the 2007 Abstract Presentations - Wound Healing Society

Abstracts
114
ROLE OF NEUROINFLAMMATORY MARKERS IN
ISCHEMIC DIABETIC WOUND HEALING
Leena Pradhan, Xuemei Cai, Nicholas Andersen, Monica Jain, Junaid Malek,
Mauricio Contreras, Frank W. LoGerfo, and Aristidis Veves
Dept. of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical
School, Boston, MA
Introduction: Abnormal wound healing is the key cause of Diabetic Foot
Ulceration (DFU). Dysregulation in the expression and activity of inflammatory
cytokines involved in the healing process, followed by reduced infiltration
and angiogenesis, can disrupt normal wound healing, contributing both to the
development of DFU and its failure to heal. Neuropeptides such as Substance P
(SP) and Neuropeptide Y (NPY) secreted from peripheral nerves are also
implicated in abnormal wound healing. The present study is designed to
investigate the role of cytokines and neuropeptides in wound healing.
Model: Diabetic and non-diabetic rabbit ears are made ischemic by interrupting
dermal circulation to the left ear by ligating the rostral and central arteries.
The right ear serves as a sham. Four full thickness circular wounds are created
in both ears using a 6-mm punch biopsy. Ten days post-surgery, rabbits are
euthanized and wounds are harvested.
Analysis: Wound healing is monitored using Medical Hyperspectral Imaging
(MHSI) collected with a HyperMed Visible MHSI System (Watertown, MA).
Wounds are monitored for infiltration using histology and Q-RT-PCR and
Immunohistochemistry is used to asses the gene and protein expression of
cytokines IL-6 and IL-8, their receptors gp130 and CXCR1 respectively, and SP
and NPY.
Results: Compared to the non-diabetic controls, the ischemic wounds heal
slower, have reduced infiltration and increased pre-wounding skin gene expression
of IL-6, IL-8, gp130 and CXCR1 in the diabetic rabbits. Post-wounding,
the increase in gene expression of IL-6, IL-8, gp130, and CXCR1 over the prewounding
baseline is reduced in diabetic rabbits compared to the non-diabetic
controls. Wounding decreased the expression of SP and NPY in both diabetic
and non-diabetic rabbits.
Conclusion: Preliminary results suggest that there is a dysregulation of immune
response to wounding in the diabetic ischemic wounds and neuropeptides are
altered in wound healing.
115
DOES HBO2T CAUSE HYPOGLYCEMIA IN DIABETIC
PATIENTS? A REVIEW OF 119 DIABETIC PATIENTS
TREATED IN A MULTIPLACE CHAMBER
Irfan Qureshi MD, Katherine Gasho SSF, Liqi FanBS, and George A.
Perdrizet MD, PhD
FACS Hartford Hospital Center for Wound Healing and Hyperbaric Medicine
Introduction: There is a perception that diabetic patients are at risk for
hypoglycemic reactions while receiving HBO2 T. We therefore established a
policy of aggressive blood glucose monitoring of all diabetic patients referred to
our wound center for hyperbaric oxygen treatments to determine the incidence
and severity of this HBO2T related hypoglycemia.
Methods: Blood glucose (BG) was tested for all diabetic patients before, after
and while receiving HBO2T, by standard point of care testing methods. IRB
approval was obtained. Comparisons were made using the Student’s t-test.
Hypoglycemia is defined as a blood sugar 60 mg/dL.
Results: One-hundred and nineteen diabetic patients had BG sampled 3, 450
times over a 3-year time period (8/2003–8/2006). The mean blood sugar values
decreased from the pre-HBO2T (174 43 mg%), to the during HBO2T
(137 36 mg%) and the post-HBO2 T (157 42 mg% measurements. The
differences between the pre HBO2 T measurement and subsequent two time
points were statistically significant with p o 0.04. The overall incidence of a
hypoglycemic episode was found to be 68 out of 2,068 (3.3%) blood sugar
values which occurred in 24 out of 119 (20%) patients. All hypoglycemic
episodes were asymptomatic.
Conclusion: Mean BG values are significantly elevated above normal in
patients presenting to our center for daily HBO2T. Mean BG values do
decrease during treatment, however the majority of patients remain in the
hyperglycemic range. The incidence of hypoglycemia is low and likely reflects
our policy of aggressive blood sugar monitoring and liberal administration of
glucose BG less than 70 mg/dL.
