Perioperative mechanical circulatory support for transplantation.

Mechanical circulatory assistance has become a necessary supplement to more conventional means of hemodynamic support as a shortage of donor organs and associated increase in waiting time have contributed to an increased incidence of hemodynamic deterioration in potential transplant recipients. This review summarizes the experience with circulatory support before and after transplantation of the Utah Transplantation Affiliated Hospitals (UTAH) Cardiac Transplant Program and draws conclusions on the efficacy of one program's use of mechanical circulatory support. Between March 1985 and October 1990, 401 patients were accepted for first-time heart transplantation by the UTAH program. One hundred and eighty patients (46%) were supported before transplantation with conventional hemodynamic therapies, 72 patients (18%) with oral enoximone, 96 patients (25%) with intravenous inotropes, and 34 patients (9%) with an intraaortic balloon; nine patients (2%) required centrifugal blood pump circulatory support. Not included in these statistics are 10 patients awaiting transplantation as of October 10, 1990. Thirty-eight candidates (10%) died awaiting transplantation, 329 (84%) received transplantation, and 24 (6%) were removed from the transplantation list for other reasons. Ten patients (3%) required mechanical circulatory support after transplantation with 38% of this group surviving 1 year after after transplantation. No single factor, including either hemodynamic support before transplantation or donor heart ischemic time, was found to be predictive of the need for mechanical circulatory support after transplantation. One-year survival rates after transplantation of patients requiring mechanical circulatory support before transplantation (86%) were not significantly different than for all transplant patients (88%). The experience of the UTAH Cardiac Transplant Program shows that with the judicious use of mechanical circulatory support transplant patients with advanced forms of hemodynamic support can have as equal a probability of survival as patients who undergo elective transplantation.

Aortic input impedance in infants and children.

Flow and pressure measurements were performed in the ascending aortas of six pediatric patients ranging in age from 1 to 4 yr and in weight from 7.2 to 16.4 kg. From these measurements, input impedance was calculated. It was found that total vascular resistance decreased with increasing patient weight and was approximately one to three times higher than those of adults. Conductance per unit weight was relatively constant but was approximately three times higher than for adults. Strong inertial character was observed in the impedance of four of the six patients. Among a three-element and two four-element lumped-parameter models, the model with characteristic aortic resistor (R(c)) and inertance in series followed by parallel peripheral resistor (R(p)) and compliance fitted the data best. R(p) decreased with increasing patient weight and was one to three times higher than in adults, and R(c) decreased with increasing patient weight and was 2 to 15 times higher. The R(p)-to-R(c) ratio differed significantly between infants and children vs. adults. The results suggested that R(p) developed more rapidly with patient weight than did R(c). Compliance values increased with increasing patient weight and were 3 to 16 times lower than adult values.

Neonatal piglet model of intraaortic balloon pumping: improved efficacy using echocardiographic timing.

BACKGROUND: Pediatric intraaortic balloon pumping (IABP) has met with little success because of technical difficulty in tracking rapid heart rates. This study was designed to evaluate the efficacy of M-mode echocardiography for IABP timing in a neonatal piglet model. METHODS: Two groups of piglets underwent mitral valve avulsion to create a model of shock. Group 1 (n = 8; mean weight, 7.7+/-1.8 kg) underwent IABP timed with both the ascending aortic pressure and M-mode echocardiogram. Group 2 (n = 6; mean weight, 7.5+/-1.4 kg) underwent two separate periods of IABP: one with echocardiographic timing and the second using standard timing points from the femoral arterial pressure tracing and electrocardiogram. Measurements included ascending aortic flow, left anterior descending arterial flow, ascending aortic pressure, left atrial pressure, and heart rate. RESULTS: Mitral valve avulsion produced a shock model with a significant decrease in mean aortic pressure and aortic flow and a significant increase in left atrial pressure and heart rate. Compared with the shock state, IABP in group 1 animals resulted in a significant increase in aortic flow (353+/-152 versus 454+/-109 mL/min; p < 0.05) and a significant decrease in left atrial pressure (23+/-6 versus 17+/-7 mm Hg; p < 0.05). Group 2 animals with echocardiogram-timed IABP had significantly increased aortic flow (365+/-106 versus 458+/-107 mL/min; p < 0.05) and mean aortic pressure (43+/-11 versus 52+/-8 mm Hg; p < 0.05). However, standard-timed IABP failed to show any improvement. CONCLUSIONS: In piglets with rapid heart rates, echocardiogram-timed IABP results in increased aortic flow and pressure and decreased left atrial pressure compared with standard-timed IABP.

