Gender-specific ischemic tissue tolerance in critically perfused skin.

Purpose: The purpose of this study is to determine gender-specific differences in the development of necrosis in persistent ischemic tissue and to analyze whether differences are due to gender-specific loss of vascular reactivity or change in ischemic tolerance.
Methods: Hairless mice (skh-1) of both genders were assigned to three groups of adolescent, adult, and senescent age. Critical ischemia was induced by transection of the two distal pedicles of the animal's ear. Microcirculation was assessed over a 5-day period using intravital epifluorescence microscopy. Tissue necrosis, blood flow, functional capillary density (FCD), red blood cell (RBC) velocity, and capillary diameter were analyzed.
Results: Induction of persistent ischemia caused an age-dependent demarcation of nonperfused flap tissue. Adult and senescent females developed markedly more necrosis than age-matched males (49 +/-1% vs. 37 +/-3% and 53 +/- 3% vs. 44 +/- 2%, respectively; p<0.05), whereas no gender-specific difference in flap necrosis was observed in adolescent animals (31 +/- 2% vs. 33 +/- 3%). Gender did not affect the amount of microcirculatory dysfunction in the flap. Thus, age-matched females and males exhibited a comparable decrease of FCD, RBC velocity, and capillary dilatory response.
Conclusions: Both age and female gender may predispose for an increased susceptibility to develop ischemic tissue necrosis. The increased necrosis in female animals does not apply to an aggravated microvascular dysfunction, but rather to a reduced ischemic tissue tolerance.