Artificial blood

artificial blood

1. Shailesh kumar sahu ARTIFICIAL BLOOD

2. 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 .

3. 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…

4. Why artificial blood? Increasing demand Decreasing supply Safety Infectious disease transmission Transfusion reactions Immunosuppression Cost

5. Ideal Characteristics of Artificial Blood Safe to use Compatible in the human body Able to transport and release oxygen where needed Storable and durable for longer time periods free of pathogens and toxins Viscosity similar to blood Low cost

6. Blood Substitute O2 Carriers Lack coagulation Immune function Nutrition Plasma protiens HB Solutions PFC

7. 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.

8. 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 )

9. Perfluorocarbons (PFC) emulsions Structure: Perfluorocarbon core Surrounded by a phospholipid surfactant that reduces the surface tension of the liquid in which it is dissolved .

10. PFC Synthetic organic liquid compounds 8-10 carbon atoms H+ atoms Halogens ! st Generation Fluosol 20% Stored Frozen Limited O2 carrying capacity. Allergic reaction 2 nd Generation Oxygent 90% Stored at 4’c High O2 Carrynig capacity

11. 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.

12. Second generation perfluorocarbon large oxygen dissolving capacity Faster excretion (4 days) and less tissue retention Lack of significant side effects e.g Perfluorooctyl bromide( Oxygent ) Bisperfluorobutyl ethylene Oxygent can deliver upto 1.3 ml oxygen per 100 ml.

13. 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

14. 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

15. Adverse Effects Of PFC Allergy Especially 1 st Gen Bleeding Tendency Decrease Plt Count Increase Liver Enzymes Acute Rt sided heart Failure Pulmonary edema Early: Headache Late: Flu like symptoms

16. 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.

17. HB Tetramer Monomers Dimers Filtered by the kidney NO scavenger Increase plasma osmotic pressure High O2 affinity Ultrastructural modification 2. Artificial Blood Cells HB Solutions

18. 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.

19. Cross linking ( diaspirin ) Conjugation ( Albumin,PEG ) Polymerization Microspheres ( Dendrimer,Polymersome ) Recombinant DNA technology Monomers and Dimers Ultrastructural modification Tetramers Ultra purification

20. 2. Artificial Blood Cells Liposomes = Pseudoerythrocyte Nanocapsules Encapsulated Hb in cell like structure Coated with Phospholipid Bilayer and Cholesterol Coated with Polylactide

21. PRODUCTION OF HBOCs Synthetically produced Hb:E.coli ( P678-54 ) Isolated Hb:human or animal blood(bovine blood)

22. Current Hb -based oxygen carriers

23. Adverse Effects Of Hb Solutions Immunsuppression Decreased phagocytic activity Nephrotoxicity Coagulopathy Free radicals Vasoconstriction NO inactivation Endothelins Neurotoxicity Lab Interference

24. Advantages Available in much larger quantities Can be stored for long durations. Can be administered rapidly without typing or cross-matching Can be sterilized via pasteurization Disadvantages reduced circulation half-life disrupts certain physiological structures, especially the gastrointestinal tract. the release of free radicals into the body

25. Higher O2 Solubility Coefficient. V. low viscosity High Density High N2 Solubility Inactivate NO Resuscitation Periop hemodilution Organ preservation Sickle crisis Alveolar recruitment Liquid ventilation Decompression sickness Septic shock

26. Potential clinical applications 1. Therapeutic (a) Blood substitutes : hemorrhagic shock; hemorrhage (war, surgery); anaemia. (b) Whole-body rinse out : acute drug intoxication; acute hepatic failure. (c) Local ischemia : acute MI; evolving MI; cardiac failure; brain infarction; acute arterial thrombosis and embolism; PTCA of coronary artery. (d) General ischemia : CO intoxication.

27. (e) Aid for organ recovery : acute renal failure; acute hepatic failure;acute pancreatitis . (f) Adjuvant therapy : radiotherapy; chemotherapy 2. Perfusional protection of organs during surgery – cardiopulmonary bypass 3. Preservation of donor organ. 4. Drug carrier - drug-conjugated haemoglobin and perfluorochemicals . 5. Contrast agent - ( Perfluoro-octylbromide )

28. Non-Clinical Applications 1. Culture medium 2. Chemical examination - oxygen sensor; standard solution for oxygen calibrator 3. Bioreactor P aradoxical Utilisations (of high-oxygen affinity) 1. Oxygen absorbent 2. Oxygen pulse therapy for malignant tumour in combination with radiotherapy or chemotherapy.

29. 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.

30. Thank you