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Ann Thorac Surg 1996;62:91-93
© 1996 The Society of Thoracic Surgeons

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Original Articles: Cardiovascular

Twelve-Hour Canine Heart Preservation With a Simple, Portable Hypothermic Organ Perfusion Device

Division of Cardiothoracic Surgery, Department of Surgery and Department of Anesthesiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. Cardiac transplantation is limited to an ischemic time of around 6 hours by available preservation solution and technique. Complex organ preservation devices have been developed that extend this time to 24 hours or more, but are clinically impractical. This study evaluates a portable oxygen-driven organ perfusion device weighing approximately 13.5 kg.

Methods. Organs are perfused with the University of Wisconsin solution at low perfusion pressure using less than 400 L of oxygen per 12 hours. Left ventricular parameters were measured in anesthetized adult beagles to establish control values (n = 5). Hearts were procured after cardioplegia with 4°C University of Wisconsin solution, weighed, then stored for 12 hours in University of Wisconsin solution at 4°C. Hearts were perfused (n = 3) or nonperfused (n = 2) during storage. Organ temperature, partial pressure of oxygen in the aorta and right atrium, perfusion pressure, and aortic flow were recorded hourly in perfused hearts. After 12 hours, hearts were transplanted into littermates and left ventricular parameters measured after stabilization off bypass.

Results. Organ weight for both groups was unchanged. Nonperfused hearts required both pump and pharmacologic support with significantly depressed left ventricular function. Perfused hearts needed minimal pharmacologic support, with left ventricular end-diastolic pressure, cardiac output, and rate of change of left ventricular pressure showing no statistical difference from control.

Conclusions. These findings confirm the potential for extended metabolic support for ischemia-intolerant organs in a small, lightweight, easily portable preservation system.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
See also page 93.

Organ transplantation has grown from experimental to accepted and successful clinical practice. Technical aspects of transplantation have been standardized leading to successful outcomes. Limitations to current clinical outcomes include the relative lack of donors, imperfect immunosuppression, and difficulties with controlling infection in an immunocompromised host. The relatively short viability time of an explanted organ limits tissue typing and transportation. Improvement in preservation solutions allows routine implantation of livers and kidneys after 24 hours or more of cold ischemia. Heart and lung transplantation is limited by a short ischemic time. A member of our group (LB) co-developed a simple, portable organ preservation device. This article presents preliminary data from canine hearts perfused for 12 hours with this device and then implanted.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The organ preservation device consists of five parts (Fig 1) [1]: a fluid-filled container that functions as the organ chamber, an interface plate having inflow and outflow valves to which the organ was attached, a large O-ringgasket, an oxygen permeable membrane, and a lid combine to form three stacked sealed chambers. The donor heart is attached to the central inflow check valve on the interface plate and both are placed into a 2-L container filled with preservation solution, thus forming an organ storage compartment. A large O-ring gasket is placed onto the interface plate and additional fluid is added filling the container to the top of the O-ring. An oxygen permeable membrane is placed onto the O-ring forming the perfusion compartment. A domed lid secures the membrane, forming a gas-filled cavity that functions as both the pumping and gas exchange compartment. A fluidic, monostable device based on the Coanda effect functions as a pump actuator [2]. It operates at low gas flow and pressure and can be configured for pulsatile operation with output pressure limitation. Temperature is maintained between 4 and 5°C within a Styrofoam chest containing cooling packs.

View larger version (32K): [in this window] [in a new window]   Fig 1. . Hypothermic organ perfusion device: Pressurized oxygen supplied to the fluidic device leads to cyclic variation of pressure within the oxygenation chamber. Oxygen diffuses across the semipermeable membrane oxygenating the perfusion chamber fluid and causes cyclic flow to the coronary circulation of the heart within the storage chamber. (PO2= partial pressure of oxygen.)

All animals have received humane care in compliance with the "Guide for the Care and Use of Laboratory Animals" published by the National Institutes of Health (NIH publication 85-23, revised 1985).

