Right Ventricular Assist System Feedback Flow Control Parameter for a Rotary Blood Pump

Artificial Organs 24(8):659–666, Blackwell Science, Inc. © 2000 International Society for Artificial Organs

Right Ventricular Assist System Feedback Flow Control Parameter for a Rotary Blood Pump *Masaharu Yoshikawa, *Kin-ichi Nakata, *Kenji Nonaka, *Joerg Linneweber, *Shinji Kawahito, *Tamaki Takano, *Sebastian Shulte-Eistrup, *Tomohiro Maeda, *Julia Glueck, †Heinrich Schima, †Ernst Wolner, and *Yukihiko Nose´ *Baylor College of Medicine, Houston, Texas, U.S.A.; and †University of Vienna, Vienna, Austria

Abstract: At least 25–30% of patients with a permanent implantable left ventricular assist device (LVAD) experience right ventricular failure; therefore, an implantable biventricular assist system (BiVAS) with small centrifugal pumps is being developed. Many institutions are focusing and developing a control system for a left ventricular assist system (LVAS) with rotary blood pumps. These authors feel that the right ventricular assist system (RVAS) with rotary blood pumps should be developed simultaneously. A literature search indicated no recent reports on the effect of hemodynamics and exercise with this type of nonpulsatile implantable RVAS. In this study, a calf with an implantable right ventricular assist system (RVAS) was subjected to 30 min of exercise on a treadmill at 1.5 mph, resulting in excellent hemodynamics. The input voltage remained unchanged. Hemodynamic recordings were taken every 5 min throughout the testing period, and blood gas analysis was done every 10 min. Oxygen uptake (VO2), oxygen delivery (DO2), and oxygen extraction (O2ER) were calculated and analyzed. Two different

pump flows were investigated: Group 1 low assist (3.5 L/min). In both groups, the RVAS flow rates were unchanged while the pulmonary artery (PA) flow increased during exercise; also, the heart rate and right atrial pressure (RAP) increased during exercise. There were no significant differences in the 2 groups. The PA flow correlates to the heart rate during exercise. In all of the tests, the VO2 and DO2 increased during exercise. Regarding VO2, no changes were observed during the different flow conditions; however, the DO2 of Group 2 was higher than that of Group 1. Because the implantable RVAS did not have pump flow changes during the test conditions, it was necessary to incorporate a flow control system for the implantable RVAS. During exercise with an implantable RVAS rotary blood pump, incorporating the heart rate and VO2 as feedback parameters is feasible for controlling the flow rate. Key Words: Right ventricular assist system— Implantable right ventricular assist device—Gyro pump— Flow control—Feedback parameter—Exercise test.

Right ventricular failure is one of the major complications in patients assisted with a left ventricular assist system (LVAS) (1). At least 25–30% of the patients with a permanent implantable left ventricular assist device (LVAD) experience right ventricular failure. Some reports suggested that the percentage of these patients needing a biventricular assist system (BiVAS) was 50% to 60% of the patient population having a ventricular assist system (VAS)

(2). Currently, 2 implantable pulsatile LVAS are being used clinically with satisfactory results; however, they cannot be used as a right ventricular assist system (RVAS) or BiVAS because of their structure and device size (3,4). Based on these clinical demands, it is necessary to develop not only a small implantable LVAS but also small implantable RVAS rotary pumps. In addition, it is necessary to develop a control system. However, many institutions are focusing and developing only a control system for an LVAS. These authors feel that the control system for the RVAS with rotary blood pumps should be developed simultaneously. The literature search indicated no recent reports on the effect of hemodynamics and exercise with this type of nonpulsatile implantable RVAS.

Received December 1999. Presented in part at the 7th Congress of the International Society for Rotary Blood Pumps, held August 26–27, 1999, in Tokyo, Japan. Address correspondence and reprint requests to Dr. Masaharu Yoshikawa, Nagoya University, School of Medicine, Department of Cardio-thoracic Surgery, 65 Tsurumai-cho, Showa-ku, Nagoya, 466–0065, Japan.