Long-term mechanical circulatory support system reliability recommendation: American Society for Artificial Internal Organs and The Society of Thoracic Surgeons: long-term mechanical circulatory support system reliability recommendation.

Jointly developed by members of the American Society for Artificial Internal Organs and the Society of Thoracic Surgeons along with staff from the Food and Drug Administration, the National Heart, Lung and Blood Institute and other experts, this recommendation describes the reliability considerations and goals for Investigational Device Exemption and Premarket Approval submissions for long-term, mechanical circulatory support systems. The recommendation includes a definition of system failure, a discussion of an appropriate reliability model, a suggested in vitro reliability test plan, reliability considerations for animal implantation tests, in vitro and animal in vivo performance goals, the qualification of design changes during the Investigational Device Exemption clinical trial, the development of a Failure Modes Effects and Criticality Analysis, and the reliability information for surgeons and patient candidates. The document will be periodically reviewed to assess its timeliness and appropriateness within five years.

In vitro evaluation of forward and reverse volumetric flow across a regurgitant aortic valve using Doppler power-weighted mean velocities.

To determine the accuracy of using power-weighted mean velocities for quantitating volumetric flow across a cardiac valve, we equipped pulsatile flow-tank systems with a 25 mm porcine or a 27 mm mechanical valve with various sizes of regurgitant orifices. Forward and reverse volumetric flows were measured over a range of hemodynamic conditions using two insonating angles (0 and 45 degrees). Pulsed Doppler power-weighted mean velocity measurements were obtained simultaneously with electromagnetic or ultrasonic transit-time probe measurements. For the porcine valve, Doppler measurements correlated well with electromagnetic flow measurements for all (r = 0.75 to 0.97, p < 0.05) except the smallest (2.7 mm) orifice (r = 0.19). For the mechanical valve, power-weighted mean velocity measurements correlated well with ultrasonic transit-time measurements for each hemodynamic condition defined by pulse rate, mean arterial pressure, and insonating angle (r = 0.93 to 0.99, p < 0.01), but equations varied unpredictably. Thus, although power-weighted mean velocity volumetric flow measurements correlate well with flow probe measurements, equations vary widely as hemodynamic conditions change. Because of this variation, power-weighted mean velocity data are not useful for quantitation of volumetric flow across a cardiac valve at this time. Further investigation may show how different hemodynamic conditions affect power-weighted mean velocity measurements of volumetric flow.

A justification for high resolution hematocrit measurement.

The purpose of this study was to determine the feasibility of using a 6" digital caliper and a 20x viewing microscope to measure hematocrit (HCT) from microhematocrit tubes. The reliability and validity of the digital caliper technique (DC) was simultaneously compared with that of the conventional "turntable" style microhematocrit method (MC) and the Coulter Counter hematocrit (CC) for a comprehensive comparison of the three methods. The reliability of the three methods was assessed by computing the standard error of the measurement (SEm) on triplicate readings of human blood samples. The SEm for MC, CC, and DC methods were 0.3555, 0.3004, and 0.1491, respectively. Validity was assessed by comparing the average of the triplicate HCT readings for each method with HCT determined by densitometry. Average HCT values (+/- SE) for the MC, CC, DC, and densitometry methods were 42.3 +/- 3.2, 42.4 +/- 3.4, 43.1 +/- 3.4, 43.7 +/- 3.3, respectively. Only the DC HCT values were not different from the densitometry HCT (P > 0.05). The MC and CC values were significantly lower (P < 0.01). It is concluded that accurate, highly precise measurements of HCT are obtainable using the digital caliper. The significance for this is the increased ability to perform extremely accurate measurement of changes in plasma volume. With this information, research labs can reliably measure smaller changes in plasma than was previously possible with commercial procedures.

