Avoiding free nipple grafting with the inferior pedicle technique.

In cases of severe macromastia, the free nipple graft technique has been the traditional alternative to pedicle transposition. Distress over nipple survival in large reduction mammaplasty and long pedicle transposition is largely responsible for this.A retrospective investigation of the records of 142 reduction mammaplasty patients was carried out to determine whether nipple survival or overall complication rates were significantly different in patients undergoing larger (>1500 g per side) as compared with smaller reductions (< 1500 g per side). The 2 patient groups were compared with respect to mild or severe complications. Data were analyzed using Fisher exact test and 2-sample t tests. A P value of < 0.05 was considered statistically significant. No patient in either group had total nipple loss. There were no statistically significant differences in major or minor complications between the 2 groups. In our experience, the inferior pedicle, Wise pattern reduction is a reliable and predictable method of reduction, appropriate for all breast sizes and pedicle lengths.

Vascular endothelial growth factor (VEGF) expression and the effect of exogenous VEGF on survival of a random flap in the rat.

The induction of endogenous vascular endothelial growth factor (VEGF) production in the skin flap with ischemic injury and the effect of exogenous VEGF on survival of the ischemic skin flap were studied in rats. A dorsal flap model (3x10 cm(2)) was used in this study. In Part I, biopsies were taken from the flap at 2.5, 5.5, and 8.5 cm distances from the distal edge at 0, 6, 12, and 24 h after the flaps were sutured. Malonyldialdehyde (MDA) and VEGF(165) protein level were measured. In Part II, exogenous VEGF (1 microg/ml) was injected subdermally into the flaps in 14 rats before the flaps were replaced. Flaps that received a saline injection were used as the controls. The skin paddle survival was measured on postoperative day five. The results showed that the MDA level in the distal part of the flap significantly increased at 24 h postoperatively when compared to MDA in other parts of the flap. However, VEGF levels in the distal part of the flap significantly decreased when compared to the middle part of the flap. Subdermal injection of exogenous VEGF to the distal area of the flap could significantly improve survival of the distal flap (89% of total skin paddle) when compared to the control, which had a 64% mean percent survival. We conclude that production of endogenous VEGF protein is significantly increased in the skin flap with mild ischemia, but decreased in the flap with severe ischemia. Administration of exogenous VEGF could significantly enhance survival of ischemic flaps.

Accelerating flap maturation by vascular endothelium growth factorin a rat tube flap model.

The effect of exogenous vascular endothelium growth factor (VEGF) on the survival of the distal skin paddle with early pedicle division was studied in a rat tubed pedicle flap model. In part I, tubed pedicle skin flaps were created on the backs of 14 rats. The pedicle was divided after an interval of 3, 4, 5 or 7 days, and the survival area of each distal skin paddle was measured 5 days after the pedicle was divided. The percentages of survival were 0, 24.9%, 89.9% and 100%, respectively. In part II, tube flaps were created in 20 rats. In the experimental group, 2 ml of VEGF (50 microg ml(-1)) was injected into the recipient bed during tube flap creation in each rat. In the control group, 2 ml of saline was given. The tubed pedicle was divided 4 days after creation. The mean survival area of the distal skin paddle in the group treated with VEGF was 7.32 +/- 1.36 cm(2) (80.91%) at 5 days after pedicle division, which was of statistical significance when compared with the survival in the control group of 2.70 +/- 1.89 cm(2) (27.9%). The histology showed angiogenesis at the skin paddle-recipient bed interface following VEGF injection. These results demonstrate that the subcutaneous administration of VEGF into the recipient bed of the tube flap transfer can induce angiogenes is at the junction between the donor and the recipient bed, and improve skin paddle survival with early pedicle division.

Injuries associated with mandible fractures sustained in motor vehicle collisions.

Motor vehicle collisions are second only to altercations as the most common cause of mandible fractures. This article details in a retrospectively studied group the incidence of isolated mandible fractures and associated injuries in patients who were involved in motor vehicle collisions. This group consisted of 148 patients with mandible fractures listed in the University of Mississippi's trauma registry during the past 5 years. In almost all patients, associated injuries occurred with mandible fractures that were caused by motor vehicle collisions, with an incidence of 99.3 percent. Facial and head lacerations and facial fractures were the leading associated injuries, occurring in more than half of the patients who had a mandible fracture. Closed head injury is the major life-threatening associated injury and cause of mortality. The life-threatening injuries occurred in 64.8 percent of patients in this study. The mortality rate in this group of patients was 8.1 percent. These data suggest that mandible fractures from motor vehicle collisions should never be viewed as an isolated injury but rather as part of a spectrum of significant and sometimes life-threatening injuries that require thorough trauma evaluation at the time of presentation.

