Effects of isoniazid and niacin on experimental wound-healing.
BACKGROUND
There is a need for effective treatments of ischemic wounds. Our aim was to test the hypothesis that systemic administration of isoniazid or niacin can enhance wound healing in ischemic as well as nonischemic tissues.


METHODS
One 8-mm, full-thickness wound was made in a standardized, ischemic skin flap and 1 in adjacent nonischemic skin on the back of male Sprague-Dawley rats. Starting just after wounding, twice-daily intraperitoneal isoniazid (10 mg/kg b.i.d.), xanthinol nicotinate (30 mg/kg), or saline (control) were given for 14 days. Wound-healing was monitored by planimetry and oxygen tension in periphery of the wound using a microcatheter probe. Cellular proliferation in granulation tissue was assessed by immunohistochemical detection of proliferating cell nuclear antigen. The angiogenic activity of isoniazid and niacin was assessed using in vitro and ex vivo models.


RESULTS
Although wound ischemia was evident by decreased oxygen tension (26 +/- 10 mmHg; n = 9) compared with the adjacent nonischemic wounds (51 +/- 8 mmHg; n = 8), neither compound significantly influenced intracutaneous oxygen tension. Isoniazid (P < .0001), but not niacin, promoted ischemic wound-healing even though both compounds increased proliferation measured on day 14 (P < .01). In normal wounds, the cumulative change in relative wound area over 14 days was increased by niacin (P = .002), but not by isoniazid, although both niacin (P = .011) and isoniazid (P = .036) increased cellular proliferation. Neither isoniazid nor niacin showed activity in either an endothelial tube formation assay or organotypic angiogenic assay under normoxic conditions.


CONCLUSIONS
Isoniazid was capable of stimulating wound-healing in ischemic tissue to the level of nonischemic wounds and might offer a novel treatment option for wounds associated with arterial insufficiency. Although active in normal wounds, niacin did not promote ischemic wound-healing.
Weinreich
Jürgen
J
Department of General and Transplant Surgery, University of Tübingen, Tübingen, Germany.
Agren
Magnus S
MS
Bilali
Erol
E
Kleinman
Hynda K
HK
Coerper
Stephan
S
Königsrainer
Alfred
A
Beckert
Stefan
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D007511:Ischemia / Q000209:etiology / Q000517:prevention & control; D007538:Isoniazid / Q000627:therapeutic use*; D008297:Male; D009525:Niacin / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016038:Skin Transplantation / Q000379:methods; D013524:Surgical Flaps; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000150:complications / Q000503:physiopathology
D000900:Anti-Bacterial Agents; D009525:Niacin; D007538:Isoniazid