Ann Thorac Surg 1997;64:1374-1380
© 1997 The Society of Thoracic Surgeons
Original Articles: Cardiovascular
Evaluation of a Pulsatile Pediatric Ventricular Assist Device in an Acute Right Heart Failure Model
Dominique Shum-Tim, MD,
Brian W. Duncan, MD,
Victor Hraska, MD,
Ingeborg Friehs, MD,
Toshiharu Shin'oka, MD,
Richard A. Jonas, MD
Department of Cardiovascular Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts
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Abstract
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Background. The development of pulsatile ventricular assist devices for children has been limited mainly by size constraints. The purpose of this study was to evaluate the MEDOS trileaflet-valved, pulsatile, pediatric right ventricular assist device (stroke volume = 9 mL) in a neonatal lamb model of acute right ventricular failure.
Methods. Right ventricular failure was induced in ten 3-week-old lambs (8.6 kg) by right ventriculotomy and disruption of the tricuspid valve. Control group 1 (n = 5) had no mechanical support whereas experimental group 2 (n = 5) had right ventricular assist device support for 6 hours. The following hemodynamic parameters were measured in all animals: heart rate and right atrial, pulmonary arterial, left atrial, and systemic arterial pressures. Cardiac output was measured by an electromagnetic flow probe placed on the pulmonary artery.
Results. All results are expressed as mean ± standard deviation and analyzed by Student's t test. A p value less than 0.05 was considered statistically significant. Baseline measurements were not significantly different between groups and included systemic arterial pressure, 80.6 ± 12.7 mm Hg; right atrial pressure, 4.6 ± 1.6 mm Hg; mean pulmonary arterial pressure, 15.6 ± 4.2 mm Hg; left atrial pressure, 4.8 ± 0.8 mm Hg; and cardiac output, 1.4 ± 0.2 L/min. Right ventricular injury produced hemodynamics compatible with right ventricular failure in both groups: mean systemic arterial pressure, 38.8 ± 10.4 mm Hg; right atrial pressure, 16.8 ± 2.3 mm Hg; left atrial pressure, 1.4 ± 0.5 mm Hg; and cardiac output, 0.6 ± 0.1 L/min. All group 1 animals died at a mean of 71.4 ± 9.4 minutes after the operation. All group 2 animals survived the duration of study. Hemodynamic parameters were recorded at 2, 4, and 6 hours on and off pump, and were significantly improved at all time points: mean systemic arterial pressure, 68.0 ± 13.0 mm Hg; right atrial pressure, 8.2 ± 2.3 mm Hg; left atrial pressure, 6.4 ± 2.1 mm Hg; and cardiac output, 1.0 ± 0.2 L/min.
Conclusions. The results demonstrate the successful creation of a right ventricular failure model and its salvage by a miniaturized, pulsatile right ventricular assist device. The small size of this device makes its use possible even in small neonates.
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Introduction
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See also page 1380.
Mechanical circulatory support using ventricular assist devices (VAD) has become standard in adult patients with cardiac failure refractory to pharmacologic therapy. A variety of devices have been used as a bridge to recovery of ventricular function or cardiac transplantation with acceptable morbidity and mortality [1–5]. Infants and small children who experience profound ventricular dysfunction, however, have fewer treatment options for mechanical circulatory support. The development of a pulsatile VAD for children has been limited by size constraints and the requirement of multiple pumps with different volumes to accommodate a wide range of pediatric sizes. In addition, children are more likely to experience pulmonary and biventricular failure than pure left ventricular dysfunction as seen in adults with coronary artery disease. These factors and the familiarity of many pediatric centers with the use of extracorporeal membrane oxygenation have led to its widespread use of mechanical circulatory support in children.