In vitro evaluation of the effect of aortic compliance on pediatric intra-aortic balloon pumping.

OBJECTIVES: To evaluate the effect of aortic compliance on pediatric intra-aortic balloon pumping (IABP). DESIGN: In vitro study using a mechanical model of the pediatric left heart circulation. SETTING: Cardiovascular fluid dynamics research laboratory. SUBJECT: Pulsatile flow system simulating the pediatric left heart circulation and two different aortas with compliances comparable to those of the pediatric aorta (0.12 and 0.07 mL/mm Hg). INTERVENTIONS: Measurements were made at a baseline peak aortic flow of 4 L/min, at simulated shock (1.7 L/min), and with 1:1 IABP (rates, 130 and 150 bpm; balloon volumes, 2.5 and 5.0 mL). MEASUREMENTS AND MAIN RESULTS: Peak flow rates were measured in the ascending aorta, coronary arterial system, and brachiocephalic arterial systems. Aortic pressure was measured in the ascending aorta. For both aortas (0.12 and 0.07 mL/mm Hg), IABP resulted in diastolic augmentation (38 +/- 8 and 43 +/- 16 mm Hg) and afterload reduction (4 +/- 2 and 6 +/- 3 mm Hg). For both aortas, compared to shock, IABP resulted in significant increases in coronary arterial and brachiocephalic arterial flow and aortic pressure for both aortas. Aortic flow significantly increased only in the less-compliant aorta. CONCLUSIONS: In a laboratory model of pediatric left heart circulation, IABP results in diastolic augmentation, afterload reduction, and improved hemodynamics, even in aortas of greater compliance.

Compact compliance chamber design for the study of cardiac performance in microgravity.

A need was identified for a Mock Circulation System (MCS) of small size and weight that could function in a microgravity environment for the investigation of cardiovascular response to the weightlessness of space flight. Part of the MCS development involved the redesign of the compliance chamber from a Penn State MCS using a coil spring instead of the leaf spring system employed in the Penn State system. The new compliance chambers achieve a weight reduction of 47% and a volume reduction of 64% over the original Penn State design. Testing showed the coil spring compliance chambers retained physiologic characteristics and adjustability by using coil springs of various stiffness, and functioned equivalently to the original Penn State design.

Feedback control of mean aortic pressure in a dynamic model of the cardiovascular system.

Orbital measurements of the cardiac function of Space Shuttle crew members have shown an initial increase in cardiac stroke volume upon entry into weightlessness, followed by a gradual reduction in stroke volume to a level approximately 15% less than preflight values. In an effort to explain this response, it was hypothesized that gravity plays a role in cardiac filling. A mock circulatory system was designed to investigate this effect. Preliminary studies carried out with this system on the NASA KC-135 aircraft, which provides brief periods of weightlessness, showed a strong correlation between cardiac filling, stroke volume, and the presence or absence of gravity. The need for extended periods of high quality zero gravity was identified to verify this observation. To accomplish this, the aircraft version of the experiment was reduced in size and fully automated for eventual integration into a Get Away Special canister to conduct an orbital version of the experiment. This article describes the automated system, as well as the development and implementation of a control algorithm for the servoregulation of the mean aortic pressure in the orbital experiment. Three nonlinearities that influence the ability of the apparatus to regulate to a mean aortic pressure of 95 mm Hg were identified and minimized. In preparation for a Space Shuttle flight, the successful function of the servoregulatory scheme was demonstrated during ground tests and additional test flights aboard the KC-135. The control algorithm was successful in carrying out the experimental protocol, including regulation of mean aortic pressure. The algorithm could also be used for the automated operation of long-term tests of circulatory support systems, which may require a scheduled cycling of the pumping conditions on a daily basis.

