Extracorporeal Circulation Devices Research Articles

Abstract 10926: Warfarin Dosing Algorithms With the Information on Genotype and Amiodarone for Patients Without Extracorporeal Circulation Devices Could Be Beneficial for Those With Left Ventricular Assist Devices

Introduction: Many prediction algorithms for warfarin maintenance dose (WD) were constructed based on the clinical and genetic information of the patients without extracorporeal circulation devices (ECDs). However, it is unclear whether might be useful for the patients with ECD, such as left ventricular assist devices (LVAD), who still require warfarin. Hypothesis: The WD algorithms constructed using non-ECD patients could be useful for LVAD patients. Methods: An observational study, the Human Genome Research Ethics Committee of OU approved (#756), was conducted at the Osaka University (OU) Hospital on 108 LVAD patients receiving warfarin therapy. Genetic polymorphisms of CYP2C9*1, *3, and VKORC1-1639G>A were tested using TaqMan genotyping assay kits. WD was defined as the administered dose during the periods when the PT-INR value was within its target range. We investigated the difference between the actual warfarin dose (AWD) and the calculated warfarin dose (CWD) using an algorithm proposed by the International Warfarin Pharmacogenetics Consortium (IWPC), which we verified with 125 Japanese non-ECD patients previously (Eur J Clin Pharmacol, 75:901). Results: The percentage of patients whose difference between CWD and AWD was within 20% of AWD showed no significant difference between the LVAD and the non-ECD (%; I, LVAD, 41.7, non-ECD, 49.6, p=0.23). The root mean squared percentage error (RMSPE) to the AWD was similar between the groups (%; LVAD, 42, non-ECD, 37). As the algorithm requires if amiodarone is concomitant with warfarin, we probed the effect of the amiodarone dose on the CWD. Interestingly, RMSPE of the LVAD with ≥ 200 mg/day of amiodarone (≥ 200A) was higher compared to those with < 200 mg/day (<200A) and without amiodarone (%; 85.5, 25.9, 36.8). The difference between AWD and CWD of ≥ 200A was significantly higher than <200A (mg/day; 0.87, -0.07; p=0.012). We verified similar tendencies using other algorithms published before. Conclusions: The WD algorithm with the information on genotype and concomitant use of amiodarone for the non-ECD could be beneficial for the LVAD. Besides them, extra careful attention should be required for patients with ≥ 200 mg/day of amiodarone not to have warfarin overdosed.

Superhydrophobic Biological Fluid-Repellent Surfaces: Mechanisms and Applications.

Superhydrophobic biological fluid-repellent surfaces (SBFRSs) have attracted great attention in the treatment of blood and urine-related diseases because of their unique wettability and compatibility, which creates a new path for the development of medical apparatus and instruments, and are expected to create advances in various fields. Here, this review provides an up-to-date summary of research progress on the repellent mechanism and application of SBFRSs. The underlying physical and chemical principles for designing superhydrophobic surfaces are first introduced. Then, the dialectical influences of solid-liquid interactions between superhydrophobic surfaces and biological fluids on the wettability and compatibility are emphatically expounded. Subsequently, attention is drawn to the recent applications of SBFRSs in biomedical fields, such as surgical medical apparatus, implant materials, extracorporeal circulation devices, and biological fluid detection. Finally, the outlook and challenges in terms of employing SBFRSs are also discussed. This review is expected to provide a comprehensive guidance for the preparation of SBFRSs with compatibility and long-term superhydrophobic stability that is closely related to clinical applications.

Functionalized Silicone Elastomer via Alkaline Solution to Coat Phosphorylcholine-Based Copolymer Containing Organosilane to Improve Hemocompatibility for Medical Devices

Surface modification of hemocompatible copolymers on silicone elastomers (SEs) is crucial for the long-term use of medical devices. Both physical adsorption and chemical conjugation are important for modification of SE. Oxygen plasma treatment is widely used to produce silanol groups on SE for silane coupling. However, the plasma reaction is difficult to apply to the surface modification of three-dimensional complex devices. This study demonstrated an appropriate and efficient method with alkaline solution for producing silanol groups on SE for modifying phosphorylcholine-based copolymer with organosilane (cross-MPC copolymer). A 2.5 wt% aqueous solution of potassium hydroxide (KOH) was effective in producing silanol groups and for coating the cross-MPC copolymer. Additionally, we successfully modified the cross-MPC copolymer on the inner surface of SE tubes after pretreatment with the 2.5 wt% KOH aqueous solution, and the copolymer film was coated homogeneously. The cross-MPC copolymer film on SE was stable for one month under fluidic condition with a shear stress of 3.2 Pa. The hollow fiber membrane with the polymer coating inhibited blood coagulation after one week implantation with extracorporeal circulation device using a goat. Therefore, pretreatment of SE using an alkaline solution is an appropriate method for producing silanol groups for coating the cross-MPC copolymer by silane-coupling reaction.

