title: Effect of long-term cyclosporine administration on muscle flap hemodynamics.
abstract: Long-term use of cyclosporine A (CsA) is associated with deleterious effects such as nephrotoxicity and hypertension as a result of its toxicity on microvasculature. These effects raise the possibility that long-term CsA use harms the microvasculature of the skeletal muscle tissue. An experimental study was conducted to investigate the effect of chronic systemic cyclosporine administration on the microvasculature of the cremaster flap model in the rat. Thirty male Sprague-Dawley rats were divided into five groups of 6 animals each. The control group received no treatment. The four CsA treatment groups received a daily subcutaneous injection of 2 mg per kilogram, 4 mg per kilogram, 8 mg per kilogram, and 16 mg per kilogram of cyclosporine for 6 weeks before surgery. The effect of long-term CsA administration on cremaster flap microcirculation was evaluated in vivo using an intravital microscopy system. Hemodynamic parameters of the cremaster muscle flap such as vessel diameter, red blood cell velocity, capillary density, leukocyte-endothelial interaction, and microvascular permeability were measured. There was no significant (p > 0.05) difference in vessel diameter in all groups. There was a significant increase in the number of adherent leukocytes in the 8-mg and 16-mg CsA group compared with the control (12 +/- 4.8 leukocytes per 100 microm and 12 +/- 4.5 leukocytes per 100 microm vs. 6 +/- 4.3 leukocytes per 100 microm; p < 0.05). Microvascular permeability indices increased significantly at 0 and 30 minutes after fluorescent isothiocyanate-albumin injection in the 8-mg and 16-mg CsA groups compared with the control (0 minutes: 0.6 +/- 0.2% and 0.5 +/- 0.1% vs. 0.4 +/- 0.05%; 30 minutes: 0.8 +/- 0.2% and 0.7 +/- 0.1% vs. 0.5 +/- 0.04%; p < 0.05). Histologically, the cremaster muscle flaps in all cyclosporine groups showed evidence of interstitial inflammation and venous vasculitis. In the 8-mg and 16-mg CsA groups there was also focal muscle injury. The toxic effect of CsA on the microvascular tree of a muscle flap was demonstrated by the increased permeability index in vivo, and the moderate venulitis and focal muscle injury histologically. Systemic CsA administration seems to have minimal impact on the viability of the muscle flaps, which was confirmed by preserved capillary function and muscle flap perfusion. These data suggest that there is a minimal risk in undertaking a pedicled muscle flap transfer procedure using a CsA immunosuppressive protocol.
authors.affiliation: Cleveland Clinic Foundation, Department of Plastic and Reconstructive Surgery, OH 44195, USA.
authors.forename: Murat
authors.initials: M
authors.lastname: Unsal
authors.forename: Raffi
authors.initials: R
authors.lastname: Gurunluoglu
authors.forename: Orhan
authors.initials: O
authors.lastname: Babuccu
authors.forename: Kevin
authors.initials: K
authors.lastname: Carnevale
authors.forename: Maria
authors.initials: M
authors.lastname: Siemionow
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D002196:Capillaries / Q000033:anatomy & histology / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000033:anatomy & histology / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013524:Surgical Flaps / Q000098:blood supply*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine