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An Overview of Different Methods of Myocardial Protection Currently Employed Peri-Transplantation

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An Overview of Different Methods of Myocardial Protection Currently Employed Peri-Transplantation Singh et al. Vessel Plus 2017;1:213-29 DOI: 10.20517/2574-1209.2017.26 Vessel Plus www.vpjournal.net Review Open Access An overview of different methods of myocardial protection currently employed peri-transplantation Sanjeet Singh Avtaar Singh1,3, Sudeep Das De1, Cristiano Spadaccio1, Colin Berry2,3, Nawwar Al-Attar1 1Department of Cardiothoracic Surgery, Golden Jubilee National Hospital, Glasgow G81 4DY, UK. 2Department of Cardiology, Golden Jubilee National Hospital, Glasgow G81 4DY, UK. 3Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow G81 4DY, UK. Correspondence to: Mr. Sanjeet Singh Avtaar Singh, Department of Cardiothoracic Surgery, Golden Jubilee National Hospital, Glasgow G81 4DY, UK. E-mail: [email protected] How to cite this article: Singh SSA, Das De S, Spadaccio C, Berry C, Al-Attar N. An overview of different methods of myocardial protection currently employed peri-transplantation. Vessel Plus 2017;1:213-29. Mr. Sanjeet Singh Avtaar Singh, MBChB (Edin), MSc (Edin), MRCS (Edin), is a cardiothoracic research fellow who is currently the Cardiothoracic Advisory Group (CTAG) Audit Fellow based in Scotland at the Golden Jubilee National Hospital. He is currently pursuing his PhD at the University of Glasgow. His research interests surround primary graft dysfunction in heart transplantation. ABSTRACT Article history: Myocardial protection is integral to the functioning of hearts in day to day cardiac surgery. Received: 26 Jul 2017 However, due to the longer ischaemic times, it becomes pivotal in the management of organs First Decision: 7 Sep 2017 during transplantation. There are many different strategies employed to ensure diligent and Revised: 17 Sep 2017 judicious myocardial protection during donor management, transportation of the heart and the Accepted: 20 Sep 2017 post-operative period. Given the limited supply of organs and the increasing waiting lists for Published: 28 Dec 2017 heart transplants worldwide, it has become an area of renewed interest with many innovations and inventions using the principles of basic sciences to improve outcomes of transplanted Key words: hearts. The heart procurement process encompasses several of the different myocardial Myocardial protection, protection strategies in tandem to provide the greatest benefit to the recipients. This review cardiac surgery, looks at the different modalities employed, which include different types of cardioplegia, cardiac transplantation the role of biomarkers, the cutting-edge novel therapies, hormonal therapies and ischaemic conditioning strategies. This is an open access article licensed under the terms of Creative Commons Attribution 4.0 International Quick Response Code: License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original author is credited and the new creations are licensed under the identical terms. For reprints contact: [email protected] www.oaepublish.com © The Author(s) 2017 213 Singh et al. Myocardial protection in cardiac transplantation INTRODUCTION to approximately 80% by the 80s. Cardiac surgery is a rapidly evolving specialty when The number of heart transplants performed worldwide compared to other forms of surgery. In the 19th century, continued to increase until the shortage of donors professor Theodor Billroth, one of the pioneers of in the 1990s became a limiting factor[8]. In 2005, modern abdominal surgery once stated: “A surgeon almost half (48%) of patients had spent at least 2 who tries to suture a heart wound deserves to lose the years on the heart transplant waiting list worldwide[9] esteem of his colleagues” in 1896[1]. In 1951, Russian leading to challenging decisions about the eligibility physiologist Vladimar Petrovich Demikhov performed of donor hearts. Abuanzeh et al.[10] described steps the first thoracic transplants recorded. He transplanted utilized by their retrieval team to optimize donors. the heart and lungs of a male dog into a 3-year-old This was included standardizing protocols which female dog. The dog survived 6 days exhibiting normal includes insertion of a pulmonary artery catheter and behaviour but succumbed to respiratory complications. performance of cardiac output studies, weaning other This was the first recorded history of any animal vasopressors and commencing arginine vasopressin, surviving any length of time with a transplanted heart and administration of hormone replacement. This supporting its circulation[2]. included tri-iodothyronine, methylprednisolone and insulin. They managed to retrieve 14 additional hearts Stanford University Medical Center led the field in in that time