REQUIREMENTS FOR LONG-TERM 
CARDIOPULMONARY BYPASS CIRCULATION: 
HYPOTHESES AND DATA FROM RESEARCH ANIMALS 
R. B. Shepard, E. I. McGowan, J. W. Scott, H. J. Baker, D. M. Bowen and K. M. Pruitt* 
Methods for studies designed to separate the eifects 
of protein denaturation from those of lack of normal 
pulsatile flow during cardiopulmonary bypass were 
developed. Hemodynamic energy carried by the pul- 
satile component of blood flow in various physiologic 
situations and during cardiopulmonary bypass was 
measured. Oxygen consumption in calves during bypass 
circulation with pulsatile blood flow of normal pul- 
satile energy content was found to be significantly 
greater than when flow was non-pulsatile. Blood and 
cerebrospinal fluid protein changes occurring in calves 
across the bypass period are described. In study of 
isolated and mixed gamma globulin and albumin pro- 
tein fractions in a disc oxygenator, albumin was found 
to retard development of gross turbidity in mixtures 
of the two, and also to be present in precipitate which 
eventually formed. Human plasma from which gamma 
globulin and fibrinogen were removed did not develop 
precipitate. Mortality in calves given blood reconsti- 
tuted from plasma oxygenated 20 hours was 60%. 
When Pluronic F-68 had been in the plasma through the 
oxygenation period, mortality was zero. A set of hypoth- 
eses regarding interaction between pulsatile flow and 
protein denaturation effects during cardiopulmonary 
bypass is proposed. 
INTRODUCTION** 
Total cardiopulmonary bypass circulation us- 
ing pump oxygenators is extremely successful 
as now used clinically for an hour or two. Very 
long perfusions, however, are avoided, partially 
because of multiple organ system damage at- 
tributed to the perfusion process. No laboratory 
animal has been reported as a long-term sur- 
vivor following twenty-four hours of total car- 
diopulmonary bypass. For long-term support 
of circulation alone, Bernhard and associates 
have described simultaneous biventricular 
pumping in normal calves for periods of 7 to 
* The School of Medicine and The Medical Center, University of 
Alabama in Birmingham and the Veterans Administration Hospi- 
tal, Birmingham, Alabama 35233. 
** This work supported by National Heart and Lung Institute 
Grants H5884, H6167, HE 6353 and HE 11310. It was also supported 
in part by the Veterans Administration Medical and Surgical 
Services. 
52 days, and total mechanical circulatory sup- 
port for periods up to 32 hours. ^ For respira- 
tory assistance alone, Kolobow and associates 
have reported partial extracorporeal blood gas 
exchange, using unanesthetized lambs, a spiral 
membrane lung, a veno-venous system, and a 
flow of 400 to 700 cc of blood per minute for 
one week with long-term survival, and for 
sixteen days with accidental death.^ For cardio- 
pulmonary bypass using peripheral arterio- 
venous cannulation and a bubble oxygenator, 
with induced ventricular fibrillation, Proctor 
and Parker have reported postoperative sur- 
vival of unstated duration in some of twenty- 
five dogs kept on bypass for eight hours.^ 
The hypotheses proposed below concern total 
cardiopulmonary bypass circulation. Reasons 
for consideration of these hypotheses will be- 
come apparent, although the data are incom- 
plete. 
1. Blood flow with normal pulsatile hemo- 
dynamic energy content is necessary for 
normal whole-body oxygen consump- 
tion, and for prevention of problems 
related to tissue hypoxia, in long-term 
cardiopulmonary bypass. 
2. Pulsatile flow is more lethal than steady 
flow when blood protein denaturation 
becomes appreciable during prolonged 
cardiopulmonary bypass circulation. 
3. Particulate matter formation, and the 
deleterious physiologic effects of plasma 
protein denaturation, may be reduced 
markedly during prolonged cardiopul- 
monary bypass by using a surface active 
agent to change the gas-liquid inter- 
facial forces acting on the plasma pro- 
tein. 
Experimental evaluation of these hypotheses 
will be examined in reverse order. 
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