Heparin coating of vascular prostheses reduces thromboemboli.

BACKGROUND: Synthetic conduits made from currently available materials are suboptimal for use in small-diameter vascular reconstruction because of their high surface thrombogenicity, which leads to failure. METHODS: In this study control, heparin-irrigated, or heparin-bonded expanded polytetrafluoroethylene (ePTFE) grafts (4 mm long by 1 mm inner diameter) were implanted to reconstruct the iliac artery in male rats. The cremaster muscle was isolated as an island flap based on branches of the iliac artery downstream from the graft. Emboli were quantitated by using intravital fluorescent microscopy of the cremaster muscle's microcirculation. RESULTS: The mean number of emboli observed per animal during a 20-minute period was 91 for the control group, 84 for the heparin-irrigated group, and 22 for the tridodecylmethylammonium chloride (TDMAC)-heparin group. The mean area of each embolus was 1057 microns 2 for control, 940 microns 2 for heparin-irrigated, and 808 microns 2 for TDMAC-heparin-coated grafts (p < 0.05 for TDMAC-heparin versus control or heparin-irrigated). CONCLUSIONS: A TDMAC-heparin coating of ePTFE microvascular prostheses significantly reduces downstream microemboli.

Effects of method of hemostasis on wound-infection rate.

Adequate hemostasis is important in preventing postoperative wound infection. This study compared four methods of hemostasis: specific pinpoint vessel electrocautery (SPC), specific vessel ligation with 4-0 vicryl (SVL), nonspecific electrocautery of vessel plus excessive surrounding tissue (NSC), and nonspecific ligation of vessel and excessive surrounding tissue with 4-0 vicryl (NSL), on the rate of wound infection in rabbits that were contaminated with 10(6) Staphylococcus aureus. There was no statistical significant increase in the rate of wound sepsis when electrocautery was used in a fashion producing minimal nonviable tissue compared to specific vessel ligation. Electrocautery use for specific vessel hemostasis does not result in a higher wound infection rate in contaminated wounds.

Heparin bonding increases patency of long microvascular prostheses.

The high thrombogenicity of synthetic biomaterials has limited their use for reconstructive microsurgery. Prime factors in the thrombogenicity of synthetic materials in contact with blood include gas nuclei at the blood gas interface as well as the inherent thrombogenicity of the materials themselves. Expanded polytetrafluoroethylene (ePTFE) vascular prostheses were denucleated by placement in acetone and ethanol followed by degassed saline or by placement in degassed saline subjected to hydrostatic pressure. Heparinized grafts were prepared by coating with tridodecylmethylammonium chloride (TDMAC), followed by immersion in heparin. Grafts were installed to reconstruct the femoral artery (1 x 10 mm) or as renal-iliac bypasses (1 x 50 mm) in rats. In the femoral artery reconstruction model, control grafts thrombosed within 10 minutes of implantation. All acetone denucleated femoral grafts remained patent for 60 minutes but were occluded at day 1. All pressure denucleated femoral grafts remained patent for 60 minutes, whereas six were patent at 1 month. In contrast, 11 of 15 heparinized femoral grafts were patent at 1 month. In the renal iliac bypass model, all control grafts were thrombosed within 10 minutes, whereas all heparin bonded grafts remained patent at 1 month. This finding confirms that removal of air from small diameter ePTFE grafts decreases acute thrombogenicity and that heparin bonding further decreases thrombogenicity, suggesting that clinically useful lengths of microvascular prostheses may be possible.

Stimulation of DNA synthesis in human epidermis by UVB radiation and its inhibition by difluoromethylornithine.

The purpose of this study was to determine whether the rate of DNA synthesis in human skin could be increased by UVB radiation and to determine the potential for reversing the stimulatory effects of UVB radiation by alpha-difluoromethylornithine (DFMO). Split-thickness facial skin was grafted onto athymic CD-1 Nu/Nu mice on the anterolateral dorsal surface. Following graft healing for 6 weeks, grafts were treated with 0%, 2%, or 5% DFMO (a potent inhibitor of polyamine biosynthesis) and subsequently irradiated with 0.15 J/cm2 of UVB light. Two days after UVB exposure, [3H]thymidine was injected and the grafts were dissected and counted. Ultraviolet radiation significantly increased thymidine incorporation, indicating increased DNA synthesis. The stimulatory effects of UV radiation were significantly reduced by topical application of 5% DFMO. Thus administration of DFMO most likely decreased the polyamine level and decreased the rate of DNA synthesis, which may have caused a decreased rate of epidermal proliferation. Thus the topical application of DFMO may prove beneficial for UVB exposure and other hyperproliferative states where a decrease in the rate of cell turnover might be desirable.

