The Journal of Bone and Joint Surgery, Vol 70, Issue 10 1500-1513, Copyright © 1988 by Journal of Bone and Joint Surgery, Inc
The bioenergetics of preservation of limbs before replantation. The rationale for intermediate hypothermia
AA Sapega, RB Heppenstall, DP Sokolow, TJ Graham, JM Maris, AK Ghosh, B Chance and AL Osterman
Philadelphia Veterans Administration Medical Center, Pennsylvania.
Of all tissues of the extremities, muscle is the least tolerant of
ischemia. Hypothermia of tissue is considered beneficial for the
maintenance of viability of muscle in amputated limbs before surgical
replantation, but it has never been established that conventional cooling
in an ice bath or its equivalent (temperature of tissue, approximately 1
degree Celsius) is the optimum level of hypothermia for minimizing
metabolic derangement in ischemic muscle. In this study, we first defined
the time course and level of metabolic derangement of muscle in
twenty-eight ischemic hind limbs in cats at 22, 15, 10, 5, and 1 degree
Celsius. The levels of adenosine triphosphate and phosphocreatine and the
mean intracellular pH of the muscles in the lateral aspect of the thigh in
each limb were monitored with phosphorus nuclear magnetic-resonance
spectroscopy over time. The excised muscles from six freshly amputated legs
of live humans were then similarly studied to determine whether muscles
from cats and from humans exhibit comparable bioenergetic responses to
hypothermic ischemia. A final series of ten ischemic hind limbs from cats
was studied by nuclear magnetic resonance and muscle biopsy for direct
biochemical assay of tissue energy metabolites to compare the metabolic
benefits of two different methods of preserving limbs: continuous cooling
in an ice bath, and a newly devised protocol for the rapid induction and
maintenance of so-called intermediate (10 +/- 5 degrees Celsius)
hypothermia of tissue. Ischemic skeletal muscle in cats exhibited a
paradoxical metabolic response to extreme cold (1 degree Celsius). The rate
of metabolic deterioration progressively declined with decreasing
temperature of tissue to 10 degrees Celsius. However, at 5 degrees Celsius,
no additional benefit was detected, and at 1 degree Celsius, there was a
significant acceleration in the rates of degradation of adenosine
triphosphate and phosphocreatine and in the production of lactate. The rate
of degradation of adenosine triphosphate in human ischemic muscle was also
faster at 1 degree Celsius than at 10 degrees Celsius. This paradoxical
response is apparently due to a severe inhibition of the calcium pump of
the sarcoplasmic reticulum of the muscle cell at temperatures of less than
5 degrees Celsius. The inhibition permits an efflux of calcium to the
myofibrils, which stimulates both glycolysis and the degradation of
adenosine triphosphate by myofibrillar adenosine triphosphatase.
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