Jung Joo Lee

In vitro evaluation of the performance of Korean pulsatile ECLS (T-PLS) using precise quantification of pressure-flow waveforms

The Twin-Pulse Life Support System (T-PLS) is a novel pulsatile extracorporeal life support system developed in Korea. It has been reported that the T-PLS achieves higher levels of tissue perfusion of the kidney during short-term extracorporeal circulation and provides more blood flow to coronary artery than nonpulsatile blood pumps. However, these results lack pulsatility quantifications and thus make it hard to analyze the effects of pulsatility upon hemodynamic performance. We have adopted the concepts of hemodynamic energy, energy equivalent pressure (EEP), and surplus hemodynamic energy (SHE) to evaluate pulsatility performance in the different circuit configurations of the T-PLS and a membrane oxygenator (MO) in vitro. In a mock system, three different circuits were constructed depending on the location of an MO: pump-MO-pump (serial), MO-pumps (parallel A), and pumps-MO (parallel B). In parallel A, a low-resistance MO was used to preserve the pulsatility from the pump. All circuits showed good pulsatility in terms of EEP (serial: 13.2% ± 3.2%, parallel A: 10.0% ± 1.6%, parallel B: 7.00% ± 1.1%; change from aortic pressure to EEP; p < 0.003). The SHE levels were 17,404 ± 3,750 ergs/cm3, 13,170 ± 1,486 ergs/cm3, and 9,192 ± 1,122 ergs/cm3 in each circuit setup (p < 0.001). Although EEP levels were somewhat lower, both parallel types provided higher pump output compared with the serial type (serial: 1.87 ± 0.29 l/min, parallel A: 3.09 ± 0.74 l/min, parallel B: 3.06 ± 0.56 l/min; p < 0.003 except parallel A vs. parallel B, p = 0.90). Conclusively, the precise quantifications of pressure flow waveforms, EEP, and SHE are valuable tools for evaluating pulsatility of the mechanical circulatory devices, and are expected to be used as additional performance indexes of a blood pump. The pulsatility performances are different according to circuit setups. However, the parallel A circuit could achieve higher pump output and generate adequate pulsatility level. Thus, the parallel A circuit is suggested as the optimal configuration in T-PLS applications.

Hemodynamic energy generated by a combined centrifugal pump with an intra-aortic balloon pump.

We examined the pulsatility generated by an intra-aortic balloon pump/centrifugal pump (IABP/CP) combination in terms of energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE). In five cardiac-arrested pigs, the outflow cannula of the CP was inserted into the ascending aorta, the inflow cannula in the right atrium. A 30-ml IABP was subsequently placed in the descending aorta. Extracorporeal circulation was maintained for 30 minutes using a pump flow of 75 ml/kg per minute by CP alone or by IABP/CP with pressure and flow measured in the right internal carotid artery. The IABP/CP combination converted the flow to pulsatile and increased pulse pressure significantly from 9.1 ± 1.3 mm Hg to 54.9 ± 6.1 mm Hg (p = 0.012). It also significantly increased the percent change from mean arterial pressure to EEP from 0.2 ± 0.3% to 23.3 ± 6.1% (p = 0.012) and SHE from 133.2 ± 234.5 erg/cm3 to 20,219.8 ± 5842.7 erg/cm3 (p = 0.012). However, no statistical difference was observed between CP and IABP/CP in terms of mean carotid artery pressure (p = NS). In a cardiac-arrested animal model, pulsatility generated by a IABP/CP combination may be effective in terms of energy equivalent pressure and surplus hemodynamic energy.

Optimization of the circuit configuration of a pulsatile ECLS: An in vivo experimental study

An extracorporeal life support system (ECLS) with a conventional membrane oxygenator requires a driving force for the blood to pass through hollow fiber membranes. We hypothesized that if a gravity-flow hollow fiber membrane oxygenator is installed in the circuit, the twin blood sacs of a pulsatile ECLS (the Twin-Pulse Life Support, T-PLS) can be placed downstream of the membrane oxygenator. This would increase pump output by doubling pulse rate at a given pump-setting rate while maintaining effective pulsatility. The purpose of this study was to determine the optimal circuit configuration for T-PLS with respect to energy and pump output. Animals were randomly assigned to 2 groups in a total cardiopulmonary bypass model. In the serial group, a conventional membrane oxygenator was located between the twin blood sacs of the T-PLS. In the parallel group, the twin blood sacs were placed downstream of the gravity-flow membrane oxygenator. Energy equivalent pressure (EEP), surplus hemodynamic energy (SHE) and pump output were collected at the different pump-setting rates of 30, 40, and 50 beats per minute (BPM). At a given pump-setting rate the pulse rate doubled in the parallel group. Percent changes of mean arterial pressure to EEP were 13.0 ± 1.7, 12.0 ± 1.9, and 7.6 ± 0.9% in the parallel group, while 22.5 ± 2.4, 23.2 ± 1.9, and 21.8 ± 1.4 in the serial group at 30, 40, and 50 BPM of pump-setting rates. SHE at each pump setting rate was 20,131 ± 1,408, 21,739 ± 2,470, and 15,048 ± 2,108 erg/cm3 in the parallel group, while 33,968 ± 3,001, 38,232 ± 3,281, 37,964 ± 2,693 erg/cm3 in the serial group. Pump output was higher in the parallel circuit at 40, and 50 BPM pump-setting rates (3.1 ± 0.2, 3.7 ± 0.2 L/min vs. 2.2 ± 0.1 and 2.5 ± 0.1 L/min, respectively, p =0.01). Either parallel or serial circuit configuration of T-PLS generates effective pulsatility. As for the pump out, the parallel circuit configuration provides higher flow than the serial circuit configuration by doubling the pulse rate at a given pump-setting rate.

