PURPOSE:
Existing animal chronic wound models have limited application to humans due to differences in mechanism of wound closure and dermal architecture. While most common laboratory species heal primarily through contracture from the wound margins, porcine and human skin heal mainly by reepithelialization. This similarity has lead researchers to view porcine skin as a valuable resource for the study of wound physiology, but a reproducible porcine model of delayed healing has not yet been described. Such a model would be an asset in the study and understanding of human wound healing. We have devised a protocol to generate delayed healing of full thickness cutaneous wounds in the porcine hindlimb.
METHODS:
Three Yorkshire swine underwent ligation of the common femoral artery (CFA), medial circumflex femoral artery (MCFA), external iliac artery (EIA), internal iliac artery (IIA), and deep circumflex iliac artery (DCIA) supplying the right hindlimb. Following ligation, thrombin, 5000 units, and Surgifoam™ (Johnson & Johnson, Somerville, NJ), 0.5 grams, were injected into the CFA by direct cannulation of the vessel. The left hindlimb underwent sham operation (incision and dissection without ligation) and served as a control. Ischemia was confirmed by physical examination and observation of a sustained decrease in transcutaneous partial pressure of oxygen (TCpO₂) in comparison to preoperative values and control limb readings. Two weeks after the first operation, full-thickness wounds measuring 2 cm x 2 cm were created on the dorsal aspect of each hind limb, 5 cm proximal to the hoof. The wounds were measured and photographed at regular intervals and fluid was extracted from the bandages for cytokine analysis.
RESULTS:
Over a follow up period of 28 days, two of the animals demonstrated a three-day delay in arriving at the 50% percent closure level when compared to the control limb. Furthermore, while control limbs in both animals were fully closed at or before the 20^th day, the experimental limbs remained open until day 25 post-wounding. The third animal did not show any appreciable delay in healing between the control and experimental wounds, and instead ischemia and distal necrosis on the plantar aspect of the experimental limb was noted. This is attributed to a procedural error in which the injection of embolic agents was directed to the posterior circulation of the distal hindlimb. Histology and cytokine analysis for all wounds are pending.
CONCLUSION:
Our findings indicate that the above-described combination of ligation and angio-embolization of porcine hindlimb vasculature generates a state of tissue ischemia that results in measurable delay in the healing of full thickness cutaneous wounds. Additional operations are planned to ensure the reproducibility of these results, and we are currently developing an endovascular approach to accomplish the vascular occlusion and angioembolization in a more expeditious and super-selective manner.