The role of fructose-1,6-diphosphate in cell migration and proliferation in an in vitro xenograft blood vessel model of vascular wound healing.

Both smooth muscle cells and endothelial cells play an important role in vascular wound healing. To elucidate the role of fructose-1,6-diphosphate, cell proliferation and cell migration studies were performed with human endothelial cells and rat smooth muscle cells. To mimic blood vessels, endothelial and smooth muscle cells were used in 1:10, 1:5, and 1:1 concentrations, respectively, mimicking large-, mid-, and capillary-sized blood vessels. Cell migration was studied with fetal bovine serum-starved cells. For cell proliferation assay, cells were plated at 30-50% confluency and then starved. The cells were incubated for 48 h with fructose-1,6-diphosphate at (per ml) 10 mg, 1 mg, 500 microg, 250 microg, 100 microg, and 10 microg, pulsed with tritiated-thymidine and incubated with 1 N NaOH for 30 min at room temperature, harvested, and counted. For migration assay, confluent cells were starved, wounded, and incubated for 24 h with same concentrations of fructose-1,6-diphosphate as in proliferation assay. The cells were fixed and counted. Smooth muscle cell proliferation was inhibited by fructose-1,6-diphosphate at 10 mg/ml. In the xenograft models of 1:10, 1:5, and 1:1 fructose-1,6-diphosphate inhibited proliferation at 10 mg/ml. In migration studies 10 mg fructose-1,6-diphosphate per ml was inhibitory to both cell types. In large-, mid-, and capillary-sized blood vessels, fructose-1,6-diphosphate inhibited proliferation of both cell types at 10 mg/ml. At the individual cell level, fructose-1,6-diphosphate is nonstimulatory to proliferation of endothelial cells while inhibiting migration, and it acts on smooth muscle cells by inhibiting both proliferation and migration.

Effect of lipectomy on growth and development of hyperinsulinemia and hyperlipidemia in the Zucker rat.

The Zucker fat rat inherits obesity and hyperinsulinemia, exhibits insulin resistance, and is, therefore, a model of adult onset, or type II, diabetes. The purpose of this study was to determine if excision of fat depots from the infant Zucker (fa+/fa+) rat would affect growth, fat cell number, hyperinsulinism, and hyperlipidemia. In the experimental design, 10 percent of the total body weight (inguinal and interscapular depots) was excised at 6 weeks of age from 18 fat and 18 lean (fa+/fa-) litter mates, with 18 fat and 18 lean rats serving as nonoperated controls. At intervals, serum glucose, insulin, cholesterol, and triglycerides were measured. Initially, the operated fat group was significantly (p < 0.01) lighter than the nonoperated group. By 9 weeks postoperatively, the operated fat rat group had regained weight and continued to grow at the same rate as the nonoperated fat rats because of intra-abdominal fat depots. Lipectomy had no effect on growth rate of the lean rat group. Although lipectomy caused no consistent change in serum glucose or insulin levels, it caused a significant decrease in lipid levels. For example, the operated fat rats had a reduction in cholesterol from 876 to 171 mg/dl by 15 weeks postoperatively, and serum cholesterol persisted at about 50 percent of the nonoperated group throughout the rest of the study (38 weeks postoperatively). Even a greater reduction in triglyceride levels occurred, for example, from 7415 to 1082 mg/dl at 24 weeks postoperatively. Lipectomy did not cause a change in lipid levels in the lean group. It is concluded that the lipectomy in the Zucker fat group is an excellent model to evaluate the effects of changes in fat cell number on lipid metabolism.

Nerve regeneration in diabetic rats.

