Mean Plasma Free Hemoglobin Research Articles

Predictors of circuit health in neonatal patients receiving extracorporeal membrane oxygenation (ECMO)

To identify predictors of neonatal ECMO circuit health, a retrospective analysis of circuit functional pressure and flow parameters as well as infant clotting values were collected 48 h prior to and 24 h post circuit change. Circuit impairment was defined as need for partial or total circuit change. Statistical analysis used multivariate statistics and non-parametric Mann–Whitney U-test with possible non-normality of measurements. A total of 9764 ECMO circuit and clotting values in 21 circuits were analyzed. Circuit delta-P mean, and maximum values increased from 8.62 to 48.59 mmHg (p < 0.011) and 16.00 to 53.00 mmHg (p < 0.0128) respectively prior to need for circuit change. Maximum and mean Pump Flow Revolutions per minute (RPM) increased by 75% (p < 0.0043) and 81% (p < 0.0057), respectively. Mean plasma free hemoglobin (pfHb) increased from 26.45 to 76.00 mg/dl, (p < 0.0209). Sweep, venous pressure, and clotting parameters were unaffected. ECMO circuit delta-P, RPM, and pfHb were early predictors of circuit impairment.

One‐Month Biocompatibility Evaluation of the Pediatric TinyPump in Goats

The TinyPump is an extracorporeal, magnetically driven centrifugal blood pump with its impeller suspended magnetically and hydrodynamically to provide short-term mechanical circulatory support for children and infants. We have previously demonstrated that the in vivo experiments of the experimental TinyPump showed acceptable stable performance at pump flows averaging around 1.0 L/min with low hemolytic and thrombogenic properties for up to 2 weeks. We present here the 1-month in vivo evaluation of the TinyPump, whose design was modified further for more durable operation. The pump was implanted as a left ventricular assist device in five goats (12.5-26.7 kg), with inflow inserted into the left ventricular apex and outflow anastomosed to the descending aorta. Five animals were supported for 110 pump days, with mean pump flow of 1.19 ± 0.03 L/min at a pump speed of 2679 ± 97 rpm. Two animals reached the scheduled end point of 30 days without device failure, and mean plasma-free hemoglobin was 1.7 ± 0.8 mg/dL. Hematologic and biochemical data of these two animals showed no evidence of cardiovascular, renal, or hepatic dysfunction. Although further experiments are needed, the modified TinyPump offers promise as a short-term mechanical circulatory support device in pediatric population.

In Vivo Experience of the Child-Size Pediatric Jarvik 2000 Heart: Update

Data from early in vivo experiments demonstrated that the child-size Jarvik heart was capable of providing partial to nearly complete circulatory support with acceptable adverse effects on blood. However, bearing thrombosis was responsible for device malfunction in most cases. To overcome this problem, original pin bearings were replaced with novel conical bearings. This study evaluated chronic in vivo performance of the modified child-size Jarvik heart in the pediatric setting. Six juvenile sheep were implanted with the modified child-size Jarvik heart. Cardiac and pump output were measured daily. Serial blood samples were drawn to evaluate hematology, biocompatibility, and end-organ function. End-organ damage and device thrombosis were examined at necropsy. No device malfunction occurred during animal experiments up to 70 days. Mean cardiac output of the animals was 3.4 L/min. The child-size Jarvik heart was able to deliver a blood flow ranging from 1.4 to 2.5 L/min at speed from 10,000 rpm to 14,000 rpm. Mean plasma-free hemoglobin was 9.8 +/- 5.6 mg/dl, indicating no hemolysis. Acute elevation occurred in some organ function tests after the implant surgery but returned to normal range thereafter. These indices and necropsy showed no end-organ damage. No device thrombosis was observed. The current in vivo experience shows that the modified child Jarvik 2000 heart retained its hemodynamic function and excellent biocompatibility, and the conical bearings permitted it to remain free of thrombus.

