Showing papers in "Asaio Journal in 2002"

Early experience with a polymethyl pentene oxygenator for adult extracorporeal life support.

Abstract: Silicone oxygenators are the standard devices used for Extracorporeal Life Support (ECLS), but they have some limitations. Microporous polypropylene hollow fiber oxygenators overcome many of these problems but, unfortunately, develop plasma leak. Polymethyl-pentene (PMP) is a novel oxygenator material. We report our initial experience with the Medos Hilite 7000LT, a PMP hollow fiber oxygenator, in six adult respiratory ECLS patients with these characteristics: age, mean 32.2 (+/-13) years; weight, mean 81.2 (+/-17) kg; PaO2/FIO2, mean 62.8 [+/-33] mm Hg; Murray Score, mean 3.4 [+/-0.3]; and sepsis related organ failure assessment score, mean 9.6 [+/-2.3]. One patient was cannulated within 10 hours of multiple trauma and 1 hour after thoracolaparotomy; another patient was cannulated 12 hours after a thoracotomy. All six patients survived. Heparin was infused (7.8-32.5 u/kg/hr) to maintain activated clotting time at 162 to 238 seconds; international normalized ratio was 0.9 to 3.4. Two of the six patients required transfusions of fresh frozen plasma, receiving one and five units, respectively. Fibrinogen was 1.4 to 6 g/dl; no cryoprecipitate was needed. Platelet counts were between 65 and 306, and very little platelet transfusion (mean 2.33; +/-3.03 units per patient) was required to maintain these levels. Two patients did not require any platelet transfusion. Maximum blood flow was 5.3 L/min, sweep was 3 to 10 L/min, and resistance was 11 to 43 Paul Wood Units. There were no oxygenator failures. Mean duration of ECLS was 151.7 hours (+/-75.6). Our initial experience with PMP oxygenators in adults was satisfactory, and platelet consumption and resistance to blood flow seem to be greatly reduced with PMP.

Regeneration of the vocal fold using autologous mesenchymal stem cells

Abstract: The aim of this study was to regenerate the injured vocal fold by means of selective cultured autologous mesenchymal stem cells (MSCs). Eight adult beagle dogs were used for this experiment. Selective incubation of MSCs from bone marrow was done. These MSCs were submitted to 3-dimensional incubation in 1% hydrochloric acid atelocollagen. Three-dimensional incubated MSCs were injected into the left vocal fold, and atelocollagen only was injected into the right vocal fold of the same dog as a control. Four days after injection, the posterior parts of the vocal folds were incised. The regeneration of the vocal fold was estimated by morphological and histologic evaluations. Our results showed that 3-dimensional incubated MSCs were useful in the regeneration of the injured vocal fold. This study shows that damaged tissues such as an injured vocal fold would be able to be regenerated by tissue engineering.

Modeling and control of a brushless DC axial flow ventricular assist device.

Abstract: This article presents an integrated model of the human circulatory system that incorporates circulatory support by a brushless DC axial flow ventricular assist device (VAD), and a feedback VAD controller designed to maintain physiologically sufficient perfusion. The developed integrated model combines a network type model of the circulatory system with a nonlinear dynamic model of the brushless DC pump We show that maintaining a reference differential pressure between the left ventricle and aorta leads to adequate perfusion for different pathologic cases, ranging from normal heart to left heart asystole, and widely varying physical activity scenarios from rest to exercise.

Effect of well defined dodecahedral porosity on inflammation and angiogenesis

Abstract: Porosity is an important factor in the healing of prosthetic devices. To better understand this phenomenon, porous polyurethane scaffolds were produced by a variation of the phase inversion/porogen extraction technique in which a prepacked column of spherical porogen particles was infiltrated with a polymer solution before polymer precipitation and porogen extraction. Scaffolds contained pores of well defined shape (approaching open faced pentagonal dodecahedra), narrow size distributions (66.1 +/- 1.3 microm, 84.2 +/- 1.7 microm, and 156.9 +/- 1.2 microm) and high interconnectivity (interconnecting windows of 30.1 +/- 0.8 microm, 41.9 +/- 1.5 microm, and 76.4 +/- 2.0 microm, respectively). A high degree of accessible macroporosity (>80%) could be achieved while limiting the mostly inaccessible microporosity to below 2%. The neovascularization and inflammatory responses to the scaffolds were evaluated in the subcutaneous rat model for 4 weeks. The inflammatory response index and foreign body giant cell index could be reduced by 56% (p < 0.05) and 21% (p < 0.02), respectively, when the pore size was increased from 66 microm to 157 microm, whereas the vascularization index and arteriolar index remained unchanged. Thus, a significant decrease in inflammatory response could be achieved without adversely affecting the degree of neovascularization by increasing the size of the pores.

Dialysis adequacy and health related quality of life in hemodialysis patients.