This study evaluated the capacity of diabetic rats to recover the ability to walk after nerve repair or nerve graft of the posterior tibial nerve at thigh level. Functional recovery of the posterior tibial nerve was evaluated by walking track analysis during regeneration in streptozotocin-induced diabetic rats. Surgical procedures were performed 8 weeks after induction of diabetes. The nerve repair was epineurial. The nerve graft was a 1.5 cm segment orthotopically replaced. There was no significant difference in functional recovery between normal and diabetic rats for both the nerve repair and nerve graft groups at 6, 12, and 24 weeks after nerve reconstruction. It is concluded that the presence of diabetes is not a contraindication for nerve reconstruction.

Role of reactive oxygen species in optic nerve compression injury: a preliminary study.

Optic nerve compression is one of the complications in craniofacial surgery and blepharoplasty. We have shown previously that acute and chronic nerve compression produce significant tissue injury in rat sciatic nerve. In the present study the optic nerve was evaluated for possible ischemia/reperfusion injury after acute compression in an animal model. Male New Zealand White rabbits were used in the experiment. The optic nerve was subjected to 2-hour compression followed by reperfusion for 1 hour. Nerve compression was established by banding the optic nerve with silastic tubing. The compressed optic nerve was assayed for malondialdehyde, an indicator of lipid peroxidation, measured as thiobarbituric acid reactive substances (TBARS). The TBARS levels increased significantly to 2.5 times normal, from 37+/-6 pmoles per milligram tissue (N=6) to 90+/-12 pmoles per milligram tissue dry weight (N=5) in the compressed/reperfused nerve (p < 0.05). Much of these increases were prevented by treatment with deferoxamine, an iron chelator and antioxidant. The results indicate that optic nerve is injured by acute compression followed by reperfusion. The nerve compression injury appears to be due to reactive oxygen species and can be ameliorated by treatment with free radical scavengers.

Effect of turmeric, turmerin and curcumin on H2O2-induced renal epithelial (LLC-PK1) cell injury.

Cell injury by oxidative stress is an important mechanism for renal epithelial cell destruction. This study observed the protective effect of turmeric and its constituents on H2O2-induced injury. Turmeric consists of a water soluble turmerin and lipid soluble curcumin with potent antioxidant properties. Confluent LLC-PK1 cells were labelled with 3H-arachidonic acid at 0.1 microCi/ml over 18 h and then further labelled with 51Cr. Turmeric ( 100 microg/ml-0.1 microg/ml), turmerin (800 ng/ml-0.8 ng/ml), curcumin (100 microg/ml-0.1 microg/ml), vitamin E (100 microM) and 21-aminosteroid (20 microM) were added and incubated for 3 h at 37 degrees C in 24-well plate. The adherent cells were washed and incubated for 3 h with 1.5 mM H2O2 at 37 degrees C. 3H-arachidonic acid release, 51Cr release and lipid peroxidation by the thiobarbituric acid reaction was determined. Turmeric ( 100 microg/ml) and curcumin (100 microg/ml, 10 microg/ml) gave as much protection as did vitamin E in both chromium release assay and lipid degradation while Turmeric (100 microg/ml) and curcumin (100 microg/ml) gave comparable inhibition of lipid peroxidation. Turmerin and 21-aminosteroid showed no protection. These findings provide evidence that turmeric and curcumin provide protection against oxidative stress in a renal cell line.

Secondary ischemic tolerance improved by administration of L-NAME in rat flaps.

Nitric oxide (NO) under basal conditions is an important regulator of vascular tone. Under ischemic conditions, however, NO can combine with superoxide anion to produce the damaging hydroxyl free radical. The current project observes the effect of inhibiting NO production (L-Nitro-amino-methyl-arginine, L-NAME) on flaps rendered ischemic by secondary (2 degrees) venous obstruction. Eighty rats had 3 x 6 cm skin flaps based on the epigastric vessels. Primary (1 degree) ischemia was produced by arteriovenous occlusion for 2 hours; (2 degrees) venous ischemia was induced by clamping the vein, alone for either 3 or 5 hours. Thirty minutes prior to 2 degrees ischemia, rats received either L-NAME (30 mg/kg) or saline buffer. Flap survival was assessed 7 days later and Chi-square analysis was used. At 3 hours of ischemia, treatment improved survival from 55% to 85% (P < 0.05). Treatment also improved survival at 5 hours of ischemia from 5% to 35% (P < 0.04). Although under resting conditions, NO is a potent vasodilator, during 2 degrees venous obstruction it may contribute to flap necrosis.

