Page 314 - Read Online

Page 4 of 17 Singh et al. Vessel Plus 2018;2:33 I http://dx.doi.org/10.20517/2574-1209.2018.28

EARLY IMMUNOSUPPRESSION
Robert Schwartz and William Dameshek discovered that 6-mercaptopurine (6-MP), which was primarily
[14]
used for treatment of malignancies, also reduced the antibody response of rabbits to bovine albumin .
[20]
Roy Calne used 6-MP on canine kidney homografts and noted that it significantly prolonged survival .
His findings however were not replicated when 3 kidney transplant recipients treated with 6-MP died.
Calne began a research fellowship with Joseph Murray and despite the trend of total body irradiation, pur-
[14]
sued work with 6-MP and later azathioprine .

In 1963, at a National Research Council conference in Washington, the preliminary results of total body
irradiation versus immunosuppressive drugs had reached equipoise with few patients surviving beyond 1
year. The practice of transplantation was questioned due to its poor long-term survival. Every represented
centre demonstrated poor survival bar one. Thomas Starzl, combining azathioprine with prednisone
[21]
achieved > 70% survival at 1-year follow up . He noted that large doses of prednisone could reverse early
rejection that occurred and this could then be tapered down. This led to the formation of 50 new trans-
[16]
plant centres in the United States alone that year and remained the mainstay of immunosuppression for
the next 20 years. Immunosuppression also brought a new pathology, opportunistic infections and malig-
nancy. Starzl himself noted that there were a high rate of bacterial, viral, fungal and protozoal infections
[22]
found in post-mortem examination .
Antilymphocyte serum (ALS) was first discovered by Elie Metchnikoff in 1899. In 1961, Byron Waksman
[23]
identified that lymphocytic depletion could suppressed delayed hypersensitivity reactions . Combining
the two concepts, Michael Woodruff demonstrated that ALS administration alongside thoracic duct drain-
age via a fistula extended skin allograft survival in rodents, a finding later replicated by Medawar [24,25] . In
1966, Polyclonal antilymphocyte globulin (ALG) was successfully synthesized from human leukocyte in-
[26]
oculated horses and became the staple of a triple regimen alongside steroids and azathioprine .
HISTORY OF CARDIAC SURGERY AND TRANSPLANTATION
Unlike its other surgical counterparts, cardiac surgery was a relatively unknown subspecialty in the early
20th century. In 1881 at the Vienna Medical Society, Theodore Billroth once proclaimed.

“No surgeon who wished to preserve the respect of his colleagues would ever attempt to suture a wound of
[27]
the heart” .
The first cardiac procedure of the modern era was performed by Henry C. Dalton in St. Louis to repair a
[28]
pericardial wound in a victim of a stabbing . In 1923, Elliot Carr Cutler and Samuel A. Levine success-
fully relieved a stenotic mitral valve in a 12-year-old girl. F. John Lewis, performed the first successful re-
[29]
pair of an atrial septal defect in 1952 using hypothermia to protect the myocardium . C. Walton Lillehei
performed 45 open heart surgeries utilizing a technique called controlled cross-circulation using parents of
[30]
the children as “pump oxygenators” .
The introduction of the cardiopulmonary bypass circuit revolutionised cardiac surgery. John Gibbon per-
fected the device in 1953 and subsequently perfored the successfully performed an atrial septal defect clo-
[31]
sure . John Kirklin modified the pump and achieved relative success in small series of patients at the Mayo
[32]
Clinic . However it was Richard DeWall’s cardiopulmonary bypass device with a disposable bubble oxy-
[33]
genator and simple pump action that enabled the correction of cardiac conditions under direct vision .
The ensuing period saw numerous attempts to correct myocardial ischaemia until the Robert Hans Goetz suc-
cessful grafted the right internal mammary artery to the right coronary artery, thereby performing the first
[34]
coronary artery bypass graft in 1960, much to the chagrin of the medical and surgical fraternity at the time .