Anesthesia was induced in adult dogs using 25 mg/kg sodium pentobarbital. After intubation, animals were ventilated with 40% oxygen establishing normal arterial oxygen and carbon dioxide tensions. A midline sternotomy followed by longitudinal incision in the pericardium was made exposing the heart and great vessels. The azygos vein was ligated. After dissection of the vena cava, aorta, and the brachiocephalic artery, the superior vena cava was ligated and divided. The aorta was catheterized for infusion of the cardioplegia solution, clamped and 10 to 15 mL/kg of body weight of cold (2 to 4°C) cardioplegia solution (DuPont's [Wilmington, DE] commercial preservation solution Viaspan [Food and Drug Administration approved]) was infused at a pressure of 70 to 80 mm Hg [3]. The inferior vena cava was divided. Two or three right pulmonary veins were incised for decompression of the left side of the heart. Cold (4°C) saline was poured over the heart removing the accumulated fluids from the thoracic cavity by suction. After cessation of myocardial function, the heart was removed from the chest by further dissection and division of the pulmonary vessels and aorta distal to the clamp. The heart was further cooled in cold saline solution and fitted with an aortic flow probe, followed by coronary sinus catheterization and placement into the perfusion apparatus. The apparatus was placed into the storage chest and maintained at 4°C. The heart was perfused at a flow rate between 0.1 and 0.3 mL•g^-1•min^-1 of O₂ at approximately 80 pulses/min with Viaspan for approximately 12 hours. Perfusion pressure was continually monitored by taking the difference between the pressure in the aorta and the storage compartment, and was not allowed to exceed perfusion pressure of 25 mm Hg.

The control arm of the experiment used the same techniques with 10 to 15 mL/kg of body weight of cold 2 to 4°C cardioplegia solution (Viaspan) and the organ was attached and placed in the perfusion chamber immersed in Viaspan. The perfusion device was simply not activated and the organ preserved in Viaspan solution for 12 hours at 4°C. Organ temperature was monitored during storage in both perfused and nonperfused hearts and was constant at 5°C [4]. Donor recipient animals were between 18 and 25 kg in weight. Hearts were perfused (n = 3) or nonperfused (n = 2) during storage.

Preservation medium was sampled from the coronary sinus and the aorta at 1-hour intervals for the entire 12-hour preservation period and analyzed for oxygen content.