Effects of tissue expansion on secondary ischemic tolerance in experimental free flaps.

The effects of tissue expansion on free flap tolerance and metabolic response to secondary ischemia were evaluated. A total of 178 male syngeneic Lewis rats were used: 28 in perfusion study and 75 donor and 75 recipient animals in flap survival study. Animals were organized in three experimental groups: control, sham operation, and expansion group. Sham group animals had the expander implanted but not insufflated. After 4 weeks of tissue expansion, 3 x 5-cm epigastric free flaps were transplanted to recipient animals. Twenty-four hours later, secondary ischemia was produced by 3-hour venous occlusion. Flap survival, perfusion, and enzyme activities were determined. Pre-expanded skin flaps had an increase in perfusion of approximately 700% as measured by fluorescein levels compared with control flaps (p < 0.001) and demonstrated a better success rate (76%) compared with those of the control (40%) (p < 0.05) and sham (28%) groups (p < 0.05). Glutathione peroxidase, glutathione reductase, and glucose 6-phosphate dehydrogenase of the antioxidant defense systems significantly increased in skin in both the sham and the expansion groups. In response to secondary ischemia, the control and sham groups exhibited a decrease in enzyme activities of the glutathione redox cycle, whereas the expansion group showed no significant changes from the elevated baseline activities. Tissue expansion improved flap tolerance to secondary ischemia by increasing flap circulation and probably by augmenting tissue metabolic response to oxidative stress.

Free radical damage in acute nerve compression.

Nerve compression causes injury by local ischemia and direct mechanical distortion. Peripheral nerves in diabetes mellitus are more prone to injury than those of nondiabetics. We sought to determine whether reperfusion-induced, oxygen-derived free radical injury occurs in peripheral nerves subjected to acute compression in normal and chronically diabetic rats. Female Sprague-Dawley rats weighing 250 to 275 g (N = 347) were divided into two groups: normal and streptozocin-induced diabetics. A total of 187 normal and 160 diabetic nerves were analyzed. After 8 weeks of untreated hyperglycemia, the sciatic nerves of normal and diabetes mellitus rats were subjected to one of three operations: a sham operation, 24-hour compression alone, and 24-hour compression followed by 1-hour reperfusion (CR). Nerve compression was established by banding the right sciatic nerve with a Silastic tubing, 1 cm long and 0.62 mm internal diameter, which was secured with 6-0 nylon suture. In the CR group, after 24 hours of compression, the tubings were released for 1 hour to permit reperfusion. Nerve tissue within the zone of compression underwent biopsy examination and was frozen for subsequent analysis. Blood flow to the nerve was quantified by injecting fluorescein (10 mg/kg intravenously) 10 minutes before harvest and measuring tissue levels fluorometrically. Compression with the Silastic tubing significantly reduced neural blood flow by 75%. Blood flow improved but failed to return to baseline levels after tubing release in diabetes mellitus nerves while perfusion returned to baseline in non-diabetes mellitus nerves. Nerve homogenate was assayed for malonyldialdehyde, an indicator of lipoperoxidation, as well as enzymes of cellular defense and glucose metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of 21-aminosteroid U74389F on skin-flap survival after secondary ischemia.

The effect of 21-aminosteroid, a lazaroid (U74389F), on tissue injury after secondary ischemia was evaluated in 3 x 5 cm island skin flaps in male Sprague-Dawley rats (n = 30). Primary ischemia was produced by arteriovenous occlusion for 1 hour. Eighteen hours later, secondary ischemia was inflicted by 4-hour venous occlusion. The treatment group received intravenous lazaroid (3 mg/kg) 30 minutes before the start of secondary ischemia. The control group received the same volume of citrate buffer vehicle using the same route and schedule. Skin-flap survival was an all-or-none phenomenon and assessed at 7 days after secondary ischemia. Malondialdehyde (MDA) content was measured to determine the occurrence of lipid peroxidation. Myeloperoxidase (MPO) activity was assayed to assess the degree of neutrophil infiltration. Treatment with this lazaroid significantly improved the survival rate from 0 percent (0 of 13) to 53 percent (9 of 17) (p < 0.01). Malondialdehyde content was 62 +/- 10 (mean +/- SEM, n = 4) pmol/mg dry weight in normal skin. Malondialdehyde increased by 3 times normal in the flaps destined to survive and by 13 times in the flaps destined to undergo necrosis (p < 0.001). Myeloperoxidase activity was negligible in normal skin. At the end of secondary ischemia, the flaps destined to survive exhibited a high myeloperoxidase activity. The flaps destined to necrosis showed the enzyme activity 2.2 times more than surviving flaps (p < 0.01). The results suggest that the lazaroid U74389F may improve survival by attenuating neutrophil infiltration and by reducing lipid peroxidation.