Questionnaire survey for grasping the current situation of clinical engineers regarding drug treatment at the time of extracorporeal circulation device

Questionnaire survey for grasping the current situation of clinical engineers regarding drug treatment at the time of extracorporeal circulation device

Biocompatibility of a polymer-coated membrane possessing a hydrophilic blood-contacting layer: Adsorption-related assessment.

Currently, the foreign surfaces of extracorporeal circulation devices are coated with an acrylate-based copolymer that creates a hydrophilic blood-contacting layer to enhance biocompatibility. Several reports of acrylate-based copolymer with respect to biocompatibility have been published; however, the adsorption of peptide compounds on acrylate-based copolymer-coated membranes still requires clarity. In this study, we aimed to understand the adsorption of several peptide compounds of various molecular weights, including albumin, lysozyme, and vancomycin, on acrylate-based copolymer-coated membranes using in vitro studies. Six experimental circuits consisting of acrylate-based copolymer-coated tubes and membranes, and six comprising acrylate-based copolymer-coated tubes and non-coated membranes were prepared for comparison. An experimental solution, composed of albumin, lysozyme, vancomycin, and saline, was continuously stirred in a reservoir, recirculated in each experimental circuit, and then filtered. Concentrations of albumin, lysozyme, and vancomycin were measured after 0, 15, 30, 45, 60, 90, and 120 min of recirculation. Similar experiments were performed in all the prepared circuits. The ratio of measured values at each time point to those at 0 min was not significantly different between acrylate-based copolymer-coated and non-coated membranes for albumin and lysozyme, but differed significantly for vancomycin; the ratios were higher in acrylate-based copolymer-coated than in non-coated membranes. This study suggests that albumin is not adsorbed on either acrylate-based copolymer-coated or non-coated membranes, that lysozyme is not adsorbed on either membrane or is adsorbed at a similar rate on both membranes, and that vancomycin is less adsorbed on acrylate-based copolymer-coated membranes. Thus, acrylate-based copolymer coating could inhibit the adsorption of various peptide compounds.

Deep Penetration of Targeted Nanobubbles Enhanced Cavitation Effect on Thrombolytic Capacity.

Sonothrombolysis with microbubbles can enhance the dissolution of thrombus through the cavitation effect of microbubbles under ultrasound irradiation. However, the detailed mechanism of thrombolysis with microscaled or nanoscaled bubbles is still not so clear. This study compared the thrombolytic capacity of cRGD-targeted or nontargeted bubbles with different particle sizes combined with urokinase (UK). The size of the microscaled bubbles (Mbs or Mbs-cRGD) was mostly approximately 3 μm, while the nanoscaled bubbles (Nbs or Nbs-cRGD) were mainly around 220 nm. In vitro testing was performed on an extracorporeal circulation device that mimics human vascular thromboembolism. The rabbit clots in Mbs with UK groups showed peripheral worm-like dissolution, while the clots in Nbs with UK groups showed internal fissure-like collapse. In addition, the thrombolysis rate of Nbs-cRGD with the UK group was the highest. Furthermore, the scanning electron microscopic images showed that the fibrin network was the most severely damaged by the Nbs-cRGD, and most of the fibrin strands were dissolved. Especially, the Nbs-cRGD can penetrate much deeper than Mbs-cRGD into the thrombus and loosen the fibrin network. Taken together, benefiting from the specific identification and deep penetration to thrombus, our developed novel targeted Nbs may have broad application prospects in the clinic.

A magnetic resonance imaging-compatible small animal model under extracorporeal circulation.

