Grants We Funded

Abstract
Partial or complete flap loss can have devastating consequences during reconstructive and cosmetic surgery. The incidence of these complications may be related to comorbid factors such as obesity, smoking, and prior history of radiation therapy. Although a number of techniques have been developed to address this issue, to date, no non-invasive measures have been proven effective. Recently, a number of studies have demonstrated that administration of culture expanded endothelial progenitor cells (EPCs) is capable of improving ischemic flap survival. The circulating concentrations of these cells can be manipulated using commonly available oral medications such as statins. Statins (eg. simvastatin) have been used effectively in millions of patients for cholesterol reduction. However, recent studies have shown that these medications also increase circulating EPC levels 2 to 3 fold. In addition, treatment with statins has been effective in diminishing neointimal hyperplasia in a carotid artery injury model. Therefore, the purpose of these studies is to evaluate the effect of presurgical treatment with statins on ischemic flap survival. This will be performed using the following specific aims: 1. Evaluate effect of oral statin therapy on concentrations of circulating EPCs in mice. In this specific aim we will identify the optimal dose and timing of oral simvastatin on mobilization of bone marrow derived PCs. 2. Evaluate the effect of oral statin therapy on ischemic flap healing in mice. This specific aim will assess the effects of oral Simvastatin on ischemic flap survival using the optimal oral dose identified in specific aim 1. 3. Demonstrate that alterations in ischemic flap survival are due to bone marrow stimulation. In this specific aim we will demonstrate that statins augment EPC production by changes in bone marrow production of these cells. In addition, we will track the newly formed EPCs to the wound bed using transgenic animals.

Biography
Dr. Mehrara is a graduate of Columbia University College of Physicians and Surgeons. He completed his Plastic Surgery Residency at New York University Medical Center followed by microsurgical fellowship at UCLA Medical Center. Dr. Mehrara’s laboratory research is focused on the etiology of lymphedema and deleterious effects of radiation therapy. These fields are intimately related since radiation therapy is a significant risk factor for lymphedema. His recent research has demonstrated that the pathological findings associated with radiation therapy are related in large part to the depletion and dysfunction of resident tissue stem cells and that targeted protection of these cells can decrease tissue injury.