1. Topical Oxygen Therapy
Gayle Gordillo, M.D.
Assistant Professor
Division of Plastic Surgery and
The Comprehensive Wound Center
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2. Overview Review significance of wound tissue oxygenation
Identify determinants of wound tissue oxygenation
Demonstrate TO enhancement of wound tissue oxygenation
Report TO clinical outcomes
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3. All wounds are hypoxic
45-60 mm Hg
0-10 mm Hg
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4. 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
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5. 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
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6. Determinants of Oxygen Availability
Wound pO2 determined by
Arterial pO2
Diffusion distance
Blood flow rate
rate of O2 consumption
Local perfusion a predominant factor
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7. 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
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8. Why Topical Oxygen? Large potential patient population Low risk
Convenient patient use
Good scientific evidence to support the concept
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9. Topical Oxygen Administered at 1.03 ATM Used at home
90 min treatment intervals that are cycled 4 days on and 3 days off
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10. 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:
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11. 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
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12. Topical oxygen increases wound pO2
real-time pO2 measurement
(mmHg) 20 40 60 80
100
120
O2 treatment
begin 1 2 3 4
time (minutes)
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13. Topical oxygen promotes wound closure
days after wounding 5 10 15 20 25
(% of original wound)
wound closure 40 60 80
100
120
140
160 * **
Day 0
Day 4
Day 10
Day 23 A B
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14. Skin histology in response to TO treatment – day 22
Control G A B
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control
oxygen treated 14

15. Angiogenic responses A C * B A = VEGF day 7 B = SMA day 15
C = pO2 day 22
control
oxygen treated A B 5 6 C
pO2 (mmHg) *
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16. Conclusions – topical oxygen
Increases wound tissue pO2
Promotes new blood vessel formation in wounded tissues
favorable wound epithelialization structures
Significantly improved wound closure rates
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17. Clinical & Experimental Pharmacology & Physiology
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): )
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18. Objective
Identify mechanism mediating beneficial effects of TO in promoting wound healing
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19. 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)
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20. 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
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21. Results – TO VEGF
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22. Scatter plot analysis of VEGF expression in TO patients54 63 52 46 58 50 47 68 64 55 53 40 48 67
numbers indicate patient age
Topical
Oxygen
.05 .1 .2 .5 1 2 5 10 20
VEGF Ratio (T1:T0) a
VEGF Ratio (T2:T1)
.01
.025
.25
2.5 b 60
VEGF Ratio (T2:T0)
Wound Volume Ratio (T2:T0) c
Scatter plot analysis of VEGF expression in TO patients
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23. Topical oxygen as an adjunct to wound healing: a clinical case series
Kalliainen LK, Gordillo GM, Schlanger R, Sen CK Pathophysiology 2003; 9:
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27. Patient Outcomes A Total # patients = 32 Total # wounds = 58 E D C B
healed top O2 only (n=38)
did not heal (n=11)
lost to follow up (n=2)
died during tx (n=3)
healed top O2 + surg (n=4)
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28. 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
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29. 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
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30. Acknowledgements Chandan Sen, Ph.D Sashwati Roy, Ph.D
Savita Khanna, Ph.D
Gary Phillips, MS
Lynn Lambert, RT
Richard Schlanger, MD, PhD
Samantha Bellamy, RN
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