© 1999 American Heart Association, Inc.
Editorials |
Sodium Regulation During Ischemia Versus Reperfusion and Its Role in Injury
From the National Institute of Environmental Health Sciences, Research Triangle Park, NC; and Department of Pathology, Duke University Medical Center, Durham, NC.
Correspondence to Elizabeth Murphy, 111 Alexander Dr, Room E216, Mail drop D2-03, Box 12233, NIEHS, Research Triangle Park, NC 27707. E-mail murphy1@niehs.nih.gov
Key Words: Na+/H+ exchange • Na+/Ca2+ exchange • Ca2+ overload • stunning
There are considerable data to support the general
hypothesis that accumulation of
[Na+]i during
ischemia and early reperfusion leads, via
Na+/Ca2+ exchange, to
elevated [Ca2+]i,
resulting in myocardial damage.1 2 3 4 5 6 7 8 9 10 Despite the strong
support for the general aspects of this hypothesis, there is
controversy regarding some details that have important implications for
the design of therapeutic interventions. The relative importance of the
increase in [Na+]i during
ischemia versus the increase in
[Na+]i during reperfusion
in contributing to the rise in
[Ca2+]i and resultant
injury is debated. These issues are important because it has been
suggested that inhibition of the
Na+/H+ exchanger (NHE)
during reperfusion alone would be beneficial. This would allow clinical
intervention after an ischemic episode. It is also important to
understand why an increase in
[Na+]i is detrimental. It
is commonly assumed that
[Na+]i is detrimental
because it leads to increased
[Ca2+]i during
reperfusion, either due to diminished Ca2+ efflux
via Na+/Ca2+ exchange or
due to increased Ca2+ influx due to reverse
Na+/Ca2+ exchange. Recent
data presented by Cross et al9 suggest that
reverse Na+/Ca2+ exchange
is involved in postischemic contractile dysfunction.
However, an increase in
[Na+]i could also be
detrimental because of effects on K+
loss11 or energetics. An understanding of the mechanism
responsible for the detrimental effects of Na+ accumulation
is important for the design of therapeutic interventions. A
study12 published in this issue of Circulation
Research adds new insight into these
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