SHAILESH KUMAR SAHU

ARTIFICIAL BLOOD

Artificial Blood

Artificial blood or blood surrogate is a substance used to mimic and fulfil some functions of biological blood,usually in the oxygen carrying sense.

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 WBCs.

The History of Artificial Blood

Milk was one of the first substances used as a blood substitute in order to treat patients with Asiatic cholera.

After several patients died by receiving milk transfusions, other substances were discovered as potentials :• Salt or saline solutions: used primarily as a plasma volume expander,

rather than as artificial blood• Hemoglobin isolated from red blood cells• Animal plasma could be used as a substitute for human blood.However,

since many of the materials in animal plasma are toxic to humans, this posed a problem to using it as a substitute

The problem of not having a workable substitute led to Ringer’s Solution…

Why artificial blood?

Increasing demandDecreasing supplySafety Infectious disease transmission Transfusion reactions ImmunosuppressionCost

Ideal Characteristics of Artificial Blood

Safe to useCompatible in the human bodyAble to transport and release oxygen where

neededStorable and durable for longer time periods free of pathogens and toxins Viscosity similar to bloodLow cost

Blood Substitute

O2 Carriers

Lack coagulation

Immune functionNutrition

Plasma protiens

HB Solutions PFC

Perfluorocarbons

These are chemically and biologically inert,water insoluble,synthetic aromatic or aliphatic compounds with F substituted for all H atoms of hydrocarbon.

water insoluble:so used as emulsion with Puronic-68,egg yolk phospholipids and triglycerides as emulsifying agent.

They achieve O2 delivery by using organic chemicals with high gas solubility.

The O2 carrying capacity of PFCs is linearly related to PO2 and obeys Henry’s law.

Short half life(2-4hr):eliminated from body unmetabolised through the lungs.

Process of production: Water, salts, and phospholipids

surfactant,antibiotics,vitamins,nutrients are added and emulsified through high-pressure homogenization

Purified through high temperatures of steam. Common PFCs:Perfluorodecalin Perfluorooctyl bromide(oxygent)

Perfluorocarbons (PFC) emulsionsStructure:

Perfluorocarbon core Surrounded by a phospholipid surfactant that reduces the surface tension of the liquid in which it is dissolved.

PFC

Synthetic organic liquid compounds

8-10 carbon atomsH+ atoms Halogens

!st GenerationFluosol 20%

•Stored Frozen•Limited O2 carrying capacity.Allergic reaction

!st GenerationFluosol 20%

•Stored Frozen•Limited O2 carrying capacity.Allergic reaction

2nd GenerationOxygent 90%

•Stored at 4’c•High O2 Carrynig capacity

2nd GenerationOxygent 90%

•Stored at 4’c•High O2 Carrynig capacity

First generation perfluorocarbon

FLUOSOL-DA20%-It consists of two PFCs, perfluorodecalin (PFD) and perfluorotrypropylamine (FTPA) and Pluronic F-68, as an emulsifying agent, and is able to maintain a balance between the oxygen carrying capacity and tissue retention.

It can deliver 0.4ml oxygen per 100ml.

Second generation perfluorocarbon

large oxygen dissolving capacityFaster excretion (4 days) and less tissue retentionLack of significant side effectse.g Perfluorooctyl bromide(Oxygent) Bisperfluorobutyl ethyleneOxygent can deliver upto 1.3 ml oxygen per 100 ml.

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 symptomsunable 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

Adverse EffectsOf PFC

AllergyEspecially 1st Gen

Bleeding TendencyDecrease Plt Count

Increase Liver

Enzymes

•Acute Rt sided heart Failure •Pulmonary edema

•Early: Headache

•Late: Flu like symptoms

Hemoglobin-based Oxygen Carriers (HBOCs)

Hemoglobin-based Oxygen Carriers were created as a mechanism to mimic the oxygen-carrying role of hemoglobin in the body, while still reducing the need for real human hemoglobin. Hemoglobin:a tetramer with two alpha and two beta polypeptide

chains; each is bound to an iron heme group which successively binds to an oxygen molecule.it has a higher affinity for oxygen, thus making it an excellent source of blood substitutes.

HBTetramer

Monomers Dimers

1. Filtered by the kidney2.NO scavenger3.Increase plasma osmotic

pressure4.High O2 affinity

1. Ultrastructural modification

2. Artificial Blood Cells

HB Solutions

To avoid such spontaneous dissociation native Hb is modified by intramolecular cross-linking between alpha and beta Chains, polymerization, pyridoxylation, or conjugation to larger molecules, such as albumin or polyethyleneglycol ("pegylation"),encapsulation of hemoglobin into a liposome or polymer structure.

Cross linking(diaspirin)

Conjugation(Albumin,PEG)

Polymerization

Microspheres(Dendrimer,Polym

ersome)

Recombinant DNA

technology

Monomers and Dimers

1. Ultrastructural modification

Tetramers

Ultra purification

2. Artificial Blood Cells

Liposomes=

Pseudoerythrocyte

Nanocapsules

Encapsulated Hb in cell like structure

Coated withPhospholipid Bilayer and Cholesterol

Coated withPolylactide

PRODUCTION OF HBOCs

Synthetically produced Hb:E.coli(P678-54)

Isolated Hb:human or animal blood(bovine blood)

Current Hb-based oxygen carriers

Adverse EffectsOf Hb

Solutions

ImmunsuppressionDecreased

phagocytic activity

NephrotoxicityCoagulopathy

Free radicals VasoconstrictionNO inactivation

Endothelins

NeurotoxicityLab Interference

AdvantagesAvailable in much larger quantitiesCan be stored for long durations.Can be administered rapidly without typing or cross-matching Can be sterilized via pasteurization

Disadvantagesreduced circulation half-lifedisrupts certain physiological structures, especially the

gastrointestinal tract.the release of free radicals into the body

1. Higher O2 Solubility Coefficient.

2. V. low viscosity

3. High Density

4. High N2 Solubility

5. Inactivate NO

• Resuscitation•Periop hemodilution•Organ preservation

•Sickle crisis

•Alveolar recruitment•Liquid ventilation•Decompression sickness

•Septic shock

Potential clinical applications

1. Therapeutic(a) Blood substitutes : hemorrhagic shock; hemorrhage (war,surgery); anaemia.(b) Whole-body rinse out : acute drug intoxication; acute hepaticfailure.(c) Local ischemia : acute MI; evolving MI; cardiac failure; braininfarction; acute arterial thrombosis and embolism; PTCA ofcoronary artery.(d) General ischemia : CO intoxication.

(e) Aid for organ recovery : acute renal failure; acute hepatic failure;acute pancreatitis.

(f) Adjuvant therapy : radiotherapy; chemotherapy2. Perfusional protection of organs during surgery –

cardiopulmonary bypass3. Preservation of donor organ.4. Drug carrier - drug-conjugated haemoglobin and

perfluorochemicals.5. Contrast agent - (Perfluoro-octylbromide)

Non-Clinical Applications1. Culture medium2. Chemical examination - oxygen sensor; standard

solution for oxygen calibrator3. BioreactorParadoxical Utilisations (of high-oxygen affinity)1. Oxygen absorbent2. Oxygen pulse therapy for malignant tumour in

combination with radiotherapy or chemotherapy.

Conclusion

Artificial blood is a good tool for the survival of patients at the time of surgery when blood loss is higher.

It carries oxygen to tissues and can support life temporarily until patients can either regenerate their own red cells or can be transfused with banked blood.

It can be sterilised against infectious diseases.In short term,the prospective benefits of artificial blood

overshadow the shortcomings.

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