How to teach artificial organs.

Artificial organs education is often an overlooked field for many bioengineering and biomedical engineering students. The purpose of this article is to describe three different approaches to teaching artificial organs. This article can serve as a reference for those who wish to offer a similar course at their own institutions or incorporate these ideas into existing courses. Artificial organ classes typically fulfill several ABET (Accreditation Board for Engineering and Technology) criteria, including those specific to bioengineering and biomedical engineering programs.

Performance characterization of a rotary centrifugal left ventricular assist device with magnetic suspension.

The MiTiHeart (MiTiHeart Corporation, Gaithersburg, MD, USA) left ventricular assist device (LVAD), a third-generation blood pump, is being developed for destination therapy for adult heart failure patients of small to medium frame that are not being served by present pulsatile devices. The pump design is based on a novel, patented, hybrid passive/active magnetic bearing system with backup hydrodynamic thrust bearing and exhibits low power loss, low vibration, and low hemolysis. Performance of the titanium alloy prototype was evaluated in a series of in vitro tests with blood analogue to map out the performance envelop of the pump. The LVAD prototype was implanted in a calf animal model, and the in vivo pump performance was evaluated. The animal's native heart imparted a strong pulsatility to the flow rate. These tests confirmed the efficacy of the MiTiHeart LVAD design and confirmed that the pulsatility does not adversely affect the pump performance.

The effect of left ventricular function and drive pressures on the filling and ejection of a pulsatile pediatric ventricular assist device in an acute animal model.

Penn State is currently developing a 12-mL, pulsatile, pneumatically driven pediatric ventricular assist device intended to be used in infants. After extensive in vitro testing of the pump in a passive-filling, mock circulatory loop, an acute animal study was performed to obtain data with a contracting ventricle. The objectives were to determine the range of pneumatic pressures and time required to completely fill and empty the pediatric ventricular assist device under various physiologic conditions, simulate reductions in ventricular contractility and blood volume, and provide data for validation of the mock circulatory loop. A 15-kg goat was used. The cannulation was achieved via left thoracotomy from the left ventricle to the descending aorta. The pump rate and systolic duration were controlled manually to maintain complete filling and ejection. The mean ejection time ranged from 280 ms to 382 ms when the systolic pressure ranged from 350 mm Hg to 200 mm Hg. The mean filling time ranged from 352 ms to 490 ms, for the diastolic pressure range of -60 mm Hg to 0 mm Hg. Esmolol produced a decrease in left ventricular pressure, required longer pump filling time, and reduced LVAD flow.

Mechanical heart valve performance in a pulsatile pediatric ventricular assist device.

A pulsatile pediatric ventricular assist device with a dynamic stroke volume of 12 ml is currently under development at the Pennsylvania State University. A monoleaflet valve (Björk-Shiley Monostrut) and a bileaflet valve (CPHV, CarboMedics Prosthetic Heart Valve) were examined in this study. A high-speed video and data acquisition system was used to simultaneously record video images, pressure waveforms, and flow waveforms for an array of in vitro test conditions that varied heart rate and systolic duration. The CPHV in both the horizontal and vertical orientations have larger regurgitant volumes than the Monostrut valves at all operating conditions in both the inlet and outlet positions. However, the CPHV has higher stroke volumes and cardiac outputs than the Monostrut valve at higher heart rates and longer systolic durations. In addition, the hydrodynamic performance of the Monostrut valve is more sensitive to changes in operating conditions for the pulsatile pediatric ventricular assist device than the CPHV in both orientations. Additional testing is under way to identify the optimal operating conditions for each type of valve.

Quantification of perfusion modes in terms of surplus hemodynamic energy levels in a simulated pediatric CPB model.

