ACIM October 2015 ~ Orlando Tom Butler, MSOm Mark Squibb, CEO Dr. Angelique Hart, MD

1. Protocols for Brain Oxygenation & Cognitive Recovery ACIM October 2015 ~ OrlandoTom Butler, MSOmMark Squibb, CEO Dr. Angelique Hart, MD

2. Tom Butler, MSOM

3. perspective Current events might indicate society is largely approaching Healthcare backwards Equivalent to talking about how pedestrians keep getting in the way of automobiles Suggest that health-creation is approached from a perspective that gives the right of way to the pedestrians Taking a whole body approach to most health issues, especially, brain health, can revolutionize health practice, medicine and research Good science is also helpful.

4. omst via Dr. von Ardenne positive feedback loop reversible switching prioritized oxygen usage across the organ systems dissolved oxygen in plasma to 4x normal is where the therapeutic benefits live

7. specialized roles vessels of the same caliber in different organs are as different as the organ parenchymal cells through which they course  micro vascular bed components and the tissues they perfuse are designed to meet the special needs of different organs and even unique neighborhoods within organs

9. basic dis-function (1) Blood Micro Circulation • NEED Diagram Page 7 OMST book The Endothelial Cell ( micro switch ) Reduced blood flow (< pO2 -ven reduced ) Increased viscosity ( patterns of blood stasis and stagnation ) H20 flows into the cells as a result of K+/Na+ pump (inflammation / edema of tissues )

10. Organ Prioritization • Diagram page 12 OMST book

11. blood

12. blood patterns stasis stagnation blood cracking loss of glutathione with age protein degradation

13. oxygen delivery • three modes • Red Blood Cells ( RBC ~ 98%) • Plasma • RBC water Oxygen has a low solubility (CO competes) Hemoglobin ~ 200 different structures Primary Hemoglobin A Variants have different O2 binding properties

14. shift to the left (hemoglobin)

15. dissolved fraction (plasma)

16. priorityclasses • pO2-ven resting (mmHg) normal 30 yrs • Heart ~22 • Lower Ext ~ 28 • Brain ~ 33 • Upper Ext ~ 35 • Liver ~ 40 • Stomach/GI ~ 48 • Skin ~ 50 • Kidney ~ 62 • Spleen ~ 68 What will override auto-regulation and trigger vasodilation?

17. bioenergy production aerobic respiration “with air” Glucose + Oxygen  > Carbon dioxide + Water + Energy C6H12O6 + 6O2>   6CO2 + 6H2O + 2900 kJ/mol creates ~ 38-34 atp molecules / glucose only net positive energy production availabe in body anaerobic respiration “without air” Glucose   >    Lactic acid + Energy C6H12O6>   2C3H6O3 + 120 kJ/mol creates ~ 2 atp molecules / glucose not net positive ( lactic acid conversion -6 atp )

18. How is gene activation related to bioenergy?

19. bioenergy cascade protein folding consumes 2/3 of cellular ATP by ER protein quality control failure degradation of blood brain barrier unfolded protein response overwhelm accumulation & aggregation of mis-folded proteins is the hallmark of most neurodegenerative diseases

20. mircobiota Of 254 reference genomes, only 29 genomes (11%) are aerophilic, 111 (44%) are microaerophilic, and 115 (45%) are anaerobic. symbiotic • aerobic ( 55 % ) pathogenic • anaerobic ( 45 % ) The details of the annotated respiratory reductases are captured as a subsystem “Respiration HGM”.

21. the basic protocol whole body oxygenation basic liveO2 protocol ~increased dissolved oxygen in plasma ~left shift affinity for hemoglobin binding to oxygen ~increase partial pressure

22. functionality support of the whole is the basis of supporting Neuroregeneration. foundations oxygenation fluid balance nutrition

23. Mark Squibb, CEO

24. cerebral hemodynamics the brain uses 20% of available oxygen for normal function1 Radius is the most powerful determinant of coordinated blood flow2 keys to breakthrough auto regulation cardiac output 3 altitude ( O2-) Co2 NO arterial blood pressure 4

25. systemic circuit flow

26. cbf normal The human brain represents approximately 2% of total body weight, yet it receives approximately 20% of cardiac output and uses 20% of total body oxygen consumed under normal conditions. In this situation, most of the energy of the brain is obtained exclusively from aerobic metabolic process. Impairment in the supply of nutrients and oxygen to the brain can cause cellular damage. CBF varies directly with cerebral perfusion pressure (CPP), which is defined as the difference between mean arterial and intracranial pressures, and inversely with cerebrovascular resistance (the sum of vascular resistance to flow, particularly at the level of the small pial arteries and penetrating pre-capillary arterioles). The contribution of any given cerebral vessel to overall CBF is defined by factors, such as its radius and length, and both blood viscosity and pressure.

