|Year : 2020 | Volume
| Issue : 3 | Page : 264-269
A Survey of the Practices of Storage and Transport for Donor Heart in India
Sarvesh Pal Singh1, Milind Padmakar Hote1, Sandeep Seth2, Manoj Durairaj3, Anvay Mulay4, Thirugnanasambandan Sunder5, KG Suresh Rao6, Kewal Krishan7, Julius Punnen8, KR Balakrishnan6, Alla Gopala Krishan Gokhale9
1 Department of Cardiothoracic and Vascular Surgery, C T Center, All India Institute of Medical Sciences, New Delhi, India
2 Department of Cardiology, C T Center, All India Institute of Medical Sciences, New Delhi, India
3 Marian Cardiac Center and Research Foundation, Pune, India
4 Department of Cardiothoracic and Vascular Surgery, Sir HN Reliance Hospital, Mumbai, Maharashtra, India
5 Department of Heart and Lung Transplantation, Apollo Hospitals, Chennai, Tamil Nadu, India
6 Department of Cardiothoracic and Vascular Surgery, Institute of Heart and Lung Transplant, MGM Healthcare, Chennai, Tamil Nadu, India
7 Department of Cardiovascular Surgery, Max Heart and Vascular Institute, New Delhi, India
8 Department of Cardiovascular Surgery, Narayana Institute of Cardiac Sciences, Bengaluru, Karnataka, India
9 Department of Cardiothoracic Surgery, Apollo Hospitals, Hyderabad, Telangana, India
|Date of Submission||26-May-2020|
|Date of Decision||07-Sep-2020|
|Date of Acceptance||15-Sep-2020|
|Date of Web Publication||23-Dec-2020|
Dr. Sarvesh Pal Singh
Department of Cardio-Thoracic and Vascular Surgery, C T Center, All India Institute of Medical Sciences, Room No 5, 7th Floor, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
Background: Heart transplant remains the gold standard for the treatment of end-stage heart failure. The most common method of donor heart preservation, during transport, is “triple-bag technique” with static cold storage (SCS). The safe duration of storage (ischemic time) for a donor heart with SCS is 4 h shortest among all the transplantable solid organs. One of the factors determining the donor heart's quality is the storage and transport of the donor organ. This study identified the centers which perform heart transplants routinely (≥7 per year) for the past 3 years and compared the differences between their donor heart storage and transport practices. Methodology: After obtaining ethical clearance from the Institutional Ethics Committee, this survey was done among the centers performing heart transplants in India. Centers performing an average of ≥7 heart transplants per year for the past consecutive 3 years were identified and included in the study. Centers that refused to participate or did not respond to a maximum of 3 reminders to send the filled questionnaire were excluded from the survey. A total of 11 transplant teams fulfilled the inclusion criteria, but only eight units responded to the request. The authors identified the team leaders in all the transplant teams and obtained concurrence before sharing an indigenous questionnaire about the practice of storage and transport of donor heart followed in their centers. Teams were contacted by digital platforms and telephone. Results: The analysis of current practices for donor heart preservation reveals that the triple-bag technique is the most commonly used method for SCS of donor heart, and Custodiol HTK is the most commonly used solution for cardioplegia. The dose of Custodiol varies between 25 and 50 ml/kg in different centers. It is also a common practice to immerse the heart in cold Custodiol solution in the first bag. Although any donor retrieval team does not measure the temperature, every team claims the temperature of the preservative solution used for flushing is 0°C–4°C. All the participating teams use ice cubes or slush in the transport box around the heart encased in 3 plastic bags. Conclusions: The authors of this survey conclude that the triple bag technique use may not be essential and can be converted to a two-bag technique as practiced by a couple of units. The use of cold Custodiol solution in the first bag probably has no rationale, and the use of 0.9% saline is a non-inferior cost-effective option. Ice slush may be avoided in the first bag because of the theoretical possibility of triggering a freeze in the donor heart.