The objective of this investigation was to compare pulsatile versus nonpulsatile perfusion modes in terms of surplus hemodynamic energy (SHE) levels during cardiopulmonary bypass (CPB) in a simulated neonatal model. The extracorporeal circuit consisted of a Jostra HL-20 heart-lung machine (for both pulsatile and nonpulsatile modes of perfusion), a Capiox Baby RX hollow-fiber membrane oxygenator, a Capiox pediatric arterial filter, 5 feet of arterial tubing and 6 feet of venous tubing with a quarter-inch diameter. The circuit was primed with a lactated Ringers solution. The systemic resistance of a pseudo-patient (mean weight, 3 kg) was simulated by placing a clamp at the end of the arterial line. The pseudo-patient was subjected to five pump flow rates in the 400 to 800 ml/min range. During pulsatile perfusion, the pump rate was kept constant at 120 bpm. Pressure waveforms were recorded at the preoxygenator, postoxygenator, and preaortic cannula sites. SHE was calculated by use of the following formula {SHE (ergs/cm) = 1,332 [((integral fpdt) / (integral fdt)) - Mean Arterial Pressure]} (f = pump flow and p = pressure). A total of 60 experiments were performed (n = 6 for nonpulsatile and n = 6 for pulsatile) at each of the five flow rates. A linear mixed-effects model, which accounts for the correlation among repeated measurements, was fit to the data to assess differences in SHE between flows, pumps, and sites. The Tukey multiple comparison procedure was used to adjust p values for post hoc pairwise comparisons. With a pump flow rate of 400 ml/min, pulsatile flow generated significantly higher surplus hemodynamic energy levels at the preoxygenator site (23,421 +/- 2,068 ergs/cm vs. 4,154 +/- 331 ergs/cm, p < 0.0001), the postoxygenator site (18,784 +/- 1,557 ergs/cm vs. 3,383 +/- 317 ergs/cm, p < 0.0001), and the precannula site (6,324 +/- 772 ergs/cm vs. 1,320 +/- 91 ergs/cm, p < 0.0001), compared with the nonpulsatile group. Pulsatile flow produced higher SHE levels at all other pump flow rates. The Jostra HL-20 roller pump generated significantly higher SHE levels in the pulsatile mode when compared with the nonpulsatile mode at all five pump flow rates.

Short-term in vivo studies of surface thrombosis in a left ventricular assist system.

Thrombosis continues to be a major adverse and at times fatal event in patients with left ventricular assist systems (LVAS). To assess acute thrombosis in an LVAS, multiscale analysis of surface thrombosis was performed on LVAS blood sacs retrieved after implantation in seven calves for 3 days. Two study groups were evaluated: One group was given heparin and warfarin sodium throughout the study; the second received no postoperative anticoagulation. On explantation, the blood sacs were examined for macroscopic thrombi; microscale thrombosis was assessed with the use of scanning electron microscopy. Macroscopic thrombi about 1 mm in diameter were seen in all sacs from both groups. Although macroscopic thrombi occurred in all sac regions, scanning electron microscopy revealed differences in microscale topography between the port regions and the other sac regions. The primary structure was spherical particles approximately 400 nm in diameter, found to occur at a lower density in the ports. In contrast, the highest densities of proteinaceous rough topography and fibrillar structures consistent with fibrin clot were seen in the port regions. The density distribution of these structures was different in the eight sac regions, and anticoagulation therapy appeared to have no effect on surface thrombosis in these short-term LVAS implants.

Microtextured materials for circulatory support devices: preliminary studies.

Thromboembolic events (TE) associated with circulatory support devices are a major source of mortality and morbidity. Clinically, the lowest TE rates are claimed with devices that incorporate textured blood-contacting materials. The textured materials currently used in circulatory assist devices are composed of small, attached fibers that form the boundaries of connected cavities. These cavities entrap blood components to form a "neointimal" layer, which is believed to minimize thromboembolic events. We believe that the three-dimensional surface topography of blood-contacting materials is a major controlling factor in the formation of a stable neointimal layer upon the material. Particle-cast cavities were used to form geometric features in segmented polyurethane. This microtextured material was incorporated as part of a flexible blood-contacting surface in a blood pump that was implanted as a left ventricular assist device in calves. The structure, thickness, stability, and development of the neointimal layer were then evaluated. These preliminary studies have shown that a stable neointimal layer can be formed upon the particle-cast surfaces. The results also indicate that the cavity size on the particle-cast surfaces has a significant effect on neointimal adhesion. The methods employed can be used in the design of future circulatory support devices.

Comparison of hollow-fiber membrane oxygenators with different perfusion modes during normothermic and hypothermic CPB in a simulated neonatal model.