Abstract: Patients with end-stage renal disease have significant impairments in health related quality of life (HRQOL). The determinants of HRQOL, including the effect of dialysis adequacy, have not been well studied. This study was designed to investigate whether dialysis adequacy is associated with HRQOL in hemodialysis patients. A cross-sectional survey of 128 patients who had been on hemodialysis for more than 6 months was conducted. Baseline information on demographic factors and detailed clinical information was collected. Average Kt/V levels (for the 3 months preceding HRQOL assessment) were determined. HRQOL was assessed with the Kidney Disease Quality of Life Short Form, the Short Form-36 (SF-36), and the EuroQol EQ-5D. Multiple linear regression was performed to control for differences in important baseline covariates. Patients with average Kt/V levels greater than or equal to 1.3 had better HRQOL as measured by significantly higher scores (p < 0.05) in 4 of 11 kidney disease targeted domains, 6 of 8 SF-36 domains, and on the EQ-5D visual analog scale and index score. Using multiple linear regression to control for important covariates, the adjusted EQ-5D index score was higher by 0.036 (95% confidence intervals 0.015, 0.057) for each 0.1 increment in Kt/V, which is both statistically and clinically significant. Dialysis adequacy was significantly associated with HRQOL in hemodialysis patients. Controlled studies that examine the effect of increasing Kt/V on HRQOL are needed.

Current clinical status of pulsatile pediatric circulatory support.

Abstract: Whereas circulatory support with pulsatile assist devices is an established therapy in adults today, it remains unusual and extremely challenging in children. Specifically designed smaller size pumps are, to date, only available in Europe. This review summarizes the experience with both adult size pumps in the U.S. and pediatric pumps in Europe. Thoratec ventricular assist devices (VADs) were implanted in 101 patients worldwide who were between 7 and 17 years of age. Survival in this group was 68.8%, which is comparable with that in adult patients and was independent of age or body size. Berlin Heart VADs, available in several sizes, were implanted at the Deutsches Herzzentrum Berlin in 45 patients between 2 days and 16 years old. Survival in patients with myocarditis and cardiomyopathy was 66.7% and 71.4%, respectively; overall survival was 48.9%. In a number of European centers, 64 children up to 16 years of age received Medos devices, which are also available in several sizes, with an overall survival of 36.2%, similar for all pump sizes. End-stage congenital heart defects or failure to wean off bypass carried a poorer prognosis than cardiomyopathies or myocarditis for all devices.

Biventricular support in patients with profound cardiogenic shock: a single center experience.

Abstract: Options for managing heart failure patients with cardiogenic shock refractory to inotropic and intra-aortic balloon pump (IABP) therapy are limited. Ventricular assist devices (VADs) can bridge these patients to heart transplantation. However, controversy exists over whether extracorporeal membrane oxygenation (ECMO) before VAD placement is beneficial. We report our use of biventricular assist devices (BiVADs) as a direct bridge to transplant. Since July 1999, 19 Thoratec BiVADs were implanted for heart failure unresponsive to medical therapy. Patient ages ranged from 20 to 67 years. Causes of heart failure included idiopathic 32%, ischemic 26%, postcardiotomy 21%, and other 21%. All patients were in cardiogenic shock, and three were receiving cardiopulmonary resuscitation (CPR) before implant. Preimplant conditions included IABP 89%, mechanical ventilation 68%, three or more inotropes 84%, hyperbilirubinemia 59%, acute renal failure 63%, and hemodialysis 16%. Fifty-nine percent of patients bridged successfully to transplantation, with 90% posttransplant survival. Duration of BiVAD support ranged from 0 to 91 days, with two patients currently on support awaiting transplantation. Complications included bleeding requiring reoperation 26%, stroke 11%, infection (any positive culture) 68%, and cannula site infection 5%. The Thoratec BiVAD can successfully be used as a direct bridge to transplantation in heart failure patients with cardiogenic shock. ASAIO Journal 2003; 49:475‐479. Approximately 5 million people in the United States and 23 million people worldwide suffer from heart failure. If left untreated, heart failure carries a 50% mortality at 1 year. According to the American Heart Association, 500,000 new cases of heart failure are diagnosed in the United States annually, and it is the most frequent cause of hospital admission for patients 65 years of age and older. 1,2 Heart failure can usually be treated medically. However, nearly 300,000 patients die from heart failure each year despite advances in medical treatment. 3 The majority of patients will eventually fail medical treatment and progress to endstage heart failure. These patients can then only be managed by heart transplantation. Nearly 4100 endstage heart failure patients are currently listed for heart transplantation. Unfortunately, each year, only approximately 2100 donor hearts become available to these patients. Therefore, 15% of patients per year on the waitlist succumb to their heart failure and die while awaiting transplantation. 4 Ventricular assist devices (VADs) are available for those patients with endstage heart failure who would otherwise not survive to transplant. These devices replace the function of the human heart and can support a patient while they wait for a donor heart to become available. Heart failure patients who decompensate to a state of cardiogenic shock despite maximum medical therapy and intraaortic balloon counter-pulsation (IABP) provide a considerable challenge to the clinician. Options for managing these patients are limited. VADs may be used in this setting to bridge patients to heart transplantation. However, controversy exists over whether univentricular or biventricular assist devices (BiVADs) should be used in this setting. Furthermore, conflict exists over whether these patients should initially be stabilized with a short-term interim device such as extracorporeal membrane oxygenation (ECMO), centrifugal pumps, or the Abiomed system (Danvers, MA) before VAD placement (bridge-to-bridge technique). We report here our experience using exclusively biventricular support with the Thoratec VAD (Thoratec Corporation, Pleasanton, CA) as a direct bridge to transplantation in heart failure patients with refractory cardiogenic shock.