Keywords: Donor, heart, practices, storage, transport
|How to cite this article:|
Singh SP, Hote MP, Seth S, Durairaj M, Mulay A, Sunder T, Suresh Rao K G, Krishan K, Punnen J, Balakrishnan K R, Krishan Gokhale AG. A Survey of the Practices of Storage and Transport for Donor Heart in India. J Pract Cardiovasc Sci 2020;6:264-9
|How to cite this URL:|
Singh SP, Hote MP, Seth S, Durairaj M, Mulay A, Sunder T, Suresh Rao K G, Krishan K, Punnen J, Balakrishnan K R, Krishan Gokhale AG. A Survey of the Practices of Storage and Transport for Donor Heart in India. J Pract Cardiovasc Sci [serial online] 2020 [cited 2022 Jan 21];6:264-9. Available from: https://www.j-pcs.org/text.asp?2020/6/3/264/304527
| Introduction|| |
Heart transplant remains the gold standard for the treatment of end-stage heart failure. There is an undisputed shortage of donor organs for transplantation worldwide. Researchers and innovators always endeavor to increase the availability of organs by increasing the duration of safe storage (cold static storage) and transport.,,, Newer advancements in technology are leading to attempts at cryopreservation, xenotransplantation (CRISPR technology), and development of artificial hearts (tissue engineering). The most common donor heart preservation method during transport is the “triple bag technique” with static cold storage (SCS). SCS involves administering the preservative solution into the heart at 0°C–4°C and storing it at the same temperature by immersing it into a preservation solution. The safe duration of storage (ischemic time) for a donor heart with SCS is 4 h shortest among all the transplantable solid organs.
Compared to any other organ, the heart consumes maximum energy of approximately 6 Kg of ATP every day. The average level of ATP in the myocardium is approximately 10 mmol/L. An ideal perfusate should have the ability to deliver oxygen to tissues, osmotic effects, buffers, metabolic substrates, electrolytes, growth factors, and hormones. In the past decade, the composition of different preservative solutions was altered in many ways to achieve the best outcomes and possibly increase the limit of safe allograft ischemic time.,,,,,, However, the era of improving preservation strategies based on preservative solutions for SCS is nearing its end.
The other shortcomings of the SCS of the heart (triple-bag technique) are single administration of the preservative solution, no measurement of myocardial temperature (drifting of temperature), and the possibility of freezing the donor's heart by reaching sub-zero temperatures, non-uniform cooling, and unregulated warming during thawing. Before the administration of preservation solution, a brief period of warm ischemia is inevitable between aortic clamping and administration of cardioplegia. During this warm ischemia, there is an accumulation of harmful levels of succinate, which leads to the formation of reactive oxygen species (ROS) at the time of reperfusion. Therefore, accumulation of succinate in tissues is a marker of hypoxia and possibly of injury to the myocardium.
One of the factors determining the quality of donor heart (function, ischemic changes, and arrhythmias) is the storage and transport of the donor organ. The practice of storing and transport the donor heart is both uniform and variable. All the centers use the same “Triple Bag Technique” and cold storage for transport. However, there is no uniform laid down “objective” criteria for this practice. This study identified the centers which perform heart transplants routinely (≥7 per year) for the past consecutive 3 years and compared the differences between their donor heart storage and transport practices.
| Methodology|| |
After obtaining ethical clearance from the Institutional Ethics Committee (IEC/472/5/2020; RP 7/2020), this survey was done among the centers performing heart transplants in India.
Inclusion Criteria: Centers performing an average of ≥7 heart transplants per year for the past consecutive 3 years were identified based on personal communications, published research, and news articles.
Exclusion criteria: Centers that refused to participate or did not respond to a maximum of 3 reminders to send the filled questionnaire were excluded from the survey.
A total of 11 transplant teams fulfilled the inclusion criteria, but only eight units responded to the request for participation. The authors identified the team leaders in all the transplant teams and obtained concurrence before sharing an indigenous questionnaire about the practice of storage and transport of donor heart followed in their centers. The questionnaire and the responses are detailed in [Table 1]. Teams were contacted by digital platforms and telephone.
|Table 1: Practices followed by different heart transplant teams who participated in this survey|
Click here to view
The following transplant teams participated in the survey: Bengaluru 1, Hyderabad 1, Chennai 1, Chennai 2, Pune 1, Delhi 1, Delhi 2, and Mumbai 1.
| Results|| |
The practices of all the responding teams are summarized in [Table 1]. All the participating heart transplant teams in the survey universally follow the triple-bag technique for SCS of donor heart. There exist a few exceptions. The team Bengaluru 1 keeps the second bag empty but still uses three bags for preservation. Similarly, the team Delhi 1 keeps the third bag empty. All participating centers use cold Custodiol HTK solution for the preservation of donor heart. The dose of Custodiol varies between 25 and 50 ml/kg in different centers. Only one team (team Chennai 1) decreases the dose of cardioplegia to 25 ml/kg for shorter transport periods (<1 h).
Except for teams Delhi 1 and 2, all teams use only cold Custodiol solution between 500 ml and 2 L to preserve the heart in the first bag. The team Delhi 2 uses cold 0.9% saline (70%) and ice (30%) in the first bag, whereas team Delhi 1 uses cold 0.9% saline (100 ml) and cold Custodiol (500 ml) solution in the first bag. Although any donor retrieval team does not measure the temperature, every team claims the temperature of the preservative solution used for flushing is 0°C–4°C.