The impact of different extracorporeal circulation (ECC) scenarios on arterial blood flow profiles has not yet been revealed. To allow for exact measurements, magnetic resonance imaging (MRI) during ECC is required. Therefore, the present study addressed the feasibility of a high-resolution MRI-compatible animal model of ECC. For usage in New Zealand White rabbits, we developed an ECC device, the tubes of which were long enough to eliminate impacts of the magnetic field on the blood pump and heart-lung control machine. The miniaturized ECC system via thoracic access comprised an infant oxygenator, a pulsatile centrifugal pump, 1/8″ tubes, a 10-Fr aortic cannula and a 12-Fr venous cannula for vacuum-assisted drainage. This miniaturized ECC system has very low priming volume (230-255 ml) to reduce the system-inherent haemodilution to 50%. Consequently, haemoglobin rates remained high enough to guarantee adequate oxygenation (arterial pressure of oxygen >200 mmHg). Optimized venous drainage by an additionally inserted pulmonary artery vent catheter resulted in sufficient blood flow (31.6-65.8 ml/min/kg) that was maintained for 60 min with pulsatility. The current study demonstrates the feasibility of MRI-compatible ECC in rabbits, and this model allows for real-time blood flow profile measurements during different ECC scenarios in future projects.

Antithrombotic properties of hemofilter coated with polymer having a hydrophilic blood-contacting layer.

Objective:Extracorporeal circulation devices are coated with a biocompatible polymer coating agent (BPCA) that has a hydrophilic blood-contacting layer, but hemofilters are not. We aimed to investigate the antithrombotic properties of a BPCA-coated hemofilter.Methods:Four experiments using BPCA-coated circuits and non-coated hemofilters and four experiments using BPCA-coated circuits and BPCA-coated hemofilters were performed with whole human blood and compared by measuring the circuit pressure every 5 min, antithrombin activity every 40 min, and thrombin–antithrombin complex every 40 min, for a total of 240 min of recirculation.Results:The mean time required for the pressure at the inlet of the hemofilter to increase sharply was longer in BPCA-coated than in non-coated hemofilters (66 ± 11 min vs 25 ± 9 min, p < 0.01). The mean antithrombin activity value at 200 and 240 min of recirculation was significantly higher in the experiments with BPCA-coated versus non-coated hemofilters (43.3 ± 2.87 vs 33.3 ± 5.74, p = 0.04; 42.8 ± 3.59 vs 31.0 ± 5.35, p = 0.01, respectively); the antithrombin activity values at the other time points were not significantly different. Furthermore, all thrombin–antithrombin complex values in experiments with the BPCA-coated hemofilters achieved overrange at 80 min of recirculation, whereas those with the non-coated hemofilter achieved overrange at 40 min.Conclusion:This study suggests that BPCA-coated hemofilters can inhibit antithrombin consumption, contributing to antithrombotic effects in extracorporeal circulation circuits.

226. Microfluidic platform to restore the angiogenic balance in preeclampsia

Introduction Preeclampsia is a hypertensive disorder of pregnancy linked to placenta insufficiency. Clinical studies have shown that the severity of preeclampsia is associated with the excess or the lack of angiogenic factors such as the sFlt-1/PlGF ratio (soluble Fms-like tyrosine kinase 1 and placental growth factor). Objectives Our objective is to readjust the angiogenic balance of factors that play a causative role in preeclampsia by a competitive bioassay. A specific ligand, here VEGF (Vascular Endothelial Growth Factor), is used to both capture the protein sFlt-1 in excess and release its ligand PlGF in default. Method A microfluidic extra corporal technology of micro-fluidized bed was developed to be used as a platform to screen strategies of competitive bioassay. This fluidic configuration enhances transfer between a fluid and the surface of the beads, with low back pressure and reduced risks of clogging. By grafting specific ligands on the surface of the beads, we can use this asset to capture a target present in the sample. Results This device was able to capture sFlt-1 (up to 46% ± 1 of capture) in culture supernatant and maternal plasma. We demonstrate more importantly that compared to classical apheresis columns the nonspecific absorption is completely controlled ( Discussion Continuous flow analysis enables to reach a good capture efficiency of sFlt-1. This dynamic platform mimics an extracorporeal circulation device at high flow rate, low cost and needs small volumes of sample. This last property enables us to work with precious samples such as maternal pathologic plasma.

Hemodialysis membrane coated with a polymer having a hydrophilic blood-contacting layer can enhance diffusional performance.