Mechanism of complement activation during extracorporeal blood-biomaterial interaction: effects of heparin coated and uncoated surfaces.

Abstract: In vitro studies with miniaturized rotating circuits and heparinized human blood, as well as long-term extracorporeal membrane oxygenation with either heparin coated (HBS) or uncoated surfaces connected to adult sheep, were performed comparing the impact on complement activation in blood and on surfaces. Analysis of surface bound complement proteins revealed significantly reduced binding of activated C3 and C5b-9 to HBS in vitro, compared with uncoated surfaces, which was probably due to more HBS bound complement inhibitors (C1-Inhibitor, factor H) being present. This was reflected by significantly reduced activation of the alternative pathway (C3bBbP) and terminal complex (SC5b-9) by HBS but slightly increased levels of classic pathway complex (C1rs-C1-inhibitor). These results were confirmed during in vivo study by analysis of hemolytic complement function, activation specific C3 derived split products, and surface bound complement proteins. Increased binding of complement regulators to HBS appears to effectively reduce complement activation by biomaterials, leading to improved long-term biocompatibility.

Pulsatile perfusion improves regional myocardial blood flow during and after hypothermic cardiopulmonary bypass in a neonatal piglet model.

Abstract: Pediatric myocardial related morbidity and mortality after cardiopulmonary bypass (CPB) are well documented, but the effects of pulsatile perfusion (PP) versus nonpulsatile perfusion (NPP) on myocardial blood flow during and after hypothermic CPB are unclear. After investigating the effects of PP versus NPP on myocardial flow during and after hypothermic CPB, we quantified PP and NPP pressure and flow waveforms in terms of the energy equivalent pressure (EEP) for direct comparison. Ten piglets underwent PP (n = 5) or NPP (n = 5). After initiation of CPB, all animals underwent 15 minutes of core cooling (25 degrees C), 60 minutes of hypothermic CPB with aortic cross-clamping, 10 minutes of cold reperfusion, and 30 minutes of rewarming. During CPB, the mean arterial pressure (MAP) and pump flow rates were 40 mm Hg and 150 ml/kg per min, respectively. Regional flows were measured with radiolabeled microspheres. During normothermic CPB, left ventricular flow was higher in the PP than the NPP group (202+/-25 vs. 122+/-20 ml/l 00 g per min). During hypothermic CPB, no significant intragroup differences were observed. After 60 minutes of ischemia and after rewarming (276+/-48 vs. 140+/-12 ml/100 g per min; p < 0.05) and after CPB (271+/-10 vs. 130+/-14 ml/100 g per min; p < 0.05), left ventricular flow was higher in the PP group. Right ventricular flow resembled left ventricular flow. The pressure increase (from MAP to EEP) was 10+/-2% with PP and 1% with NPP (p < 0.0001). The increase in extracorporeal circuit pressure (ECCP) (from ECCP to EEP) was 33+/-10% with PP and 3% with NPP (p < 0.0001). Pulsatile flow generates significantly higher energy, enhancing myocardial flow during and after hypothermic CPB and after 60 minutes of ischemia in this model.

Pediatric circulatory support systems.

Abstract: Ventricular assist devices (VADs) are a valid option for long term circulatory support in pediatric patients with postoperative myocardial failure or debilitating heart defects. Most clinical experience to date has involved the short-term support of patients weighing 6 kg and larger. For cases of VAD implementation in pediatric patients, the assist device showed tremendous promise in reversing cardiac failure and providing adequate support as a bridge to cardiac transplantation. The Medos-HIA system, Berlin Heart, Medtronic Bio-Medicus Pump, Abiomed BVS 5000, Toyobo-Zeon pumps, and Hemopumps have proven successful for short-term circulatory support for the pediatric population. The Jarvik 2000 and Pierce-Donachy pediatric system further demonstrate the potential to be used for pediatric circulatory support. The clinical and experimental success of these support systems provide encouragement to believe that long-term support is possible.

Left ventricular assist device infections: three case reports and a review of the literature.

Abstract: Left ventricular assist device (LVAD) infections are a major device complication and are associated with significant morbidity. We report three cases of LVAD infections in our institution and review the literature to assess clinical parameters associated with infection, causative organisms, treatment modalities, and patient outcomes. A total of 46 cases were reviewed. Fever, leukocytosis, and drainage from the exit site were the most commonly reported symptoms. Left ventricular assist devices were in place an average of 65 days before the onset of infection. The most common site of LVAD infection was the drive line. Staphylococcus aureus was the most common organism, followed by gram negative rods, Candida, and enterococcus species and coagulase negative Staphylococcus. Treatment consisted primarily of surgical intervention, including incisional debridement, pump pocket exploration, and LVAD replacement and adjunctive intravenous antibiotics, especially vancomycin. Only eight infected patients died before transplantation, with five deaths due to sepsis. Four of these five patients were infected with a gram negative rod. In general, patients who developed an LVAD infection were able to undergo successful transplantation without recurrence, but infection with a gram negative rod was associated with a poor outcome.

A hybrid mock circulatory system: testing a prototype under physiologic and pathological conditions.