27. cbf regulation Cerebral or pressure auto-regulation is the inherent ability of blood vessels to keep CBF relatively constant over a wide range of arterial blood pressure (ABP) levels by the interplay of numerous physiological mechanisms. A sudden change in mean ABP leads to a simultaneous change in CBF initially, but it also triggers a number of other responses. For instance, ABP augmentation produces dilatation of cerebral arteries, which leads to a chain of events: changes in smooth muscle ionic permeability, muscle contraction, vessel narrowing, and increase in cerebrovascular resistance (myogenic mechanism). Concomitantly, CBF elevation due to ABP augmentation causes both increase in tissue O2 and decrease in the concentration of CO2 and other products of cerebral metabolism. In the absence of greater demand for O2, a complex sequence of events restores the balance between O2 supply and demand by means of vasoconstriction mediated by activation of nitric oxide (NO) and other metabolites in the arterial endothelium (metabolic mechanism). Recently, sympathetic neural control has been implicated as one of the mechanisms of cerebral auto-regulation (neurogenic mechanism)1.

29. CBF and ABP with increasing PE

30. cardiac output There is a linear relationship between CBF velocity and cardiac output at rest and during exercise1. Interestingly, decreased CBF velocity was confirmed even though mean arterial pressure was increased. This is possible due to the fact that the lowering of cardiac output can be accompanied by increases in arterial pressure. Therefore, in clinical practice, blood pressure augmentation may not necessarily imply an associated increase in CBF2. The dependence of CBF on cardiac output is also seen in cardiac patients, in which decreased cerebral oxygenation during exercise can be noted in cardiac patients with decreased perfusion as a result of compromised cardiac output3.

31. high altitude The mechanisms underlying the regulation of CBF during acute exposure to high altitude are complex and depend partly on the degree of hypoxic stimulus and on the cerebrovascular sensitivity to hypoxia and CO21. Neurological disorders associated with altitude have an intimate relationship with disturbances of cerebrovascular regulation due to high altitude and with the process of acclimatization. Subjects exposed to hypoxia at high altitudes develop an increase in steady-state CBF velocity associated with impairment of cerebral autoregulation2. Note: patients with intracranial hematomas or some degree of brain swelling, irrespective of etiology, can develop or experience worsening intracranial hypertension when adapting through acute hypoxic events3.

32. inflammation in the brain creates cellular noise that interferes with information processing excitatory chemicals created by glial cells neglected house keeping irritation of excitotoxicity reinforces pattern

33. tuning a brain with cell health problems will get detuned very easily healthy brain has the best chance of being optimally tuned electrically worse brain cell health: more noise + static + less signal = poor bandwidth Can an adaptive response break or shift the pathology?

34. balance the brain can be physically displaced by trauma even subtle displacement can interfere with fluid circulation and nerve supply, and subtle brain movements associated with health

35. network synchronization when different parts of the brain oscillate together at the same frequencies, this gets information transferred synchronization is not just a function of hardware (like neuronal cables) but also of waves that move rapidly across the brain Are adaptation events capable of resetting normal Oscillatory patterns and Synchronization of the Neural-networks?

36. premises The brain has a high metabolic demand for oxygen. Acute hypoxia triggers dilation of cerebral microcirculation and increase in CBF In general, CBF does not change substantially until tissue PO2 falls below 50 mmHg1. As hypoxia decreases PO2 further, CBF can rise to 400% of resting levels2. Acute hypoxia can cause an increase in the CBF by means of direct effects on cerebral arterioles. A hypoxia-induced decrease in ATP levels opens KATP channels in arteriole smooth muscle inducing hyperpolarization and vasodilation. Moreover, hypoxia rapidly increases NO and adenosine production resulting in vasodilation3

