Here, we present a protocol using two centrifugal pumps as a total artificial heart replacement.
Mechanical circulatory support (MCS) has been introduced as a viable alternative to heart transplantation primarily through the use of intracorporeal ventricular assist devices (VADs) for support of the left ventricle. However, certain clinical scenarios warrant biventricular mechanical support. One strategy for some patients is the excision of both ventricles and the implantation of two VAD pumps as a total artificial heart (TAH). This has recently been made possible by the improvements in device design and the small profile of centrifugal devices. This TAH approach remains experimental with many important challenges such as the device settings to balance the right and left circulation, the orientation of the devices and the outflow graft with their influence on hemolysis and stability, and the outcome of chronic support using such an orientation. This protocol aims to provide a reproducible approach for total artificial heart replacement with two intracorporeal centrifugal VADs in a cow model.
There has been growth in the number of patients with heart failure, with an estimated 5.7 million adults suffering from this condition in the United States today1. Around 300,000 patients have end stage heart failure with a life expectancy of less than one year. While heart transplantation remains the gold standard therapy for end stage heart failure, it is greatly limited by the number of available donor organs. MCS has been introduced as a viable alternative to heart transplantation especially through the use of VADs2. VADs work by unloading the left ventricle and providing forward flow (supported by a pump) directly into the arterial circulation. VADs may be implanted as a bridge to transplantation as well as a destination therapy for patients that do not qualify for a transplantation3. Since their FDA approval less than a decade ago, the annual number of VADs implanted has surpassed heart transplant numbers, with this number exponentially increasing4. However, in a subset of patients, heart failure is biventricular (i.e. affecting both the left and right ventricle) and simply supporting the left ventricle alone may not provide adequate perfusion. In these situations, the right ventricle requires temporary mechanical support5. This type of "RVAD" requires the use of large cannulas connected to an extracorporeal pump that restricts the patient to the Intensive Care Unit (ICU) while the ventricle recovers. For a limited subset of patients, another option is a TAH6,7. The indications for TAH usage are: a biventricular failure after post infarct, a ventricle septal defect (VSD), a severe restrictive myopathy which precludes ventricular cannulation, and a failed heart transplant requiring chronic support. However, the currently FDA approved TAH device is large and cannot be used in smaller patients. In addition, the pneumatic drivers are sizable and limit the mobility of the patient.
One experimental strategy for some patients is the use of a second VAD to support the right ventricle8,9,10. In this scenario, both ventricles are excised, and two VADs are implanted as a TAH. This has been made possible by the improvements in device design and the shrinking of the device profile. New centrifugal VADs are much smaller, allowing for two VADs to be implanted next to each other to support both the left and right circulation. This approach remains experimental with many important challenges including the device settings to balance the right and left circulation, the orientation of the devices and outflow graft with their influence on hemolysis and other adverse events. The purpose of this protocol is to provide a reproducible approach to TAH replacement with two centrifugal VADs in a cow model.
Age-matched (for blood donation if needed) calves (weight 80–90 kg) are cared for in the animal facility. Housing and all treatment procedures are performed in accordance with the guidelines of the Animal Care and Use Committee of Duke University Medical Center.
1. Initiation of Anesthesia
2. Vital Signs and Central Line Settings
3. Central Vascular Access
4. Median Sternotomy and Cardiopulmonary Bypass (CPB)
5. Ventriculectomy
6. Implantation of Centrifugal Flow Pumps (CFP)
7. Establishment of Biventricular Assist Device Flow
Demonstrated in Figure 1 is the attachment of the sewing rings. Figure 1A shows the "bunching" of the ventricle tissue that may create a problem with pump attachment. Figure 1B represents the correct attachment.
Figure 2 and Figure 3 are two different orientations of the pumps. In Figure 2, the pumps are positioned so that the outflow grafts are short and exit directly into the connected arteries. In Figure 3, the pumps are oriented so that the outflow grafts of both the right CFP and left CFP rotate around prior to being anastomosed to the pulmonary artery and aorta, respectively. It remains unanswered which orientation allows for less sheer stress on the blood, and has better overall hemodynamic profile for the pump. Furthermore, it is unclear which orientation allows for less kinking.
Figure 1: Attachment of the sewing rings.
Panel A demonstrates incorrect attachment of the right heart replacement sewing ring with the "bunched up" ventricular tissue. Panel B demonstrates the correct sewing ring incorporation into the ventricular tissue. Please click here to view a larger version of this figure.
Figure 2: Direct outflow graft orientation demonstrating direct attachment of the right heart replacement to the pulmonary artery and the left heart replacement to the aorta. Please click here to view a larger version of this figure.
