The NASA artificial heart driver: A pneumatic power source developed for Willem Kolff's artificial heart program.

The sprint to create a viable, implantable heart replacement device started in the 1950s, with current technologies still lacking a permanent solution. Early development of artificial hearts was littered with obstacles related to the power source. A pneumatic driver suggested and developed by NASA aimed to discover a more suitable pressure curve through offering highly manipulable parameters, but also enable automatic regulation of hemodynamics. While improved electric function waveforms were identified, the driver was ultimately abandoned due to minimal clinical applicability and an incomplete understanding of cardiovascular physiology. The opportunity for further waveform studies was simultaneously lost.

Percutaneous Cavopulmonary Assist: From Design to 96 Hour Survival in Lethal Cavopulmonary Failure Sheep.

We are developing a clinically practical percutaneous double lumen cannula (DLC)-based cavopulmonary assist (CPA) system to support failing Fontan patients. In this study, our CPA DLC was redesigned for even blood flow, minimal recirculation, and easy insertion/deployment. After bench testing, this new CPA system was evaluated for 4 hours (n = 10) and 96 hours (n = 5) in our clinically relevant lethal cavopulmonary failure (CPF) sheep model for ease of cannulation/deployment, reversal of CPF hemodynamics/end-organ hypoperfusion, and durability/biocompatibility. Cavopulmonary failure was achieved in all sheep. All DLCs were successfully inserted/deployed into Fontan anatomy. Cavopulmonary assist reversed CPF with normalized central venous pressure and cardiac output. All survival sheep were ambulatory with normal eating/drinking. One sheep was euthanized after 6 hours from cannula kinking, and one sheep died of hypokalemia after 8 hours. Three sheep survived 96 hours with normal hemodynamics. Free hemoglobin was only 3.7 ± 1.2 mg/dl at 96 hours, indicating negligible hemolysis. Creatinine, blood urea nitrogen, and lactate increased from hypoperfusion but normalized by 72 hours CPA. Necropsy showed only a small, immobilized thrombus ring at umbrella attachment to DLC. Our DLC-based system provided total ambulatory CPA in a lethal CPF sheep model with 96 hour survival and complete reversal of hemodynamics and end-organ hypoperfusion.

AvalonElite Double Lumen Cannula for Total Cavopulmonary Assist in Failing Fontan Sheep Model with Valved Extracardiac Conduit.

The AvalonElite double lumen cannula (DLC) provides total cavopulmonary assist (CPA) in failing Fontan sheep, but recirculation limits reliability. To improve CPA performance, a two-valve extracardiac conduit (ECC) was used to bracket infusion blood toward pulmonary artery (PA). A total cavopulmonary connection with failing Fontan circulation adult sheep model was created with valved ECC (n = 6). The valved ECC was connected to superior/inferior venae cavae (SVC/IVC) and right PA. The AvalonElite DLC was inserted from right jugular vein with infusion opening between the ECC valves. The DLC drainage lumen withdrew blood from SVC/IVC, and the infusion lumen returned blood to ECC. A failing Fontan sheep model with valved ECC was successfully created. Central venous pressure increased from 9 ± 1 to 17 ± 1 mm Hg, systolic arterial pressure decreased from 103 ± 9 to 51 ± 13 mm Hg, and cardiac output decreased from 3.6 ± 0.3 to 1.4 ± 0.2 L/min. Serum lactate significantly increased, indicating poor tissue perfusion. At 4 L/min pumping flow, the AvalonElite DLC returned hemodynamics/lactate to baseline levels throughout 6 hour CPA. Necropsy revealed intact/well-functioning ECC valves and well-positioned DLC with no visible thrombosis. The AvalonElite DLC provides reliable CPA performance in failing Fontan sheep with valved ECC.

A transapical-to-aorta double lumen cannula-based neonate left ventricular assist device efficiently unloads the left ventricle in neonate lambs.

OBJECTIVE: We are developing a transapical-to-aorta double lumen cannula (TAA DLC) for a less-invasive/more dependable neonatal left ventricular assist device. METHODS: The 18-Fr TAA DLC prototypes were bench tested and evaluated for 6 hours in neonate lambs (n = 6, 7.7-10 kg). The cardiac apex was exposed through a left anterolateral thoracotomy through the sixth intercostal space. The TAA DLC was inserted through a mattress stitch on apex, passing LV-aortic valve, into the ascending aorta with insertion/deployment guided by pressure waveform. The DLC was connected to blood pump. Cardiac output and aortic root blood flow were measured with perivascular flow sensors. Activated clotting time was maintained at 180-250 seconds. RESULTS: The DLC pumped up to 1.8 L/min flow against 63 mm Hg drainage pressure and 145 mm Hg infusion pressure in bench testing. In all lambs, the DLC was inserted/deployed properly within 1 minute on the first attempt. Pumping flow was maintained at 1.2-1.3 L/min. Systolic arterial pressure decreased and diastolic arterial pressure/mean arterial pressure increased, indicating decreased afterload and increased perfusion pressure. Left ventricular end-diastolic pressure decreased from 13 ± 1 mm Hg to 6 ± 2 mm Hg, indicating decreased preload. Aortic root backward flow was 2.4% ± 0.6% without DLC and 3.5% ± 0.8% of cardiac output with DLC, indicating no significant DLC-induced aortic valve regurgitation. After 6 hours, free hemoglobin was <5 mg/dL with hemoglobin/platelets unchanged. No significant thrombus was found in pumps/DLCs. No trauma was found in LV, aortic valve, and aorta. CONCLUSIONS: Our TAA DLC-based neonate left ventricular assist device efficiently unloaded the LV in lambs.