INITIAL ANIMAL EXPERIENCE WITH THE HEARTWARE VAD

During the past six years, HeartWare has developed a miniaturized passively magnetically suspended centrifugal VAD. The new pump design was evaluated in a series of 22 animal experiments for a total of 618 cumulative implant days. The animal studies were conducted for a variety of purposes, including anatomical fit, design iteration, and confirmation of hemocompatibility. We report on a study of the five long term sheep implants that led to the final pump design. All experiments were conducted over a mean period of 83 +/−12 days without antico-agulation. Animals were electively terminated after 90 days except one, which had an electrical failure in a controller prototype. Overall pump performance at a rotational speed of 3000 rpm was excellent with a mean pump flow rate of 6.1 +/− 1.4 I/min and a range of 3 to 11 I/min. During the study no pump thrombus formation or pump failures occurred. Hemolysis was low with mean plasma free hemoglobin of 5.1 +/− 5.0 mg/dl. End organ function remained within the physiological range expressed by a mean creatinine-level of 1.O +/− 0.2 mg/dl and mean bilirubin of 0.1 +/− 0.05 mg/dl. Animals necropsy revealed clean pumps and no signs of pump related end organ damage. Initial animal experiments demonstrated excellent performance of the proprietary Heartware pump technology. Based upon these results, pump design was finalized. Further animal experiments with the final design are now underway in preparation for clinical trials.

IN VIVO EVALUATION OF THE BIOCOMPATIBILTY OF A TOTALLY IMPLANTABLE VAD (HEARTSAVER VAD)

Purpose: A series of multi-centre in vivo studies have been conducted to assess biocompatibility and device performance of the HeartSaver VAD, a totally implantable pulsatile VAD. Methods: The first series of experiments (n = 13) were conducted in bovine (10 Holstein, 2 Ayreshire, 1 Hereford) with a mean weight of 99 Kg (75–152 Kg). Two implantation techniques were utilized, one with cardiopulmonary bypass, and one without. Device function and biochemistry was monitored and explant histopathologic analysis conducted. Results: The mean duration ot device support was 37 days 10–91 days). Mean device flow was 6.4 L/min (3.8–8.8 L/min). None of the 13 cases presented thrombosis inside the pump or life threatening infections. No severe bleeding occurred after 24 hours post-operatively. The mean plasma free hemoglobin (5.3 +/−2.5 mg/dl) indicates a clinically acceptable level of hemolysis. Renal and hepatic functions were normal (mean creatinine0.8 +/−0.1 mg/dl and mean ALT 14.6 +/−4.5 mg/dl) in all experiments. Several device related improvements were identified and have been implemented. Additional implants with an optimized device are underway in preparation for human trials.

In vivo hemodynamic performance of the Cleveland Clinic CorAide blood pump in calves

Background. The Cleveland Clinic CorAide left ventricular assist system is based on a small implantable continuous-flow centrifugal blood pump with a completely suspended rotating assembly designed for long-term circulatory support (5 to 10 years). Methods. Between June 1999 and August 2000, the CorAide blood pump was implanted in 10 calves for 1 month and in 3 calves for 3 months. Results. The mean pump flow and arterial pressure were 6.1 ± 1.1 L/min and 97 ± 5 mm Hg, respectively. The mean plasma free-hemoglobin level after postoperative day 3 was 2.0 ± 1.8 mg/dL. Renal and hepatic function remained normal in all cases. There was no incidence of mechanical failure, hemolysis, bleeding, or systemic organ dysfunction in any of the cases. Significant findings at autopsy were limited to two cases of renal infarction, one of which was associated with an outflow graft infection. Conclusions. The CorAide blood pump is easily implanted, reliable, nonhemolytic, and nonthrombogenic, positioning it as a leading third-generation, continuous-flow left ventricular assist system with a completely suspended rotor.