The majority of teams use ice slush in second and third bags with 0.9% saline. The team Hyderabad 1 does not use ice slush in any of the bags. The team Chennai 1 does not use 0.9% saline and instead use Plasmalyte (balanced crystalloid solution) in second and third bags. All the participating teams use ice cubes or slush in the transport box around the heart encased in 3 plastic bags.
| Discussion|| |
SCS is the method of choice for the preservation of the donor heart. The storage of a donor heart in a cold preservative solution can lead to cold-induced cellular injury. This injury occurs by an increase in the redox-active iron pool that converts low ROS (O2-and H2O2) into highly ROS (OH-or iron oxygen species) and does not appear to be due to an increased release of ROS. These highly ROS increase the microvascular permeability of small venules leading to edema.
In our survey, we found that Custodiol is used by all the centers to preserve the donor heart. The amount of Custodiol used is variable among different centers. The use of Custodiol is associated with a low rate of severe primary graft dysfunction. Custodiol contains Histidine, Tryptophan and Ketoglutarate with low concentrations of Sodium (15 mmol/l), Potassium (10 mmol/l), Chloride (32 mmol/l), and Magnesium (4 mmol/l). Histidine is a strong buffer that compensates metabolic acidosis at the cellular level. Tryptophan and alpha-ketoglutaric acid stabilizes cell membranes and prolong anaerobic glycolysis. Tryptophan also protects against oxidative stress and has high scavenging capacity. Mannitol acts as an antioxidant by up-regulating the levels of catalase decreased during oxidative stress. A modification of Custodiol solution, Tiprotec, has chelators of iron (deferroxamine and LK 614), and increased concentration of potassium and amino acids (L glycine and L alanine) to inhibit hypoxic injury. Arginine is added to Tiprotec to increase the supply of nitric oxide. Furthermore, N acetyl Histidine is used as a buffer instead of Histidine because it improves endothelial function in isolated rat hearts.
All the participating heart transplant teams in the survey universally follow the triple-bag technique. The scientific explanation for such a technique is still not clear. Our survey poses many questions regarding the current practices of donor heart storage and transport in India. First, is the use of Custodiol in the first bag beneficial, or is it just makes storage expensive? During cardiac surgery, many surgeons flood the pericardial cavity with ice slush or cold 0.9% saline and not cardioplegia. There is no evidence that the use of the preservative solution for the donor heart's storage is beneficial. The use of cold 0.9% saline (at 4°C) in the first bag should suffice, provided the preservative solution has been flushed in an adequate amount and in an optimum way. The team Delhi 2 uses only 0.9% saline in all bags without any complications.
Only one team uses ice slush in the first bag that too in sparing quantity (only 30%). The use of ice slush to preserve the donor's heart in the first bag can freeze the heart, mainly by providing a nucleating agent. The addition of minimal ice may help maintain temperature but still risks uneven freezing (at points of contact of the myocardium with ice). The team Hyderabad 1 does not use ice in any of the bags and have not reported any adverse events.
In comparison to the first bag, there is no uniformity in the solution for the second bag. The team Chennai 1 uses Plasmalyte (a balanced salt solution) in the second bag, and rest other teams use 0.9% saline with ice slush. When the heart is not in direct contact with the second bag's solution, there should not be any impact on the heart of the type of solution. However, the temperature of the solution might affect allograft. The team Bengaluru 1 keeps the second bag dry, which begs the question, is it even required?
Similarly, the team Delhi 1 keeps the third bag dry. Again for the third bag, some teams use ice slush, and some do not. However, the use of ice in the transport box to cover the surrounding space around the bag is universal.
None of the teams surveyed reported any loss of donor hearts while practicing their storage and transport protocols in the last 5 years. [Table 1] shows that all the surveyed teams successfully transplanted all the harvested hearts. The team Chennai 1 could not utilize one heart out of the 284 harvested due to triple vessel coronary artery disease. This heart was supported with an organ preservation system (ECMO console) after harvesting, and angiography was performed, which revealed the CAD.
