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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 successful wound healing.Parameter values for this simulation are shown in Table 1, except here . Multiple day intervals are shown (dark blue = 2, red = 4, green = 6, black = 8, yellow = 10, light blue = 12, pink = 14). The top graph shows oxygen tension (mmHg), the middle graph shows tip density (capillaries/cm2) and the bottom graph shows blood vessel density (vessels/cm).
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pcbi-1000451-g001: Simulation of successful wound healing.Parameter values for this simulation are shown in Table 1, except here . Multiple day intervals are shown (dark blue = 2, red = 4, green = 6, black = 8, yellow = 10, light blue = 12, pink = 14). The top graph shows oxygen tension (mmHg), the middle graph shows tip density (capillaries/cm2) and the bottom graph shows blood vessel density (vessels/cm).

Mentions: We simulate an acute healing wound with the choice of parameters outlined in Table 1, noting that this choice of values yields a steady state oxygen concentration behind the wave front (behind the healing front the oxygen concentration, , tends to as ) above the lower threshold for capillary tip production, , so that healing will be initiated. Fig 1 shows such a normal situation in which a wound of length 2 cm (that is, ) is almost completely reoxygenated within 2 weeks. It would take longer than this, roughly 2.5 weeks, for the simulated wound to completely revascularise. We note that the vessel density can rise above the carrying capacity, , due to rapid chemotaxis and may remain elevated until the remodelling process drives the density to return to normal levels.


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 successful wound healing.Parameter values for this simulation are shown in Table 1, except here . Multiple day intervals are shown (dark blue = 2, red = 4, green = 6, black = 8, yellow = 10, light blue = 12, pink = 14). The top graph shows oxygen tension (mmHg), the middle graph shows tip density (capillaries/cm2) and the bottom graph shows blood vessel density (vessels/cm).
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1000451-g001: Simulation of successful wound healing.Parameter values for this simulation are shown in Table 1, except here . Multiple day intervals are shown (dark blue = 2, red = 4, green = 6, black = 8, yellow = 10, light blue = 12, pink = 14). The top graph shows oxygen tension (mmHg), the middle graph shows tip density (capillaries/cm2) and the bottom graph shows blood vessel density (vessels/cm).
Mentions: We simulate an acute healing wound with the choice of parameters outlined in Table 1, noting that this choice of values yields a steady state oxygen concentration behind the wave front (behind the healing front the oxygen concentration, , tends to as ) above the lower threshold for capillary tip production, , so that healing will be initiated. Fig 1 shows such a normal situation in which a wound of length 2 cm (that is, ) is almost completely reoxygenated within 2 weeks. It would take longer than this, roughly 2.5 weeks, for the simulated wound to completely revascularise. We note that the vessel density can rise above the carrying capacity, , due to rapid chemotaxis and may remain elevated until the remodelling process drives the density to return to normal levels.

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