Quantitative bacterial analysis of porous, fabric, and smooth non-blood contacting implant surfaces and their tissue interfaces in a 169 day pneumatic total artificial heart animal recipient.

All long-term total artificial heart (TAH) survivals are subject to sepsis. Survival can be prolonged, but the source of the infection cannot be eliminated with any known course of antibiotics or treatment regimen. Sambo, a U-100 pTAH calf, survived 169 days. At week 6, he became septic, growing a Pseudomonas species (Ps). Weekly blood cultures were intermittently positive until week 13 when they became continuously positive until his demise, from a ruptured left ventricular pumping diaphragm. Spatially specific porous silicone rubber (SSP) was used for surface modifications on the drive lines and as cuffs around the Dacron TAH graft to large vessel anastomoses. This gave an excellent opportunity to examine two types of porous implants surfaces (Dacron grafts and SSP) to the smooth Biomer ventricular surfaces with their respective adjoining tissue interfaces for bacterial colonization. Nine tissue samples and 13 implant surfaces were processed with Costerton's quantitative bacterial techniques. The largest numbers of bacteria (> 10(6)/cm2 Ps.) were grown from the smooth ventricular surface and in the cul-de-sac where the SSP delaminated from the driveline (two smooth implant surfaces in contact but without tissue apposition). The Dacron grafts were intermediate in bacterial concentrations and SSP surface modified drivelines and tissues were sterile. In this model, the more intimate biointegration found in the porous implants showed improved bacterial resistance in a chronically infected pTAH. The more completely biointegrated and neo-vascularized porosity SSP was the only implant surface and opposing implant tissue interface sampled to remain sterile.

Estimation of timing errors for the intraaortic balloon pump use in pediatric patients.

The use of the intraaortic balloon pump (IABP) for managing acute left ventricular failure in pediatric patients is less successful than in adults. It is often reported that rapid pediatric heart rates make accurate timing difficult to achieve. Traditional IABP theory requires that the balloon inflate during diastole (after aortic valve closure), for optimum coronary pressure and flow augmentation, and deflate just before the next systole for optimal ventricular afterload reduction. Errors in timing balloon inflation and deflation may result in the reduced IABP efficacy seen in children. To investigate timing errors when using the traditional IABP inflation and deflation markers in pediatric patients, six patients (age, 2.2+/-1.4 years; weight, 11.5+/-3.9 kg) were studied intraoperatively. Radial artery pressure (RAP) waveforms from a standard, fluid-filled pressure monitoring system were recorded on an FM data tape recorder simultaneously with high-fidelity, aortic root pressure waveforms, aortic root flow waveforms, and M-mode echocardiography. For each patient, a sequence of five recorded waveforms was analyzed. The mean +/- standard deviation of the time delay between aortic root and RAP markers and percentage delay of the corresponding part of the cardiac cycle were determined. When compared with aortic root waveforms, the RAP waveform consistently showed a delay in the IABP timing markers. A 107+/-23 msec (53+/-11%) delay in diastolic inflation and a 92+/-11 msec (40+/-4%) delay in presystolic deflation was found. If IABP timing to the RAP markers were to be used, the delay in IABP inflation would result in reduced diastolic augmentation, and the delay in IABP deflation into the systolic period would increase afterload. M-mode echocardiography provided timing markers that were identical to those provided by high-fidelity aortic root pressure waveforms. The combined effect of these delays on IABP function could substantially reduce the efficacy of the IABP in pediatric patients, indicating the need for more accurate indices for IABP timing in this patient group.

Successful repair of a ventricular assist system percutaneous lead.