Development of a Double-Lumen Cannula for a Percutaneous RVAD.

The objectives were to design/fabricate a double-lumen cannula (DLC) for a percutaneous right ventricular assist device (pRVAD) and to test the feasibility/performance of this pRVAD system. A 27 Fr DLC prototype was made and tested in six adult sheep. The pRVAD DLC was inserted into the right jugular vein; advanced through the superior vena cava, the right atrium (RA), the right ventricle (RV); ending in the pulmonary artery (PA). A CentriMag pump and optional gas exchanger were connected to the DLC. Blood was withdrawn from RA, pumped through gas exchanger, and perfused PA. Maximal pumping flow was maintained for 2 hours. The pRVAD DLC was successfully deployed in all six sheep. In first three sheep, maximal average pumping flow was less than 3 L/min because the DLC was advanced too far with drainage opening against RA side wall. In last three sheep with well-positioned DLC, average maximal flow was more than 3.5 L/min. The gas exchanger provided up to 230 ml/min CO2 removal and 174 ml/min O2 transfer. Our DLC-based pRVAD system is feasible for percutaneous right heart and respiratory assistance through a single cannulation. The pRVAD DLC can be easily placed prophylactically during left ventricular assist device implantation and removed as needed without additional open chest procedures.

A paired membrane umbrella double-lumen cannula ensures consistent cavopulmonary assistance in a Fontan sheep model.

OBJECTIVES: The Avalon Elite (Macquet, Rastatt, Germany) double-lumen cannula can provide effective cavopulmonary assistance in a Fontan (total cavopulmonary connection) sheep model, but it requires strict alignment. The objective was to fabricate and test a newly designed paired umbrella double-lumen cannula without alignment requirement. METHODS: The paired membrane umbrellas were designed on the double-lumen cannula to bracket infusion blood flow toward the pulmonary artery. Two umbrellas were attached, one 4 cm above and one 4 cm below the infusion opening. Umbrellas were temporarily wrapped and glued to the double-lumen cannula body to facilitate insertion. A total cavopulmonary connection mock loop was used to test cavopulmonary assistance performance and reliability with double-lumen cannula rotation and displacement. The paired umbrella double-lumen cannula also was tested in a total cavopulmonary connection adult sheep model (n = 6). RESULTS: The bench test showed up to 4.5 L/min pumping flow and approximately 90% pumping flow efficiency at 360° rotation and 8-cm displacement of double-lumen cannula. The total cavopulmonary connection model with compromised hemodynamics was successfully created in all 6 sheep. The cavopulmonary assistance double-lumen cannula with paired umbrellas was smoothly inserted into the superior vena cava and extracardiac conduit in all sheep. At 3.5 to 4.0 L/min pump flow, the systolic arterial blood pressure and central venous pressure returned to normal baseline and remained stable throughout the 90-minute experiment, demonstrating effective cavopulmonary assistance support. Double-lumen cannula rotation and displacement did not affect performance. Autopsy revealed well-opened and positioned paired umbrellas, and double-lumen cannulas were easily removed from the right jugular vein. CONCLUSIONS: Our double-lumen cannula with paired umbrellas is easy to insert and remove. The paired umbrellas eliminated the strict alignment requirement and ensured consistent cavopulmonary assistance performance.

Resolution of pulmonary hypertension complication during venovenous perfusion-induced systemic hyperthermia application.

We are developing a venovenous perfusion-induced systemic hyperthermia (vv-PISH) system for advanced cancer treatment. The vv-PISH system consistently delivered hyperthermia to adult healthy swine, but significant pulmonary hypertension developed during the heating phase. The goal of this study was to develop a method to prevent pulmonary hypertension. We hypothesized that pulmonary hypertension results from decreased priming solution air solubility, which causes pulmonary gas embolism. Healthy adult sheep (n = 3) were used to establish a standard vv-PISH sheep model without priming solution preheating. In subsequent sheep (n = 7), the priming solution was preheated (42-46°C) and the hyperthermia circuit flushed with CO2. All sheep survived the experiment and achieved 2 hours of 42°C hyperthermia. In the group lacking priming solution preheating, significant pulmonary hypertension (35-44 mm Hg) developed. In the sheep with priming solution preheating, pulmonary artery pressure was very stable without pulmonary hypertension. Blood electrolytes were in physiologic range, and complete blood counts were unaffected by hyperthermia. Blood chemistries revealed no significant liver or kidney damage. Our simple strategy of priming solution preheating completely resolved the problem of pulmonary hypertension as a milestone toward developing a safe and easy-to-use vv-PISH system for cancer treatment.