Development of an Affordable Diaphragmatic Pump for Cardiopulmonary Bypass: An In Vivo Evaluation

A new diaphragmatic pump (L-Y pump) and its drive unit were developed in our institute. The pump has a priming volume of 80 ml. The pump housing is 72 mm in diameter and 42 mm in height. Its total weight is 139 g. To assess and confirm the function and controllability of this pump, comparative studies of cardiopulmonary bypass (CPB) with L-Y pump (group A) and conventional roller pump (Group B) were performed using dogs. Both pumps provided pump flow of 90 to 100 ml/kg/min. The hemodynamics of both groups were stable and within the normal range. No leakage or thrombus formation was observed in the L-Y pump. All biochemistry data showed no significant differences between the 2 groups. This data demonstrated low plasma-free hemoglobin levels in the L-Y pump group; after 120 min of CPB, mean plasma free hemoglobin levels were 48.7 +/- 8.6 mg/dl in the roller pump group and 21.4 +/- 7.1 mg/dl in the L-Y pump group, and minimal hemolysis was indicated. In conclusion, this L-Y pump and its controller system might be useful for CPB in terms of its low hemolysis and good pump quality. This pump demonstrated easy manipulation, good controllability, and provided a sufficient pulsatile flow. This pump is suitable not only for CPB, but also as a long-term circulatory support system.

Development Progress of the University of Pittsburgh Streamliner

A magnetically-suspended mixed-flow blood pump is being developed a a permanently implantable ventricular assist device. The pump impeller i supported by hybrid passive radial and active axial magnetic bearings, resulting in an energy-efficient suspension system. The internal fluid dynamics of the Streamliner pump were optimized with a combined computational and experimental fluid dynamics approach. In-vitro hydrodynamic experiments with a water/glycerol solution demonstrate hydraulic efficiency of 28% and a broad operating range. In-vitro evaluation with bovine blood demonstrated very low hemolysis (N.I.H. 0.0015±0.0010 g/100L) at 7000 RPM, 6 lpm against 100 mmHg. Shock testing demonstrated ability to withstand a peak acceleration of 8g along al three axes. An in-vivo experiment was conducted with a titanium-nitrid coated pump connected between the LV apex and the descending aorta i an 87 kg calf. The study was electively terminated after 34 days. The pum operated at a mean flow of 5.9 liters/minute and a mean arterial pressur of 96 mmHg. Mean plasma free hemoglobin was 7.3±3.9 mg/dl and platelet count was normal. Hematological and blood chemistry indicate normal organ function throughout the course of the study. Post morte examination revealed there were no pathological changes in the animal with the exception of renal infarctions. All blood-contacting surfaces of the pump were found to be free of thrombus with the exception of crevices at the inflow cannula junction and between the leading edge of th stator blades and housing. These results were quite encouraging, but emphasize the need to eliminate all sources of steps, grooves, and crevice in the manufacturing process.

Development of an Implantable Ventricular Assist System

Background. This study describes the present state of progress in the development of the Jarvik 2000 ventricular assist system.Methods. Designed for implantation in the human thorax, the system consists of a small (25 cm3, 90 g) intraventricular axial-flow blood pump that transmits power and data via internal electronics and a transcutaneous energy transfer system. The pump is powered by portable internal and external polymer lithium ion batteries. The only moving part, the pump rotor, contains a permanent magnet of a brushless direct-current motor that mounts an axial-flow impeller and partial magnetic thrust support, with blood-immersed radial and thrust bearings. The motor uses a redundant coil and electric lead design, which permits continued operation in case of wire breakage.Results. Seven calves have been supported for an average of 107 days (range, 40 to 162 days) with prototypes of the Jarvik 2000 ventricular assist system. No physiologic complications have occurred. When its user is at rest, the pump produces flows of 5 to 6 L/min with a decreased arterial pulse contour. Renal and hepatic functions have remained normal throughout the duration of all studies. Mean plasma free hemoglobin levels ranged from 4.3 to 11.4 mg/dL (mean, 6.3 mg/dL) for each study. Pathologic analyses of the heart and kidneys revealed no damage related to the device.Conclusions. These studies indicate that the Jarvik 2000 ventricular assist system is feasible in animals and holds promise for long-term support of patients.(Ann Thorac Surg 1997;63:367–70)

