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Tissue Oxygenation

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Tissue Oxygenation Powered By Docstoc
					Topical Oxygen Therapy
          Gayle Gordillo, M.D.
          Assistant Professor
    Division of Plastic Surgery and
  The Comprehensive Wound Center
              Overview
• Review significance of wound tissue
  oxygenation
• Identify determinants of wound tissue
  oxygenation
• Demonstrate TO enhancement of wound
  tissue oxygenation
• Report TO clinical outcomes
All wounds are hypoxic

       45-60 mm Hg



        0-10 mm Hg
    Oxygen Promotes healing
• Collagen synthesis
  – Positive correlation between wound pO2 and collagen
    deposition demonstrated
  – Wound strength determined by collagen cross-linking
• Angiogenesis
  – Stimulates VEGF expression in wound macrophages
  – upregulates PDGF-B receptor expression
     Oxygen promotes healing

• Resistance to infection
  – Oxygen as a rate-limiting substrate for
    NADPH oxidase
  – Km= 75 mmHg
  – Loss of oxidative burst pO2 < 20mmHg
  – ischemic wounds more susceptible
     Determinants of Oxygen
           Availability

• Wound pO2 determined by
  – Arterial pO2
  – Diffusion distance
  – Blood flow rate
  – rate of O2 consumption
• Local perfusion a predominant factor
 Optimizing Oxygen Availability
• Avoid vasoconstriction
  –   body temperature
  –   intravascular volume
  –   pain
  –   anxiety
  –   Smoking
• Decrease diffusion distance
  – Decrease peripheral edema
  – Debride wound surface
  – Avoid petrolatum based dressings
      Why Topical Oxygen?
• Large potential patient population
• Low risk
• Convenient patient use
• Good scientific evidence to support
  the concept
          Topical Oxygen
• Administered at 1.03 ATM

• Used at home

• 90 min treatment intervals that are
  cycled 4 days on and 3 days off
Topical Oxygen Increases
  Wound Oxygenation
Fries R, Wallace WA, Roy S, Kuppusamy P,
Bergdall V, Gordillo G, Melvin WS, Sen CK,
  Mutation Research 2005; 579:172-81.
Pre-clinical Wound Healing
           Model
                • 2 sets 5 wounds –
                  dermal excisional
                  1x1 inch
                • 5 wounds -topical
                  O2 3 hours x 7days
                • 5 wounds – room
                  air only
Topical oxygen increases
      wound pO2
                                120


    real-time pO2 measurement
                                100

              (mmHg)            80
                                60

                                40
                                      O2 treatment
                                20       begin

                                 0       1      2      3      4

                                             time (minutes)
Topical oxygen promotes
     wound closure
                *
                         A
  160
        B           **
            *
  140
                                 Day 0       Day 23
  120                                Day 4            Day 10
                             *
  100
  80
                                    **
  60                                         **

  40                                                  **

  20
   0
       0            5      10        15      20                25
                         days after wounding
Skin histology in response to
     TO treatment – day 22
  A Control




                    G            G


  B


                             G

                    G


          control       oxygen treated
      Angiogenic responses
    A = VEGF day 7   B = SMA day 15        C = pO2 day 22

A
                                       C   50 pO2 (mmHg)
                                                           *
                                           40


                                           30


                                           20
B
                                           10


                                           0    control treated
                                                5     6




        control       oxygen treated
  Conclusions – topical oxygen
• Increases wound tissue pO2
• Promotes new blood vessel formation in
  wounded tissues
• favorable wound epithelialization
  structures
• Significantly improved wound closure rates
Topical Oxygen Therapy Induces Vascular
 Endothelial Growth Factor Expression &
  Improves Closure of Chronic Wounds
  Gayle Gordillo, Sashwati Roy, Savita Khanna,
  Richard Schlanger, Sorabh Khandelwal, Gary
          Phillips and Chandan K Sen
   Clinical & Experimental Pharmacology & Physiology
                    (2008; 35(8):957-964)
               Objective
• Identify mechanism mediating beneficial
  effects of TO in promoting wound healing
                Study Design
• Each patient serves as own control
• All wounds O2 naive
• Wound tissue biopsy taken immediately prior
  and immediately after completion of oxygen
  treatment at 3 different time points (6 biopsies)
   – T0 day of 1st O2 tx = baseline
   – T1 50% closure (TO) or 50% tx completed (HBO)
   – T2 < 1 cm2 wound area (TO) or 14 weeks, last tx
     (HBO)
             Study Design
• Tissue samples analyzed using real-time PCR
  for change in expression of VEGF
• Difference between pre-treatment levels
  (baseline =1) and post-treatment levels of
  mRNA quantitated by real-time PCR – generates
  fold change per patient
• Wound measurements
• Demographic data
• Wound healing outcomes
Results – TO VEGF
                           a 20            63
                                                                                             Topical

VEGF Ratio (T1:T0)
                             10
                                                                                     55
                              5                          52
                                                                                   64        Oxygen
                                                               58
                                                                         47         53                        Scatter plot analysis of
                              2
                                                               54
                              1
                                                                              68
                                                                                    40           54
                                                                                                         67   VEGF expression in TO
                                          54
                             .5
                                                               50                                             patients
                             .2
                                                              46
                             .1
                            .05     numbers indicate patient age
                                                                                               48

                           b 20
      VEGF Ratio (T2:T1)




                             10                               46

                              5                                                                  54
                                                               50
                                          54                                         53        48
                              2                                                                          67
                                                                         47
                              1                                                      40
                             .5                                                    64
                                                         52
                             .2
                             .1
                            .05
                           c 20 .01      .025 .05    .1            .25        .5         1     2.5       5
    VEGF Ratio (T2:T0)




                             10
                                                                                     53
                              5                                                                     54
                                                                         47        64                    67
                              2                           46
                                          54        52             50                   40
                              1                                               60

                             .5

                             .2
                             .1                                                                 48
                            .05
                                  .01    .025 .05    .1            .25        .5         1     2.5       5

                                        Wound Volume Ratio (T2:T0)
  Topical oxygen as an adjunct to
wound healing: a clinical case series
   Kalliainen LK, Gordillo GM, Schlanger
   R, Sen CK Pathophysiology 2003; 9:
                   81-87.
           Patient Outcomes
  Total # patients = 32
  Total # wounds = 58
                                A

a) healed top O2 only (n=38)             E
b) did not heal (n=11)                  D
c) lost to follow up (n=2)          C
                                B
d) died during tx (n=3)
e) healed top O2 + surg (n=4)
     TO case series - conclusions
•   No reported adverse effects to top O2 tx
•   75% overall healing rate achieved
•   Average length of tx time = 10 weeks
•   Upper ext & trunk wounds most responsive
•   Decubiti & neuropathic ulcers least responsive
•   Size matters
                Summary
• Oxygen is a critical requirement for wound
  healing
• Supplemental oxygen administration can
  improve wound outcomes
• TO can increase wound tissue oxygenation
• TO promotes angiogenesis through increased
  expression of VEGF in healing wounds
           Acknowledgements
•   Chandan Sen, Ph.D     • Lynn Lambert, RT
•   Sashwati Roy, Ph.D    • Richard Schlanger,
•   Savita Khanna, Ph.D     MD, PhD
•   Gary Phillips, MS     • Samantha Bellamy,
                            RN

				
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