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Singh et al. Vessel Plus 2018;2:33 I http://dx.doi.org/10.20517/2574-1209.2018.28 Page 5 of 17
Inspired by the work of Carrel and Loeb, Frank C Mann identified 2 techniques for heterotopic cardiac
[35]
transplantation . In his experimental model, he described using either a distal or proximal end of a di-
vided carotid artery to supply blood to the aorta and assist circulation. The coronary sinus blood returned
to the right atrium with both the vena cavae closed off and drained into the right ventricle. The pulmonary
artery was anastomosed to the jugular vein. They noted that the pulse generated by the heart gradually
faded with the longest lasting heart failing after 8 days.

Vladimir Demikhov, a visionary surgeon developed a mechanical device too large to be inserted entirely
within the thorax of a dog, but it functioned as a substitute for the heart for as long as 5.5 h. Till 1946,
intrathoracic transplantation had never been accomplished in a warm-blooded animal. The first issue en-
countered was ongoing nourishment of the heart using arterialised blood. He ligated of the aorta, venae ca-
vae, azygos, and brachiocephalic and left subclavian arteries perfused the heart with arterialised blood was
returned to the left atrium after passing through the pulmonary circuit and delivered by the left ventricle
into the coronaries. He used this method in around 300 experiments and maintained the heart in good
[36]
condition for up to 4 h .

Despite multiple initial failures of intrathoracic transplant of the heart, one dog survived for 32 postopera-
tive days. Perhaps his greatest achievement was a series of orthotopic heart transplants that he performed
without hypothermia or the use of a cardiopulmonary bypass machine. He performed and end-to-side
anastomosis of the donor aorta, pulmonary artery and venae cavae to the corresponding recipient vessels
and reattached the pulmonary veins to the recipients left atrium and closed off with a purse strings. He
reported survival times of up to 15.5 h, thereby creating the first model of an orthotopic heart transplant
[37]
providing the entirety of the pumping function . Demikhov’s research was not published in English
until 1962.

Interest in Frank C Mann’s work was rekindled in 1951. Marcus et al created a technique using 3 dogs, a
donor, a recipient and a receptacle for the donor heart when disconnected from the circulation . The final
[38]
model was not to dissimilar to the cross-circulation utilized by Lillihei. This “interim parabiotic perfusion”
was used to place the heart in the 2 previously mentioned configurations as described by Mann. In 1953,
[39]
Marcus and associates managed to achieve a survival time of 48 h for heterotopic heart transplantation .
Wilfred Neptune and colleagues were the first to utilise hypothermia with a heart-lung block and achieved
[40]
a survival time of 6 h in a canine model .
Webb, Howard and Neely produced 12 successful orthotopic heart transplants surviving as long as 7.5 h us-
ing a different method of anastomosing the pulmonary veins of the donor to recipient compared to Demik-
[41]
hov . The first involvement of British cardiac surgeons occurred in 1959 when Cass and Brock described
a series of methods for autotransplantation while including leaving the recipients atria and septal crest
[42]
behind to avoid pulmonary vein and vena cavae anastomosis .
In 1960, Lower and Shumway published results of their experiments with orthotopic homotransplantations
using an oxygenator and partial atrial preservation as described by Cass and Brock. They yielded excellent
[43]
results with 5 of the 8 dogs experimented on surviving between 6-21 days . To date, the bi-atrial anasto-
mosis is still noted as the Shumway Technique.

Shumway paid meticulous attention to surgical technique and myocardial protection using isotonic saline at
4 °C. In addition they introduced the concept of assistance time whereby the recipient dogs were left on the
[44]
cardiopulmonary bypass for a short period of time to ease the heart into assuming the circulatory load .

Shumway’s group also described initial issues such as the incidence of complete atrioventricular block. On
learning lessons from rejection in renal transplant patients, Reemtsa et al attempted to use methotrexate