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March 1997
Volume 61 |
Number 3
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FAER REPORT
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| Fellowship and
Grant Award Recipients Announced |
The Board of Directors of the Foundation for Anesthesia Education
and Research (FAER) is pleased to announce recipients of the Anesthesiology
Research Fellowship, the Educational Research Grant and a sixth
Research Starter Grant from the July 1996 competition. FAER is
grateful to ASA, its individual members, component societies,
subspecialty societies and corporations for their generous contributions,
which allow the funding of these awards. Funding for both Research
Fellowships and the sixth Research Starter Grant was included
in the figure published in the February
ASA NEWSLETTER. The descriptions of the projects were
provided by the investigators.
Anesthesiology Research Fellowship
FAER is appreciative of Hoechst Marion Roussel, Inc. and the
Society of Cardiovascular Anesthesiologists, which cosponsored
the two Fellowships.
Daniel R. Brown, M.D., Ph.D.
Johns Hopkins Hospital, Baltimore, Maryland, Hoechst Marion Roussel,
Inc., Anesthesia Research Fellowship Recipient: "Mechanisms
of Cachexia"
Cachexia accounts for significant morbidity in a variety of disorders,
including cancer, AIDS and critical illnesses. Little is known
regarding mechanisms contributing to this pathological weight
loss. Recent investigations have identified two important regulators
of caloric balance: leptin, an adipocyte product, which modulates
appetite and metabolism; and the b-3 adrenoreceptor (b3AR), which
is present on adipocytes and stimulates lipolysis and thermogenesis.
The central hypothesis of this proposal is that changes in these
two regulatory systems contribute to cachexia. Studies in cachectic
cancer-bearing mice will quantify leptin and b3AR mRNA expression
and functional activity and evaluate whether specific b3AR antagonists
attenuate weight loss. Parallel studies will be conducted in pancreatic
cancer patients to determine whether similar mechanisms are relevant
in humans. These studies will provide new information about the
role of these two important regulatory systems in cachexia and
may lead to new therapies for this major clinical problem.
Mark A. Gerhardt, M.D., Ph.D.
Duke University Medical Center, Durham, North Carolina, Society
of Cardiovascular Anesthesiologists, Anesthesia Research Fellowship
Recipient: "Acute b-Adrenergic Receptor (bAR) Desensitization
During Cardiopulmonary Bypass in Patients With Cardiac Valve Disease"
Management of patients with cardiac valve disease (CVD) is challenging
for anesthesiologists during heart surgery with cardiopulmonary
bypass (CPB). CVD patients frequently have congestive heart failure
and chronically elevated catecholamine levels, resulting in chronic
myocardial bAR desensitization and poor response to AR drugs.
Separation from CPB is a critical event during surgery, frequently
marked by abnormal cardiac performance despite correction of valvular
lesions. Acute myocardial bAR desensitization is known to occur
during CPB in coronary artery bypass graphing (CABG) surgery;
if this process is superimposed on pre-existing chronic bAR desensitization,
severely depressed myocardial function may result. We therefore
plan to test two hypotheses: 1) Acute myocardial bAR desensitization
occurs during CPB in patients with CVD, and 2) bAR antagonists
(given at CPB initiation) prevent acute myocardial bAR desensitization
in patients with CVD, resulting in better clinical outcome. A
total of 150 patients will be enrolled in a clinical trial in
three groups: 1) Control CVD patients, 2) CVD patients who receive
10 mg metoprolol upon initiation of CPB, and 3) Control CABG patients
(this group added to confirm that baseline chronic bAR desensitization
occurs in CVD patients and to directly compare resultant percent
desensitization). Pharmacological and biochemical analysis of
atrial biopsies obtained at the beginning and end of CPB will
be performed to determine the existence of desensitization and
underlying mechanism(s). Primary clinical outcomes will be transesophageal
echocardiographic area ejection fraction (pre- and post-CPB) and
post-CPB inotropic support. These studies should provide novel
targets for therapeutic intervention to facilitate better patient
outcome during valve surgery.
Bryan E. Marshall, M.D.
University of Pennsylvania Medical Center, Philadelphia, Pennsylvania,
Educational Research Grant Recipient, "Pulmonary Hemodynamics
and Gas Exchange: A Self-Teaching Program"
While every anesthesiologist involved in perioperative care understands
that pulmonary hemodynamics and gas exchange are interdependent,
the number of variables involved and the complexity of their interactions
reduce quantitative evaluations to "educated guesses."
These relationships are recognized as difficult to understand
by both teacher and student. We have developed a computer program
(V/Q-P/Q Model) that unites the familiar V/Q ratio distribution
model of gas exchange with a newer model of pulmonary hemodynamics.
This proposal is to develop a graphically based, self-teaching
computer program, incorporating the V/Q-P/Q Model, to permit users
to acquire a systematic understanding of the pathophysiological
basis for the interactions of pulmonary hemodynamics and gas exchange
and the fundamental mechanisms responsible for their effects.
The general principles guiding the development are that each topic
will be developed from first principles using interactive diagrams,
graphs and animations. The aim of the first year is to produce
a prototype of the teaching program.
Sixth Research Starter Grant
The February 1997 "FAER Report" (pages 35-36) highlighted
five Research Starter Grants. The following project is an example
of the type of application we anticipate for the new Clinical
Research Starter Grant.
Elliott Bennett-Guerrero, M.D.
Mount Sinai Medical Center, New York, New York, Research Starter
Grant Recipient, "Preoperative Serum Anti-Endotoxin-Core
Antibody (EndoCAb) Levels and Adverse Outcome Following Liver
Transplantation"
As many as 30 percent of patients either die or have a prolonged
hospital length of stay (>3 weeks) following liver transplantation
surgery. Most known risk factors of postoperative complications
cannot be altered so as to improve outcome. Liver transplant recipients
are exposed to large amounts of endotoxin, a toxic part of the
cell wall of bacteria, during surgery. Antiendotoxin antibodies
are naturally present in serum, but there is marked interpatient
variability in their amount. Our study will test the hypothesis
that patients with low preoperative antiendotoxin antibody levels
are at greater risk of having postoperative complications. This
study involves measuring antiendotoxin antibody levels in 150
patients prior to their undergoing liver transplantation. A multivariable
logistic regression analysis will determine if preoperative antiendotoxin
antibody level is able to predict postoperative complications,
independent of the effects of known perioperative risk factors.
Confirmation of this hypothesis could lead to the development
of effective therapeutic interventions.
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