Abstract: Hydraulic models of circulation are used to test mechanical heart assist devices and for research and training purposes. However, when compared with numerical models, they are rather expensive and often not sufficiently flexible or accurate. Flexibility and accuracy can be improved by merging numerical models with physical models, thus obtaining a hybrid model where numerical and physical sections are connected by an electrohydraulic interface. This concept is applied here to represent left ventricular function. The resulting hybrid model is inserted into the existing closed loop model of circulation. The hybrid model reproduces ventricular function by a variable elastance numerical model. Its interaction with the hydraulic sections is governed by measuring left atrial and systemic arterial pressures and computing the left ventricular output flow by the resolution of the corresponding equations. This signal is used to control a flow generator reproduced by a gear pump driven by a DC motor. Results obtained under different circulatory conditions demonstrate the behavior of the ventricular model on the pressure-volume plane and report the trend of the main hemodynamic variables.

Tissue engineering of heart valves: formation of a three-dimensional tissue using porcine heart valve cells.

Abstract: Tissue engineering is a promising approach to obtaining lifetime durability of heart valves. The goal of this study was to develop a heart valve-like tissue and to compare the ultrastructure with normal valves. Myofibroblasts and endothelial cells were seeded on a type I collagen scaffold. The histologic organization and extracellular matrix were compared in light and electron micrographs. Radiolabeled proteoglycans were characterized by enzymatic degradation experiments. In tissue engineered specimens, cross sectional evaluation revealed that the scaffold (300 microm) was consistently infiltrated with myofibroblasts. Both sides were covered with a multicellular layer of myofibroblasts and overlaid by endothelial cells (50 microm). A newly formed extracellular matrix containing collagen fibrils and proteoglycans was found in the interstitial space. Collagen fibrils with a 60 nm banding pattern were found in both specimens. Small sized proteoglycans (65 nm) were associated and aligned at intervals of 60 nm with collagen fibrils. Large sized proteoglycans (180 nm) were located outside the collagen bundles in amorphous compartments of the extracellular matrix. The majority of glycosaminoglycans were chondroitin/dermatan sulfate, and a minority were heparan sulfate. The morphology and topography of cells and the organization of extracellular matrix in artificial tissues strongly resembles those of native valve tissues.

Cytokine dialysis: An ex vivo study

Abstract: To test the hypothesis that dialysis using a new large pore membrane would achieve effective cytokine removal, blood from six volunteers was incubated with endotoxin (1 mg) and then circulated through a closed circuit with a polyamide membrane (nominal cut-off: 100 kDa). Hemodialysis was conducted at 1 or 9 L/hr of dialysate flow at the start of circulation and after 2 and 4 hours. The peak dialysate/plasma concentration ratios were 0.92 for interleukin (IL)-1beta, 0.67 for IL-6, 0.94 for IL-8, 0.33 for tumor necrosis factor (TNF)-a, and 0.11 for albumin. The dialysate/plasma ratios for all cytokines and albumin were decreased with increased dialysate flow from 1 to 9 L/hr (p < 0.05). Clearances for IL-1beta, IL-6, and IL-8, however, were significantly improved with increased dialysate flow (p < 0.01). There was no increase in TNF-a clearance (not significant) and a decrease in albumin clearance (p < 0.01). The peak clearance at 9 L/hr was 33 ml/min for IL-1beta, 19 for IL-6, 51 for IL-8, 11 for TNF-alpha, and 1.2 for albumin. No adsorption of cytokines was observed. We conclude that cytokine dialysis is achievable through a membrane with a high cut-off point with negligible albumin loss. These findings support the technical feasibility of this new approach to blood purification in sepsis.

Central, peripheral, and other blood volume changes during hemodialysis.

Abstract: Volume overload is a factor in development of hypertension in hemodialysis patients. Fluid removal by hemodialysis (HD), however, may cause intradialytic hypotension and associated symptoms. A better understanding of the relationships between blood pressure volume status and the pathophysiology of fluid removal during HD are, therefore, necessary to control blood pressure and to eliminate intradialytic hypotension. The objectives of the study were to determine the amount and direction of change of body fluid compartments after ultrafiltration (UF) and to determine whether any correlations exist between mean arterial pressure (MAP), change in circulating blood volume (deltaBV), total body water (TBW), central blood volume (which constitutes the volume of blood in the lungs, heart, and great vessels [CBV]), and intracellular and extracellular fluid volumes (ICF, ECF). The study population included 20 patients on regular HD. Each individual had their CBV, cardiac output, and peripheral vascular resistance (PVR) measured by means of saline dilution technique and deltaBV monitored by an online hematocrit sensor (Crit Line). MAP was calculated from measured blood pressure and ICF and ECF were measured using bioelectric impedance analysis techniques. Measurements were obtained before and after maximum UF measured by deltaBV (reduction of 6-10% by Crit Line). Ten healthy controls also had ECF and ICF values measured by bioelectric impedance analysis. Before HD, MAP correlated with TBW (r = 0.473, p = 0.035) and CBV (r = 0.419, p = 0.066), suggesting that hypertension here may be due to volume overload. Patients were ECF expanded before HD with an ECF:ICF ratio of 0.96, which was significantly higher than the control ratio of 0.74 (p < 0.0001). During UF, fluid was removed from both ECF and ICF, but more from the ECF volume ratio 0.92 post UF, a significant reduction (p < 0.0001). After UF, MAP no longer correlated with TBW or CBV but correlated with peripheral vascular resistance (r = 0.4575, p = 0.043). After UF, deltaBV correlated inversely with PVR (r = -0.50, p = 0.024). Despite the fall in deltaBV (7.11+/-2.49%) with UF, CBV was maintained. CBV were 0.899 L and 0.967 L pre and post UF, respectively. These data suggest that in hemodialysis patients, predialysis volume status influences predialysis blood pressure. UF causes BV to fall, but CBV is preferentially conserved by increasing PVR, which also maintains blood pressure. Failure of a PVR response likely leads to intradialytic hypotension.

