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FOR RELEASE UNTIL
August 8, 2007
APS Contact
Donna Krupa
Office:
(301) 634-7253
Cell: (703) 967-2751
dkrupa@the-aps.org
Sugar And Spice And
Everything Nice: Health Differences In Newborn Girls And Boys
Two new
studies seek to understand why death rates for female infants are higher
after heart surgery and why female donor livers may be less effective for
transplants
Austin, TX – For generations, girls have
whimsically been said to be made of “sugar and spice and everything nice,”
and boys from “snakes and snails and puppy dog tails.” Inherent in these
loving references is the fact that females and males are different, both
when they are healthy and when they are ill.
Two new studies using an animal model may lead to a
better understanding of sex-based health discrepancies found among some
newborns. One study has found that gender differences in the heart may help
explain why infant girls are more likely to die following heart surgery. The
other study has determined that the rapid accumulation of acid in newborn
female livers may shed light on why pediatric liver transplants are less
successful when the livers are donated from infant girls.
The studies were conducted by Danny Quaglietta,
Department of Physiology, Michael P. Belanger, Department of Surgery, and
Carin Wittnich, Departments of Physiology and Surgery, at the University of
Toronto, Toronto, Ontario, CN. Their studies are entitled, “Ability to
Buffer Changes in pH During Ischemia – Are There Sex Differences in the
Newborn Heart?” and “Orthotopic Liver Transplantation in Newborns –
Lower Success Rates From Female Donors and Why
Ischemic Metabolism May Play A Role,” respectively. Their research is among
the 100 presentations being offered at the upcoming conference, Sex and
Gender in Cardiovascular-Renal Physiology and Pathophysiology.
The meeting, sponsored by The American Physiological Society (APS;
www.The-APS.org), is being held August 9-12, 2007 at the Hyatt
Regency Austin on Town Lake, Austin, TX.
Study 1: Sex Differences in the Newborn Heart
Clinical studies in children have shown that girls are
at higher risk for death than boys following cardiac surgery. A recent
nationwide study in the US has found that females under 20 years of age are
at a 31 percent greater risk of in-hospital death following heart surgery.
As studies have ruled out gender-differences based on access to and
utilization of services, the Canadian team has explored a biological basis
for the differences. In this study they considered whether a more rapid
development of tissue acidity (acidosis) in the heart during a lack of blood
flow (ischemia) might play a role.
The researchers used 20 young (3-5 days) male (n=7) and
female (n=13) Yorkshire piglets to examine their theory. They took a full
thickness left ventricular biopsy to compare the baseline levels of
metabolites in both sexes prior to isolating the hearts. The hearts were
then subjected to 60 minutes of normothermic ischemia and left ventricular
biopsies were collected at the end of the period. All tissues were analyzed
for adenosine adenosine triphosphate (ATP; the main energy source of the
heart), creatine phosphate (CP; a readily available stored form of energy),
lactate, and hydrogen ion (H+) concentration. Histidine concentration,
which protects against acidosis, was also determined in baseline tissue
alone.
The researchers found that the newborn female hearts
had accumulated a significant 47 percent greater H+ level within 60 minutes
of ischemia. This was associated with a significant 13 percent greater
accumulation of lactate. They also found the CP reserve was 22 percent lower
than baseline compared to males.
Based on these and other findings the investigators
concluded that, for this study:
-
male and female newborn hearts are not metabolically
identical and have different metabolic responses to ischemia; and
-
newborn female hearts can develop greater acidosis during
ischemia, which may place them at greater metabolic risk
According to the research team, the results suggest
that the response of the newborn female heart (i.e., myocardium) to ischemia
may increase its susceptibility to injury during ischemia and offer a
potential explanation for the poorer clinical outcomes found in infant
females following cardiac surgery.
Study 2: Lower Success Rates When Using Female
Newborn Liver Donors
As many as 500 children undergo liver transplantation
in the US each year. Data on pediatric liver transplantation shows that the
outcomes are worse for children who receive organs from female donors.
Clinical studies have shown that, compared to males receiving male livers,
males receiving female livers experience a higher incidence of early
complications and almost twice the amount of graft losses.
During liver transplantation, the organ undergoes a
period of no-flow ischemia, or complete lack of blood flow, and therefore
must rely in part on internal nutrient stores to produce energy
anaerobically (without oxygen). The end-products of this process (anaerobic
metabolism) are lactate and hydrogen ions (H+) which can accumulate in the
liver cells during ischemia leading to detrimental affects.
Thus, to better understand the gender effects of infant
liver transplantation, the researchers examined
anaerobic end-product accumulation in newborn male and female livers
during no-flow ischemia. Baseline liver biopsies were harvested from
anesthetized three-day-old male (n=4) and female (n=6) piglets and
immediately afterward the liver was excised and placed in a normothermic
bath for 45 minutes. Biopsies were then taken at 15, 30, and 45 minutes of
ischemia. All biopsies were analyzed for anaerobic end-products lactate and
hydrogen ion (H+) content.
The research team found that both male and female
livers showed similar low levels of both lactate and H+ at baseline. But
during ischemia, newborn female livers accumulated a greater amount of H+
compared to males. This difference persisted throughout the entire ischemic
period. The results were paralleled by a similar greater and more rapid
accumulation of lactate in newborn female livers, a difference that was
sustained throughout the ischemic period.
Based on these findings and other considerations, the
researchers concluded that:
-
the newborn female liver developed a greater and more
rapid tissue acidosis compared to males during normothermic ischemia,
which may be due in part to greater anaerobic glycolysis in females; and
-
more rapid lactic acidosis in newborn female livers may
result in greater metabolic damage during ischemia.
According to Quaglietta, the lead researcher, “These
findings may offer a potential explanation for pediatric studies reporting
worse outcome of recipients receiving livers from female donors.”
# # #
The
American Physiological Society (APS) has been an integral part of the
scientific discovery process since it was established in 1887. Physiology
is the study of how molecules, cells, tissues and organs function to create
health or disease.
***
NOTE TO EDITORS: The APS meeting is being held
at the Hyatt Regency Austin on Town Lake, Austin, TX, August 9-12, 2007.
Members of the media are invited to attend the sessions. To schedule an
interview with a member of the research team, please contact Donna Krupa at
301.634.7209 (direct dial), 703.967.2751 (cell) or
DKrupa@the-APS.org.
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