on the use of multiple parallel silicone tubes which, for partial bypass, results in a priming volume of 5.8 ml. per kilogram of body weight within the oxygenating section, to which must be added