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Topical Oxygen Therapy Gayle Gordillo, M.D. Assistant Professor Division of Plastic Surgery and The Comprehensive Wound Center.

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Presentation on theme: "Topical Oxygen Therapy Gayle Gordillo, M.D. Assistant Professor Division of Plastic Surgery and The Comprehensive Wound Center."— Presentation transcript:

1 Topical Oxygen Therapy Gayle Gordillo, M.D. Assistant Professor Division of Plastic Surgery and The Comprehensive Wound Center

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

3 All wounds are hypoxic 0-10 mm Hg mm Hg

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

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

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

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

8 Why Topical Oxygen? Large potential patient population Low risk Convenient patient use Good scientific evidence to support the concept

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

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:

11 Pre-clinical Wound Healing Model 2 sets 5 wounds – dermal excisional 1x1 inch 5 wounds -topical O 2 3 hours x 7days 5 wounds – room air only

12 Topical oxygen increases wound pO2 real-time pO 2 measurement (mmHg) O 2 treatment begin time (minutes)

13 Topical oxygen promotes wound closure

14 Skin histology in response to TO treatment – day 22 Control G G A B G G control oxygen treated

15 Angiogenic responses control oxygen treated A B 5 6 C pO 2 (mmHg)  A = VEGF day 7 B = SMA day 15 C = pO 2 day 22

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

17 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): )

18 Objective Identify mechanism mediating beneficial effects of TO in promoting wound healing

19 Study Design Each patient serves as own control All wounds O 2 naive Wound tissue biopsy taken immediately prior and immediately after completion of oxygen treatment at 3 different time points (6 biopsies) –T 0 day of 1 st O 2 tx = baseline –T 1 50% closure (TO) or 50% tx completed (HBO) –T 2 < 1 cm 2 wound area (TO) or 14 weeks, last tx (HBO)

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

21 Results – TO VEGF

22 Scatter plot analysis of VEGF expression in TO patients

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 B C D E Total # patients = 32 Total # wounds = 58 a)healed top O 2 only (n=38) b)did not heal (n=11) c)lost to follow up (n=2) d)died during tx (n=3) e)healed top O 2 + surg (n=4)

28 TO case series - conclusions No reported adverse effects to top O 2 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

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

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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