37. cognitive case 1 • Patient History      Physiological systems model      Condition(s) & Symptoms      Quality of Life Improvement      Initial versus final      Speed of change      Opinion of durability & maintenance      Role of LiveO2 in change      Generalization     Clinical Results      Blood Tests      Other before/after testing Protocol      Body Systems targeted by protocol Protocol element list      Reason for each      Relationships      Roles of LiveO2 – reasons      Anti- Inflammatory?      Hypoxic region?      Immunological?      Low energy tissues?      Detox catalyst? Efficacy Model      Animated view of effect of therapy combination      Affected tissues      Energetic dysfunction      Immune, etc.      How LiveO2 oxygen catalyzes recovery      Inflammatory inhibitor      Regional hypoxia inhibitor Doctor: What went wrong      Did oxygen-deficiency in enable pathology      Was there a stress event?      Was there a probable systems failure process?      Will avoidance of hypoxia improve prognosis?      Usage Recommendation for Patient      Daily, etc.      Intensity  Why/how does doctor feel Live O2 will help this patient in the future      Optimize      Doctors opinion on quality of life with vs without Live 02

38. cognitive case 2 • Patient History      Physiological systems model      Condition(s) & Symptoms      Quality of Life Improvement      Initial versus final      Speed of change      Opinion of durability & maintenance      Role of LiveO2 in change      Generalization     Clinical Results      Blood Tests      Other before/after testing Protocol      Body Systems targeted by protocol Protocol element list      Reason for each      Relationships      Roles of LiveO2 – reasons      Anti- Inflammatory?      Hypoxic region?      Immunological?      Low energy tissues?      Detox catalyst? Efficacy Model      Animated view of effect of therapy combination      Affected tissues      Energetic dysfunction      Immune, etc.      How LiveO2 oxygen catalyzes recovery      Inflammatory inhibitor      Regional hypoxia inhibitor Doctor: What went wrong      Did oxygen-deficiency in enable pathology      Was there a stress event?      Was there a probable systems failure process?      Will avoidance of hypoxia improve prognosis?      Usage Recommendation for Patient      Daily, etc.      Intensity  Why/how does doctor feel Live O2 will help this patient in the future      Optimize      Doctors opinion on quality of life with vs without Live 02

39. adaptive protocol adaptive training keys artifacts of being in the zone

40. Angelique Hart, MD

41. Case Study A      Patient History      Physiological systems model      Condition(s) & Symptoms      Quality of Life Improvement      Initial versus final      Speed of change      Opinion of durability & maintenance      Role of LiveO2 in change      Generalization Clinical Results      Blood Tests      Other before/after testing Protocol      Body Systems targeted by protocol Protocol element list      Reason for each      Relationships      Roles of LiveO2 – reasons      Anti- Inflammatory?      Hypoxic region?      Immunological?      Low energy tissues?      Detox catalyst? Efficacy Model      Animated view of effect of therapy combination      Affected tissues      Energetic dysfunction      Immune, etc.      How LiveO2 oxygen catalyzes recovery      Inflammatory inhibitor      Regional hypoxia inhibitor Doctor: What went wrong      Did oxygen-deficiency in enable pathology      Was there a stress event?      Was there a probable systems failure process?      Will avoidance of hypoxia improve prognosis?      Usage Recommendation for Patient      Daily, etc.      Intensity  Why/how does doctor feel Live O2 will help this patient in the future      Optimize      Doctors opinion on quality of life with vs without Live 02

42. Case Study B Patient History      Physiological systems model      Condition(s) & Symptoms      Quality of Life Improvement      Initial versus final      Speed of change      Opinion of durability & maintenance      Role of LiveO2 in change      Generalization     Clinical Results      Blood Tests      Other before/after testing Protocol      Body Systems targeted by protocol Protocol element list      Reason for each      Relationships      Roles of LiveO2 – reasons      Anti- Inflammatory?      Hypoxic region?      Immunological?      Low energy tissues?      Detox catalyst? Efficacy Model      Animated view of effect of therapy combination      Affected tissues      Energetic dysfunction      Immune, etc.      How LiveO2 oxygen catalyzes recovery      Inflammatory inhibitor      Regional hypoxia inhibitor Doctor: What went wrong      Did oxygen-deficiency in enable pathology      Was there a stress event?      Was there a probable systems failure process?      Will avoidance of hypoxia improve prognosis?      Usage Recommendation for Patient      Daily, etc.      Intensity  Why/how does doctor feel Live O2 will help this patient in the future      Optimize      Doctors opinion on quality of life with vs without Live 02

43. clinical protocols

44. #1takeaway ”obstruction of capacities rather than impairment” re-balance

45. questions Thank you for attending. Demonstrations and Trainings are available at the LiveO2 booth. Contact information: LiveO2.com 970-372-4344 tom@whnlive.com