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In this study, the effect of exercise on the animal implanted with an RVAS was investigated, and the hemodynamic parameters were assessed as feedback factors for the RVAS control system. MATERIALS AND METHODS The experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH publication No. 86–23, Revised 1985) and the Principles of Laboratory Animal Care formulated by the National Society for Medical Research. A half Dexter strain calf (70 kg) was subjected to an implanted ventricular assist devise (VAD) study. The cell blood counts (CBC), blood chemistries, plasma free hemoglobin, and prothrombin time were examined 1 week prior to implantation after the calf was quarantined for 3 weeks. Experimental system configuration of the Gyro Implantable ventricular assist system In this RVAS study, the pump-actuator system was implanted in the preperitoneal space under the diaphragm, and the percutaneous actuator cable was tunneled through the calf’s back. A custom-made inflow cannula was inserted into the infundibulum. The outflow extension was an albumin-coated vascular prosthesis (Bard Albumin Coated DeBakey Vascular II, C.R. Bard, Inc., Billerica, MA, U.S.A.) that carries the blood to the main pulmonary artery. Blood pump The tested blood pump was the Gyro PI 700 series, which has been developed as an implantable VAS. The PI 700 series is a centrifugal pump with the following dimensions: impeller diameter of 50 mm, casing diameter of 65 mm, height of 45 mm, and priming volume of 25 ml. Also, this pump has the following design characteristics. First it has a magnetic coupling system and a pivot bearing system to obtain a sealless pump casing. Next, secondary vanes are located at the bottom of the impeller to accelerate blood flow. Third, an eccentric inlet port enables the top female pivot bearing to be embedded into the top housing of the pump. The housing and impeller of the PI 700 series are fabricated from titanium alloy, titanium 6 aluminum 4 vanadium (5) (Fig. 1). Actuator and driver The actuator-driver system used in this study was developed and supplied by the University of Vienna. This actuator contains a DC brushless motor that is constituted with the coil fixed in a plastic mount and has a rotating disk with permanent magnets. The Artif Organs, Vol. 24, No. 8, 2000

FIG. 1. The photograph shows the Gyro PI700 series made of titanium alloy and actuator.

actuator housing is made of titanium and is hermetically sealed (Fig. 1). Inlet cannula The prototype inlet cannula for the RVAS was designed and fabricated. This cannula consists of 2 parts: a hat-shaped silicone tip covered with Dacron fabric and an angled wire reinforced tube made of polyvinylchloride. If these 1 month feasibility studies with an RVAS implantation are successful, an inflow cannula will be fabricated utilizing a polyurethane copolymer for long-term experiments. The surface of the cannula tip was biolized with gelatin to obtain a superior antithrombogenic surface (6,7) (Fig. 2). Exercise test Once the animals recovered from the effects of surgery and anesthesia and reached a stable state, exercise was performed on a specially devised treadmill for 30 min. The experimental animal was put on the treadmill, and the pump flow was set 15 min before exercise because it takes at least 5 min to relax the

FIG. 2. The photograph shows the inlet cannula for the RVAS.

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calf and attain a steady pump flow. The control data and blood sample were taken just before exercising the animal. The treadmill speed was gradually increased to 1.3 mph at 0 slope. The pump voltage was never changed during the exercise period. Blood samples were taken every 10 min, and other pertinent data were recorded every 5 min. The exercise period lasted for 30 min, and then the postexercise data were recorded every 5 min for 15 min. If repeating the exercise, at least a 30 min interval was taken before starting the next exercise study.

the body surface area (BSA) of the calf does not exist. Hgb is hemoglobin, SaO2 is arterial oxygen saturation, and SvO2 is mixed venous oxygen saturation (8,9). In this study, the initial flow rate of the implantable RVAS was divided into 2 groups; an initial flow rate over 3.5 L/min was the high flow group and an initial flow rate below 3.5 L/min was the low flow group. All data were compared in these 2 groups. All data was expressed as mean ± standard error of the mean (SEM) and their statistical significance