Regional hemodynamics in 1-day-delayed rodent island flaps.

We have studied the recovery of microvascular function in ischemic epigastric skin flaps by characterizing the regional hemodynamics in the axial and random portions of double- and single-pedicle island skin flaps in the rat. Blood flows were measured with radiolabeled microspheres 1 day after bipedicle flaps were elevated and at 4 hr, 72 hr, and 1 week after ligation of one of the pedicles. These hemodynamic measurements were correlated with assessments of angiogenesis and skin necrosis performed by lectin histochemistry and histopathology. Twenty-four hours after the skin flap elevation, the mean blood flow was 0.26 ml.min-1.g-1. After the ligation of one pedicle, the blood flow in the axial portion of the skin flap was unchanged at 4 hr (0.22 ml.min-1.g-1), declined insignificantly at 72 hr (0.15 ml.min-1.g-1), and remained normal at 1 week. In the random portion of the skin flap very little collateral blood flow was present at 4 hr (0.06 ml.min-1.g-1) and 72 hr (0.09 ml.min-1.g-1). Blood flow in the random skin flap returned to normal by 1 week (0.27 ml.min-1.g-1). Reelevation of the skin flap at 1 week caused an insignificant decline (10%) in total blood flow to the skin flap. Skin necrosis was detected histologically at 72 hr only in the lateral portion of the random skin flap, where blood flow was less than 0.03 ml.min-1.g-1. Increased areas of lectin binding to vascular endothelium were seen in the subdermal layers of the skin flap by 1 week, presumably due to angiogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Dimethyl sulfoxide increases the survival of primarily ischemic island skin flaps.

There is ample evidence of the involvement of free radicals in mediating skin flap necrosis. Dimethyl sulfoxide (DMSO) is a well-tolerated, safe drug that is a powerful scavenger of the hydroxyl free radical. The current study investigated the effect of DMSO on the survival of 9 x 4 cm skin flaps based on the epigastric vessels subjected to primary venous occlusion. Forty-seven skin flaps were elevated and the epigastric vein was occluded by a microvascular clamp for 8 hours. Group 1 received DMSO (1.5 gm/kg) intraperitoneally at reperfusion. Group 2 received saline solution, group 3 received DMSO at reperfusion and every day for 5 days, group 4 received DMSO preoperatively and then as in group 3, and group 5 was the saline solution control for groups 3 and 4. DMSO did not increase percent flap survival when given as a single dose at reperfusion (40.6% +/- 42.7%) compared with saline solution (33.7% +/- 41.2%). When DMSO was continued in the postoperative period, group 3 (86.2% +/- 25.8%) and group 4 (78.0% +/- 32.5%) had significantly better survival than the saline solution control group (32.6% +/- 39.8%) (p < 0.01 and p < 0.03, respectively). There was no significant difference between groups 3 and 4. DMSO administered at reperfusion and postoperatively for 5 days significantly increased flap survival. It is hypothesized that this occurs through scavenging deleterious free radical species. This effect may have clinical significance.

Effects of combined cold and hyperbaric oxygen storage on free flap survival.