Biofeedback regulation of ultrafiltration and dialysate conductivity for the prevention of hypotension during hemodialysis.

Abstract: Intradialytic hypotension remains a frequent complication of dialysis, occurring in up to 33% of patients. We tested a fully integrated biofeedback system (the Hemocontrol system) that monitors and regulates blood volume contraction during hemodialysis. Seven hypotension prone patients were selected for the study. We conducted a prospective crossover study alternating dialysis sessions using the blood volume regulation system and standard dialysis sessions. Event free sessions were defined as dialysis sessions not requiring any therapeutic intervention for hypotension related signs or symptoms. There was a significant improvement in the number of event free sessions with blood volume regulation compared with standard dialysis (50.8% of sessions vs. 29.2%; p < 0.01). Percentages of event free sessions and mean postdialysis systolic blood pressure improved progressively over the course of the study, indicating improved hemodynamic stability over the study period. Therefore, the use of a biofeedback system to monitor and regulate blood volume during dialysis was helpful in restoring cardiovascular stability in a population of hypotension prone hemodialysis patients. Further studies are needed to confirm these preliminary results and to establish the role of blood volume regulation systems in reducing the incidence of hypotension during hemodialysis.

Computational fluid dynamics modeling of impeller designs for the HeartQuest left ventricular assist device.

Abstract: To finalize the design of the next generation of the HeartQuest left ventricular assist device, a suitable impeller had to be designed and tested. The new prototype was based on calculations and test results of previous designs, but required several changes to decrease the size. For most pump designs, this is a simple matter of altering impeller geometry and rotational speed to achieve the desired pressure rise and flow rate. However, this particular pump was limited by housing geometry and the magnetic bearings that support the impeller. Without much freedom in the overall impeller size, the only parameters open to the designers were the blade profiles and the rotating speed. Rather than build several candidates and test them in a rig at enormous cost, computational models of several designs were tested and analyzed. This not only saved money, but also sped up the development time for the project. The computer models were developed in TASCflow, a computational fluid dynamics software package from AEA Technologies. This paper analyzes the data from several of the selected models, paying close attention to pumping performance and general trends from specific design changes.

Novacor left ventricular assist system long-term performance: comparison of clinical experience with demonstrated in vitro reliability.

Abstract: Since the first implant of the Novacor wearable left ventricular assist system (LVAS) in 1993, median implant duration worldwide has increased from 93 days (max 2.2 years) to 202 days (max 4.1 years) in May 2001. In vitro reliability/durability testing of the Novacor LVAS has previously demonstrated a mean time to failure of 4.2 (3.04-5.59) years. These tests revealed a single failure mode--main bearing wear--with measurable symptoms gradually appearing before degradation of pump function. An ongoing clinical study of 37 recipients implanted for more than 1 year has shown that a simple noninvasive method of pump surveillance, derived from the in vitro experience, is well tolerated in the clinical setting. The overall clinical experience is consistent with in vitro reliability/durability tests that demonstrated 99.9%, 98.5%, and 87.4% freedom from wear at 1, 2, and 3 years (80% confidence). So far, the clinical study has shown 99.4%, 91.5%, and 91.5% freedom from wear at the same 1, 2, and 3 year intervals (95% confidence). Furthermore, the clinical findings have corroborated the in vitro experience that the wear mechanism is generally measurable and gradual, enabling elective clinical LVAS replacement or transplantation. Clinical valve performance was also monitored, using an exercise protocol and collecting comparative data on peak flows across the valves. It was determined that developing valve dysfunction could be diagnosed early and, in the failures that did occur (n = 2), these were related to the patient's disease state. In conclusion, although clinical conditions exposed the LVAS to a wide range of different environmental and hydraulic stresses, the surveillance program described appears practical and reliable, and its findings broadly parallel those of the earlier in vitro study. Additional data needed to complete formal validation continue to be collected.

Continuous monitoring of plasma, interstitial, and intracellular fluid volumes in dialyzed patients by bioimpedance and hematocrit measurements.

Abstract: Bioimpedance spectroscopy (BIS) permits evaluation of extra- and intracellular fluid volumes in patients. We wished to examine whether this technique, used in combination with hematocrit measurement, can reliably monitor fluid transfers during dialysis. Ankle to wrist BIS measurements were collected during 21 dialysis runs while hematocrit was continuously monitored in the blood line by an optical device. Extracellular (ECW) and intracellular (ICW) water volumes were calculated using Hanai's electrical model of suspensions. Plasma volume variations were calculated from hematocrit, and changes in interstitial volume were calculated as the difference between ECW and plasma volume changes. Because accuracy of ICW was too low, changes in ICW were calculated as the difference between ultrafiltered volume and ECW changes. Total body water (TBW) volumes calculated pre- and postdialysis were, respectively, 3.25+/-3.2 and 1.95+/-2.5 liters lower on average than TBW given by Watson et al.'s correlation. Average decreases in fluid compartments expressed as percentage of ultrafiltered volume were as follows: plasma, 18%; interstitial, 28%, and ICW, 54%. When the ultrafiltered volume was increased in a patient in successive runs, the relative contributions of ICW and interstitial fluid were augmented so as to reduce the relative drop in plasma volume.