The Role of the Centrifugal Pump in Hemolysis During Neonatal Extracorporeal Support

While the use of the centrifugal vortex ECMO pump as an alternative to a roller-occlusion pump offers distinct advantages, unacceptable hemolysis may occur during its use in newborn infants. The authors studied 87 consecutive neonatal patients with respiratory failure supported with venoarterial ECMO using a centrifugal vortex pump. Baseline mean plasma free hemoglobin level for all patients during the first 48 hours of bypass was 31.3 +/- 3.1 md/dl. In 51 patients, an abrupt rise in the plasma free hemoglobin occurred. In 48 of 51 patients, the pump head alone was changed at 91.9 +/- 6.6 hours after initiation of bypass. Mean plasma free hemoglobin decreased to baseline values following pump head change. The authors could not determine any factors that distinguish the infants who developed hemolysis from those who did not. Changing only the pump head provides a simple approach to hemolysis during use of the centrifugal vortex pump on newborn infants.

Subchronic Use of the St. Jude Centrifugal Pump as a Mechanical Assist Device in Calves.

The purpose of this experiment was to study the effects of the St. Jude Lifestream centrifugal pump on hemodynamic and hematologic parameters and the incidence of postmortem findings in a subchronic ex vivo left ventricular assist animal model. Five calves were implanted with the pump as a left ventricular assist device (left atrial to thoracic aorta bypass) and studied for 96 h of continuous pumping under identical conditions. Heparin (100 IU/kg) was administered only in the initial saline pump prime. Throughout the protocol, mean arterial and central venous pressures averaged 102.1 ± 4.6 and 3.4 ± 2.2 mm Hg, respectively. Pump flow was 47.8 ± 8.4 ml/kg/min at a mean pump speed of 1,676.3 ± 106.1 rpm. No clinical abnormalities or mechanical malfunctions attributable to the pump were detected during the 96 h of continuous pumping for each calf. Mean plasma-free hemoglobin after 96 h was 3.9 ± 3.7 u, mol/L (p = 0.337 compared to baseline). At post mortem, renal infarctions were detected in 1 calf. No other pump-associated lesions were detected in any of the other calves. We have concluded that the St. Jude Lifestream centrifugal pump functions reliably during 96 h of continuous left heart bypass in a calf model.

In vivo evaluation of an intraventricular electric axial flow pump for left ventricular assistance.

In vivo studies have begun to evaluate a new intraventricular electric axial flow left ventricular assist device (LVAD), the Jarvik 2000, which is a small, valveless pump that is placed inside the left ventricle through the left ventricular apex. The operation, which is performed through a left thoracotomy, may be done without cardiopulmonary bypass and aortic cross-clamping. Outflow is provided through a 16 mm softly woven, Dacron graft anastomosed to the descending thoracic or abdominal aorta. Pump flow, which varies from 2 to 16 l/min in vitro, is changed by adjusting the speed of pump rotation. Preliminary studies were done to evaluate the ease of implantation, hematologic and anatomic compatibility, and pump performance. The device has been implanted in seven healthy, preconditioned calves (83-138 kg), one of which is currently undergoing support. The implantation procedure averaged 3 hours. There were no operative deaths, and blood transfusions were not required. Postoperatively, anticoagulation was achieved with heparin followed by warfarin sodium to maintain prothrombin time or partial thromboplastin time at 1.5-2.0 times baseline. In the six completed studies, support time ranged from 2 to 120 days (mean, 36 days). The seventh calf has been supported for 30 days. In the four long-term studies (20, 70, 120, > 30 days), the mean plasma free hemoglobin values during support were 11.0, 7.7, 6.6, and 3.4 mg/dl, respectively. Under normal conditions, the average daily flow rate ranged from 5 to 6 l/min. During treadmill exercise (10% grade, 1.5 km/h) lasting 20 minutes, peak flow rates exceeded 8 l/min. These pilot studies suggest that this intraventricular axial flow pump is relatively easy to implant, operate, and control. In addition, it is hemocompatible, provides physiologic flow rates, and may be able to provide long-term circulatory support.