PurposeCurrently, the foreign surfaces of various extracorporeal circulation devices are coated with a biocompatible polymer coating agent (BPA), which creates a hydrophilic blood-contacting layer to reduce thrombogenicity, while the membranes in hemodialyzers are not. We aimed to clarify other side effects of BPA-coated membranes by examining the diffusion performance in in vitro experiments.MethodsWe used a polyethersulfone membrane (sieving coefficient of albumin is ≤0.01) coated with BPA product, SEC-1™ (Toyobo), in a hemodialyzer. To estimate the diffusion rates of a wide range of molecules, 2 L of saline containing vancomycin, lysozyme, and albumin were recirculated in the circuit configured with a hemodialyzer, and dialyzed continuously using water. The concentrations of sodium, vancomycin, lysozyme, and albumin were measured every 5 minutes for 30 minutes and compared in experiments with BPA-coated (n = 4) and BPA-noncoated (n = 4) membranes.ResultsThe removal rates of sodium and vancomycin after 5 minutes of dialysis (n = 24) were significantly higher in BPA-coated than noncoated membranes, while those of lysozyme and albumin were not significantly different. The removal rates of sodium and vancomycin after 30 minutes of dialysis (n = 4) were significantly higher, and those of lysozyme were significantly lower in BPA-coated than noncoated membranes, while those of albumin were not significantly different.ConclusionsThe preliminary study suggests that BPA-coated membranes enhanced the diffusion rate of molecules with low and middle molecular weight without affecting the sieving coefficient of albumin. Thus, BPA coating can enhance the dialysis performance of membranes.

A phase II study of laparoscopic hyperthermic intraperitoneal chemoperfusion (HIPEC) for gastric carcinomatosis or positive cytology.

TPS186 Background: Over the last 2 decades, intraperitoneal chemotherapy has been found to have activity for select subgroups of patients with carcinomatosis from colon, ovarian, appendiceal, and recently, gastric origins. However, there is little data to support an aggressive surgical approach of cytoreduction (debulking) and HIPEC for patients with gastric cancer and positive cytology or carcinomatosis. The morbidity and mortality rates of cytoreduction and HIPEC, in combination with gastrectomy, are significant and the survival rates of this approach may not extend beyond that of treatment with systemic chemotherapy. The purpose of this clinical trial, therefore, is to perform HIPEC in a neoadjuvant fashion via a minimally invasive approach without cytoreduction for patients with gastric cancer and positive cytology or low volume carcinomatosis. Patients found to have resolution of all extra-gastric disease will then be candidates for gastrectomy. Methods: Patients with gastric and gastroesophageal adenocarcinoma and positive peritoneal cytology or radiologically-occult carcinomatosis that have completed treatment with systemic chemotherapy are offered participation in the study. Type and duration of systemic chemotherapy is left to the discretion of the treating medical oncologist. Laparoscopic HIPEC consists of Mitomycin C 30 mg and Cisplatin 200 mg in 3-7 liters of infusate circulated using an extracorporeal circulation device at a flow rate of 700-1500 mL/minute for 60 minutes, performed no sooner than 3 weeks after completion of systemic chemotherapy. The Laparoscopic HIPEC procedure may be performed up to 5 times, with a minimum of 3 weeks between procedures. After laparoscopic HIPEC, subjects whose disease did not progress will proceed to surgery with diagnostic laparoscopy and possibly exploratory laparotomy to assess resectability, and if their cancer is resectable will undergo gastrectomy. After completion of study–related treatment, subjects will be followed until recurrence and/or death for up to five years. Fourteen of planned 30 patients have been enrolled (NCI-2014-01105). Clinical trial information: NCI-2014-01105.

On the Use of the Platelet Activity State Assay for the In Vitro Quantification of Platelet Activation in Blood Recirculating Devices for Extracorporeal Circulation.