Donor leg morbidity and function after fibula free flap mandible reconstruction.

The purpose of this study was to determine the donor leg morbidity and function after removal of the fibula free flap for mandible reconstruction. In the past 24 months, 29 consecutive patients underwent a total of 30 fibula free flap mandible reconstructions. A muscle-sparing technique was used to harvest the fibula flap, and the proximal 6 cm and distal 8 cm of fibula were left intact. Patients included 20 men and 9 women; their mean age was 58.8 years (range 29 to 82 years); the mean length of fibula removed was 14.5 cm (range 8 to 25 cm); osteocutaneous flaps were used in 27 patients (90 percent); and 16 patients (53 percent) required skin grafts to the donor leg. Donor leg morbidity and function were determined by patient questionnaire, physical examination, and isokinetic testing, with the opposite, unoperated leg serving as a control. Immediate postoperative morbidity occurred in 5 patients (17 percent) (infection, wound separation, or partial graft loss); none required additional surgery for donor complications. Patient questionnaires were completed by all patients at an average of 7.3 months after surgery. Patients were able to ambulate pain-free an average of 5.1 weeks (range 2 to 32 weeks) postoperatively and were all fully able to engage in all daily and recreational activities. Most (21 patients, 72 percent) were free of any donor pain, and the remainder (28 percent) had only occasional mild discomfort. Other complaints included ankle stiffness (41 percent), mild ankle instability (10 percent), and transient peroneal motor (7 percent) or sensory (28 percent) loss, which resolved in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of ultraviolet light-induced epidermal damage: beneficial effects of tocopherol.

Oxygen free radicals have been shown to result from and mediate deleterious effects of ultraviolet radiation on the skin. The purpose of this study was to determine if topical DL-alpha-tocopherol (vitamin E) could reduce ultraviolet-induced damage to the epidermis. Twenty mice were treated with either ethanol or a 1:1 mixture of tocopherol and ethanol. Treatments consisted of once-daily 0.1-ml topical applications for 1 week, followed by irradiation with 0.30 mW/cm2 of ultraviolet B irradiation. A statistically significant decrease in Schiff base formation was noted between tocopherol-treated animals and their controls. Histologic study revealed a statistically significant increase in epidermal thickness in tocopherol-treated skin versus controls or vehicle alone. The thicker epidermis was accompanied by the presence of parakeratosis, implicating increased proliferation as the cause of the increasing thickness. The number of sunburn cells was decreased by tocopherol treatment. Tocopherol protection from ultraviolet irradiation may have been due to both direct protection from free radicals and indirect protection by means of increased epidermal thickness. The demonstration of beneficial effects of tocopherol administration suggests that further studies in clinically relevant models to define optimal dosage, frequency of administration, vehicle, and quantitation of the possible protective effects afforded to Langerhans cells may be useful.

Management of the buried penis in adults.

PURPOSE: Buried penis, most commonly seen in children, is particularly debilitating in adults, resulting in the inability to void standing and it affects vaginal penetration. The pathophysiology, including scar contracture of the distal soft tissue and skin envelope with concurrent descent of the abdominal fat pad, represents a surgical challenge. We developed a management algorithm to evaluate and treat adults with buried penis. MATERIALS AND METHODS: From January 1, 1994 to May 1, 1996, 7 patients 23 to 66 years old presented with buried penis. Diabetes mellitus, a common co-morbid condition, was present in 5 patients, and 5 of 7 were morbidly obese. RESULTS: Surgical correction was performed in 5 patients with excellent results in 3. Resection of scar contracture was sufficient to provide adequate length and none required release of the suspensory ligament. Panniculectomy was performed in 1 patient. One man requiring a graft to achieve adequate penile coverage required reoperation. This patient had undergone a previous attempted repair with extensive contracture. All patients regained potency postoperatively. CONCLUSIONS: With appropriate planning and adherence to basic reconstructive surgical principles, correction of the buried penis can yield a high success rate.

Calcitonin gene-related peptide mediates hypotension and tachycardia in endotoxic rats.

Circulating calcitonin gene-related peptide (CGRP) concentrations are elevated in experimental and clinical sepsis. CGRP causes hypotension and tachycardia, suggesting that the peptide might mediate the acute circulatory changes in sepsis. To test this hypothesis we administered Escherichia coli endotoxin (8 mg/kg iv) to Nembutal- (pentobarbital sodium; 50 mg/kg) anesthetized rats. Endotoxin caused hypotension and tachycardia within 60 min that stabilized for 90 min. After 2 h more severe hypotension developed, and 80% of rats died spontaneously after 3 h. In other endotoxic rats we administered 20 nmol of the CGRP receptor antagonist hCGRP (8-37) intravenously at 60 min. hCGRP (8-37) transiently reversed tachycardia (from 469 +/- 11 to 407 +/- 7 beats/min, P < 0.05) and increased mean blood pressure (from 63 +/- 4 to 93 +/- 11 mmHg, P < 0.05) over 30 min, after which hemodynamics and survival rates were no different from untreated animals. The results suggest that CGRP plays an important role in the acute circulatory changes of endotoxemia. More detailed work is necessary to determine the effects of CGRP antagonism on cardiac function, regional blood flow, and overall survival rates in sepsis.