116
HEME OXYGENASE EXPRESSION IN HUMAN WOUNDS
L.A. Gilman 1 , R.A. Kulina 1 , T. Dechert 2 , C.R. Pruitt 1 , R.G. Lewis 2 , and
D.R. Yager 1,2
1 Department of Physiology and the
2 Division of Plastic & Reconstructive Surgery of the Department of Surgery,
Virginia Commonwealth University, Richmond, Virginia
Heme oxygenase is a major acute-phase protein that catalyzes the conversion of
free heme into biliverdin/bilirubin, carbon monoxide, and iron. Heme oxygenase
has been shown to provide important cytoprotective functions in tissues
subject to oxidative stress. Free heme possesses pro-oxidant and pro-inflammatory
properties whereas biliverdin/bilirubin is an extremely potent anti-oxidant
system. In addition, carbon monoxide is a vasodilator, an inhibitor of
inflammatory adhesion molecule expression, and an inhibitor of inflammatory
cell recruitment. Because of its potential importance in modulating oxidative
stress and inflammation, we examined the expression of heme oxygenase
protein in human acute healing wounds and in pressure ulcers. Histochemistry
revealed the presence of the inducible isoform of heme oxygenase (HO-1) in the
granulation tissue of human open (4 mm) dermal wounds. HO-1 protein colocalized
with cells expressing CD68 suggesting expression by macrophages.
Immunoblot analysis (n = 5) indicated that peak expression of HO-1 occurred
7–14 days post-wounding. This correlated with markers of neutrophil infiltration
and oxidative stress. Immunoblot analysis revealed constitutive expression
of HO-2 that did not correlate with specific cells, tissues, or time. HO-1 protein
staining also co-localized with CD68 positive cells in pressure ulcers. Immunoblot
analysis indicated that the mean level of HO-1 protein in pressure ulcers
(n = 10) was significantly higher than at any time point of healing wounds. This
is the first report examining heme oxygenase expression in normal and
pathologic human wounds. The potential of this enzyme and its products to
reduce oxidative stress and inflammation makes it an appealing target.
Acknowledgments: This research was funded by the A.D. Williams Fund.
117
MALIGNANCY IN CHRONIC WOUNDS
F.J. Agullo, A.A. Santillan, H. Palladino, W.T. Miller
Texas Tech University Health Sciences Center School of Medicine, Department
of Surgery, El Paso, TX USA
The prevalence of malignancy within chronic skin ulcers is low, resulting in
frequent inappropriate diagnosis and treatment. These malignancies may arise
from chronic wounds or the ulceration itself may be caused by the cancer.
Commonly, these lesions are treated as chronic wounds, leading to delayed
diagnosis and resulting in the need for more extensive surgery and increased
risk of metastasis and mortality. Three cases are presented depicting varied
pathophysiology, diagnosis, and treatment of malignancies encountered within
chronic ulcers. All cases resulted in delayed treatment, ranging between 18
months to a year, due to inadequate diagnosis and treatment as chronic
wounds. On referral, due to clinical suspicion, biopsies demonstrated malignancies
including melanoma, basosquamous carcinoma, and squamous cell
carcinoma. Excision and wound coverage was the mainstay of therapy.
Suspicion of malignant change should be raised with wounds that are
malodorous, crusted, ulcerated, bleeding, or have had an increase in pain or
size. Wounds that have an irregular base or margins, a change in drainage, or
exophytic growth should also be suspect and merit a biopsy. Some clinicians
advocate performing biopsies on wounds that have been present for longer than
3 or 4 months. Marjolin ulcers, giant basosquamous carcinomas, and melanomas
are malignant entities with high metastatic potential that can present as
chronic skin ulcerations. The cases described represent extremes in the presentation
of malignant transformation in chronic wounds and serve as
important reminders of the need for clinicians to aggressively evaluate and
manage chronic wounds of any etiology that follow a stagnant progressive
course. These reports highlight the possibility of malignancy in chronic wounds
and ulcers, and the importance of early identification and treatment.
Acknowledgments: No financial interests.
Wound Rep Reg (2007) 15 A14–A54 c 2007 by the Wound Healing Society
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