A consensus statement recently published in the Journal of Heart and Lung Transplantation advocates placing the harvested donor heart in 1000 ml of solution at 4°C in the first bag, sealing it and then placing the first bag in a second bag again containing 1000 ml of solution at 4°C and sealing the second bag. Significantly, the authors do not describe the use of 3 bags as a standard practice but as an optional one and recommend placing the two bags with the heart into a rigid, sterile container with a cold solution. This rigid container is then placed into the transport box filled with crushed ice. This consensus statement mentions the use of either 0.9% saline or preservative solution (cardioplegia) in either of the bags and recommends replacing the 3rd bag with a rigid, sterile container. The use of a rigid container appears to avoid direct contact of the bags with ice and prevents freezing. The use of a third bag filled with cold saline, instead of a rigid container, may achieve the same goal. The protocol in the United Kingdom uses 2 L cold saline for all three bags and then places them in the transport box with ice. Some surgeons make a clear zone around the 3rd bag (containing two other bags) after placing it inside the icebox to prevent direct contact with the ice.
Earlier studies in dogs demonstrated that after cold cardioplegic arrest and storage with a 2-bag and Icebox technique the temperature in hearts drifted fastest during the 1st h (left ventricle, 10.3°C–1.3°C; right ventricle 7.5°C–1.3°C and interventricular septum 7.6°C–0.7°C). These hearts' myocardium showed a progressive increase in intra and intercellular edema from 0 to 4 h of storage. An ischemic allograft time of fewer than 4 h is associated with better survival than an ischemic time of more than 4 h. The ventricular function and high energy stores are well preserved with least cold-induced injury when donor's hearts are stored at 4°C–8°C.,, An attempt to achieve a myocardial temperature of 4°C risks exposes the heart to near-freezing temperatures. Amir et al. studied antifreeze proteins (AFP I and III) for sub-zero preservation of rat hearts.,, The storage of hearts at sub-zero temperatures (−1.3°C) with the use of AFP III not only prevented the freezing of heart but provided better preservation than at 4° for 24 h., The AFP research was primarily aimed at cryopreservation of hearts and was never studied for prolonging the storage for short durations (6 or 12 h). Therefore, the addition of AFP to cold solutions (saline) may be studied for prolonging storage times. More specific biomarker and electron microscopy-based studies of SCS preserved hearts are required to find the ideal preservation method.
Limitations of the study
The number of centers doing ≥7 heart transplants every year is less, and therefore, there are fewer participants in our survey. All the harvested hearts were transplantable is a subjective and gross estimate of the quality of the donor organ. The details of clinical, radiological, and biochemical evaluation of the harvested hearts are not available and hence not discussed.
| Conclusions|| |
The analysis of current practices for donor heart preservation reveals the following facts: the triple bag technique may not be essential and can be converted to a two-bag technique as practiced by a couple of units. The use of cold Custodiol solution in the first bag probably has no rationale, and the use of 0.9% saline is a non-inferior cost-effective option. Ice slush may be avoided in the first bag because of the theoretical possibility of triggering a freeze in the donor heart.
The study is approved by the Institutional Ethics Committee.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Airan B, Singh SP, Seth S, Hote MP, Sahu MK, Rajashekar P, et al
. Heart transplant in India: Lessons learned. J Pract Cardiovasc Sci 2017;3:94-9. [Full text]
Caplan AL. Finding a solution to the organ shortage. CMAJ 2016;188:1182-83.
Ribeiro RV, Alvarez JS, Yu F, Paradiso E, Adamson MB, Maria Ruggeri G, et al
. Hearts donated after circulatory death and reconditioned using normothermic regional perfusion can be successfully transplanted following an extended period of static storage. Circ Heart Fail 2019;12:e005364.
Schaefer M, Gebhard MM, Gross W. The efficiency of heart protection with HTK or HTK-N depending on the type of ischemia. Bioelectrochemistry 2019;125:58-69.
Rudd DM, Dobson GP. Eight hours of cold static storage with adenosine and lidocaine (Adenocaine) heart preservation solutions: Toward therapeutic suspended animation. J Thorac Cardiovasc Surg 2011;142:1552-61.
Ferng AS, Schipper D, Connell AM, Marsh KM, Knapp S, Khalpey Z. Novel vs clinical organ preservation solutions: Improved cardiac mitochondrial protection. J Cardiothorac Surg 2017;12:7.
Giwa S, Lewis JK, Alvarez L, Langer R, Roth AE, Church GM, et al
. The promise of organ and tissue preservation to transform medicine. Nat Biotechnol 2017;35:530-42.
Michel SG, LaMuraglia GM 2nd
, Madariaga ML, Anderson LM. Innovative cold storage of donor organs using the Paragonix Sherpa PakTM devices. Heart Lung Vessels 2015;7:246-55.
Jing L, Yao L, Zhao M, Peng LP, Liu M. Organ preservation: From the past to the future. Acta Pharmacol Sin 2018;39:845-57.
