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Articles |
Departments of
1
Pathology and Laboratory Medicine and
2
Biochemistry and Molecular Biology, University of Louisville, School of Medicine, Louisville, KY 40292.
a Address correspondence to this author at: Department of Pathology and Laboratory Medicine, University of Louisville, Louisville, KY 40292. Fax 502-852-1177; e-mail rvaldes{at}louisville.edu
Background: Xenotransplantation of pig hearts to humans could be
hampered by the reportedly reduced affinity for digoxin of pig heart.
We examined the hypothesis that expression of the individual
-subunit isoforms of the sodium pump
[Na+,K+-ATPase (NKA)], the receptor for the
plant-derived cardiac glycosides, may be responsible for this
difference.
Methods: We used a NKA-inhibition assay in combination with
Western analysis, immunohistochemistry, and phosphorylation of the NKA
subunit to identify the distribution and expression of
isoforms
in four chambers of porcine and human hearts.
Results: We confirmed that tissue from porcine heart is less
sensitive to digitalis (IC50 = 1740 nmol/L) when
compared with human heart (IC50 = 840 nmol/L), whereas
porcine cerebral cortex-mix had an affinity comparable to that of human
heart (IC50 = 910 nmol/L). Our data show that porcine
cerebral cortex-mix and human heart contain all three
isoforms,
whereas porcine heart expresses only the
1 isoform.
Conclusions: The different expressions of sodium pump isoforms in human vs porcine cardiac tissues suggests that porcine hearts may not be pharmacologically or endocrinologically compatible when used in humans. Studies of both pharmacologic and endocrinologic tissue compatibility are needed prior to selection of organs for xenotransplantation.
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