A patient with an implanted, electrically powered, ventricular assist device (Thermo Cardiosystems VE HeartMate) experienced a partial break of the percutaneous lead 5 months after implantation. The break (limited to the Silicone rubber tube) occurred at the junction of the lead with the Y-connector to the controller and vent, leaving approximately 5 cm of exposed lead from the skin exit site to the connector. Electronic and pumping functions of the pump continued, but the opening in the lead (which went more that half way around the circumference) prevented the use of pneumatic actuation as a back-up mode for pump operation, and placed the pump at risk for contamination. Repair of the lead without surgical intervention was desirable, with ease of repair and minimal risk to the patient being the top priorities. The use of multiple layers of heat-shrink tubing or external metal stents was ruled out in favor of a three stage repair procedure. The first stage involved the removal of the Dacron velour in-growth material from the lead to expose the underlying Silicone rubber tube. While the opening in the tube was held shut, a coating of medical grade Silicone rubber adhesive was applied to the tube, then wrapped with a woven Dacron mesh, followed by two layers of plastic wrapping material to protect the adhesive. This initial layer was secured by an external stent of tubing with cable ties. After several days to allow for complete curing of the adhesive, the adhesive coating with mesh was repeated. The final step involved a double layer wrap of a 1 mm thick Silicone rubber sheeting with mesh incorporation and adhesive secured in place with cable ties. After completion of the repair and verification of the ability to operate the device with pneumatic actuation, the patient was discharged with no recurrence of the problem after 8 months of weekly follow-up. This experience demonstrates the need to clinically anticipate component repair or replacement without total device replacement in future implantable blood pump systems.

The development of a valveless cardiac assist device attached to the ventricular apex.

Konstantinov et al, in October, 1991, published a novel way to bridge a patient for heart transplantation. They proposed to cut off both ventricles high under the atrioventricular groove, leaving the atria, aorta, and pulmonary artery and their valves intact and to attach pneumatically driven, valveless pulsating pouches to assist the heart until a donor could be found. The removal of the ventricles just below the atrioventricular groove is called the "high cut"; it, however, destroys the chordae tendineae rendering the mitral and tricuspid valves insufficient. These have to be replaced by tissue inflow valves. We chose to cut off the ventricles at a lower level (the "low cut") to leave the papillary muscles on both sides intact, thereby saving the integrity of the mitral and tricuspid valves. Pulsating pouches were made to fit the heart at this lower level. They can be easily connected to the remaining heart after a specially disigned cuff has been sutured over the ventricular stumps. The pouches were pumped during the systole of the natural heart, but the myocardium may have to be electrically stimulated during systole to prevent undue distension. If the turgor is too weak to prevent distension, a sleeve over the ventricles is provided. To find the best location for these pouches, human cadaver implantations were done and the pre peritoneal cavity was found to be the most suitable. In vitro testing to determine how much flow could be pumped was done by attaching the pouches to fresh pig hearts and connecting them to a double sided mock circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal implantation results with the Utah-100 total artificial heart.

The Utah-100 total artificial heart was designed to have increased reliability over the Jarvik-7 total artificial heart, achieve better fit, and minimize device associated thrombus formation, without decreasing the function. The Utah-100 heart was tested in 28 calves and 3 sheep. The smallest animal at the time of implantation weighted 54 kg. Mean survival duration was 78 days (range, 1-331 days), with 14 animals surviving longer than 60 days. Multiple organ function was maintained satisfactorily with the Utah-100 artificial heart, and mean plasma free hemoglobin values in the calves that survived longer than 100 days were less than 10 mg/dl. Hemorrhage was the main cause of death in animals dying within 30 days after implantation (5/13, 38%); infection was another primary cause of death or termination (4/31, 13%). Deaths due to mechanical failure occurred from valve or diaphragm failure in two cases, yielding a 91% reliability at a 90% confidence level for 60 days' support. No animal died because of driver or other technical failure. Utah-100 hearts showed superior antithrombogenicity in the connector and valve-related areas when compared with the results of the Jarvik-7 heart, which was also fabricated and implanted in our laboratory (p less than 0.01). With these test results, the authors anticipate that the Utah-100 heart will be a safe and effective device for interim use as a bridge to heart transplantation.

