Abstract
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.
Similar content being viewed by others
References
Mustoe TA, O’Shaughnessy K, Kloeters O (2006) Chronic wound pathogenesis and current treatment strategies: a unifying hypothesis. Plast Reconstr Surg 117:35S–41S
Harder Y, Amon M, Georgi M, Banic A, Erni D, Menger MD (2005) Evolution of a “falx lunatica” in demarcation of critically ischemic myocutaneous tissue. Am J Physiol Heart Circ Physiol 288:H1224–H1232
Ng RL, Youssef A, Kronowitz SJ, Lipa JE, Potochny J, Reece GP (2004) Technical variations of the bipedicled TRAM flap in unilateral breast reconstruction: effects of conventional versus microsurgical techniques of pedicle transfer on complications rates. Plast Reconstr Surg 114:374–384 discussion 385–378
Dimick JB, Chen SL, Taheri PA, Henderson WG, Khuri SF, Campbell DA Jr (2004) Hospital costs associated with surgical complications: a report from the private-sector National Surgical Quality Improvement Program. J Am Coll Surg 199:531–537
Vemuri C, Wainess RM, Dimick JB, Cowan JA Jr, Henke PK, Stanley JC, Upchurch GR Jr (2004) Effect of increasing patient age on complication rates following intact abdominal aortic aneurysm repair in the United States. J Surg Res 118:26–31
Harder Y, Amon M, Georgi M, Scheuer C, Schramm R, Rucker M, Pittet B, Erni D, Menger MD (2007) Aging is associated with an increased susceptibility to ischaemic necrosis due to microvascular perfusion failure but not a reduction in ischaemic tolerance. Clin Sci (Lond) 112:429–440
Croce MA, Fabian TC, Malhotra AK, Bee TK, Miller PR (2002) Does gender difference influence outcome? J Trauma 53:889–894
McGwin G Jr, George RL, Cross JM, Reiff DA, Chaudry IH, Rue LW 3rd (2002) Gender differences in mortality following burn injury. Shock 18:311–315
Wichmann MW, Inthorn D, Andress HJ, Schildberg FW (2000) Incidence and mortality of severe sepsis in surgical intensive care patients: the influence of patient gender on disease process and outcome. Intensive Care Med 26:167–172
George RL, McGwin G Jr, Windham ST, Melton SM, Metzger J, Chaudry IH, Rue LW 3rd (2003) Age-related gender differential in outcome after blunt or penetrating trauma. Shock 19:28–32
Isles CG, Hole DJ, Hawthorne VM, Lever AF (1992) Relation between coronary risk and coronary mortality in women of the Renfrew and Paisley survey: comparison with men. Lancet 339:702–706
Grady D, Rubin SM, Petitti DB, Fox CS, Black D, Ettinger B, Ernster VL, Cummings SR (1992) Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med 117:1016–1037
Barker JH, Hammersen F, Bondar I, Galla TJ, Menger MD, Gross W, Messmer K (1989) Direct monitoring of nutritive blood flow in a failing skin flap: the hairless mouse ear skin-flap model. Plast Reconstr Surg 84:303–313
Hedrich H (2004) The laboratory mouse. Elsevier Academic, Amsterdam
Vollmar B, Morgenthaler M, Amon M, Menger MD (2000) Skin microvascular adaptations during maturation and aging of hairless mice. Am J Physiol Heart Circ Physiol 279:H1591–H1599
Menger MD, Pelikan S, Steiner D, Messmer K (1992) Microvascular ischemia–reperfusion injury in striated muscle: significance of “reflow paradox”. Am J Physiol 263:H1901–H1906
Klyscz T, Junger M, Jung F, Zeintl H (1997) Cap image—a new kind of computer-assisted video image analysis system for dynamic capillary microscopy. Biomed Tech 42:168–175
Menger MD, Barker JH, Messmer K (1992) Capillary blood perfusion during postischemic reperfusion in striated muscle. Plast Reconstr Surg 89:1104–1114
Amon M, Menger MD, Vollmar B (2003) Heme oxygenase and nitric oxide synthase mediate cooling-associated protection against TNF-alpha-induced microcirculatory dysfunction and apoptotic cell death. FASEB J 17:175–185
Gross JF, Aroesty J (1972) Mathematical models of capillary flow: a critical review. Biorheology 9:225–264
Liu PY, Christian RC, Ruan M, Miller VM, Fitzpatrick LA (2005) Correlating androgen and estrogen steroid receptor expression with coronary calcification and atherosclerosis in men without known coronary artery disease. J Clin Endocrinol Metab 90:1041–1046
Jovanovic A (2006) Ageing, gender and cardiac sarcolemmal K(ATP) channels. J Pharm Pharmacol 58:1585–1589
Menger MD, Vollmar B (1996) In vivo documentation of an arteriovenous shunt in rat pancreatic acinar tissue. Pancreas 13:125–129
Contaldo C, Plock J, Sakai H, Takeoka S, Tsuchida E, Leunig M, Banic A, Erni D (2005) New generation of hemoglobin-based oxygen carriers evaluated for oxygenation of critically ischemic hamster flap tissue. Crit Care Med 33:806–812
Kamler M, Lehr HA, Barker JH, Saetzler RK, Galla TJ, Messmer K (1993) Impact of ischemia on tissue oxygenation and wound healing: intravital microscopic studies on the hairless mouse ear model. Eur Surg Res 25:30–37
Albrecht ED, Koos RD, Gottlieb SF (1977) Pregnant mare serum and human chorionic gonadotropin stimulate ovarian delta5-3beta-hydroxysteroid dehydrogenase in aged mice. Fertil Steril 28:762–765
Kubota K, Kubota R, Matsuzawa T (1987) Growth and differentiation of teratocarcinoma OTT6050 affected by host hormonal changes in old mice. Tohoku J Exp Med 151:253–259
Araneo BA, Ryu SY, Barton S, Daynes RA (1995) Dehydroepiandrosterone reduces progressive dermal ischemia caused by thermal injury. J Surg Res 59:250–262
Daynes RA, Araneo BA, Ershler WB, Maloney C, Li GZ, Ryu SY (1993) Altered regulation of IL-6 production with normal aging. Possible linkage to the age-associated decline in dehydroepiandrosterone and its sulfated derivative. J Immunol 150:5219–5230
Mo Q, Lu SF, Simon NG (2006) Dehydroepiandrosterone and its metabolites: differential effects on androgen receptor trafficking and transcriptional activity. J Steroid Biochem Mol Biol 99:50–58
Acknowledgements
Y. H. is a recipient of a fellowship of the Swiss National Science Foundation (SNF-No. PBBSB-102601), the “Freiwillige Akademische Gesellschaft” (FAG), and the “Margarete und Walter Lichtenstein Stiftung, Medical Department” in Basel, Switzerland.
Conflict of interest
None of the authors has any conflict of interest with the present study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Harder, Y., Amon, M., Wettstein, R. et al. Gender-specific ischemic tissue tolerance in critically perfused skin. Langenbecks Arch Surg 395, 33–40 (2010). https://doi.org/10.1007/s00423-009-0558-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00423-009-0558-9