Enhancing fibula free flap skin island reliability and versatility for mandibular reconstruction.

Although the fibula osteocutaneous free flap has many advantages when used in mandibular reconstruction, many investigators have found the skin island is not always reliable. We present a technique that enhances skin island reliability by including a maximal number of skin perforators. This method has been used in 10 consecutive osteocutaneous free flaps without any skin loss. This technique also expands the usefulness of the fibula free flap, allowing it to be used for shorter bone defects or in cases when skin coverage is needed at a distance from the bone. In addition, this method provides additional vascularized soft tissue for neck contour restoration and coverage of fixation plates.

The course of the inferior alveolar neurovascular canal in relation to sliding genioplasty.

The anterior course of the inferior alveolar neurovascular canal was determined in 52 hemimandibles using high-resolution radiographs. Significant variability was found in its course. It was noted that if the osteotomies for sliding genioplasty were performed at least 6 mm below the inferior border of the mental foramen, injury to the mental nerve would be reduced.

Improved microsurgical anastomotic patency with low molecular weight heparin.

Blood flow to a free flap may be impaired by thrombotic occlusion at the anastomosis or by microemboli occluding microvessels. The purpose of this study was to test the hypothesis that unfractionated heparin (UFH) or low molecular weight fractions of heparin (LMWH) could improve both the patency of microvascular anastomoses and microcirculatory perfusion. Sixty-six rats underwent orthotopic elevation of 3- x 10-cm epigastric free flaps. Animals received a single injection of either vehicle, UFH or LMWH, prior to microvascular clamp application and pedicle division. Anastomotic patency and tissue survival area were assessed on postoperative day 7. Anastomotic patency was significantly improved in both the UFH and LMWH groups. Total tissue survival area in those flaps with anastomotic patency was significantly improved in the UFH and the LMWH groups. Although both UFH and LMWH significantly elevated activated partial thromboplastin times (APTT) and anti activated clotting factor X (anti-Xa) activity over controls, UFH had its greatest effect on APTT, and LMWH on anti-factor Xa activity. Hematomas developed only in the UFH group. Thus, although both UFH and LMWH improved microcirculatory perfusion, as indicated by increased flap survival, only LMWH improved anastomotic patency while minimizing hemorrhage.

Hydrostatic pressure reduces thrombogenicity of polytetrafluoroethylene vascular grafts.

A prime factor in the thrombogenicity of synthetic materials in contact with blood is the blood-gas interface. Small pockets of gas, known as gas nuclei, are trapped within surface interstices. The resulting blood-gas interface denatures plasma proteins and activates clotting factors and platelets. Expanded polytetrafluoroethylene (ePTFE) vascular prostheses 1 mm in internal diameter were placed in saline under 6,000 psig hydrostatic pressure for 2 h in an attempt to dissolve all gas nuclei (i.e., to denucleate). Carotid-carotid bypasses were performed in rats using 280-mm lengths of ePTFE. All 10 control grafts lost patency in 5 min, whereas the 14 denucleated grafts had a median patency duration of 300 min (P less than 0.01). In 15-mm-long rat femoral artery interpositional ePTFE grafts, 90% of controls thrombosed within 10 min, whereas only 7% of denucleated grafts thrombosed over the duration of the 7-day observation period (P less than 0.001). Denucleation also resulted in a significant reduction (P less than 0.02) in 111In-labeled platelet adhesion to 36% of control. Scanning electron microscopy confirmed the reduced accumulation of platelets on denucleated grafts. These data suggest that the removal of trapped air with hydrostatic pressure significantly reduces the thrombogenicity of ePTFE microvascular prostheses and may have application to other clinical (catheters, valves, tubing, etc.) or experimental (micropipettes, electrodes, etc.) materials that interface with blood.

Advances in prevention of radiation damage to visceral and solid organs in patients requiring radiation therapy of the trunk.

BACKGROUND: As a part of multimodality therapy, many patients with tumors of the trunk receive radiation therapy. The major morbidity of this therapy is often secondary to incidental radiation damage to tissues adjacent to treatment areas. METHODS: We detail our use of saline breast implants placed in polyglycolic acid mesh sheets to displace visceral and solid organs away from the radiation field. RESULTS: Analysis of CT scans and dose volume histograms reveal that this technique successfully displaces uninvolved organs away from the radiation fields, thereby minimizing the radiation dose to such organs and tissues. CONCLUSION: We believe this is a safe and efficacious method to prevent radiation damage to visceral and solid organs adjacent to trunk tumor sites.