Myocardial mechanics, energetics, and hemodynamics during intraaortic balloon and transvalvular axial flow hemopump support with a bovine model of ischemic cardiac dysfunction.

Unlike the mechanisms of intraaortic balloon pump (IABP) support, the mechanisms by which transvalvular axial flow Hemopump (HP) support benefit dysfunctional myocardium are less clearly understood. To help elucidate these mechanisms, hemodynamic, metabolic, and mechanical indexes of left ventricular function were measured during conditions of control, ischemic dysfunction, IABP support, and HP support. A large animal (calf) model of left ventricular dysfunction was created with multiple coronary ligations. Peak intraventricular pressure increased with HP support and decreased with IABP support. Intramyocardial pressure (an indicator of intramyocardial stress), time rate of pressure change (an indicator of contractility), and left ventricular myocardial oxygen consumption decreased with IABP and HP support. Left ventricular work decreased with HP support and increased with IABP support. During HP support, indexes of wall stress, work, and contractility, all primary determinants of oxygen consumption, were reduced. During IABP support, indexes of wall stress and contractility were reduced and external work increased. These changes were attributed primarily to changes in ventricular preload, and geometry for HP support, and to a reduction in afterload for IABP support. These findings support the hypothesis that both HP and IABP support reduce intramyocardial stress development and the corresponding oxygen consumption, although via different mechanisms.

Anaerobic threshold in total artificial heart animals.

The anaerobic threshold represents an objective measure of functional capacity and is useful in assessment of pulmonary and cardiovascular dysfunction. This study determined the anaerobic threshold in total artificial heart animals and evaluated the performance of the total artificial heart system. Five animals with total artificial hearts were put under incremental exercise testing after exercise training. The intensity of exercise ranged from 2.0 to 4.5 km/hr, with an increment of 0.5 km/hr every 3 min. The anaerobic threshold was 6.72 +/- 0.84 ml/kg/min as detected by the lactate method, and 6.48 +/- 0.79 by the CO2 method. The value of the anaerobic threshold in total artificial heart animals implies that the performance capacity of a total artificial heart is not sufficient to meet the oxygen requirements of vigorously exercising skeletal muscle. The protocol does not allow for driving parameter changes during exercise, and this situation, combined with the manual mode of the control system used, was inadequate to allow the total artificial heart animals to exercise more vigorously. Using an automatic control mode might be helpful, as well as considering the relationship between indices of oxygen metabolism, such as oxygen delivery, oxygen consumption, and oxygen extraction rate, in the control algorithms in total artificial heart control systems.

Oxygen metabolism in animals with total artificial hearts.

The relationship between indices of oxygen metabolism has been widely used in clinical practice to evaluate the adequacy of tissue perfusion, to predict the outcome of the critically ill patient, and to evaluate the effectiveness of therapies. This study quantitated and correlated the relationship between oxygen delivery (DO2), oxygen consumption (VO2), and oxygen extraction rate (EO2) in 14 animals with total artificial hearts (TAH) to investigate the oxygen metabolism in animals with TAH during different physiologic and pathologic conditions. These 14 animals were subdivided into healthy, critical, and exercise groups. There was a physiologic dependence of DO2 to VO2 in animals in the healthy and exercise groups, whereas a pathologic dependence of VO2 to DO2 appeared to occur in animals in the critical group. Reduced or inadequate VO2 leads to organ dysfunction, shock syndrome, multiple organ failure, and finally, mortality. Providing a higher level of DO2 by restoring circulating blood volume, increasing cardiac output, raising hematocrit levels, and improving pulmonary function to achieve a higher level of oxygen extract efficiency and oxygen consumption in animals with TAH that are in a critical condition might be helpful for the treatment of complications and result in decreasing mortality. Using the relationship between indices of oxygen metabolism as a physiologic modifier for TAH control algorithms also might improve the physiologic performance and quality of life of TAH recipients.

