| ObjectiveFlap necrosis mainly results from leukocyte-mediated inflammatory response and ischemia-reperfusion injury. Dexamethasone (in short, DXM) and amlodipine besylate (in short, AB), two of them could respectively interrupt this pathogenesis, have been used to prevent skin flap necrosis. Yet the former medicine application such as taking orally or intravenous administration or infusing medicine under flap by a catheter inevitably had their disadvantages. We have made the DXM-AB compound gel to avoid, at least reduce, the demerits and improve their preventive effects, and at the same time investigate their abilities of percutaneous penetration and observe their therapeutic effects on rat dorsal ischemic skin flap.MethodsSodium carboxymethylcellulose was used to make gel matrix, with which DXM, AB, azone (in short, AZ) and progylene glycol (in short, PG) was mixed respectively to make the compound 0.3% DXM-0.5% AB gel containing 3% AZ+2% PG,3% AZ, 2% PG and the compound 0.3% DXM+0.5% AB gel without AZ and PG as well as 0.3%DXM gel and 0.5%AB gel containing 3% AZ+2% PG. The accumulative quantities of DXM and AB in compound gel, DXM gel and AB gel through excised rat skin and its quantities within flap tissue were investigated by ultraviolet spectrophotometry. Twenty-four SD rats were randomly divided into 2 groups and a 10 mm×100 mm random ischemic dorsal flap was made on each of them. To investigate the quantities of DXM and AB within skin flap, 1g skin tissue within two sides of the flap axis at proximal pedicel one-third was excised at 2 and 6 hours after application of compound gel containing 3% AZ+2% PG and peritoneal injection of DXM (5 mg/kg)+AB (2 mg/kg), then cut into small pieces, shredded, homogenated, extracted by the ether and finally detected by ultraviolet spectrophotometry. Fifty SD rats, ischemic skin flap also made on each of them, were randomly divided into 5 groups to assess the flap survival area:compound gel group, DXM gel group, AB gel group, gel matrix group and peritoneal injection of DXM (5 mg/kg)+AB (2 mg/kg) group. The survival area of rat's ischemic random skin flap was measured on the 7th day by planimetry.Statistical analysis:All the dates were expressed asχ±s. Significant differences for the accumulative quantities of DXM, AB and the survival area of rat's ischemic random skin flap were assessed by variance analysis. Significant differences for the quantities of DXM and AB within skin flap between application compound gel and peritoneal injection were assessed with a t test. Values of P<0.05 were considered significant.Results1. The accumulative penetrative quantities of DXM and AB in compound gel were increased in time-dependent manner (P<0.05), and it was higher in compound gel containing 3% AZ+2% PG group than that containing 3% AZ or 2% PG (P＜0.01), but it was insignificant when compared with DXM gel group or AB gel group (P>0.05).2. At 2 and 6 hours after application of compound gel containing 3% AZ+2% PG and peritoneal injection of DXM (5 mg/kg)+AB (2 mg/kg), the quantities of DXM and AB within skin flap tissue of compound gel containing3% AZ+2% PG group was significantly higher than that of peritoneal injection group (P<0.05).3. After 7 days, the survival area was improved from 215.2±3.8mm2 of gel matrix to 695.0±4.6mm2 of compound gel containing 3% AZ+2% PG,477.5±14.5mm2 of DXM gel,439.3±7.1mm2of AB gel,569.4±9.7mm2 of peritoneal injection group; the survival area of compound gel containing 3% AZ+2% PG group was significantly higher than other groups (P<0.05).Conclusions1. Dexamethasone and amlodipine in 0.3% dexamethasone+0.5% amlodipine compound gel might penetrate into skin tissue.2. Dexamethasone(0.3%)+amlodipine(0.5%) compound gel could significantly increase the survival area of ischemic skin flap. |
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