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A three species model to simulate application of Hyperbaric Oxygen Therapy to chronic wounds.

Flegg JA, McElwain DL, Byrne HM, Turner IW - PLoS Comput. Biol. (2009)

Bottom Line: Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds.Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective.The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the cost-effectiveness of this therapy.

View Article: PubMed Central - PubMed

Affiliation: School of Mathematical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.

ABSTRACT
Chronic wounds are a significant socioeconomic problem for governments worldwide. Approximately 15% of people who suffer from diabetes will experience a lower-limb ulcer at some stage of their lives, and 24% of these wounds will ultimately result in amputation of the lower limb. Hyperbaric Oxygen Therapy (HBOT) has been shown to aid the healing of chronic wounds; however, the causal reasons for the improved healing remain unclear and hence current HBOT protocols remain empirical. Here we develop a three-species mathematical model of wound healing that is used to simulate the application of hyperbaric oxygen therapy in the treatment of wounds. Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds. Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective. We provide constraints that depend on the model parameters for the range of HBOT protocols that will stimulate healing. More specifically, we predict that patients with a poor arterial supply of oxygen, high consumption of oxygen by the wound tissue, chronically hypoxic wounds, and/or a dysfunctional endothelial cell response to oxygen are at risk of nonresponsiveness to HBOT. The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the cost-effectiveness of this therapy.

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Related in: MedlinePlus

Simulation of a normal wound under HBOT.Multiple day intervals are shown (dark blue = 2, red = 4, green = 6, black = 8, yellow = 10, light blue = 12, pink = 14). Parameter values for this simulation are the same as in Fig 1, except .
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pcbi-1000451-g005: Simulation of a normal wound under HBOT.Multiple day intervals are shown (dark blue = 2, red = 4, green = 6, black = 8, yellow = 10, light blue = 12, pink = 14). Parameter values for this simulation are the same as in Fig 1, except .

Mentions: Many hyperbaric centers around the world advocate the use of HBOT to treat ‘normal’ wounds on the basis that HBOT may accelerate healing in sports injuries [49]. This use of HBOT is highly controversial [50]. Typically a sports injury is internal (muscular) rather than dermal, but here we consider the effect of applying HBOT to a normal healing wound. Comparing Figs 1 and 5, we see that there is little benefit (at most, a 10% increase in the rate at which blood vessels are progressing through the wound space) in applying HBOT to a wound that progresses through the healing process of its own accord. Furthermore, the relatively high-cost of HBOT further detracts from the appeal of its use to treat such wounds. This simulation also shows that the capillary tip density falls significantly towards the end of the healing process. Numerical experimentation reveals that healing will occur, even with very small levels of capillary tips, suggesting that it is the presence of capillary tips, rather than their quantity, that is important for initiating healing. Clinically, this means that stimulating capillary tip production is the crucial factor that enables a chronic wound to heal when HBOT is applied.


A three species model to simulate application of Hyperbaric Oxygen Therapy to chronic wounds.

Flegg JA, McElwain DL, Byrne HM, Turner IW - PLoS Comput. Biol. (2009)

Simulation of a normal wound under HBOT.Multiple day intervals are shown (dark blue = 2, red = 4, green = 6, black = 8, yellow = 10, light blue = 12, pink = 14). Parameter values for this simulation are the same as in Fig 1, except .
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2710516&req=5

pcbi-1000451-g005: Simulation of a normal wound under HBOT.Multiple day intervals are shown (dark blue = 2, red = 4, green = 6, black = 8, yellow = 10, light blue = 12, pink = 14). Parameter values for this simulation are the same as in Fig 1, except .
Mentions: Many hyperbaric centers around the world advocate the use of HBOT to treat ‘normal’ wounds on the basis that HBOT may accelerate healing in sports injuries [49]. This use of HBOT is highly controversial [50]. Typically a sports injury is internal (muscular) rather than dermal, but here we consider the effect of applying HBOT to a normal healing wound. Comparing Figs 1 and 5, we see that there is little benefit (at most, a 10% increase in the rate at which blood vessels are progressing through the wound space) in applying HBOT to a wound that progresses through the healing process of its own accord. Furthermore, the relatively high-cost of HBOT further detracts from the appeal of its use to treat such wounds. This simulation also shows that the capillary tip density falls significantly towards the end of the healing process. Numerical experimentation reveals that healing will occur, even with very small levels of capillary tips, suggesting that it is the presence of capillary tips, rather than their quantity, that is important for initiating healing. Clinically, this means that stimulating capillary tip production is the crucial factor that enables a chronic wound to heal when HBOT is applied.

Bottom Line: Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds.Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective.The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the cost-effectiveness of this therapy.

View Article: PubMed Central - PubMed

Affiliation: School of Mathematical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.

ABSTRACT
Chronic wounds are a significant socioeconomic problem for governments worldwide. Approximately 15% of people who suffer from diabetes will experience a lower-limb ulcer at some stage of their lives, and 24% of these wounds will ultimately result in amputation of the lower limb. Hyperbaric Oxygen Therapy (HBOT) has been shown to aid the healing of chronic wounds; however, the causal reasons for the improved healing remain unclear and hence current HBOT protocols remain empirical. Here we develop a three-species mathematical model of wound healing that is used to simulate the application of hyperbaric oxygen therapy in the treatment of wounds. Based on our modelling, we predict that intermittent HBOT will assist chronic wound healing while normobaric oxygen is ineffective in treating such wounds. Furthermore, treatment should continue until healing is complete, and HBOT will not stimulate healing under all circumstances, leading us to conclude that finding the right protocol for an individual patient is crucial if HBOT is to be effective. We provide constraints that depend on the model parameters for the range of HBOT protocols that will stimulate healing. More specifically, we predict that patients with a poor arterial supply of oxygen, high consumption of oxygen by the wound tissue, chronically hypoxic wounds, and/or a dysfunctional endothelial cell response to oxygen are at risk of nonresponsiveness to HBOT. The work of this paper can, in some way, highlight which patients are most likely to respond well to HBOT (for example, those with a good arterial supply), and thus has the potential to assist in improving both the success rate and hence the cost-effectiveness of this therapy.

Show MeSH
Related in: MedlinePlus