Comparison of myocardial loading between asynchronous pulsatile and nonpulsatile percutaneous extracorporeal life support.

We hypothesized that myocardial loading can be increased when extracorporeal pulse flow occurs during systole, and that this may adversely affect myocardial working conditions in heart failure patients supported by extracorporeal life support (ECLS). This study was designed to compare myocardial loading and myocardial oxygen consumption/supply balance between nonpulsatile ECLS and asynchronized pulsatile ECLS in a myocardial stunning model. Thirteen, 23–42 kg dogs were allotted to a nonpulsatile group and an asynchronous pulsatile group. Coronary sinus lactate level, mixed venous oxygen consumption (MvO2), and left anterior descending coronary artery flow were measured. The real-time pressure of the left ventricle and the ascending aorta was monitored, and the lowest left ventricular pressure and tension time index were calculated. Our results showed that the lactate level and the lowest left ventricular pressure were lower in the pulsatile group than in the nonpulsatile group at 30 minutes after ECLS was applicated (p < 0.05, respectively). Tension time index in the pulsatile ECLS group was substantially lower than in the nonpulsatile group. Left anterior descending coronary flow did not show significant difference between the two groups. In conclusion, asynchronous pulsatile ECLS may also be superior to nonpulsatile ECLS in myocardial volume unloading and oxygen consumption/supply balance.

Comparison of coronary artery blood flow and hemodynamic energy in a pulsatile pump versus a combined nonpulsatile pump and an intra-aortic balloon pump.

We compared the coronary artery blood flow and hemodynamic energy between pulsatile extracorporeal life support (ECLS) and a centrifugal pump (CP)/intra-aortic balloon pump (IABP) combination in cardiac arrest. A total cardiopulmonary bypass circuit was constructed for six Yorkshire swine weighing 30 to 40 kg. The outflow cannula of the CP or a pulsatile ECLS (T-PLS) was inserted into the ascending aorta, and the inflow cannula of the CP or T-PLS was placed into the right atrium. A 30-ml IABP was subsequently placed in the descending aorta. Extracorporeal circulation was maintained for 30 minutes with a pump flow of 75 ml/kg per minute by a CP with an IABP or T-PLS. Pressure and flow were measured in the right internal carotid artery. The energy equivalent pressure (EEP) and surplus plus hemodynamic energy (SHE) were recorded. The left anterior descending coronary artery flow was measured with an ultrasonic coronary artery flow measurement system. The percent change of the mean arterial pressure to EEP was effective in both groups (23.3 ± 6.1 in CP plus IABP vs. 19.8 ± 6.2% in T-PLS, p = NS). The SHE was high enough in the CP/IABP and the T-PLS (20,219.8 ± 5824.7 vs. 13,160.2 ± 4028.2 erg/cm3, respectively, p = NS). The difference in the coronary artery flow was not statistically significant at 30 minutes after bypass was initiated (28.2 ± 9.79 ml/min in CP plus IABP vs. 27.7 ± 9.35 ml/min in T-PLS, p = NS).

Development of a closed air loop electropneumatic actuator for driving a pneumatic blood pump.

In this study, we developed a small pneumatic actuator that can be used as an extracorporeal biventricular assist device. It incorporated a bellows-transforming mechanism to generate blood-pumping pressure. The cylindrical unit is 88 +/- 0.1 mm high, has a diameter of 150 +/- 0.1 mm, and weighs 2.4 +/- 0.01 kg. In vitro, maximal outflow at the highest pumping rate (PR) exceeded 8 L/min when two 55 mL blood sacs were used under an afterload pressure of 100 mm Hg. At a pumping rate of 100 beats per minute (bpm), maximal hydraulic efficiency was 9.34% when the unit supported a single ventricle and 13.8% when it supported both ventricles. Moreover, pneumatic efficiencies of the actuator were 17.3% and 33.1% for LVAD and BVAD applications, respectively. The energy equivalent pressure was 62.78 approximately 208.10 mm Hg at a PR of 60 approximately 100 bpm, and the maximal value of dP/dt during systole was 1269 mm Hg/s at a PR of 60 bpm and 979 mm Hg/s at a PR of 100 bpm. When the unit was applied to 15 calves, it stably pumped 3 approximately 4 L/min of blood at 60 bpm, and no mechanical malfunction was experienced over 125 days of operation. We conclude that the presently developed pneumatic actuator can be utilized as an extracorporeal biventricular assist device.