Figure 3: A different orientation of the outflow grafts to the pulmonary artery and the aorta. Please click here to view a larger version of this figure.
In this manuscript, we describe the use of two centrifugal flow VADs as an intracorporeal TAH. This technique maybe very useful to study the effect of artificial circulation on secondary organs such as the lungs and liver. Furthermore, it may be useful for the study of the hemodynamic changes from different pump orientations and flow scenarios. The critical steps within this protocol involve how the sewing rings are attached to the ventricular tissue while also incorporating the valvular annuli for strength. It is crucial to ensure that this is performed correctly as it will affect device stability. Furthermore, it is important to ensure that the outflow grafts are measured and cut at the appropriate length. Device instability and outflow graft obstruction represent important problems that may occur if these two steps are not carefully performed.
The protocol describes two different methods of orienting the outflow grafts that may be important to avoid outflow graft obstruction. In the first orientation, the outflow grafts are connected directly to the respective great vessels in an orientation similar to the SynCardia Total Artificial Heart. In the second orientation, the grafts rotate around the other VAD as is commonly employed in clinical VAD cases.
Using this experimental model, one can carefully study the hemodynamic scenarios associated with different combinations of pump speeds, to determine how to avoid the imbalance of left and right sided circulations. For instance, the direct measurements of aortic, pulmonary artery and pulmonary vein pressures allow for a real-time assessment of the overall hemodynamic status of the animal. This will be quite important for setting the correct speed parameters on the pumps to allow for balanced right and left circulations with: adequate arterial perfusion pressure; normal pulmonary pressures to avoid the possibility of pulmonary congestion; and normal central venous pressures to avoid renal or hepatic venous congestion. In the clinically available devices, "flow" is a calculated parameter which is not directly measured. In this protocol, we will directly measure flow in two locations for further precise assessment of the hemodynamics.
In conclusion, this manuscript describes the use of two centrifugal flow pumps as a total artificial heart for intracorporeal biventricular replacement in a cow model.
The authors have nothing to disclose.
We would like to thank Laura Janney and Abbot Medical for partial funding. We would also like to thank Duke Perfusion Services and the Large Animal Surgical Core for their assistance during the operations.
SPO2 and heart rates are to be monitored: Multiparameter | Meditech Equipment, Co., Ltd. | MD-908 | hemodynamic monitor intraoperatively |
Viscot Mini XL Surgical Markers | Amazon | B007P550WG | marking sternum before incision |
60W High Power Electric Pet Cat Rabbits Horse Animal Hair Cutting Clipper | LILY International Business CO., LIMITED | ZP-293 | Fur shaving |
No. 10 scalpel blade | Swann-Mortan, England | 301 | Skin incision |
Matzenbaum scissor | BD-V. Mueller, USA | CH2006-001 | Vascular exploration |
Scissors | Felco, USA | FELCO 200A-50, Felco Professional Bypass Lopper | For sternotomy |
A self-retractor | BD-V. Mueller, USA | AU19270 | SCHUKNECHT Self-Retaining Postauricular Retractor, |
Sternal retractor | BD-V. Mueller, USA | CH6950-007 | Cooley sternal retractor |
Pressure transducer (Millar Mikro-Tip, 5Fr) | Millar, USA | MillarMikro-Tip, SPR-350S | Assessment for pulmonary artery or venous pressure |
AD instruments (PowerLab) | AD instruments, USA | PowerLab 16/35 | Pressure signal transduction |
Umbilical tapes | Medline industries Inc., USA | U11 | For isolation and snaring of superior or inferior vena cava |
Vessel loops | Aspen Surgical, USA | 3901, 3902 and 3904 | Isolation of vessels |
Silk sutures, 2-0 | Ethicon US, LLC, USA | SA11G | For snare of superior or inferior vena cava |
Ticron 2-0 | Covidien, USA | TicronTM suture | Vascular suture |
Prolene, 7-0 | Covidien, USA | Surgipro II | Vascular suture |
Prolene, 6-0 | Covidien, USA | Surgipro II | Vascular suture |
Prolene, 4-0 | Covidien, USA | Surgipro II | Vascular suture |
Prolene, 3-0 | Covidien, USA | Surgipro II | Vascular suture |
Aortic cannula, 15-18 Fr | Medtronic, USA | Elongated-One-Piece-Arterial cannula 3D | Aortic cannula for setting of cardiopulmonary bypass |
Venous cannula, 28Fr | Edwards Lifesciences | single stage | Venous cannula for setting of cardiopulmonary bypass |