Branka Lukic

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/cm3) = 1,332 [((∫ fpdt) / (∫ 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/cm3 vs. 4,154 ± 331 ergs/cm3, p < 0.0001), the postoxygenator site (18,784 ± 1,557 ergs/cm3 vs. 3,383 ± 317 ergs/cm3, p < 0.0001), and the precannula site (6,324 ± 772 ergs/cm3 vs. 1,320 ± 91 ergs/cm3, 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.

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.

A Passively-Suspended Tesla Pump Left Ventricular Assist Device

The design and initial test results of a new passively suspended Tesla type left ventricular assist device blood pump are described. Computational fluid dynamics (CFD) analysis was used in the design of the pump. Overall size of the prototype device is 50 mm in diameter and 75 mm in length. The pump rotor has a density lower than that of blood and when spinning inside the stator in blood it creates a buoyant centering force that suspends the rotor in the radial direction. The axial magnetic force between the rotor and stator restrain the rotor in the axial direction. The pump is capable of pumping up to 10 L/min at a 70 mm Hg head rise at 8,000 revolutions per minute (RPM). The pump has demonstrated a normalized index of hemolysis level below 0.02 mg/dL for flows between 2 and 9.7 L/min. An inlet pressure sensor has also been incorporated into the inlet cannula wall and will be used for control purposes. One initial in vivo study showed an encouraging result. Further CFD modeling refinements are planned and endurance testing of the device.

Energy Equivalent Pressure and Total Hemodynamic Energy Associated with the Pressure-Flow Waveforms of a Pediatric Pulsatile Ventricular Assist Device

A pulsatile pediatric ventricular assist device (VAD) with a dynamic stroke volume of approximately 12 ml was tested to quantify the effect of flowrate and systolic duration on pulsatility as quantified by the energy equivalent pressure (EEP), defined as the hemodynamic energy per unit volume of fluid pumped. The VAD was tested on a mock circulatory loop, adjusted to maintain a systemic arterial pressure of approximately 90/60 mm Hg (systolic/diastolic) and a mean of 75 mm Hg. The EEP was calculated for each beat for 1 minute at both the proximal end of the pump outlet cannula and at the distal end (arterial EEP). Nominal mean flowrates were 0.50, 0.75, 1.00, and 1.25 l/min. Systolic duration was set at either 230 or 400 milliseconds. With a rapid systolic ejection (230 milliseconds), the arterial EEP ranged from 5.58% to 8.41% relative to the mean arterial pressure. The highest EEP occurred at the lowest flowrate. With a slower (400 milliseconds) systolic ejection, the arterial EEP ranged from 2.33% to 4.20%. Hemodynamic energy loss in the outlet cannula was also quantified by the differential EEP and shown to increase markedly as systolic duration was decreased, but was relatively insensitive to mean flowrate.

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 animals 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.

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°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 [((ffpdt)/(ffdt))-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 B < 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 10 008∓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.

Comparison of four different pediatric 10F aortic cannulae during pulsatile versus nonpulsatile perfusion in a simulated neonatal model of cardiopulmonary bypass.

We compared four commercially available 10F pediatric aortic cannulae with different geometric designs (DLP—Long tip, DLP—Short tip, RMI—Long tip, and Surgimedics—Short tip) during pulsatile versus nonpulsatile perfusion in terms of pressure drops and surplus hemodynamic energy (SHE) levels in an in vitro neonatal model of cardiopulmonary bypass. The pseudo patient was subjected to seven pump flow rates at 100 ml/min increments in the 400–1,000 ml/min range. A total of 44 experiments (n = 22, nonpulsatile; n = 22, pulsatile) were performed at each of the seven flow rates. Surgimedics had significantly higher pressure drops than the other three cannulae at various flow rates during nonpulsatile and pulsatile perfusion, respectively. When the perfusion mode was changed from nonpulsatile to pulsatile flow, SHE levels at both precannula and postcannula sites increased seven to nine times at all flow rates in all four cannulae. Surgimedics generated a significant lower SHE level when compared with the other three cannulae at all flow rates at both precannula and postcannula sites. The results suggest that different geometries of aortic cannulae have a significant impact on pressure drops of the cannulae as well as hemodynamic energy generation and delivery. Pulsatile perfusion generates more “extra” hemodynamic energy when compared with the nonpulsatile perfusion mode with all four cannulae used in this study.

Chronic In Vivo Testing of the Penn State Infant Ventricular Assist Device

The Penn State Infant Ventricular Assist Device (VAD) is a 12–14 ml stroke volume pneumatically actuated pump, with custom Björk-Shiley monostrut valves, developed under the National Heart, Lung, and Blood Institute Pediatric Circulatory Support program. In this report, we describe the seven most recent chronic animal studies of the Infant VAD in the juvenile ovine model, with a mean body weight of 23.5 ± 4.1 kg. The goal of 4–6 weeks survival was achieved in five of seven studies, with support duration ranging from 5 to 41 days; mean 26.1 days. Anticoagulation was accomplished using unfractionated heparin, and study animals were divided into two protocol groups: the first based on a target activated partial thromboplastin time of 1.5–2 times normal, and a second group using a target thromboelastography R-time of two times normal. The second group required significantly less heparin, which was verified by barely detectable heparin activity (anti-Xa). In both groups, there was no evidence of thromboembolism except in one animal with a chronic infection and fever. Device thrombi were minimal and were further reduced by introduction of the custom valve. These results are consistent with results of adult VAD testing in animals and are encouraging given the extremely low levels of anticoagulation in the second group.

Tesla-Based Blood Pump and Its Applications

A continuous flow left ventricular assist device (LVAD) that the Penn State University has developed utilizes Tesla turbomachinery technology. Tesla pumping technology patented by Nikola Tesla in the early 20th century has multiple intriguing characteristics such as simpler manufacturing process, reduced turbulent-related stress, less cavitation due to viscous flow distribution over larger surface areas, and less hemolysis by smooth transition of fluid energy. We successfully tested the 1st version of the Penn State Tesla LVAD [1, 2]. We recently tested the 2nd version of the Tesla pump; to make the pump usable in a wide range of patients, the size of the pump was significantly reduced while trying to avoid any degradation of hemodynamic and hemolytic characteristics.Copyright

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.