We designed an experimental setup to characterize the thrombogenic potential associated with blood recirculating devices (BRDs) used in extracorporeal circulation (ECC). Our methodology relies on in vitro flow loop platelet recirculation experiments combined with the modified-prothrombinase platelet activity state (PAS) assay to quantify the bulk thrombin production rate of circulated platelets, which correlates to the platelet activation (PA) level. The method was applied to a commercial neonatal hollow fiber membrane oxygenator. In analogous hemodynamic environment, we compared the PA level resulting from multiple passes of platelets within devices provided with phosphorylcholine (PC)-coated and noncoated (NC) fibers to account for flow-related mechanical factors (i.e., fluid-induced shear stress) together with surface contact activation phenomena. We report for the first time that PAS assay is not significantly sensitive to the effect of material coating under clinically pertinent flow conditions (500 mL/min), while providing straightforward information on shear-mediated PA dynamics in ECC devices. Being that the latter is intimately dependent on local flow dynamics, according to our results, the rate of thrombin production as measured by the PAS assay is a valuable biochemical marker of the selective contribution of PA in BRDs induced by device design features. Thus, we recommend the use of PAS assay as a means of evaluating the effect of modification of specific device geometrical features and/or different design solutions for developing ECC devices providing flow conditions with reduced thrombogenic impact.

Sudden Thrombosis in Coronary Artery Bypass Grafting Surgery

Sudden Thrombosis in Coronary Artery Bypass Grafting Surgery

Heart Transplantation Using Donors after Circulatory Death: From Research to Clinical Practice

Donation after circulatory death for heart transplantation was abandoned in the 1970s with the advent of the brain death law (donation after brain death), where the donor heart is beating and perfused up to the moment prior to organ retrieval. Shortage of donors has renewed the interest in animal and clinical research of donors after circulatory death for heart transplantation, aiming at optimizing heart function after the period of oxygen deprivation caused by severe hypotension and subsequent circulatory arrest. This study presents the initial experience with donation after circulatory death for heart transplantation at our institution. Papworth Hospital has performed a successful clinical investigation in which ten cardiac transplants were performed with hearts from donation after circulatory death, without mortality. Low risk recipients who had previously signed their consent were chosen. Most hearts from donation after circulatory death were reperfused with an extracorporeal circulation device, and following weaning from the circulatory support the heart was harvested and connected to the perfusion machine for transportation and simultaneous assessment of function before implantation. In conclusion, this technique could be used for cardiac transplantation with satisfactory outcomes.

Application of electrical resistance tomography for thrombus visualization in blood

Visualization of a thrombus is very important in the development of various artificial organs and extracorporeal circulation devices. This paper presents an application of electrical resistance tomography (ERT) technique for the visualization of a thrombus in blood. Experiments were conducted in static and flowing bovine and swine blood samples. Artificially created thrombi were mixed in the blood samples for visualization. Eight-electrode tomography sensor was used for the measurement. Cross-sectional resistivity distribution was reconstructed using linear back projection algorithm. A thrombus was characterized by increased local resistivity. We successfully reconstructed the time, size and cross-sectional location of a thrombus, and reached a conclusion that the concentration and orientation of the RBCs in a thrombus contributed to the increase in the resistivity. The increment was relatively higher in the static blood than in flowing blood. These findings can be helpful in the development of an instrumentation system for the real-time monitoring of blood to visualize a thrombus. Developers of left ventricular assistance devices, heart-lung machines, hemodialyzer etc., and the end-users (i.e. patients) can greatly benefit from such a system.

The Concept of Artificial Liver Support by Using the Extracorporeal Circulation System

In this study, a basic research on artificial liver was performed for its application to people on the waiting list of liver transplant or patients with hepatic insufficiency. Artificial livers are generally classified into mechanic type, bioartificial type, and hybrid type. An extracorporeal circulation device was examined herein, which is indispensable in the application of an artificial liver, for its effectiveness in supporting the recovery of liver functions. Extracorporeal circulation system is a treatment and life-support system which sends out the patient's blood, removes toxicity by various methods, and then sends the blood back to the interior of the body. This study used an extracorporeal circulation system which enables the Plasma Perfusion by CVVH method, and applied the program of Bioateco corp. Animals with acute hepatic insufficiency were produced to apply the extracorporeal circulation device. As a result, their ammonia, bilirubin, SGOT, SGPT, and bile acid levels rose, confirming the liver function restoration in the experimental animals.