There are several potential advantages that a pulsatile VAD, designed specifically for children, would provide. The lack of an oxygenator would simplify the circuit and reduce blood cell trauma. Such a device would ideally provide pulsatile flow with a range of pump volumes capable of supporting small neonates through adolescents. The MEDOS-HIA VAD system (MEDOS-Helmholtz Institute, Aachen, Germany) provides pulsatile circulatory support with a pump size as small as 9 mL. The pump uses a pneumatically driven diaphragm, with two trileaflet polyurethane inlet and outlet valves [6]. This system can be used for right ventricular assist device (RVAD), left ventricular assist device, or biventricular assist device support. The present report describes the use of this system as an RVAD in a pediatric model of acute right ventricular (RV) failure.
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Material and Methods
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Anesthesia and Instrumentation
All animals received humane care in compliance with the "Principles of Laboratory Animal Care" formulated by the National Society for Medical Research and the "Guide for the Care and Use of Laboratory Animals" prepared by the National Academy of Sciences and published by the National Institutes of Health (NIH Publication 85-23, revised 1985). The experimental protocol was approved by the institutional review board on animal experimentation at the Children's Hospital, Boston (approval number: A94-06-029).
Three-week-old lambs (average weight, 8.6 ± 0.9 kg) were used for the following studies. All animals were sedated with intramuscular ketamine hydrochloride (50 mg/kg), then intubated and mechanically ventilated. Anesthesia was maintained with intravenous fentanyl (30 µg • kg-1 • h-1), and midazolam (0.3 mg • kg-1 • h-1). Body temperature was maintained between 37.5° to 38.0°C using a warming blanket and heat lamp. Catheters were inserted into the femoral artery and vein for blood sampling, fluid infusion, and monitoring of systemic arterial pressure. The femoral venous line was advanced into the right atrium (RA) for RA pressure monitoring. A median sternotomy was then performed and the main pulmonary artery (PA) and left atrial (LA) appendage were catheterized for pressure monitoring. An electromagnetic flow probe (MFV-3200; Nihon Kohden Corp, Tokyo, Japan) was placed around the distal main PA to record the cardiac output at baseline, and at 10-minute time points after the induction of RV failure in all animals. The flow probe was removed from the PA and placed in-line with the outflow cannula for group 2 animals supported by RVAD (see below).
Device
The MEDOS HIA-VAD is a pneumatically driven pulsatile blood pump (Fig 1
). The disposable blood pump incorporates a multilayered diaphragm that separates the blood flow chamber from the pneumatic drive chamber of the device. There are two integral trileaflet, polyurethane valves at the inflow and outflow connectors. The pumps, when used as left ventricular assist devices, are available in various sizes with stroke volumes of 10, 25, 60, and 80 mL. For RVAD, there is a 10% reduction in stroke volume for each corresponding pump size (9, 22.5, 54, and 72 mL, respectively) that was found to be optimal in a right–left ventricular output balance. The stroke volume employed for this study was 9 mL. The polyurethane pumps are pneumatically activated by an integrated driving system that consists of a solid-state electronic control console with digital readout. The control console allows adjustment of pulse rate, drive pressure, and percentage systole to optimize hemodynamics. The system can be triggered by the electrocardiogram for operation in a synchronous mode to provide counterpulsation. The device was operated in asynchronous mode during this study. The second component of the MEDOS drive system is an electrically powered internal pneumatic compressor and vacuum.
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Fig 1. . (A) The MEDOS HIA-VAD system consists of pneumatically driven polyurethane blood pumps. Pumps with stroke volumes of 10, 25, and 60 mL are shown (clockwise from top). (B) Top: Integrated control unit with touch screen monitor for the MEDOS HIA-VAD. Bottom: Internal power supply unit and pneumatic compressor and vacuum.
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Right Ventricular Injury and Hemodynamic Measurements
Acute RV failure was surgically induced in group 1 animals (n = 5) without subsequent mechanical circulatory assistance. In group 2 (n = 5) animals, RV support using the MEDOS HIA-VAD was instituted after the completion of RV injury. The RVAD was maintained for 6 hours after injury until the experiment was electively terminated.