We have previously reported that hyberbaric oxygen (HBO) improved the survival rate of experimental free flaps. The purpose of this study was to evaluate the effects of combined hypothermia and HBO administered during storage on free flaps and on the xanthine oxidase system in rats. Epigastric skin flaps were stored cold for 48 and 72 hours either in room air or under HBO (2.9 atmospheres absolute, 100% oxygen) before free flap transfer. The success rates of free flaps were 80% (8/10) after 48 hours and 20% (2/10) after 72 hours of cold storage in room air. HBO produced no effect after 48 hours but significantly increased the success rate to 70% (7/10) after 72 hours of cold storage. Tissue hypoxanthine (plus xanthine) levels increased to 210% of normal after 48 hours of cold storage in room air and to 176% in HBO. Elevated hypoxanthine levels returned toward normal by 72 hours of cold storage in room air, while the increased levels remained under HBO. Xanthine oxidase activities significantly increased by 60 to 80% during 72 hours of room air storage. HBO treatment inhibited xanthine oxidase activity to 48% of normal by 72 hours of storage. Free flaps exhibited no significant alterations in GR and G6PDH activity after 48 hours of cold storage in room air or HBO. After 72 hours of cold storage, the room air control displayed a trend of decreasing GR activity and a significant 20% decrease in G6PDH activity, while HBO groups showed no significant alterations in both GR and G6PDH activity compared to normal. Protection of the antioxidative enzymes by hypothermia and inhibition of the xanthine oxidase activity by HBO appear to be one of the mechanisms of improved skin flap survival in free flaps.

Age and tolerance to secondary ischemia in rat epigastric flaps.

The use of microvascular procedures is increasing as the population continues to age. The purpose of this study was to observe the survival of skin flaps after ischemic injury. Skin flaps (n = 50) underwent either 3 hours of primary (1 degree) or secondary (2 degrees) venous occlusion in young (2-3 mo) and old (18-22 mo) rats. Skin flap survival was assessed on postoperative day 7. Survival rates for young and old after 3 hours of 1 degree ischemia was 100% and 90% (ns). Survival rats for young and old after 2 degrees ischemia were 67% and 47% (ns).

Flap tolerance to ischaemia in streptozotocin-induced diabetes mellitus.

The effects of diabetes mellitus (DM) on skin flap tolerance to 3 h of secondary venous ischaemia were evaluated. Epigastric island flaps were elevated 3, 6 and 12 weeks after induction of DM in rats. In the non-diabetic control groups, the flap survival was 85% in the 3-week group, 72% in the 6-week, and 78% in the 12-week. In untreated DM groups, the flap survival significantly decreased to 40% in the 3-week group, 25% in the 6-week, and 17% in the 12-week (P < 0.05 in all groups). Flap survival in the DM/insulin group decreased to 31% in the 3-week group. Effects of insulin therapy, however, were observed in later stages of DM: 71% and 62% survival in the 6- and 12-week group, respectively. Significant linear correlations between enzymatic responses and the flap survival were found. The results suggest that DM is detrimental to flap tolerance and is associated with the lack of metabolic responses to secondary ischaemia.

Microanalyses of enzymes and metabolites in ischemia/reperfusion-induced partial-thickness skin wounds.

A transition zone between well-perfused proximal tissue and inadequately perfused distal tissue was evaluated histologically and biochemically in skin flaps. Cranially based pedicle flaps, 3 x 7.5 cm, were made on the backs of female Sprague-Dawley rats. Flap survival was 22% of the original flap area at 7 days and 40% at 14 days after flap elevation (p < 0.001). The transition zone consisted of full-thickness skin survival proximally and partial-thickness wound distally. It is evident that skin wounds induced by ischemia or reperfusion repair continuously between 7 and 14 days after flap elevation. Tissue glucose, lactate, and hypoxanthine levels were measured to assess capillary perfusion in the transition zone on postoperative day 3. The proximal full-thickness skin 5 mm from the wound margin demonstrated no significant changes in glucose and lactate levels compared with normal skin. The partial-thickness wounds exhibited no change in glucose (a 33% decrease was not statistically significant) but a significant increase (319% of normal) in lactate level (p < 0.05). Hypoxanthine levels increased to 453% of normal in full-thickness skin (p < 0.01) and to 787% in partial-thickness wounds (p < 0.001). Metabolic response was evaluated by enzyme assays in the transition zone. Hexokinase activity increased by 251% of normal (p < 0.05), glucose 6-phosphate dehydrogenase by 245% (p < 0.01), and glutathione reductase by 184% (p < 0.05) in the proximal full-thickness skin. Hexokinase activity further increased by 482% of normal (p < 0.01), glucose 6-phosphate dehydrogenase by 379% (p < 0.05), and glutathione reductase by 346% (p < 0.01) in partial-thickness wounds. The results suggest that partial-thickness wounds have less capillary circulation but greater antioxidant enzyme activities than does the survival area with full-thickness skin.