Development of an Algorithm to Regulate Pump Output for a Closed Air-Loop Type Pneumatic Biventricular Assist Device

The closed air space-type of extracorporeal pneumatic ventricular assist device (VAD) developed by the Korea Artificial Organ Center utilizes a bellows-transforming mechanism to generate the air pressure required to pump blood. This operating mechanism can reduce the size and weight of the driving unit; however, the output of the blood pump can be affected by the pressure loading conditions of the blood sac. Therefore, to guarantee a proper pump output level, regardless of the pressure loading conditions that vary over time, automatic pump output regulation of the blood pump is required. We describe herein a pump output regulation algorithm that was developed to maintain pump output around a reference level against various afterload pressures, and verified the pump performance in vitro. Based on actual operating conditions in animal experiments, the pumping rate was limited to 40-84 beats per minute, and the afterload pressure was limited to 80-150 mm Hg. The tested reference pump output was 4.0 L/min. During experiments, the pump output was successfully and automatically regulated within the preset area regardless of the varying afterload conditions. The results of this preliminary experiment can be used as the basis for an automatic control algorithm that can enhance the stability and reliability of the applied VAD.

The effects of dopamine, ephinephrine, and esmolol on the hemodynamic energy in terms of the energy equivalent pressure

The generation of pulsatile flow depends on the hemodynamic energy gradient rather than the pressure gradient. We hypothesized that either positive or negative inotropic agents can affect the hemodynamic energy, which can be measured using the energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE). This study examined the change in hemodynamic energy induced by dopamine, epinephrine, and esmolol infusion in terms of the EEP and SHE. Dopamine (5, 10 &mgr;g/kg/min), epinephrine (0.02, 0.1 &mgr;g/kg/min) and esmolol (after bolus 1 mg/kg, 0.1, 0.3 mg/kg/min) were infused into six anesthetized dogs. The hemodynamic parameters were collected in the descending thoracic aorta. The mean arterial pressure, blood flow, EEP, and SHE increased significantly with the dopamine infusion. The mean arterial pressure and EEP decreased significantly after the esmolol infusion, while it increased after the epinephrine infusion (p < 0.05 respectively). There was a correlation between the EEP and flow on the descending aorta during the dopamine, esmolol and epinephrine infusions (p < 0.05 respectively). In conclusion, the change in hemodynamic energy induced by dopamine, esmolol, and epinephrine may be expressed in terms of the EEP and SHE. In addition, there was a strong correlation between the EEP and flow.

Development of Eddy Current Sensor systems in artificial heart for noncontact gap sensing

The axial flow pump has been developed in Korea Artificial Organ Center. It consists of an impeller, a motor and a magnetic bearing. The magnetic bearing fully levitates the impeller not to contact with other parts of pump. However, in order to control the gap between the impeller and other parts, continuous gap sensing is necessary. The conventional gap sensors are relatively large to implant in artificial heart. Thus, the compact eddy current sensor system proper for artificial heart was developed and the performances were evaluated. It showed good results and has small size. However, the dependency of the sensor upon temperature and target material was shown also. Moreover, the output of sensor had nonlinear responses. These must be calibrated in further study

The effects of vasopressor and vasodilator on hemodynamic energy in terms of surplus hemodynamic energy.

In a previous study, we reported that inotropic agents affect the hemodynamic energy, which can be measured using the energy equivalent pressure (EEP) and surplus hemodynamic energy (SHE). However, there has been no study about the effect of vasopressors and vasodilators on EEP and SHE. Thus, we investigated the change in the hemodynamic energy induced by phenylephrine, nitroprusside, norepinephrine, and milrinone in terms of the EEP and SHE. Phenylephrine (1, 3 &mgr;g/kg/min), nitroprusside (0.5, 1 &mgr;g/kg/min), norepinephrine (0.1, 0.25 &mgr;g/kg/min), and milrinone (bolus 50 &mgr;g/kg, followed by 0.5, 0.7 &mgr;g/kg/min) were infused into 13 anesthetized dogs. The hemodynamic parameters, mean arterial pressure (MAP), and flow were recorded in the descending thoracic aorta, and EEP and SHE were calculated. MAP, EEP, and SHE increased significantly with phenylephrine administration. However, the flow in the descending aorta decreased significantly (p < 0.05). Norepinehrine also significantly increased MAP, EEP, and SHE (p < 0.05 in all cases). The MAP, EEP, and SHE significantly decreased after nitroprusside infusion (p < 0.05), whereas milrinone did not have an effect on MAP, EEP, or SHE. In conclusion, vasopressors were found to increase EEP and SHE, while a vasodilator decreased EEP and SHE.