After placement of monitoring lines and recording of baseline parameters, all animals were fully heparinized (300 U/kg). A 14F arterial cannula (DLP, Inc, Grand Rapids, MI) was inserted into the main PA and secured with pursestring sutures. This PA cannula allowed blood transfusion in all animals and provided outflow cannulation for RVAD-supported group 2 animals. A patent foramen ovale, which was invariably present in lambs at this age, was closed primarily with inflow occlusion. A ventriculotomy was then performed along the RV outflow tract. Through this incision, the tricuspid valve was disrupted by division of all chordal attachments. Lethal RV injury was reliably produced by right ventriculotomy and tricuspid regurgitation.
After the induction of RV failure, the absence of right-to-left shunting at the atrial level was confirmed by measurement of RA and LA blood gases. For animals supported by RVAD, a 24F right-angled cannula (Polystan, Varlose, Denmark) was inserted through the RA appendage. The RVAD settings were adjusted to reestablish baseline cardiac output and systemic pressure. Hemodynamic parameters were recorded after 10 minutes of stabilization after injury in all animals. Hemodynamic measurements were repeated every 2 hours for 6 hours in group 2 animals with RVAD support. During the measurement period, the RVAD was turned off for 5 minutes. In this way, each animal served as its own control for hemodynamic measurements on and off RVAD. Pulmonary vascular resistance (PVR in mm Hg • min/L) was calculated by the following equation: (mean PA pressure - mean LA pressure)/cardiac output.
Statistical Analysis
All values are expressed as the mean ± standard deviation. The baseline and postinjury values were compared within and between groups by the paired and unpaired Student's t tests, respectively. Subsequent serial measurements of all parameters between assisted and nonassisted modes in the same animals were compared by paired t test. Differences were considered statistically significant when the p value was less than 0.05.
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Results
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Baseline Hemodynamics
The following baseline hemodynamic parameters were recorded in groups 1 and 2 before RV injury: mean systemic arterial pressure, heart rate, RA pressure, mean PA pressure, LA pressure, and mean PA cardiac output (CO). The PVR was calculated for each animal. Baseline measurements are summarized in Table 1.
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Table 1. . Hemodynamic Parameters in Groups 1 and 2 at Baseline, After Right Ventricular Injury, and On and Off RVAD
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Effect of Right Ventricular Injury
Right ventriculotomy and surgically induced tricuspid regurgitation resulted in lethal acute RV failure. Severe RV dysfunction developed in both groups, characterized by systemic hypotension, increased RA pressure, decreased LA pressure and decreased CO (Table 1
; Fig 2). All the animals in control group 1 died at a mean period of 71.4 ± 9.4 minutes after surgery. The RVAD-supported group 2 hemodynamics were not significantly different from control group 1 after RV injury. All group 2 animals survived the 6 hours of planned RVAD support.
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Fig 2. . Hemodynamic measurements after acute right ventricular failure in the control group were characterized by significantly elevated right atrial (RA) pressure (A), as well as significant decreases in systemic pressure (B), left atrial (LA) pressure (C), and cardiac output (D).
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Effect of Right Ventricular Assist Device on Right Ventricular Failure
Institution of RVAD resulted in significant improvements in all hemodynamic parameters. The hemodynamic effects of RVAD support for group 2 animals are summarized in Table 1 and illustrated in Figures 3 through 9. Hemodynamic values shown reflect the mean values for all group 2 animals on full RVAD support compared with the mean values obtained from the same animals with the device off for 5 minutes at the 2-, 4-, and 6-hour time points after RV injury.
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Fig 3. . Normalization of systemic mean arterial pressure in group 2 was maintained for 6 hours by the MEDOS HIA right ventricular assist device (RVAD).
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Fig 4. . Left atrial (LA) filling pressure was significantly reduced by right ventricular failure and effectively normalized by the institution of right ventricular assist device (RVAD) support.