Chambers DC, Yusen RD, Cherikh WS, Goldfarb SB, Kucheryavaya AY, Khusch K, et al
. The registry of the international society for heart and lung transplantation: Thirty-fourth adult lung and heart-lung transplantation report-2017; Focus theme: Allograft ischemic time. J Heart Lung Transplant 2017;36:1047-59.
Hamilton DJ. Mechanisms of disease: Is mitochondrial function altered in heart failure? Methodist Debakey Cardiovasc J 2013;9:44-8.
Neubauer S. The failing heart An engine out of fuel. N Engl J Med 2007;356:1140-51.
Guibert EE, Petrenko AY, Balaban CL, Somov AY, Rodriguez JV, Fuller BJ. Organ preservation: Current concepts and new strategies for the next decade. Transfus Med Hemother 2011;38:125-42.
Taylor MJ, Weegman BP, Baicu SC, Giwa SE. New approaches to cryopreservation of cells, tissues, and organs. Transfus Med Hemother 2019;46:197-215.
Pell VR, Chouchani ET, Frezza C, Murphy MP, Krieg T. Succinate metabolism: A new therapeutic target for myocardial reperfusion injury. Cardiovasc Res 2016;111:134-41.
Arnaoutakis GJ, George TJ, Allen JG, Russell SD, Shah AS, Conte JV, et al
. Institutional volume and the effect of recipient risk on short-term mortality after orthotopic heart transplant. J Thorac Cardiovasc Surg 2012;143:157-67, 167.e1.
Mokbel M, Zamani H, Lei I, Chen YE, Romano MA, Aaronson KD, et al
. Histidine-tryptophan-ketoglutarate solution for donor heart preservation is safe for transplantation. Ann Thorac Surg 2020;109:763-70.
Petrenko A, Carnevale M, Somov A, Osorio J, Rodríguez J, Guibert E, et al
. Organ preservation into the 2020s: The era of dynamic intervention. Transfus Med Hemother 2019;46:151-72.
Veres G, Hegedűs P, Barnucz E, Schmidt H, Radovits T, Zöller R, et al
. TiProtec preserves endothelial function in a rat model. J Surg Res 2016;200:346-55.
Radovits T, Lin LN, Zotkina J, Koch A, Rauen U, Köhler G, et al
. Endothelial dysfunction after long-term cold storage in HTK organ preservation solutions: Effects of iron chelators and N-alpha-acetyl-L-histidine. J Heart Lung Transplant 2008;27:208-16.
Copeland H, Hayanga JW, Neyrinck A , MacDonald P, Dellgren G, Bertolotti A, et al
. Donor heart and lung procurement: A consensus statement. J Heart Lung Trans 2020;39:501-17.
Hendry PJ, Walley VM, Koshal A, Masters RG, Keon WJ. Are temperature attained by donor hearts during transport too cold? J Thorac Cardiovasc Surg 1989;98:517-22.
Lund LH, Khush KK, Cherikh WS, Goldfarb S, Kucheryavaya AY, Levvey BJ, et al
. The registry of the international society for heart and lung transplantation: Thirty-fourth adult heart transplantation report-2017; focus theme: Allograft ischemic time. J Heart Lung Trans 2017;36:1037-46.
Guerraty A, Alivizatos P, Warner M, Hess M, Allen L, Lower RR. Successful orthotopic canine heart transplantation after 24 hours of in vitro
preservation. J Thorac Cardiovasc Surg 1981;82:531-7.
Kao RL, Conti VR, Williams EH. Effect of temperature during potassium arrest on myocardial metabolism and function. J Thorac Cardiovasc Surg 1982;84:243-9.
Jahania MS, Sanchez JA, Narayan P, Lasley RD, Mentzer RM Jr. Heart preservation for transplantation: Principles and strategies. Ann Thorac Surg 1999;68:1983-7.
Amir G, Rubinsky B, Basheer SY, Horowitz L, Jonathan L, Feinberg MS, et al
. Improved viability and reduced apoptosis in sub-zero 21-hour preservation of transplanted rat hearts using anti-freeze proteins. J Heart Lung Transplant 2005;24:1915-29.
Amir G, Rubinsky B, Horowitz L, Miller L, Leor J, Kassif Y, et al
. Prolonged 24-hour subzero preservation of heterotopically transplanted rat hearts using antifreeze proteins derived from arctic fish. Ann Thorac Surg 2004;77:1648-55.
Amir G, Horowitz L, Rubinsky B, Yousif BS, Lavee J, Smolinsky AK. Subzero nonfreezing cryopresevation of rat hearts using antifreeze protein I and antifreeze protein III. Cryobiology 2004;48:273-82.