Hemolytic characteristics of oxygenators during clinical extracorporeal membrane oxygenation.

Abstract: A connection was previously reported between the hemolytic characteristics associated with oxygenators and the pressure drop measurements in the blood chamber under experimental conditions simulating their use in cardiopulmonary bypass. We examined this association during extracorporeal membrane oxygenation (ECMO) conditions. Three oxygenators for ECMO or pediatric cardiopulmonary bypass (Menox EL4000, Dideco Module 4000, and Mera HPO-15H) were evaluated. Fresh blood from healthy Dexter strain calves anticoagulated with citrate phosphate dextrose adenine solution was used. The blood flow was fixed at 1 L/min, similar to that in ECMO. The Normalized Index of Hemolysis for Oxygenators (NIHO) has been modified according to the American Society of Testing and Materials standards, as was previously reported. The NIHO value was the lowest in the Menox (0.0070+/-0.0009) and increased from Menox to Dideco (0.0113+/-0.0099) to Mera (0.0164+/-0.0043); however, there were no significant differences among the oxygenators. This NIHO value has a close correlation to the pressure drop. In conclusion, this evaluation method is also applicable to comparison of the biocompatibility performance of different types of clinically available oxygenators for ECMO.

CardioClasp: a new passive device to reshape cardiac enlargement.

Abstract: In dilated heart failure, geometric distortions place an extra load on the myocardial cells. If this extra burden can be eliminated, the myocardial wall stress would decrease leading to improved systolic ventricular performance. In a dilated heart failure model, we wanted to see whether the CardioClasp (which uses two indenting bars to reshape the left ventricle [LV] as two widely communicating “lobes” of reduced radius) could improve systolic performance by passively reshaping the LV and reducing the wall stress. In mongrel dogs (n 7; 25–27 kg), rapid ventricular pacing (210 ppm 1st week to 240 ppm 4th week) induced dilated heart failure. After 4 weeks, LV performance was evaluated at baseline and with the CardioClasp by measuring LV enddiastolic and peak LV systolic pressure, LV dP/dt, LV dP/ dt, and cardiac output. With the Clasp on, LV wall stress was reduced to 58.6 3.5 from 108.3 8.2 g/cm 2 . The fractional area of contraction (FAC) with the Clasp on (28.4 4.4) was significantly increased (p < 0.05) from baseline (20.8 4.6) and consistent with improved systolic performance. Cardiac output, LV peak systolic and end-diastolic pressures, and regional myocardial blood flow were unaltered. The Clasp was able to acutely reshape the left ventricle, while preserving the contractile mass, and reduced the tension on the myocardial cells and increased the fractional area of contraction without decreasing the systolic blood pressure. ASAIO Journal 2002; 48:–.

A new approach to completely autologous cardiovascular tissue in humans.

Abstract: In cardiovascular tissue engineering, synthetic or biologic scaffolds serve as templates for tissue development. Currently used scaffolds showing toxic degradation and immunogenic reactions are still far from ideal. We present a new alternative method to develop completely autologous human tissue without using any scaffold materials. Human vascular cells of arterial and venous origin were cultured to form cell sheets over a 4 week period under standard conditions. Thereafter, cell sheets of each origin were folded and cultured in a newly developed frame device for an additional 4 weeks. Controls remained under standard culture conditions. Tissue development was evaluated by morphology and biochemical assays. The formation of multilayered cell sheets and production of extracellular matrix were observed in all groups. Folded and framed neo-tissue showed a solid structure, with increased matrix formation and tissue organization when compared with the control groups. DNA content indicated significantly lower cell proliferation, and hydroxyproline assay indicated significantly higher collagen content in the framed cell sheets. We present a new approach to the engineering of cardiovascular tissue without the use of biodegradable scaffold material. Three-dimensional, completely autologous human tissue may be developed on the basis of this structure, thus avoiding scaffold induced toxic degradation or inflammatory reaction. ASAIO Journal 2002; 48:234-238.

In vitro evaluation of hemolysis and sublethal blood trauma in a novel subcutaneous vascular access system for hemodialysis.

Abstract: Hemodialysis requires reliable frequent access to the patients' vasculature, with blood flow rates of > 300 ml/min. Currently in the U.S. market, there are three types of hemodialysis access systems: the native arteriovenous fistula, generally using 15G needles; the synthetic arteriovenous (AV) graft, also generally using 15G needles; and the percutaneous catheter. Some of the problems with current vascular access technologies include insufficient blood flow, blood trauma, thrombosis, infection, cardiac load, and venous stenosis. The LifeSite System (Vasca, Inc.) represents an alternative for vascular access, and consists of a subcutaneous valve and 12F cannula accessed by a standard 14G needle. The LifeSite valve is implanted in the upper torso with the cannula generally entering the right internal jugular vein. The purpose of this study was to compare the LifeSite System with two known vascular access systems: the 10F dialysis catheter (Tesio-Cath, MedComp) and the 15G A.V. Fistula Needle Set (JMS Co., Ltd.) with regard to blood damage produced by these devices in use. Mechanical hemolysis and sublethal blood trauma were evaluated by means of in vitro blood pumping through a circulating loop incorporating a hemodialysis vascular access system. Sublethal blood damage was examined by using a hemorheologic assay that included parameters such as erythrocyte mechanical fragility, plasma total protein and fibrinogen concentrations, and blood viscosity. The tests demonstrated that, at both studied flow rates of 300 ml/min and 450 ml/min, the LifeSite produced lower hemolysis and less sublethal damage to blood than either the Tesio-Cath catheter or the A.V. Fistula Needle Set.