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Fig 5. . Low cardiac output induced by acute right ventricular failure was reversed by the pulsatile MEDOS HIA right ventricular assist device (RVAD) system.
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Fig 6. . Significant reduction of the elevated mean right atrial (RA) pressure after right ventricular injury in group 2 was observed after the onset of right ventricular assist device (RVAD) use.
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Fig 7. . Evidence of severe tricuspid regurgitation after surgical induction of right ventricular failure was shown by significantly elevated right atrial (RA) pulse pressure compared with baseline value. Note the effect of the right ventricular assist device (RVAD) in ameliorating the hemodynamic characteristics of severe tricuspid regurgitation.
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Fig 8. . After the right ventricular injury, there was a transient elevation of mean pulmonary arterial (PA) pressure, possibly secondary to reactive pulmonary vasoconstriction after surgical injury. Significant reduction of pulmonary blood flow characterized by reduction of mean PA pressure was observed after 2 hours when the right ventricular assist device (RVAD) was turned off. The use of the RVAD reestablished the increased PA pressure.
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Fig 9. . Pulmonary vascular resistance (PVR) was acutely elevated by the surgical procedure of inflow occlusion, blood transfusion, and reduced left-sided pressure. The right ventricular assist device (RVAD) partially offset this elevated PVR and maintained it at the same level throughout the 6-hour period of experiment. (LAP = left atrial pressure; PAP = pulmonary arterial pressure.)
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With the initial RV injury, expected decreases were observed in mean systemic arterial pressure (Fig 3), LAP (Fig 4), and CO (Fig 5). Right atrial pressure increased significantly (Fig 6). All hemodynamic parameters were subsequently normalized by RVAD support as demonstrated. Values for CO off RVAD are demonstrated only at 10 minutes. As described above, in group 2 animals the CO flow probe was removed from the PA and placed in-line with the outflow cannula after measuring baseline hemodynamics because of size constraints.
Severe tricuspid insufficiency was demonstrated by a dramatic increase in mean RA pressure with a pulsatile waveform in all animals. The mean pulse pressure of the RA increased from a baseline of 3.2 ± 1.3 mm Hg to 10.6 ± 5.7 mm Hg (p = 0.048) immediately after the induction of RV injury (Fig 7). The mean RA pressure was rapidly reduced and the pulsatility of the waveform was obliterated by the onset of RVAD. These hemodynamic characteristics were maintained throughout the duration of study. On termination of mechanical support, the animals in group 2 survived for 58.2 ± 28.2 minutes (NS versus group 1).
The PA pressure was observed to increase immediately after the surgical insult to the RV (Fig 8), accompanied by an increase in the calculated PVR in all animals (Fig 9). These changes in PA pressure and PVR normalized after 2 hours of circulatory support. Initial increases in PA pressure probably represent the animals' response to rapid transfusion, inflow occlusion, and catecholamine surge associated with the surgical procedure. Elevations in the calculated PVR were magnified by accompanying decreases in LA pressure and CO.
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Comment
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A variety of mechanical circulatory assist devices have been successfully employed for adults with severe ventricular dysfunction [1–5]. Intraaortic balloon counterpulsation as well as VADs from several different manufacturers are currently available. The effectiveness of intraaortic balloon pumping is limited in pediatric patients because of their increased aortic elasticity, rapid heart rates with small stroke volumes, and technical difficulties related to insertion in small femoral vessels [7]. The development of VAD for pediatric patients has been limited by size constraints and differences in the pathophysiology of cardiac failure in children. A pulsatile pediatric VAD requires multiple pump sizes to provide stroke volumes in the range of patients from newborns to young adults. In contrast to predominant left ventricular failure secondary to coronary artery disease in adults, children are more likely to demonstrate right ventricular, biventricular, and pulmonary failure. These factors, in addition to the favorable experience in treating life-threatening pulmonary conditions in children, have led to the widespread use of extracorporeal membrane oxygenation for cardiac support in many pediatric centers [8, 9].