Microsurgical composite tissue transplantation at difficult recipient sites facilitated by preliminary installation of vein grafts as arteriovenous loops.

In microvascular surgery when local recipient vessels are inadequate, vein grafting is required. There are several potential inherent disadvantages of immediate vein grafting, including the development of graft thrombosis or leakage, an increased opportunity for technical errors, and an increased number of anastomoses in series. All of these may contribute to a higher failure rate for composite-tissue transplantation requiring vein grafts. The authors hypothesized that in cases where vein grafting is obviously required, the creation of a temporary, looped, arteriovenous fistula (AVF) would reduce the morbidity of vein grafting, by allowing the detection of thrombosis or technical errors predisposing to thrombosis prior to free-tissue transplantation. Since delaying the division of an AVF for 5 or more days may allow time for healing of the endothelium at the AVF anastomotic site, the hypothesis was that composite-tissue transplantation whose vein grafts were installed as an AVF divided in a delayed manner, might have better patency than those in which vein grafts were installed at the time of reconstruction. This study reviews the results of 16 patients (8 females, 8 males) who underwent 17 microvascular reconstructions using AVFs. Patient courses and outcomes were compared between those undergoing immediate (8 patients) and delayed (7 patients) AVF construction, division, and free-tissue transplantation. There was a low patency rate for AVFs which were divided in a delayed fashion (2 of 7 patients, 29 percent), compared with those which were immediately divided (10 of 10, 100 percent). These results suggest that, in spite of a strong theoretical basis for delayed division of the AVF, delayed harvesting of the AVF is empirically associated with a higher thrombosis rate (p = 0.0048, Fishers exact test).

Patency and blood flow in gas denucleated arterial prostheses.

Biomaterials exposed to blood often fail due to thrombosis. Gas nuclei (air) in the material are thrombogenic and a potential cause of failure. The effects of gas nuclei on patency and blood flow were studied in 4 mm diameter arterial grafts (Gore ePTFE; Johnson and Johnson Vitagraft ePTFE; Bard ACG EXS) in the femoropopliteal position of dogs. Control and denucleated (air-free) grafts were implanted bilaterally. Grafts were denucleated by immersion in degassed saline and exposure to 4 torr vacuum and 3,000-20,000 psig pressure. Graft patency was determined at harvest in 46 dogs. Blood flow was measured with acoustic flow probes in eight dogs. Denucleated graft patency was 60% after 2 days of implant while control patency was 22% (P < .05). Measured blood flow was higher in denucleated grafts than in control grafts (P < .02) in 4 of 5 dogs which had significantly different flows. Patency and flow decreased to zero for both control and denucleated grafts over periods of up to 80 days. Air in the control grafts may have been absorbed within several days, leading to late similarity with the denucleated grafts. Thus, removing the air from 4 mm ePTFE grafts decreased acute thrombosis and increased the patency.

Assessments of thrombogenicity by three in vitro techniques. Student Research Award in the Undergraduate, Master Candidate, or Health Science Degree Candidate Category, 21st annual meeting of the Society for Biomaterials, San Francisco, CA, March 18-22, 1995.

This study assessed three in vitro techniques designed to measure the thrombogenicity of vascular grafts. All techniques immersed vascular grafts in rotating blood. In the gravimetric analysis, the weight of adherent thrombi was recorded at 2 min intervals for 20 min. In the torque analysis, a microviscometer continuously recorded the amount of torque developed as the graft rotated for 20 min. In the thrombin analysis, the blood sample was analyzed for fibrinopeptide A production indicating fibrinogen cleavage. Expanded polytetrafluoroethylene grafts were treated by removal of air nuclei (denucleation), binding of heparin, or binding of polyethylene oxide (PEO). The gravimetric analysis determined that the time at which each group experienced clot initiation was as follows: control after 6 min, denucleation after 14 min, heparin after 18 min, and PEO after 10 min. Similarly, in the torque analysis all treatment groups significantly delayed the initial increase in torque from 8.0 min for control to 12.5 min for denucleation (P < .01), > 20 min for heparin (P < .01), and 12 min for PEO (p < .05). The thrombin analysis determined that coagulation activity was reduced relative to control at 12 min with the denucleation group (P < .05) and heparin group (P < .01) and at 18 min with all treatment groups (P < .01). The similarity of results among the techniques increases confidence that each measurement accurately predicts in vitro thrombogenicity.