Markers of thromboembolization in a bovine ex vivo left ventricular assist device model.

The production of blood microemboli (BME) was studied using an ex vivo exteriorized left ventricular assist device (LVAD) model in calves. Each of eight calves received a series of three LVADs, each operating for 24 hr. Blood microemboli were measured directly by a laser (624 nm and 828 nm) light scattering microemboli detection (LSMD) system through the LVAD outflow cannula and by constant pressure filtration (CPF) of blood samples from the LVAD outflow cannula. Hematologic parameters were also measured. After LVAD removal, perivalvular thrombi were evaluated using polar coordinate mapping. The average LSMD and CPF results correlated. For example, in one series of three calves, one ventricle exhibited significantly greater thrombogenesis than did the other ventricles, as indicated by both the LSMD and CPF results. In a series of five calves, one calf developed an abnormally high activated thromboplastin time (APTT), even in the absence of heparin. For two of the three ventricles tested in that calf, microemboli concentration (CPF), Factor XII activity, level of fibrin degradation products (FDP), and accumulated thrombus were significantly lower than for the other calves. The whole blood viscosity (WBV, at 230 s-1) in this calf also decreased to lower values than were seen with the other calves.

Adaptive responses of total artificial heart animals to treadmill exercise.

The hemodynamic and metabolic adaptations to exercise in five calves implanted with the Utah-100 total artificial heart (TAH) were investigated. The outputs of the left and right ventricles (LCO, RCO) were measured with a cardiac output monitoring and diagnostic unit (COMDU). Arterial and venous oxygen content (CaO2, CvO2) and blood lactate levels (Lac) were measured by blood gas analysis and enzymatic methods. Oxygen consumption (VO2), oxygen delivery (DO2), oxygen extraction rate (EO2), index of metabolic adequacy (IMA), and systemic and pulmonary vascular resistance (SVR, PVR) were calculated. The intensity of exercise was categorized into three horizontal grades: low speed (LS) 0.7-1.0 mph, medium speed (MS) 1.0-1.4 mph, and high speed (HS) 1.4-1.8 mph, each for 30 min. During LS, MS, and HS exercise, the LCO, RCO, LAP, RAP, VO2, DO2, and EO2 all increased, and the SVR and PVR decreased. During exercise, there was a positive correlation between DO2, EO2, and VO2. The blood pH, BE, SBE, and lactate levels were within normal ranges, and the IMA exceeded 1.5, denoting that tissue perfusion was adequate and anaerobic metabolism did not occur. This study implies that Utah-100 TAH animals could physiologically accommodate to exercise with an intensity of up to 1.8 mph for 30 min by increasing cardiac preload, cardiac output, oxygen delivery, and oxygen extraction rate, and by decreasing systemic and pulmonary vascular resistance without transition to anaerobic metabolism.

Long-term mechanical circulatory support system reliability recommendation: American Society for Artificial Internal Organs and Society of Thoracic Surgeons: long-term mechanical circulatory support system reliability recommendation.

Jointly developed by members of the American Society for Artificial Internal Organs and the Society of Thoracic Surgeons along with staff from the Food and Drug Administration, the National Heart, Lung and Blood Institute and other experts, this recommendation describes the reliability considerations and goals for Investigational Device Exemption and Premarket Approval submissions for long-term, mechanical circulatory support systems. The recommendation includes a definition of system failure, a discussion of an appropriate reliability model, a suggested in vitro reliability test plan, reliability considerations for animal implantation tests, in vitro and animal in vivo performance goals, the qualification of design changes during the Investigational Device Exemption clinical trial, the development of a Failure Modes Effects and Criticality Analysis, and the reliability information for surgeons and patient candidates. The document will be periodically reviewed to assess its timeliness and appropriateness within five years.