After 12 hours, the heart was removed from the preservation apparatus and implanted in a waiting canine of like size. The animal was anesthetized with 25 mg/kg of sodium phenobarbital, intubated, and ventilated with 40% oxygen establishing normal arterial oxygen and carbon dioxide tensions. A midline sternotomy with creation of a pericardial well was performed. The animal was heparinized and placed on cardiopulmonary bypass with an adequate activated clotting time at normothermia. The azygos vein was exposed and ligated. The aorta was cannulated opposite the innominate artery, aortic fat pad dissected away, and appropriate venous cannula placed directly into the inferior and superior vena cava. Caval tapes were placed and snared, a cross-clamp placed on the aorta, and the recipient heart was excised. Atrial and great vessel cuffs were prepared. Once the preparation was complete, the donor heart was removed from the preservation device, trimmed appropriately, and sutured into place with running monofilament atrial and great vessel suture. Deairing maneuvers were performed, cross-clamp removed, and the heart reperfused. Ten milligrams per kilogram of methylprednisolone was infused at this point. Hemostasis was secured. Once the donor heart was in place and functioning for approximately 30 minutes, an attempt to wean the animal from cardiopulmonary bypass was made. Cardiac output, left ventricular end-diastolic pressure, and rate of change of left ventricular pressure were monitored. End point for the experiment was failure to wean from the bypass under a low dose of dopamine and isoproterenol support or adequate weaning from bypass with stable hemodynamics and after data recovery. At this point, the animals were euthanized with a liberal dose of potassium and additional anesthesia.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
In the perfused organs, mean O₂ delivery to the hearts was 0.49 mL O₂•min^-1•100 g^-1 whereas consumption was 0.29 mL O₂•min^-1•100 g^-1. Aortic flow averaged 25.9 ± 13.5 mL•min^-1•100 g^-1 during the perfusion period. The mean perfusion pressure was 7.4 ± 2.9 mm Hg for the perfusion period. There was no flow measured in the nonperfused organs and hence, no perfusion pressure. Although organ weight for both groups remained unchanged after 12 hours of storage; subjectively, nonperfused hearts became more edematous and had markedly depressed cardiac function by gross observation after implantation. Objectively, the nonperfused hearts, despite supraphysiologic doses of isoproterenol and dopamine, were unable to support the circulation and left ventricular end-diastolic pressure increased as cardiopulmonary bypass support was withdrawn. Off bypass left ventricular end-diastolic pressure in the nonperfused hearts could be pushed to 18 mm Hg or more, but the heart was unable to support a viable cardiac output and rate of change of left ventricular pressure (mm Hg/s) was less than half that of control. Perfused hearts responded to 5 µg•kg^-1•min^-1 of dopamine and 0.05 µg•kg^-1•min^-1 of isoproterenol with left ventricular end-diastolic pressure that equaled the control of 6 mm Hg. The corresponding cardiac output of 2 L/min was equivalent to controls. In addition, perfused hearts generated a rate of change of left ventricular pressure similar to control (Fig 2). Subjectively, the perfused hearts seemed less edematous and had vigorous-appearing cardiac function.

View larger version (26K): [in this window] [in a new window]   Fig 2. . Experimental parameters: Storage temperature, cardiac output (CO), and left ventricular end-diastolic pressure (LVEDP) are read at the left and rate of change of left ventricular pressure (LV dp/dt) is read at the right.

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
This work supported in part by a charitable grant from Mr Paul Rochester, PO Box 2212, Ruidoso, NM 88345.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Presebted at the Forty-second Annual Meeting of the Southern Thoracic Surgical Association, San Antonio, TX, Nov 9-11, 1995.

Address reprint requests to Dr Calhoon, Department of Surgery, UTHSCSA, 7703 Floyd Curl Dr, San Antonio, TX 78284-7841.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

1. O'Dell B, Bunegin L. Combined perfusion and oxygentation apparatus. United States Patent #5,362,622, 1994.
2. Angrist SW. Fluid control devices. Sci Am 1964;211:81–8.[Medline]
3. Swanson DK, Pasaoglu I, Berkoff HA, et al. Improved heart preservation with UW preservation solution. J Heart Transplant 1988;7:456–67.[Medline]
4. Hendry PJ, Walley VM, Koshal A, et al. Are temperatures attained by donor hearts during transport too cold? J Thorac Cardiovasc Surg 1989;98:517–22.[Abstract]
5. Proctor E, Parker R. Preservation of isolated heart for 72 hours. Br Med J 1968;4:296–8.
6. Proctor E, Matthews G, Archibald J. Acute orthotopic transplantation of hearts stored for 72 hours. Thorax 1971;26:99–101.[Abstract/Free Full Text]
7. Cooper DKC, Wicomb WN, Barnard CN. Storage of the donor heart by a portable hypothermic perfusion system: experimental development and clinical experience. Heart Transplant 1983;2:104–10.
8. Takami H, Matsuda H, Jirose H, et al. Myocardial energy metabolism in preserved heart: comparison of simple storage and hypothermic perfusion. J Heart Transplant 1988;7:205–12.[Medline]

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): John H. Calhoon Mark C. Felger Edward Y. Sako Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Calhoon, J. H. Articles by Sako, E. Y. Search for Related Content PubMed PubMed Citation Articles by Calhoon, J. H. Articles by Sako, E. Y. Related Collections Related Article