frame (56% of the borderline hearts) after cardiac transplantation. Norman Shumway from the aggressive donor management and optimization[10]. University of Minnesota was well known for his work on myocardial protection. Along with Lillehei, they Despite recent advances, myocardial protection would later lead the team that refined the technique during heart transplantation remains a challenging of orthotopic heart transplantation. They reported avenue. With the increasing usage of borderline a series of orthotopic heart transplantations in dogs donor hearts as described, we review some of the and perfected a method that had been use previously myocardial protection strategies and potential markers by Cass and Brock by preserving the recipient atrial for perioperative myocardial infarction. cuffs[3]. They had also first introduced the idea of cold cardioplegia. These experiments were successful but CARDIOPLEGIA Shumway that host immunologic mechanisms were destroying the graft and survival could be prevented Ringer first noted the relationship between potassium by addressing these[4]. and sodium concentration and the heart rate in 1883[11]. Experimentations with potassium citrate were Shumway searched for biomarkers to monitor initially unsuccessful due to the excessive osmolality transplant rejection. Initial experiments with enzymes due to the high-concentration potassium citrate[12]. (hypertensin I) were unsuccessful. He settled on Most cardioplegic solutions today employ a more electrocardiography as a monitor but noted its physiological osmolality and potassium concentration. limitations and pointed out that atrial fibrillation within 7-21 days of transplant was an early sign of rejection[5]. Cardioplegic solutions are defined as intracellular and After working with transplant nephrologists, he extracellular solutions based on the concentrations assessed the potential benefits of immunosuppression of sodium and potassium ions. Extracellular solutions (6-mercaptopurine, azathioprine, and prednisolone) contain high levels of potassium, magnesium and and increased survival by up to 250 days in dogs sodium, while intracellular solutions contain low receiving orthotopic transplants. Dr. Christiaan Barnard electrolyte levels. Intracellular solutions mimic the high extended their pioneering work. Barnard undertook the potassium/low sodium conditions reducing potential first successful human-to-human heart transplant in concentration gradients across the plasma membrane, December 1967[6], before Shumway’s group followed thereby halting potassium efflux. This reduction in shortly afterwards in January 1968. membrane potential resting state prevents generation of action potentials. The function of the Na+/K+ However, the initial reported 1-year survival was ATPase channel is reduced in hypothermic conditions, only 22%, resulting in most centers abandoning this therefore permitting the intracellular concentrations procedure[7]. Shumway’s group at Stanford along to persist[13]. Extracellular cardioplegia on the other with other contemporaries (Cabrol’s group at Paris, hand works by preventing repolarization of myocytes. Lower’s group at Virginia) persevered and following Potassium rich perfusate in the extracellular space introduction of cyclosporine, 1-year survival increased reduces the membrane voltage difference causing 214 Vessel Plus ¦ Volume 1 ¦ December 28, 2017 Singh et al. Myocardial protection in cardiac transplantation depolarization. Intracellular calcium sequestration for cardiac preservation [Table 1][23]. occurs via active transport across an ATP-dependent pump allowing relaxation of the myocardium in diastole. Histidine-tryptophan-ketoglutarate (custodiol/ Repolarization however is prevented by the high bretschneider) potassium concentration of the cardioplegic solution. Reichenspurner et al.[24] studied the effect of histidine- Both intracellular and extracellular cardioplegic tryptophan-ketoglutarate (HTK) in a cohort of 600 solutions have similar long-term outcomes[14]. (524 male:76 female) patients undergoing heart transplantation over a 10-year period (1981-1991). Norman Shumway first noted the use of topical They reported good results provided the ischaemic hypothermia to reduce myocardial metabolic times were less than 4 h. requirements in 1960 when chemical cardioplegia fell out of favour[15]. Denton Cooley then attempted Sung et al.[25] compared Bretscheinder’s HTK solution intermittent aortic occlusion and utilized Kay’s work (18 patients) and cold blood cardioplegia (CBC) (49 with intracoronary blood perfusion with cross clamp patients) for myocardial protection in donor heart fibrillation[16-18]. preservation. Cold HTK solution was infused at low perfusion pressure after procurement and the donor Clinical cardioplegia was reintroduced in the 1970s by heart
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