Congenital Heart Defects: Early Surgical Correction and Heart Failure? Brief History

The first successful cardiac surgical procedure was performed by Robert Gross in 1938 in Boston. A 7 year-old patient underwent ligation of the ductus arteriosus [1]. In 1945, Crawford carried out the first correction for coarctation of the aorta in Sweden [2,3].Technological development that allowed for the introduction of extracorporeal circulation devices led to the beginning of open heart surgery. The first heart surgery using an extracorporeal circulation device was performed by Kirklin. Extracorporeal circulation devices had multiple negative effects on the physiology of the infant and the newborn, so that at the beginning of pediatric heart surgery, the delay of surgical correction was preferred. Initially, these devices required an extremely high priming volume that exposed the child to exanguinotransfusion. Inflammation mediators [4] caused excessive vascular permeability and tissue edema, all the more so as the age of the child was younger at the time of surgery.At first, anesthesia and intensive care for children were practically non-existent, and diagnosis was made using invasive techniques (cardiac catheterization), which most frequently generated complications. Surgical kits did not contain microsurgical instruments required for working on the fragile heart tissue of the newborn and infant. Thus, a number of palliative procedures were developed, in order to help the patient survive until the performance of surgical correction.The pathophysiology of congenital heart defects includes 3 main categories. There may be a volume load in which one or both ventricles must pump more blood than normal. This usually happens because of an increased pulmonary blood flow, as a result of a septal defect. There may be a pressure load of one or both ventricles. This can be the result of an obstruction at the outlet of the ventricle. The third possibility is cyanosis that can be secondary to a reduction in pulmonary blood flow or inadequate mixing between the two parallel circulations.Systemic pulmonary shunt reduces cyanosis by increasing pulmonary blood flow. Although from a conceptual point of view it is an easy procedure, systemic pulmonary shunt can be a challenge for the surgeon. Assessing the size of the shunt depending on the weight of the child is most important. The size of the shunt must take into consideration the subsequent development of the child, but it must not be too large in order to avoid postoperative ventricular volume overload. The Blalock-Taussig shunt was introduced by the surgeon Alfred Blalock and the cardiologist Helen Taussig [5]. The original BT shunt directly connected the sectioned subclavian artery to the right pulmonary artery and was of an adequate size to substitute for the pulmonary blood flow deficiency. In addition, this shunt had growth potential and thus, it could pathophysiologically support the patient for many years. The Waterston shunt is an anastomosis between the ascending aorta and the right pulmonary artery [6]. This shunt has the disadvantage to produce excessive pulmonary blood flow and a distortion of pulmonary arteries.The Potts shunt consists of the anastomosis of the descending aorta and the left pulmonary artery. This shunt has all the disadvantages of the Waterston shunt and in addition, it is extremely difficult to remove at the time of surgical correction.The modified BT shunt, which consists of the anastomosis of the arterial brachiocephalic trunk with the right pulmonary artery, by means of a vascular prosthesis, was introduced by deLeval [7]. This shunt was initially performed in the left subclavian artery and the left pulmonary artery through thoracotomy. It has the following advantages: it does not cause pulmonary artery distortion and pulmonary overload.High blood pressure and flow in pulmonary circulation, most frequently due to a septal defect, may lead in time to pulmonary hypertension and pulmonary vascular disease. In 1950, Muller and Dammann introduced pulmonary artery banding in order to reduce high blood pressure and flow in pulmonary circulation [8]. Like in the case of shunts, banding does not allow for an increase in diameter, so that in time, with the child’s growth, this becomes increasingly tight. It can also result in pulmonary artery distortion, so that correction and the removal of banding should be initiated as soon as possible after the regression of pulmonary hypertension.In 1950, Blalock and Hanlon introduced surgical atrial septectomy for children with transposition of the great vessels with insufficient mixing [9]. Nowadays, this septectomy is an interventional procedure performed through the rupture of the septum with a balloon catheter, according to the procedure described by Rashkind [10,11].

S0220105 体外循環デバイス開発評価のための小動物モデルの構築

S0220105 体外循環デバイス開発評価のための小動物モデルの構築

A novel small animal extracorporeal circulation model for studying pathophysiology of cardiopulmonary bypass.

