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MUST READ INFORMATION NOTE : LONG POST
Advanced fluorocarbon-based systems for oxygen and drug delivery, and
diagnosis. [Review] [36 refs]
SO Artificial Cells, Blood Substitutes, & Immobilization Biotechnology.
25(1-2):43-52, 1997 Jan-Mar.
JC bxe
CP United States
AB Fluorocarbons and fluorocarbon-derived materials constitute a vast
family of synthetic components that have a range of remarkable
properties
including exceptional chemical and biological inertness, gas-dissolving
capacity, low surface tension, high fluidity, excellent spreading
characteristics, unique hydro- and lipophobicity, high density, absence
of
protons, and magnetic susceptibility close to that of water. These
properties lead to a diversity of products and applications as
illustrated
by those products that are already in advanced clinical trials, which
comprise: 1) an injectable oxygen carrier, i.e. blood substitute,
consisting of a fluorocarbon-in-water emulsion for use in surgery to
alleviate the problems raised by the transfusion of homologous blood;
the
same emulsion is also being evaluated with cardiopulmonary bypass
patients; 2) a neat fluorocarbon for treatment of acute respiratory
failure by liquid ventilation; and 3) fluorocarbon-based or stabilized
gas bubbles to be used
as contrast agents for the assessment of heart function and detection of
perfusion defects by ultrasound imaging. Proper selection of the
fluorocarbon best suited for the intended application, formulation
optimization, and advanced stabilization and processing procedures led
to
effective, ready-for-use products with minimal side-effects. Further
highly
fluorinated materials, including amphiphiles and various
fluorocarbon-based
colloidal systems that have potential as pulmonary, topical and
ophthalmological drug delivery agents, and as skin protection barriers,
are
now being investigated. Such systems include drug-in-fluorocarbon
suspensions, reverse water-in-fluorocarbon emulsions,
oil-in-fluorocarbon
emulsions, multiple emulsions, microemulsions, fluorocarbon gels,
fluorinated liposomes, fluorinated tubules and other novel
supramolecular
systems. [References: 36]
USE IN IMPROVING LUNG OXYGENATION
Pulmonary blood flow distribution during partial liquid ventilation.
SO Journal of Applied Physiology. 84(5):1540-50, 1998 May.
TI Hemodilution and intravenous perflubron emulsion as an alternative to
blood
transfusion: effects on tissue oxygenation during profound hemodilution
in
anesthetized dogs.
SO Transfusion. 38(2):145-55, 1998 Feb.
AB BACKGROUND: Intravenously administered perfluorocarbon (PFC)
emulsions
increase oxygen solubility in plasma. PFC might therefore temporarily
replace red cells (RBCs) lost during intraoperative hemorrhage. In
patients
who have undergone hemodilution, the return of autologous blood may be
delayed by the administration of PFC, and autologous RBCs may be saved
for
transfusion after surgical bleeding is stopped and PFC is cleared by the
reticuloendothelial system. STUDY DESIGN AND METHODS: In 22
anesthetized,
hemodiluted dogs (hemoglobin [Hb] 7 g/dL) breathing 100-percent O2, an
intraoperative volume-compensated blood loss was simulated. The efficacy
of
three therapeutic regimens in maintaining tissue oxygenation was
compared:
1) RBC group (n = 7): maintenance of a Hb > 7 g per dL by transfusion of
autologous RBCs; 2) PFC group (n = 7): bolus application of a
second-generation PFC emulsion (60% wt/vol perflubron) and further acute
normovolemic hemodilution (ANH) to a Hb of 3 g per dL; and 3) control
group
(n = 7): further ANH alone to a Hb of 3 g per dL. Systemic and
myocardial
oxygenation status and tissue oxygenation were assessed. RESULTS:
Autologous RBCs transfused to maintain a Hb of 7 g per dL preserved
hemodynamics and tissue oxygenation during blood loss. In the PFC and
control groups, heart rate and cardiac index increased significantly in
response to further ANH. Tissue oxygenation was not different in the PFC
and the RBC groups. Direct comparison of the PFC and control groups
revealed better tissue oxygenation in the PFC group, as reflected by
significantly higher mixed venous, coronary venous, and local tissue pO2
on
liver and skeletal muscle. CONCLUSION: Bolus intravenous administration
of
60-percent (wt/vol) perflubron emulsion and further hemodilution from a
Hb
of 7 g per dL to one of 3 g per dL were as effective as autologous RBC
transfusion in maintaining tissue oxygenation during volume-compensated
blood loss designed to mimic surgical bleeding.
USE IN CARDIAC IMAGING
Intravenous perfluoropropane-exposed sonicated dextrose albumin produces
myocardial ultrasound contrast that correlates with coronary blood flow.
SO Journal of the American Society of Echocardiography. 8(5 Pt 1):710-8,
1995
Sep-Oct.