However, the complexity of the extracorporeal membrane oxygenation circuitry with the presence of an oxygenator requires increased anticoagulation, larger priming volume, and produces more blood cell trauma. For these reasons, extracorporeal membrane oxygenation may not always be the optimal methodology for prolonged circulatory support in pediatric patients. These potential disadvantages also limit its application intraoperatively and in the early postoperative period. In addition, pulsatile flow might confer advantages for end-organ preservation during long-term support.
The MEDOS HIA-VAD system provides pulsatile circulatory support with pumps available in a variety of stroke volumes to accommodate newborn to adult patients. The circuit is simple, with the disposable blood pump connected directly to the inflow and outflow cannulas. This minimizes the surface area of blood contact and reduces priming volumes. The priming volume for the circuit in this study, using the 9-mL blood pump, was less than 20 mL. Removal of air from the device is facilitated by its transparent design. Two trileaflet polyurethane valves integrated into the device have been shown to result in excellent hemodynamic properties and minimal hemolysis with low thrombogenicity [10–12]. Because of the simplicity of the circuit, setup can be performed within minutes in an emergency situation. Furthermore, the simple circuit with its self-contained power console minimizes intensive surveillance by personnel, and facilitates transportation of patients during support.
In this study, we created an acute pediatric model (lambs < 10 kg) of RV failure. The surgical technique was a combination of those reported in larger animals [13–15]. This model created RV dysfunction by making a right ventriculotomy and disrupting the tricuspid valve. The RV failure produced was progressive and rapidly fatal without mechanical assistance. The MEDOS HIA-VAD system employed as an RVAD was able to normalize systemic arterial pressure and CO while reducing the dramatically elevated RA filling pressure seen in this model. In contrast to previous studies employing RV apical cannulation, the insertion of RVAD itself did not accelerate RV dysfunction [14]. All the experimental animals in group 2 survived for a mean of 58.2 ± 28.2 minutes after the discontinuation of RVAD support, which was not significantly different from the survival time of the control group 1. The absence of deterioration of RV function in this report may reflect RA cannulation rather than RV apical cannulation in the previous study.
The benefits of pulsatile circulatory support have not been unequivocally demonstrated [16, 17]. In addition, good clinical outcomes have been reported using nonpulsatile VADs [18, 19]. Yet, subtle physiologic differences have been suggested. In the pulmonary circulation, elevated PVR and increased lung water content have been shown experimentally during nonpulsatile circulatory support [20–22]. The present study did not address the potential benefits conferred by pulsatile circulatory assistance. We are currently using the MEDOS HIA-VAD for long-term support in a model of left ventricular failure to examine these issues.
There are several points of limitation that merit further discussion. First, this study represents an acute model to assess the feasibility and reliability of the pulsatile pediatric RVAD. The long-term effects of this device remain to be evaluated and further investigations are underway in our laboratory. Second, the current protocol used full anticoagulation simulating the clinical situation of RVAD support after cardiopulmonary bypass. In addition, we used heparinized fresh blood transfusion obtained from another donor lamb for the creation of RV injury. Therefore, the anticoagulation regimen and hematologic effects of this device could not be evaluated by this particular study.
In conclusion, there is currently no pulsatile VAD available in the United States for pediatric patients, although this device has been used successfully in children in Europe [23]. The ability to supply pulsatile circulatory assistance for a range of patient sizes from small newborns to young adults makes this a potentially valuable system. This initial in vivo study demonstrates the ability of the pulsatile MEDOS HIA-VAD to maintain satisfactory hemodynamics in a pediatric lamb model of acute RV failure.
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Footnotes
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Presented at the Thirty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Feb 3–5, 1997.
Address reprint requests to Dr Jonas, Department of Cardiovascular Surgery, Children's Hospital, 300 Longwood Ave, Boston, MA 02115.
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References
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Ann. Thorac. Surg. 1997 64: 1380.
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Abstract
Introduction