Extracorporeal circulation (ECC) is indispensable for cardiac surgery. Despite the fact that ECCcauses damage to blood components and is non-physiologic, its pathophysiology has not been fully elucidated. This is because difficulty in clinical research and animal experiments keeps the knowledge insufficient. Therefore, it is desirable to have a miniature ECC model for small animals, which enables repetitive experiments, to study the mechanism of pathophysiological changes during ECC. We developed a miniature ECC system and applied it to the rat. We measured changes in hemodynamics, blood gases and hemoglobin (Hb) concentration, serum cytokines (TNF-α, IL-6, IL-10), biochemical markers (LDH, AST, ALT), and the wet-to-dry weight (W/D) ratio of the lung for assessing whether the rat ECC model is comparable to the human ECC. The ECC system consisted of a membranous oxygenator (polypropylene, 0.03 m(2)), tubing line (polyvinyl chloride), and roller pump. Priming volume of this system is only 8 ml. Rats (400-450 g) were divided into the SHAM group (n = 7) and the ECC group (n = 7). Blood samples were collected before, 60 and 120 min after initiation of ECC. During ECC, blood pressure and Hb were maintained around 80 mmHg and 10 g/dL, respectively. The levels of the inflammatory and biochemical markers and the W/D ratio were significantly elevated in the ECC group, indicating some organ damages and systemic inflammatory responses during ECC. We successfully established the ECC for the rat. This miniature ECC model could be a useful approach for studying the mechanism of pathophysiology during ECC and basic assessment of the ECC devices.

Introduction to the Anesthesiology Cardiac Arrest and Resuscitation Issue

ALTHOUGH anesthesiologists have recognized expertise in providing patient safety and comfort during surgical operations, their role largely extends beyond the operating room. Pain management, particularly but not exclusively in the postoperative setting, is a cornerstone of our clinical mission outside the operating theater. In many hospitals and medical centers, anesthesiologists are also heavily involved in critical care medicine. In France, they have been historically pioneers in building up the prehospital Emergency Medical System. In all these domains, academic and educational activities have been developed and promoted by anesthesiologists, as evidenced, for example, by the number of top-level publications by anesthesiologists in recent years in critical care. Bridging the gap between these domains is an urgent need for our specialty. It is from this perspective that the Journal chose to issue a call for articles and host a symposium at the American Society of Anesthesiologists Annual Meeting on the topic of Cardiac Arrest and Resuscitation in 2013.In 2014, cardiac arrest remains a common and life-threatening disease with poor outcome. During the past years, strategies based on translational approaches from the bench to the bedside have successfully improved mortality in other common, life-threatening diseases such as myocardial infarction, cancer, or stroke. There is no reason why cardiac arrest, through more effective resuscitation, should not benefit from these previous success stories. However, examination of the international literature on cardiac arrest and resuscitation reveals a striking paucity of groups having developed experimental models on cardiac arrest. Yet, a better understanding of the pathophysiology of altered organ perfusion (such as the brain and the kidney), as well as of reperfusion-induced injury is key to developing concepts or feasibility of organ-protective approaches or testing new drugs. In this themed issue, the reader will find a selection of high-quality experimental articles that bring original contributions in these domains. Also, robust epidemiological data on the incidence and outcome of in-hospital cardiac arrests, primarily but not exclusively those occurring in the operating room, are mandatory to identify possible unmet needs in providing care, and this statement also applies to out-of-hospital cardiac arrest. The reader will find here a panel of research articles dedicated to this task in important domains of the practice of anesthesiology, that is, anesthesia-related cardiac arrest and in hospitalization for labor and delivery. As illustrated in the themed Literature Review section included in this issue, a remarkable effort has been made by the international community toward addressing therapeutic issues related to cardiac arrest and reperfusion. As a result, robust clinical trials are now challenging previously well-accepted concepts in the clinical setting, such as the benefits of mild hypothermia or the use of large doses of epinephrine. A challenge for anesthesiologists is to lead some of these major clinical trials in future. The risk/benefit of new devices for cardiac resuscitation requires evaluation as well. These include automatic cardiac massage and extracorporeal circulation devices that may be crucial for refractory cardiac arrest. Research cooperation between emergency physicians, intensivists, and anesthesiologists, particularly those routinely using extracorporeal circulation devices, may provide important breakthroughs in this domain. Finally, a major goal successfully achieved in this issue of the Journal is to provide high-quality educational material in form of editorials, general reviews, Images in Anesthesiology, a case scenario, and some excellent case reports.We believe that this Cardiac Arrest and Resuscitation Theme Issue in Anesthesiology succeeds in highlighting the strengths and weaknesses of our specialty in this worldwide domain of interest for all physicians as it is to the general public. We hope our readers will take time to review some of this content on a problem they infrequently encounter and find material that can help them in their daily practice, just as we believe that this issue will succeed in promoting new research concepts and paradigms.The authors are not supported by, nor maintain any financial interest in, any commercial activity that may be associated with the topic of this article.