New type of tracheal bioartificial organ treated with detergent: maintaining cartilage viability is necessary for successful immunosuppressant free allotransplantation.

Abstract: The present investigation examined the key factors in the preparation of low-antigenic tracheal allografts by detergent treatment in dogs. In group 1 (n = 5), the grafts were treated by detergent at room temperature for 48 h and rinsed with running water until use. In group 2 (n = 4), detergent treatment was performed at 4 degrees C for 48 h, but the rinsing step was omitted. In group 3 (n = 6), the grafts were treated at 4 degrees C for 48 h, rinsed thoroughly with physiologic saline, and stored at 4 degrees C. The grafts were then used for tracheal replacement without immunosuppressant in dogs. The epithelium and mixed glands had been removed completely from the grafts in groups 1 and 2, and in five of the six grafts of group 3. In groups 1 and 2, cartilage viability appeared to have been lost and all animals died of airway stenosis within 38 days. In group 3, the chondrocytes were viable and all animals survived uneventfully. These results suggest that maintaining cartilage viability in a tracheal graft is necessary for successful immunosuppressant-free allotransplantation and, consequently, to maintain an open airway. The treatment temperature and sufficient rinsing are key factors for maintaining cartilage viability of grafts.

Hemoperfusion with polymyxin B immobilized fibers for urinary albumin excretion in septic patients with trauma.

Abstract: We investigated whether microalbuminuria/urinary creatinine ratio (MACR) is increased in septic patients with trauma and whether polymyxin B immobilized fiber (PMX-F) treatment decreases MACR. Twelve trauma patients without sepsis, 18 trauma patients with sepsis, and 10 healthy controls were included in this study. The 18 trauma patients with sepsis were randomly assigned to one of two groups, PMX-F treatment or conventional treatment. Urinary microalbumin and creatinine were measured before and after treatment. Plasma endotoxin levels were determined by endospecy test. Hemoperfusion with PMX-F was carried out twice, for 2 hours, at a flow rate of 100 ml/min. MACR increased in the 30 trauma patients (5.2 ′ 2.2 mg/mmol) in comparison to that in the healthy controls (1.0 ′ 0.6 mg/mmol, p < 0.01). In the 18 trauma patients with sepsis, MACR after sepsis (16.6 ′ 4.8 mg/mmol) was significantly greater than that before sepsis (5.5 ′ 2.3 mg/mmol, p < 0.01). There was a significant correlation between plasma endotoxin levels and MACR in septic trauma patients (p < 0.001). MACR was reduced from 17.0 ′ 5.0 mg/mmol to 4.2 ′ 1.5 mg/mmol (p < 0.01) with PMX-F, and plasma endotoxin levels were also reduced from 34.5 ′ 18.5 pg/ml to 10.8 ′ 6.6 pg/ml (p < 0.01). Neither MACR nor plasma endotoxin levels were affected by conventional treatment, however. In summary, trauma patients with sepsis appear to show increased MACR, and PMX-F therapy may be effective for attenuating the increase in MACR.

Ultrastructural alterations in red blood cell membranes exposed to shear stress.

Abstract: In the mechanism of damage to red blood cells (RBCs) caused by a centrifugal pump, the prolonged effects to the RBC membrane caused by exposure to shear stress remain unclear. We focused on the band 3 protein (B3), one of the major proteins in the membrane skeleton, and investigated the ultrastructural alterations of the RBC membrane with loaded shear stress. Using flow cytometry, the relative amount of B3 was examined in relation to RBC deformability. The results, with continuous exposure to low shear stress, showed cell downsizing, an increase in B3 density, and a decrease in the deformability of the RBC membrane. Exposure to high shear stress does not appear to exert any influence on the membrane skeleton of the RBC. Therefore, in addition to conventional processes including the instantaneous destruction of a cell due to intense shear stresses, the results of the present study indicate the presence of another process based on changes in membrane proteins leading to cell fragmentation. Under low shear stress, the RBC membrane skeleton shows delayed destruction, which is exhibited as a disorder of B3 distribution, and the related membrane dysfunction includes decreases in RBC deformability and stability.

Daily hemofiltration with a simplified method of delivery.