PURPOSE: The objectives of this investigation were (1) to compare two hollow-fiber membrane oxygenators (Capiox Baby RX versus Lilliput 1-D901) in terms of pressure drops and surplus hemodynamic energy (SHE) during normothermic and hypothermic cardiopulmonary bypass (CPB) in a simulated neonatal model; and (2) to evaluate pulsatile and non-pulsatile perfusion modes for each oxygenator in terms of SHE levels. METHODS: In a simulated patient, CPB was initiated at a constant pump flow rate of 500 mL/min. The circuit was primed with fresh bovine blood. After 5 min of normothermic CPB, the pseudo-patient was cooled down to 25 degrees C for 10 min followed by 30 min of hypothermic CPB. The pseudo-patient then underwent 10 min of rewarming and 5 min of normothermic CPB. At each experimental site (pre- and post-oxygenator and pre-aortic cannula), SHE was calculated using the following formula {SHE (ergs/cm3) = 1332 [((integralfpdt)/(integralfdt)) - mean arterial pressure]} (f = pump flow and p = pressure). A linear mixed-effects model that accounts for the correlation among repeated measurements was fit to the data to assess differences in SHE between oxygenators, pumps, and sites. Tukey's multiple comparison procedure was used to adjust p-values for post-hoc pairwise comparisons. RESULTS: The pressure drops in the Capiox group compared to the Lilliput group were significantly lower during hypothermic non-pulsatile (21.3 +/- 0.5 versus 50.7 +/- 0.9 mmHg, p < 0.001) and pulsatile (22 +/- 0.0 versus 53.3 +/- 0.5 mmHg, p < 0.001) perfusion, respectively. Surplus hemodynamic energy levels were significantly higher in the pulsatile group compared to the non-pulsatile group, with Capiox (1655 +/- 92 versus 10008 +/- 1370 ergs/cm3, p < 0.001) or Lilliput (1506 +/- 112 versus 7531 +/- 483 ergs/cm3, p < 0.001) oxygenators. During normothermic CPB, both oxygenators had patterns similar to those observed under hypothermic conditions. CONCLUSIONS: The Capiox oxygenator had a significantly lower pressure drop in both pulsatile and non-pulsatile perfusion modes. For each oxygenator, the SHE levels were significantly higher in the pulsatile mode.

Multiscale analysis of surface thrombosis in vivo in a left ventricular assist system.

Thrombosis limits the success of ventricular assist devices as the demand for alternatives to heart transplants is increasing. This study mapped the occurrence of thrombosis in a left ventricular assist system (LVAS) to better understand the biologic response to these devices. Nine calves divided into two groups were implanted with LVAS for 28 to 30 days. One group was anticoagulated, whereas the second group received no long-term anticoagulation. The blood-contacting poly(urethane urea) surfaces of blood sacs in the LVAS were examined for macroscopic thrombi upon retrieval. The sac was partitioned into eight sections and imaged for thrombi by scanning electron microscopy. No difference in thrombosis was observed macroscopically between the groups. Anticoagulation appeared to result in reduction of platelet-like structures, but the presence of fibrin-like structures remained similar between groups. Regional differences correlating with high and low shear stress regions were observed. At the macroscale, fewer thrombi were recorded in the high shear stress ports. At the microscale, features resembling fibrin were observed primarily in the ports and platelet-like features were common in lower shear stress regions. These variations in thrombosis with anticoagulation and location are likely due to varied fluid dynamics within the LVAS blood sac.

Effect of the diastolic and systolic duration on valve cavitation in a pediatric pulsatile ventricular assist device.

Minimization of cavitation is of high importance in the design of pulsatile ventricular assist devices because cavitation can cause blood and valve surface damage. Cavitation is associated with valve closure and has been previously correlated to high dP/dt, high valve closing velocity, and decreased pump filling. In this study, the effects of diastolic and systolic duration on the inlet and outlet valve cavitation were investigated. A low volume (280 ml) mock circulatory loop filled with room-temperature saline was used. A high-fidelity hydrophone was mounted into the inlet valve connector approximately 0.5 cm upstream from the inlet valve to quantify inlet valve cavitation. The inlet valve connector and hydrophone were placed symmetrically on the outlet side when measuring outlet valve cavitation. The RMS intensity of a 6-millisecond window pressure trace, bandpass filtered from 50 to 500 kHz, was used to quantify cavitation intensity. Approximately 80 beats were recorded at every test condition. High-speed video and an accelerometer were used to determine the position of the valves during closure. The cavitation intensity of the inlet valve was minimal when the onset of systole occurred at the moment when the pump just completed filling (RMS was approximately zero). The cavitation intensity increased when the onset of systole occurred before the pump was completely filled (valve partially opened), reaching a plateau of approximately 16 mm Hg when the valve was fully open. The cavitation intensity increased again when diastolic duration exceeded pump filling time by more than 30 milliseconds. The outlet valve cavitation intensity was very low (<4 mm Hg) regardless of the systolic duration, which can be attributed to the position of the hydrophone being on the opposite side of cavitation events. Although very small, the outlet cavitation intensities with respect to systolic duration show a trend similar to the inlet valve cavitation with respect to diastolic duration. Both inlet and outlet valve cavitation increased with increased peak regurgitant flow. An understanding of the relationship of the inlet and outlet valve cavitation to the diastolic and systolic duration can be used to determine the optimal operating conditions of the pulsatile pediatric pump.