Physiologic response to a simplified venovenous perfusion-induced systemic hyperthermia system.

Our original venovenous perfusion-induced systemic hyperthermia (vv-PISH) system appeared to significantly improve the survival of patients with lung cancer, but was too complex with numerous dialysis problems. We tested a simplified vv-PISH circuit that includes the Avalon Elite (Avalon Laboratories, LLC, Rancho Dominguez, CA) double lumen cannula, a modified heat exchanger, a water heater/cooler, and a centrifugal pump. The purpose of this study was to evaluate this simplified vv-PISH system (without hemodialyzer) and to investigate the physiologic response to whole-body hyperthermia in pigs. We tested our vv-PISH circuit in healthy adult female swine (n = 7, 55-68 kg). The therapeutic core temperature (42°C), calculated as mean of rectal, bladder, and esophageal temperatures, was achieved in six swine. A maximum difference of 0.5°C was observed between the individual temperature sensor readings, indicating homogeneous heat distribution. Heart rate and mean arterial pressure were transiently altered, but were safely managed. A significant elevation in pulmonary artery pressure occurred during the heating phase, resulting in death of one pig. In all other pigs, pulmonary artery pressure returned to physiologic values during the therapeutic phase. Arterial blood electrolytes were maintained without the need of a dialyzer. Major organ function was within normal parameters. The simplified vv-PISH circuit reliably delivered the hyperthermic dose with no need of dialysis.

Development of "plug and play" TransApical to aorta VAD.

Our TransApical to Aorta pump, a simple and minimally invasive left ventricular (LV) assist device, has a flexible, thin-wall conduit connected by six struts to a motor with ball bearings and a turbine extending into the blood path. Pulsatile flow is inherent in the design as the native heart contraction preloads the turbine. In six healthy sheep, the LV apex was exposed by a fifth intercostal left thoracotomy. The pump was inserted from the cardiac apex through the LV cavity into the ascending aorta. Aortic and LV pressure waveforms, pump flow, motor current, and pressure were directly measured. All six cannula pumps were smoothly advanced on the first attempt. Pump implantation was <15 minutes (13.6 +/- 1.8 minutes). Blood flow was 2.8 l/min to 4.4 l/min against 86 +/- 8.9 mm Hg mean arterial blood pressure at maximum flow. LV systemic pressure decreased significantly from 102.5 +/- 5.55 mm Hg to 58.8 +/- 15.5 mm Hg at the fourth hour of pumping (p = 0.042), and diastolic LV pressure decreased from 8.4 +/- 3.7 to 6.1 +/- 2.3 mm Hg (p > 0.05). The pump operated with a current of 0.4 to 0.7 amps and rotation speed of 28,000 to 33,000 rpm. Plasma free hemoglobin was 4 +/- 1.41 mg/dl (range, 2 to 5 mg/dl) at termination. No thrombosis was observed at necropsy.A left ventricular assist device using the transapical to aorta approach is quick, reliable, minimally invasive, and achieves significant LV unloading with minimal blood trauma.

Use of aortic valvo-pumps placed in valve annulus for long-term left ventricular assist.

To provide better anatomical fit and physiologic adaptation, three aortic valvo-pumps with different dimensions were developed. Each pump has a rotor with an impeller and drive magnets and a stator consisting of a motor coil with iron core and an outflow guide vane. The devices had outer diameters of 21 mm, 23 mm, and 25 mm, respectively, and weighted 27 g, 31 g, and 40 g, respectively. Laboratory testing demonstrated that the rotating speed for maintaining a diastolic pressure of 80 mm Hg at zero flow rate should be 17500 rpm, 15000 rpm, and 12500 rpm, respectively; the largest flow at these same speeds will be 5 l/min, 7 l/min, and 10 l/min, respectively, with approximately 50 mm Hg pressure head increase. Therefore, these three pumps may meet the hemodynamic requirements of patients with body weights of 40-60 kg, 60-80 kg, and 80-100 kg. The first in vivo trial exhibited that the 25 mm valvo-pump can be sewn onto the aortic valve annulus of a 80 kg body weight pig without harm to adjacent organ functions. The devices occupy no additional anatomic space and deliver the blood directly from ventricle to the aorta, thus producing less physiologic disturbance to the natural circulation. Neither connecting conduits nor bypass circuits are necessary, thus eliminating the most dangerous sites of thrombosis in traditional left ventricular assist devices.