Abstract: Observational studies of daily hemodialysis (HD) and intermittent hemofiltration (HF) therapy have been associated with improved outcomes for patients with endstage renal disease. We conducted a prospective study to evaluate the feasibility of daily HF as an alternative to intermittent HD using a simplified HF system (NxStage Medical). Each patient received 1 week of intermittent HD followed by 4 weeks of daily HF. Ringers lactate was used as the initial replacement solution; however, Hemosol LG2/L0 was used subsequently to simplify patient management. Changes in quality of life, nutrition, and laboratory values were assessed. Seven patients have completed 168 HF treatments with Hemosol. Their treatment time on HD was 232 minutes 3 days per week, and 132 minutes on HF 6 days per week. Single pool Kt/V per treatment for HD was 1.69 compared with 0.44 for HF (standard Kt/V 2.38 vs 1.93). Despite these weekly differences in urea clearance, potassium, calcium, phosphate, and nutrition remained stable. Beta-2 microglobulin tended to decline. All parameters of the Kidney Disease Quality of Life Instrument Short Form (KDQOL-SF) either remained stable or improved. In addition, blood pressure declined, allowing for a reduction in the number of antihypertensive medications. In summary, these preliminary data suggest that daily HF with this system is safe, simple, efficacious, and could potentially be used as a home based renal replacement therapy.

Left ventricular outflow tract obstruction associated with chronic ventricular assist device support.

Abstract: Favorable long-term patient outcome after insertion of a left ventricular assist device (LVAD) as a bridge to recovery or destination therapy for the treatment of end-stage cardiomyopathy is adversely affected by pathophysiologic changes affecting the heart. Alterations in the native aortic valve apparatus, specifically aortic valve cusp fusion, is an example of such a phenomenon and may especially affect patients in cases of bridge to recovery, a rare but reported event. A retrospective review of the last 33 LVAD placements at our institution was conducted, including reviews of operative reports and pathologic examinations of the native hearts. Seven hearts were found to have varying degrees of aortic valve cusp fusion after chronic LVAD support (63-1, 339 days). Five of these patients had native aortic valves, and two had bioprosthetic valves. The left ventricular outflow tracts in two patients were surgically occluded at the time of LVAD insertion. Aortic valve cusp fusion occurs in roughly 25% of patients on chronic LVAD support. This phenomenon may prove to be clinically significant by creating a potential source of emboli and infection. In addition, in the case of myocardial recovery, left ventricular outflow tract obstruction could limit parallel flow and produce suprasystemic ventricular pressures that in turn would elevate left ventricular end diastolic pressures. The latter may contribute to further myocardial injury, ultimately limiting the ability of an otherwise recovered heart to be weaned from LVAD support.

Measurement of extravascular lung water in hemodialysis patients using blood ultrasound velocity and optical density dilution

Abstract: In hemodialysis patients, volume homeostasis is an important clinical problem. The aim is to have patients at an ideal "dry weight" postdialysis, but current methods for accurately measuring dry weight are disappointing. Krivitski et al. (ASAIO J 1998;44:M535-M540) have described a novel technique whereby extravascular lung water (EVLW) may be measured using blood ultrasound velocity and electrical impedance dilution. They have tested this method in animals and achieved agreement between obtained versus gravimetric measurements. Isotonic saline is used as a nondiffusible indicator and hypertonic (5%) saline is used as a diffusible indicator. By injecting these solutions and following their transits through the cardiopulmonary circulation, a theoretic basis for the calculation of EVLW may be derived from the cardiac output, the water transferred to blood, the amount of sodium chloride moved from blood to lung, and the increase in blood osmolality measured at the moment of osmotic equilibrium. We have used this new technique to measure EVLW for the first time in humans in 18 stable hemodialysis patients with no cardiac problems. Measurements were carried out twice in each patient, the first early in dialysis, the second toward the end of a dialysis session where fluid removal took place. The values for EVLW were 260 ′ 49 ml early in dialysis and 230 ′ 48 ml late in dialysis. This fall of 30 ′ 45 ml was statistically significant (p = 0.011). EVLW normalized to body weight was 3.29 ′ 1.0 ml/kg early and 3.02 ′ 1.04 ml/kg late in dialysis, a nonsignificant difference (p - 0.073). The normalized EVLW values are almost identical to those obtained in animals (3.1 ′ 1.4 ml/kg) by Krivitski et al. (see above). We conclude that this new technique can conveniently and non-invasively give an estimate of EVLW in hemodialysis patients. The clinical value of this measurement has now to be determined.

One piece ultracompact totally implantable electromechanical total artificial heart for permanent use.

Abstract: An ultracompact, one piece, totally implantable electromechanical total artificial heart (TAH) has been developed as a permanent replacement for failing hearts. It consists of left and right pusher plate blood pumps (stroke volume 55 ml) made of titanium alloy (Ti-6Al-7Nb) sandwiching a miniaturized electromechanical actuator between them. The diameter of the TAH is 90 mm, with a thickness of 70 mm, yielding an overall volume of 400 ml. It weighs 450 g. Although it is miniaturized, it provided a maximum pump output of 8 L/min against a left afterload of 100 mm Hg. It required approximately 12 watts to provide a pump output of 6.5 L/min with maximum efficiency of 13.5%. To balance left and right flow, the right stroke length was made 10% shorter than the left, and an auxiliary compliance chamber was used to compensate for additional flow differences between them. Motor commutation pulses and a Hall effect pusher plate sensor signal were used in the controller to implement the left master alternate variable rate mode. The calf fitting study revealed excellent anatomic compatibility, and the first successful survivor was obtained in December 2001. Studies of system endurance and biocompatibility are required to ensure long-term reliability. This TAH is promising for permanent replacement of the failing heart as well as for bridge to heart transplantation for the smaller size group of end-stage cardiac patients.