FERIDA ARTICLEArzu Akcal (1), Semra Karsidag (2), Kemalettin Yildiz (3), Nebil Yesiloglu (4), Mehmet Akif Akcal (5), Fevziye Kabukcuoglu (6)

  1. Department of Plastic and Reconstructive Surgery, Akdeniz University, Medical School, Antalya, Turkey
  2. Department of Plastic and Reconstructive Surgery, Sisli Etfal Training and Research Hospital, Istanbul, Turkey
  3. Department of Plastic and Reconstructive Surgery, Bezmi Alem University, Medical School, Istanbul, Turkey
  4. Department of Plastic and Reconstructive Surgery, Kartal Lutfi Kirdar Training and Research Hospital, Istanbul, Turkey
  5. Department of Orthopedics and Traumatology, Antalya Atatürk State Hospital, Antalya, Turkey,
  6. Department of Pathology, Sisli Etfal Training and Research Hospital, Istanbul, Turkey

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The goals of this study were: (1) To determine the efficacy of 2% procaine (the most commonly used concentration) in wound healing; and (2) To determine the proper open wound injection site.

Materials and Methods: Thirty adult male Sprague-Dawley rats weighing between 250 and 350 g were used. Two full thickness defects were made on two sides of the midline 1 cm away from midline. The skin wound areas were approximately 1.5 cm × 1.5 cm. The animals were randomly divided into three groups: Group 1 (control group, n = 8), Group 2 (injection directly into the base of wound, n = 8), and Group 3 (injection into healthy skin around the peripheral margins of the wound, n = 8). Mechanical analyses of wound tensile strength of were evaluated in all groups.
Results: Wound closure was first seen in Group 3 on day 14. Mean wound healing times were 18.25 days, 16.25 days, and 15.62 days, and mean tensile strength was 777.13 cN, 988.25 cN, and 1068.25 cN in the Groups 1, 2, and 3 respectively.
Conclusions: Procaine did not cause any necrosis around the wound, did not retard wound healing, did not cause circulation deficiency, and did not reduce the breaking strength of the wound. Therefore, it can be safely used to reduce pain around the wound and to accelerate the healing process of slow-to-heal wounds.
Key words: Procaine, slow-to-heal wounds, tensile strength

Recently, surgeons have began playing an active role in modulating the healing process with the pharmological treatment of open wounds. Procaine has widespread usage in clinical practice and is also a component of mesotherapy cocktails due to its vasodilatator and analgesic effects in anti-aging agents [1-3]. However, in the United States, some agents that containe procaine and are used for dementia were banned by the Food and Drug Administration [1]. Procaine also relieves CTS because it has potent local anesthetic properties [3]. Despite this knowledge about procaine, the literature lacks information about its effects when injected into a wound or into healthy tissues around the wound.
A full thickness excisional wound model was used to detect the effects of procaine on wound healing. Open wounds heal by the same basic processes of inflammation, proliferation, and remodelling as do closed wounds. The major difference is that each sequence is much longer in open wounds [7]. It has been stated that injection of sterile water into the wound region delays wound healing, presumably because the volume of liquid injected into the skin and subcutaneous tissues causes tissue damage [7]. Thus, sterile water was not used in the control group. It has been shown that procaine retards wound healing by reducing mucopolysaccharide, and consequently, collagen synthesis [8]. Many hospitals are now using local anesthetics to relieve post-operative pain and prolong analgesia, although some studies about local anesthetics suggest that these agents should be avoided in patients with slow-to-heal wounds, leg ulcers, or when fast healing is essential [9,10]. Studies have shown that 1% and 2% concentrations of procaine delayed wound healing, and the use of 1:1,00,000 epinephrine was a factor that exacerbated this effect by allowing procaine to remain in the region longer. Thus, epinephrine injected alone in the region had no negative effect on the healing of wounds [5]. In the present study, procaine that was injected into the base of the wound and around the wound did not retard healing times and rates.
Some reports have stated that local anesthetics preserve endothelial barrier function during acute inflammation. The effects of local anesthetic agents on cytokine release and activity are dose-dependent [11]; however, it is known that local anesthetics inhibit both cytokine release and activity. Nevertheless, when one considers the diverse array of cytokines and cytokine effects involved in the inflammatory response and their complex interactions, it is clear that our knowledge of the effect of local anesthetic agents remains limited. Ester and amide local anesthetics decrease leukocyte migration [12] and are associated with decreased end organ damage. In addition, some studies have reported that local anesthetic agents decrease leukocyte migration [13] and inhibit generation of hydrogen peroxide. Local anesthetics may function by altering the distribution (rather than the magnitude of expression) of adhesion molecules. The limitation of our study was that we did not investigate leukocyte migration by microscopy, and did not perfom immunohistochemistry for adhesion molecular markers. However, both procaine treatment groups healed uneventfully, and had a shorter healing time than the control group. Also, collagen accumulations in experimental groups were more prominent.
The infiltration of local anesthetics at high concentrations (2%) decreases the breaking strength of skin wounds in rats, but at a concentration of 0.5%, the differences are not significant [6]. In our study, 2% procaine did not delay wound healing and did not lead to significant differences compared to the control group. In addition, there were no statistically significant differences between experimental groups.
In the full thickness excisional model, healing rates are often monitored based on the extent of re-epithelization, histological organization of connective tissue, angiogenesis, and biochemical content of collagen or proteoglycans [14]. In this study, we found that procaine did not cause any necrosis around the wound, did not retard wound healing, did not cause circulation deficiency, and did not reduce the breaking strength of the wound. Thus, this agent may be recommended for the healing of both open wounds and surgical wounds due to its effect on collagen accumulation. In addition, procaine can be used safely to reduce pain around the wound and to accelerate the healing of slow-to-heal wounds.

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