Data collection of hemodynamics, blood gas, pump performance The arterial pressure (AoP), the right atrial pressure (RAP), and the heart rates were recorded with a multichannel recorder (Gould Brush, Gould Inc., Cleveland, OH, U.S.A.). The implantable flow probe (Transonic System Inc., Ithaca, NY, U.S.A.) was attached on the outflow graft and connected to the Transonic animal research flowmeter model T206. The same implantable flow probe was attached on the peripheral main pulmonary artery where the outflow graft was anastomosed to measure the pulmonary artery flow as cardiac output (CO). Information of pump performance such as rotational speed, voltage, current, pump flow, waveform of current, and waveform of the pump flow was monitored on the computer display and recorded every 5 min in a personal computer. Systemic vascular resistance (SVR) was calculated according to this formula:

RESULTS

SVR ⳱ 80 × (AoP − RAP)/CO The arterial and mixed venous blood gas, which included oxygen saturation, pH, and partial pressures of oxygen and carbon dioxide, were measured with a blood gas analyzer. The relationship between oxygen transfer and implantable RVAS performance during exercise was analyzed with the blood gas data. The oxygen transfer rate (DO2), the oxygen consumption (VO2), and the oxygen extraction ratio (O2ER) were derived from the following formulas: DO2 ⳱ Q × (1.3 × Hgb × SaO2) × 10 VO2 = Q × 13 × Hgb × (SaO2 −SvO2) O2ER = VO2/DO2 × 100 where Q is CO. Cardiac index (CI), CO/BSA, is usually used clinically; however, CO was used instead of CI in this study because converting the formula for

Hemodynamic parameters and RVAS flow rate RVAS flow did not change before and during exercise and was constant throughout each exercise study in both groups (Fig. 3A). The pulmonary artery (PA) flow significantly increased during exercise in both groups (p < 0.01) (Fig. 3B). Also, the PA flow in the high flow group was significantly higher than that in the low flow group before and during exercise (p < 0.05). Furthermore, the PA flow linearly correlated with pump flow within this RVAS flow range from 1 to 6 L/min throughout the exercise study (Fig. 3C). The HR also significantly increased during exercise in both groups (p < 0.01); however, there was no significant difference between both groups (Fig. 4A). Arterial pressure did not show a significant difference before, during, and after exercise. There was no significant difference between groups (Fig. 4B). The RAP increased significantly during exercise in both groups (p < 0.01); however, there was no significant difference between groups (Fig. 4C ). SVR decreased significantly during exercise in both groups (p < 0.01), and SVR in the low flow group was significantly higher than that in the high flow group before, during, and after exercise (p < 0.05) (Fig. 5). The RVAS flow did not correlate with SVR. Oxygen consumption and delivery The VO2 significantly increased during exercise in both groups (p < 0.01); however, no significant difference was shown between groups (Fig. 6A). The DO2 significantly increased during exercise in both groups (p < 0.01), and the DO2 in the high flow group was significantly higher than that in the low flow group before, during, and after exercise (p < 0.05) (Fig. 6B). Artif Organs, Vol. 24, No. 8, 2000

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FIG. 3. The graphs show that the RVAS flow rate did not change before, during, and after exercise (A); PA flow rate increased during exercise (p < 0.01), and PA flow in the high flow group was higher than that in the low flow group before and during exercise (p < 0.05) (B); and PA flow also was linearly correlated with pump flow within this RVAS flow range from 1 to 6 L/min (C).

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FIG. 4. The graphs show that heart rate increased during exercise (p < 0.01) (A), arterial pressure did not show any difference (B), and right atrial pressure increased during exercise (p < 0.01) (C).

Regarding O2ER, this showed a significant increase during exercise (p < 0.01); however, a significant difference was not demonstrated in either group (Fig. 6C).

