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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 . In 2005,
[8]
modern abdominal surgery once stated: “A surgeon almost half (48%) of patients had spent at least 2
[9]
who tries to suture a heart wound deserves to lose the years on the heart transplant waiting list worldwide
esteem of his colleagues” in 1896 . In 1951, Russian leading to challenging decisions about the eligibility
[1]
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 . included tri-iodothyronine, methylprednisolone and
[2]
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 . They had also first introduced the idea of cold
[3]
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 . and sodium concentration and the heart rate in
[4]
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 . Cardioplegic solutions are defined as intracellular and
[5]
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 , before Shumway’s group followed thereby halting potassium efflux. This reduction in
[6]
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 . Shumway’s group at Stanford along to persist [13] . Extracellular cardioplegia on the other
[7]
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