Effects of atrial arrhytmias on the regurgitation of a monoleaflet prosthetic heart valve.

Many patients who receive a prosthetic heart valve also have or acquire cardiac arrhythmias. However, most in vitro studies of prosthetic valves examine them under normal rhythms. In this study, a monoleaflet prosthetic heart valve was tested in vitro under conditions that simulated normal sinus rhythm, first degree atrioventricular heart block, and atrial fibrillation (fixed and variable ventricular rates). Atrial contraction was simulated by an active atrial chamber. The timing between the atrium and ventricle was adjusted to simulate various types of arrhythmias. The closing, leakage, and total regurgitant volumes and fractions increased for each type of atrial arrhythmia when compared to normal sinus rhythm. The peak regurgitant flow increased for first degree atrioventricular heart block and atrial fibrillation with a fixed ventricular rate compared to normal sinus rhythm.

Durability testing of a completely implantable electric total artificial heart.

In vitro durability testing was conducted on the Penn State/3M electric total artificial heart (ETAH) to determine device durability and to evaluate device failures. A specialized mock circulatory loop was developed for this testing. Customized software continuously acquired data during the test period, and failures were analyzed using FMEA (failure modes and effects analysis) and FMECA (failure modes, effects, and criticality analysis) principles. Redesigns were implemented when appropriate. Reliability growth principles were then applied to calculate the 1 and 2 year reliability. The 1 and 2 year reliability of the Penn State/3M ETAH was shown to be 96.1% and 59.9%, respectively, at 80% confidence.

Precise quantification of pressure flow waveforms of a pulsatile ventricular assist device.

Unreliable quantification of flow pulsatility has hampered many efforts to assess the importance of pulsatile perfusion. Generation of pulsatile flow depends upon an energy gradient. It is necessary to quantify pressure flow waveforms in terms of hemodynamic energy levels to make a valid comparison between perfusion modes during chronic support. The objective of this study was to quantify pressure flow waveforms in terms of energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE) levels in an adult mock loop using a pulsatile ventricle assist system (VAD). A 70 cc Pierce-Donachy pneumatic pulsatile VAD was used with a Penn State adult mock loop. The pump flow rate was kept constant at 5 L/min with pump rates of 70 and 80 bpm and mean aortic pressures (MAP) of 80, 90, and 100 mm Hg, respectively. Pump flows were adjusted by varying the systolic pressure, systolic duration, and the diastolic vacuum of the pneumatic drive unit. The aortic pressure was adjusted by varying the systemic resistance of the mock loop EEP (mm Hg) = (integral of fpdf)/(integral of fdt) SHE (ergs/cm3) = 1,332 [((integral of fpdt)/(integral of fdt))--MAP] were calculated at each experimental stage. The difference between the EEP and the MAP is the extra energy generated by this device. This difference is approximately 10% in a normal human heart. The EEP levels were 88.3 +/- 0.9 mm Hg, 98.1 +/- 1.3 mm Hg, and 107.4 +/- 1.0 mm Hg with a pump rate of 70 bpm and an aortic pressure of 80 mm Hg, 90 mm Hg, and 100 mm Hg, respectively. Surplus hemodynamic energy in terms of ergs/cm3 was 11,039 +/- 1,236 ergs/cm3, 10,839 +/- 1,659 ergs/cm3, and 9,857 +/- 1,289 ergs/cm3, respectively. The percentage change from the mean aortic pressure to EEP was 10.4 +/- 1.2%, 9.0 +/- 1.4%, and 7.4 +/- 1.0% at the same experimental stages. Similar results were obtained when the pump rate was changed from 70 bpm to 80 bpm. The EEP and SHE formulas are adequate to quantify different levels of pulsatility for direct and meaningful comparisons. This particular pulsatile VAD system produces near physiologic hemodynamic energy levels at each experimental stage.