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[53]
to infection. He performed 2 more unsuccessful transplants before a moratorium was declared .

Denton Cooley’s group reported moderate success early on at Baylor with 7 of 10 patients surviving
[54]
4.5 months . To reduce the risk of rejection, they used blood-group compatibility, lymphocyte crossmatch
studies (histocompatibility) as described by Dr. Paul Terasaki, and developed a matching system to predict
[55]
the likelihood of a good outcome post-transplant . They also administered anti-lymphocyte globulin in
addition to the other anti-rejection medications.

EARLY ISSUES WITH HEART TRANSPLANTATION
[56]
Within a year of the Barnard’s feat, 102 heart transplantations were performed internationally . Shumway
famously quipped “Suddenly heart transplants were being done in places where one would hesitate to have
his atrial septal defect closed”.

The early promise of heart transplantation however soon diminished asthe number of transplants rapidly
fell from 100 (1968) to 18 (1970), with many inexperienced units abandoning the procedure. Kantrowitz,
who was on the review panel for the National Institute of Health agreed to support Shumway and his unit
[58]
[57]
in their ongoing research . In 1971, they identified several identifiers of acute rejection :
(1) Electrocardiographic findings: i. Increased QRS voltage; ii. Arrhythmia; iii. Right axis deviation; iv.
ST-T wave changes;
(2) Clinical Findings: i. Appearance of gallop rhythm; ii. Decreased precordial activity; iii. Hypotension;
(3) Echocardiography findings: i. Increased thickness of left ventricular wall; ii. Increased right ventricular
diameter.

Using the above-mentioned criteria, they successfully treated 57 of 60 patients with methylprednisolone,
actinomycin D and ALG. As the experience of long-term survival in heart transplants increased, Shumway
[59]
noted a condition he titled “chronic rejection” . It manifested as diffuse allograft vasculopathy and led to
episodes of sick sinus syndrome or myocardial infarction, usually proving fatal.

In 1962, Dr. Souji Konno developed the catheter-type endomyocardial biopsy (EMB) allowing samples
of myocardium of patients suspected of having intrinsic musculature abnormality to be taken using a
[60]
bioptome inserted via a peripheral vein or arterial cutdown . It was initially developed for diagnoses of
cardiomyopathies as opposed to limited thoracotomy approaches. The biotome usually provided samples
containing endocardium and myocardium, usually sufficient for microscopic examination.

In 1971, a young cardiothoracic surgeon, Dr. Philip Caves undertook a British American Research Fellow-
ship to Stanford to work with Shumway. While here, he worked with instrument maker, Werner Schulz
to create the Stanford-Caves Schulz bioptome which transformed the management of heart transplant pa-
tients. There were 2 Stanford bioptomes that differed in size and length. The longer and thinner bioptome
was used for left ventricular biopsy and the shorter and thicker one for right ventricular biopsy [61,62] . The
samples obtained were between 1-3 mm in diameter. He noted that changes seen in endomyocardial speci-
mens matched those seen in grafts at post-mortem examinations. The samples taken from the endomyocar-
dial surface were also free of post-operative inflammatory changes that complicated sub-epicardial samples
taken during thoracotomy. Finally, he noted that the pathologic changes of cardiac allograft rejection were
more prominent in the endomyocardial surface (as the graft came in direct contact with the host’s circula-
tion). Philip Caves also worked with Margaret Billingham who was a pathologist at Stanford. In 1974, they
developed a standardised histological scale to pathologically grade the severity of cardiac rejection based
[63]
on the extent of infiltrates . This was incorporated into routine practice and significantly improved the
survival of heart transplant recipients at Stanford.