DISCUSSION Currently, implantable LVAS with rotary blood pumps are being developed in many institutions; however, an implantable RVAS with a rotary blood Artif Organs, Vol. 24, No. 8, 2000

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FIG. 5. The graph shows that systemic vascular resistance during exercise (p < 0.01) and SVR in the high flow group were lower than that in the low flow group (p < 0.05).

pump is rarely a developmental undertaking. According to clinical results, it is necessary to develop not only paracorporeal RVAS but also implantable RVAS. Our final goal is the development of a totally implantable VAS with rotary blood pumps that can be universally LVAS, RVAS, and BiVAS (10). The control system for the implantable VAS is being developed. Regarding LVAS, many institutions are in the process of developing a control system; however, there is almost no data and control system for the implantable RVAS using a rotary blood pump. In this study, the physiological influence and the necessity of a flow control were studied in an experimental animal that was implanted with an RVAS rotary blood pump. In this model, the oxygen consumption increased during exercise. However, the increased oxygen delivery compensated for the oxygen demand because the total systemic and the pulmonary blood flow increased during exercise. In this study, the native heart could increase the systemic and pulmonary blood flow because the RVAS flow did not show any change throughout each study and the native heart remained almost within normal function. However, with the RV failure model, it may be necessary to control the RVAS flow in order to increase its flow rate during exercise because the failing right ventricle could not increase pulmonary blood flow. This study revealed that the heart rate, RAP, cardiac output, and VO2 increased and the systemic vascular resistance decreased during exercise with the implantable RVAS model. Unfortunately, the relationship between the pulmonary vascular resistance and RVAS flow was not proven in this study because the pulmonary artery and the left atrial pressure lines were not available. However, it was found that SVR and RAP do not influence the RVAS flow rate. Artif Organs, Vol. 24, No. 8, 2000

According to our previous experience with the implantable LVAS using rotary blood pumps, the PA flow and cardiac output do not correlate with LVAS flow. The LVAS flow fluctuates depending on the SVR and left ventricular pressure. However, in this implantable RVAS study, the PA flow and cardiac output linearly correlate with the RVAS flow. This is within the limited RVAS flow range of 1 to 7 L/min, and that should be regulated by the preload. This phenomenon also supports the result that the oxygen delivery demonstrates a significant difference between the high flow group and low flow group because the oxygen delivery is defined by arterial oxygen saturation and cardiac output, and the arterial oxygen saturation was almost constant throughout these exercise studies. Heart rate and VO2 are appropriate feedback parameters for the flow control system during exercise. The heart rate is simple and easy to monitor. However, it is necessary to combine these with other parameters that can detect exercise because the heart rate is sensitive not only to exercise but also to the factors that evoke the sympathetic nerve activation and suppress the parasympathetic nerve. A combination of heart rate and VO2 may be adequate feedback parameters for the flow control system. However, a combination of these 2 parameters may not be ample for feedback parameters because a multiple combination of activity sensors already have been used for pacemakers. The advantage of a multiple combination is to reduce a false-positive error or false-negative error. Each sensor compensates for the weak point of the other, but there is a disadvantage. An increase of the sensors may create a more complicated system and increase the risk of a feedback system malfunction that may be the result from sensor durability because each sensor has a lifetime. From the standpoint of detecting exercise, the accelerometer used for pacemakers may be another candidate for the feedback parameter although it was not used in this study. In future studies, the accelerometer will be evaluated in order to establish a flow control system (11,12). The future direction of this study will be one that encompasses both intact heart model studies and chronic right ventricular failure model studies. More information and analyses such as the relation between RVAS flow and pulmonary vascular resistance is required for the intact heart model. The same type of study should be performed and evaluated in the chronic right ventricular failure model. However, it may not be easy to create a chronic right ventricular failure model in a calf.

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FIG. 6. The graphs show that oxygen consumption (VO 2 ) increased during exercise (p < 0.01) (A); oxygen delivery (DO 2 ) increased during exercise (p < 0.01), and DO2 in the high flow group was higher than that in the low flow group (p < 0.05) (B); and oxygen extraction (O 2 ER) increased during exercise (p < 0.01) (C).

CONCLUSIONS This study revealed that it is necessary to incorporate a flow control system for the implantable RVAD with a rotary blood pump because the RVAS flow rate remains a constant and is not influ-

enced during exercise and the oxygen delivery is dependent on the RVAS flow rate. During exercise with an implantable rotary blood pump RVAS, incorporating the heart rate and VO2 as feedback parameters is feasible for controlling the flow. Artif Organs, Vol. 24, No. 8, 2000

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