AB If microbubble gas blood solubility and diffusivity are reduced, the
persistence (and hence ultrasound reflectivity) of the microbubble in
blood
is prolonged. Recently we have sonicated a multifold dilution of human
albumin with 5% dextrose while exposed to gases of low blood solubility
and
diffusivity and produced microbubbles that consistently opacify the
myocardium after intravenous injection. The objective of this study was
to
test the hypothesis that a gas with very low diffusivity,
perfluoropropane,
when introduced into dextrose albumin during sonication, would produce
visually evident myocardial ultrasound contrast after intravenous
injection
compared to sonicating with gases that have more rapid diffusivity.
Second,
we sought to determine whether the degree of contrast (peak myocardial
videointensity) achieved with this agent would correlate with coronary
blood flow. In eight open-chest dogs, intravenous injections of dextrose
albumin sonicated with either room air, sulfur hexafluoride, or
perfluoropropane (PESDA) were given under baseline conditions. PESDA
injections were repeated when coronary flow was increased during
low-dose
dobutamine infusion. Left anterior descending coronary blood flow was
monitored with transit-time flow probe. Background-subtracted anterior
myocardial peak videointensity was measured after each injection.
Visible
myocardial opacification was seen in 100% of the 0.04 to 0.08 ml/kg
intravenous injections of PESDA. No significant myocardial contrast was
observed with the same doses of intravenous room air- or sulfur
hexafluoride-exposed sonicated dextrose albumin. There was a strong
correlation between left anterior descending coronary artery flow (range
17
to 96 ml/min) and myocardial peak videointensity (r = 0.75; p < 0.0001)
in
all dogs. We conclude that intravenous injections of PESDA can safely
produce consistent myocardial ultrasound contrast. the peak
videointensity
produced correlates with changes in coronary blood flow. Therefore this
agent could be used to quantify coronary blood flow noninvasively
USES IN BYPASS SURGERY TO IMPROVE BRAIN OXYGENATION
Changes in brain pH, PO2, PCO2, cerebral blood flow, and blood gases
induced by a hyperosmolar oxyreplete hemosubstitute during
cardiopulmonary
bypass.
SO ASAIO Journal. 43(1):13-8, 1997 Jan-Feb.
AB Eleven goats (mean weight, 69 +/- 16 kg) underwent 5 hrs of
normothermic
nonpulsatile cardiopulmonary bypass (CPB) using as priming fluid either
a
Ringer's based crystalloid priming solution (CP, n = 5) of a
hyperosmolar
oxyreplete hemosubstitute (HS, n = 6). The HS contained 20% w/v
perfluorocarbon (perfluorodecalin), its osmolarity was 800-900 mOsm/1,
and
the administered dose of perfluorocarbon was 30-50 ml/kg. Otherwise, the
experimental procedure was identical for both groups. PaCO2 was
maintained
above 35 mmHg and blood flow rate at 65 ml/kg. Brain tissue pH, PO2, and
PCO2, cerebral blood flow (CBF), arterial and venous blood gases, and
other
systemic variables were monitored. During CPB, PVO2 and brain tissue PO2
were increased significantly in the HS group. The CBF per kilogram of
weight also was significantly higher in the HS group. Metabolic acidosis
developed in both groups and, surprisingly, brain tissue pH and pHV were
lower in the HS group. The mean values of PVCO2 and brain tissue PCO2
indicate that brain tissue hypercapnia also occurred in both groups. The
HS
provided long-term stability and compatibility with electrolytes, and
did
not cause major complications or allergic reactions during CPB.
Perfluorocarbon based HSs improve tissue oxygenation, eliminate the risk
of
infection due to homologous transfusions, do not require blood type
matching, have a shelf life longer than that of blood, and, therefore,
they
can be an important factor in diminishing the incidence of complications
after CPB.
ANOTHER ONE:
Enhancement of brain p0(2) during cardiopulmonary bypass using a
hyperosmolar oxygen carrying solution.
SO Artificial Cells, Blood Substitutes, & Immobilization Biotechnology.
25(3):297-308, 1997 May.
AB During the past decade a new syndrome has been recognized: cerebral
hypoxia
secondary to cardiopulmonary bypass, resulting in impairment of
cognitive
memory. The incidence of the syndrome appears to be no less that 30% in
patients over 65 years of age undergoing cardiac surgery. There are
several
factors contributing to hypoxia produced by cardiopulmonary bypass. One
of
these factors is crystalloid pump prime and replacement solutions devoid
of
1) oxygen carrying capacity and (2) devoid of protein and its colloid
osmotic pressure. This shortcoming of cardiopulmonary crystalloid
solutions
is partially responsible for two of the three major pathologic effects
of
cardiopulmonary bypass: (1) hypoxia (2) interstitial fluid accumulation
(anasarca, water-logging, edema). This report describes an oxygen
carrying
hyperosmolar solution which enhances brain p0(2) and diminishes
interstitial fluid accumulation. This blood substitute consists of
perfluorcarbons and saccharides, but could consist of a hemoglobin
variant
plus hyperosmolar ingredients other than saccharides. The advantage of a
perfluorochemical is its ability to access small channels and to be
centrifuged off the patient post-operatively with a cell saver. The
advantage of saccharides is that they can be metabolized by the patient
for
energy, and they produce a moderate diuresis coming off bypass.
This should alleviate some fears about this product and demonstrate the
incredible potential of SGNC.
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