Basic Science applied to medicine

1. Never let your sense of morals get in the way of doing what's right.
-Isaac Asimov
INTRODUCTION
● Alternatives to red blood cell transfusion
● 1800s- hemoglobin solutions were infused experimentally into humans
● Significant morbidity and mortality- nephrotoxic effects of free hemoglobin
● Infectious risks of transfusion
● None licensed by the FDA
● Main aim is to provide an alternative to blood transfusion,which is transferring blood or blood
based products from one person to another.
● It does not contain plasma,RBCs or WB
CHARACTERISTICS OF AN IDEAL OC
●Rapid availability
●Effective oxygen-carrying capacity and provision of volume expansion
●Appropriate physiologic interaction with nitric oxide (NO)
●Free of pathogens, to the extent possible
●Minimal side effects
●Viability over a range of storage temperatures
●Long shelf life
●Universal compatibility and elimination of crossmatching
●Cost effectiveness
●Adequate supply
TYPES OF OCs IN DEVELOPMENT
- Created with love
by Dr. Eashan Srivastava

2. Never let your sense of morals get in the way of doing what's right.
-Isaac Asimov
●Hemoglobin-based oxygen carriers (HBOCs)
●Perfluorocarbons (PFCs)
Hemoglobin-based oxygen carriers
● Derived from two mammalian sources: animal (bovine) and human blood
● Hemoglobin is first separated through ultrafiltration and purification
● Mammalian-derived hemoglobin is then chemically modified - to prevent the dissociation of
hemoglobin from its native four-chain configuration
● Polymerization converts the four-chain hemoglobin moiety into larger two to four hemoglobin
molecule containing polymers.
● Crosslinking of alpha chains prevents dissociation of the hemoglobin molecule into alpha-beta
dimers
● Liposome-encapsulated hemoglobin (LEH)
○ Longer intravascular half-life
○ Freeze-dried storage
○ Significant immunologic reactions
● Hemoglobin has also been produced through recombinant technology
○ Vasoconstriction attributed to scavenging of nitric oxide by the recombinant product
○ Decreased pancreatic perfusion
Perfluorocarbons
● PFCs are inert compounds in which fluorine replaces hydrogen atoms.
● Water insoluble
● Emulsification - egg yolk phospholipid
● Perfluorocarbon core Surrounded by a phospholipid surfactant that reduces the surface tension of
the liquid in which it is dissolved
● Half-life is approximately 12 hours
● Stable for up to two years under refrigeration at approximately 4°C
● PFCs do not carry gases.
● Because of their decreased surface tension and intramolecular action, they act as excellent
solvents and have the capability of absorbing significant amounts of gases
● Their oxygen-carrying capacity is linearly related to the PO2
- Created with love
by Dr. Eashan Srivastava

3. Never let your sense of morals get in the way of doing what's right.
-Isaac Asimov
Advantages of Perfluorocarbons (PFC) emulsions
● do not react with oxygen
● allow easy transportation of the oxygen to the body
● allow increased solubility of oxygen in plasma
● minimize the effects of factors like pH and temperature in blood circulation
Disadvantages
● causes flu-like symptoms
● unable to remain mixed as aqueous solutions –thus, must be prepared as emulsions
● a decrease in blood platelet count.
● PFC products cannot be used by the human body, and must be discarded.this takes approximately
18-24 months.
● because PFCs absorb oxygen passively, patients must breathe at a linear rate to ensure
oxygenation of tissues.
● Require high FiO2
- Created with love
by Dr. Eashan Srivastava

4. Never let your sense of morals get in the way of doing what's right.
-Isaac Asimov
POTENTIAL USES FOR OCs
1. Therapeutic
(a) Blood substitutes : hemorrhagic shock
(b) Whole-body rinse out : acute drug intoxication; acute hepatic failure.
(c) Local ischemia : acute MI; stroke
(d) General ischemia : CO intoxication
2. Perfusional protection of organs during surgery –​​cardiopulmonary bypass
3. Preservation of donor organ.
4.Contrast agent​​ - (Perfluoro-octylbromide)
Non-Clinical Applications
1. Culture medium
2. Chemical examination - oxygen sensor
3. Bioreactor
Paradoxical Utilisations (of high-oxygen affinity)
1. Oxygen absorbent
2. Oxygen pulse therapy for malignant tumour in combination with radiotherapy or chemotherapy
ADVERSE EFFECTS
HBOC-associated side effects
1. Vasoactivity
a. Scavenging of nitric oxide (NO) by hemoglobin
- Created with love
by Dr. Eashan Srivastava

5. Never let your sense of morals get in the way of doing what's right.
-Isaac Asimov
2. Hemostasis
a. Reversal of the inhibitory effect of NO on platelet adhesion and aggregation
3. Gastrointestinal side effects
4. Immunosuppression
5. Interference with laboratory assays
6. Myocardial infarction and death
PFC-associated side effects
1. Flu-like symptoms attributed to cytokine-mediated effects
2. Hepatosplenomegaly and lowering of the peripheral blood platelet count by as much as 40
percent
- Created with love
by Dr. Eashan Srivastava