In vivo evaluation of a trileaflet mechanical heart valve.

Design goals for a mechanical heart valve include duplicating the hemodynamic performance of the natural valve, eliminating the need for anticoagulants, and maintaining safety. The Lapeyre-Dassault (Dassault-Aviation, Paris, France) prosthetic valve, undergoing development, addresses these goals. The unique trileaflet design consists of a solid titanium ring and three leaflets. Prototypes of the valve fabricated with Delrin leaflets were implanted in the mitral position in six calves (70-90 kg). Four calves (Studies 1, 2, 3, 5) had long-term survival of 165, 158, 219, and 281 days, respectively. Two calves were killed, one on Day 37 and one on Day 39, after complications unrelated to the valve developed. In all calves heparin was given intravenously to maintain partial thromboplastin time at 1.5 to 2.0 x baseline for approximately 1 week. In Studies 1 and 2 full anticoagulation and antiplatelet therapy was given (orally administered sodium warfarin to maintain prothrombin time at 1.5 to 2.0 x baseline, along with aspirin (1 g/day) and dipyridamole 400 mg/day). In Study 3, all anticoagulation and antiplatelet therapy was discontinued at 1 month after implant. In Study 5, no anticoagulation therapy was given after the initial week of intravenous heparin; however, antiplatelet therapy was started on the fifth postoperative month and maintained until the study's end at 9 months. At 1, 2, 3, and 5 months, the mean plasma free hemoglobin level in the four long-term animals was 5.0 +/- 2.16, 6.0 +/- 3.83, 8.5 +/- 4.93, and 11.3 +/- 6.74 mg/dl, respectively. Hemolysis was not a problem. Valve performance during normal activity was excellent in all the calves, as evidenced by echocardiography and the overall appearance of good health. In the four completed long-term studies, left heart catheterization showed a mean valve pressure gradient of 11.57 +/- 1.26 mmHg and no apparent valvular regurgitation. Histopathologic examination of major organs showed no evidence of thromboembolic events. This study shows that the innovative design of this trileaflet valve performed well in initial in vivo testing, justifying further development.

The Sternotomy Hemopump

The first generation Hemopump is a VAD based on a catheter mounted intraarterial axial flow blood pump that is placed through the femoral artery. Blood is withdrawn from the left ventricle through a transvalvular inflow cannula and pumped into the aorta. Clinical trials have demonstrated hemodynamic efficacy, improved survival, and low hemolysis in cardiogenic shock. The incidence of non-insertion of the device and fracture of the flexible drive cable limited its utility, however. In addition, some processes used in pilot production could not be adapted to volume manufacturing. A second generation device, the Sternotomy Hemopump, has been developed for insertion through the ascending aorta. Design changes include a shortened inflow cannula, higher flow hydraulics, and a more durable flexible drive cable. In addition, more efficient manufacturing processes were implemented. In a pulsatile mock loop the flow was 5.7 L/min at 100 mmHg. In vivo experiments of up to 2 weeks demonstrated a mean plasma free hemoglobin of 8.7 mg/dl, minimal valve injury, and an acceptable incidence of renal infarction. In vitro endurance demonstrated a 7 day reliability of 99.9% with a 95% confidence. A new clinical trial will evaluate the use of the Sternotomy Hemopump for nonoxygenator support during aorto-coronary artery bypass surgery.

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.