Krishna Narayanan

The Critical Relationship Between Free Radicals and Degrees of Ischemia: Evidence for Tissue Intolerance of Marginal Perfusion

UNLABELLED Skin-flap ischemia has been associated with the presence of free radicals. In this study, two enzyme systems involved in free-radical metabolism were used to compare a distal skin flap to a skin graft. Forty-two rats were divided into several test groups. A 10 X 3 cm dorsal rat flap was used, and tissue biopsies for xanthine oxidase and malonyldialdehyde (MDA) were obtained 2.5, 5.5, and 8.5 cm from the base of the flap at the hours given. In group I (control), the flap was outlined but not elevated, and biopsies were obtained. In group II, the flap was elevated, and biopsies were obtained at 6 hours. In group III, the flap was elevated, the distal 4 X 3 cm was amputated and replaced as a full-thickness skin graft, and biopsies were obtained at 6 hours. In group IV, the flap was elevated, and biopsies were obtained at 12 hours. In group V, the flap was treated as in group III, and biopsies were obtained at 12 hours. In group VI, the flap was elevated, and biopsies were obtained at 24 hours. In group VII, the flap was treated as in group III, and biopsies were obtained at 24 hours. RESULTS Xanthine oxidase was significantly higher in all distal biopsies compared to proximal biopsies. Xanthine oxidase also increased with time. Malonyldialdehyde increased over time as well as with distance from the flap base. Distal flap biopsies at 24 hours had greatly increased levels of malonyldialdehyde compared to skin grafts (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Deferoxamine increases skin flap survival: additional evidence of free radical involvement in ischaemic flap surgery

This study presents further evidence of free radical involvement in skin flap necrosis in a dorsal rat flap model. Rats receiving deferoxamine, a free radical scavenger and iron chelator had significantly less necrosis (p less than 0.001) than saline treated rats. In a separate experiment, tissue determinations for malonyldialdehyde (MDA) were consistent with the survival results in showing a significant decrease in MDA in all biopsy sites (p less than 0.05 or less), indicative of reduced lipoperoxidation in the deferoxamine treated rats.

Definitive diagnosis of breast implant rupture using magnetic resonance imaging

Breast implant rupture is an important complication of augmented and reconstructed breasts. Although several techniques such as mammography, xeromammography, ultrasound, thermography, and computed tomographic (CT) scanning have been proven to be useful to detect implant rupture, they have several disadvantages and lack specificity. In the current study, we have established magnetic resonance imaging (MRI) as a definitive, reliable, and reproducible technique to diagnose both intracapsular and extracapsular ruptures. The study was conducted in 100 symptomatic patients. Our imaging parameters were able to identify ruptures in implants with silicone shells. All the ruptures showed the presence of wavy lines, free-floating silicone shell within the gel (“free-floating loose-thread sign” or “linguine sign”). We had a 3.75 percent incidence of false-positive and false-negative results. The sensitivity for detection of silicone implant rupture was 76 percent, with a specificity of 97 percent. In addition, we also were able to identify the artifacts that may interfere with the definitive diagnosis of implant rupture. (Plast. Reconstr. Surg. 92: 681, 1993.)

Hyperbaric oxygen therapy and free radical production: an experimental study in doxorubicin (Adriamycin) extravasation injuries

The role of hyperbaric oxygen (HBO) therapy in free radical-mediated tissue injury is not clear. HBO has been shown to enhance the antioxidative defense mechanisms in some animal studies, but HBO has also been reported to increase the production of oxygen free radicals. To investigate this controversy, we studied the effect of HBO in a doxorubicin (Adriamycin) extravasation model, because the cytotoxic activity of doxorubicin is partly related to its quinone structure, which leads to the formation of cytotoxic oxygen intermediates. Fifty-four Sprague-Dawley rats underwent injection of 0.3 ml doxorubicin solution (2 mg per milliliter) intradermally on both flanks as described by Rudolph and colleagues. Group I (N = 28) received HBO treatment (2 hours at 2 ATA) for 3 days prior to injection and 7 days postinjection. Group II (N = 26) received no HBO treatment. At 2, 3, and 5 weeks, the size of the ulcers and the surrounding area of alopecia in group I (+HBO) were significantly larger than in group II (-HBO): 112.2 mm2 vs. 42.8 mm2 (p < 0.01) and 1,132.2 mm2 vs. 364.8 mm2 (p < 0.005). Biochemical analysis of the biopsied skin ulcers, to measure the parameters of oxygen free radical production, indicated (similar) low levels of xanthine oxidase for both groups. However, significantly elevated levels of malonyldialdehyde (MDA), indirect evidence of free radical production, was observed in group I (+HBO) in comparison with group II (-HBO): 36.58 vs. 5.84 ng per minute per milligram protein (p ≤ 0.001), which might indicate free radical-induced cellular injury. It is concluded that in this animal study the cytotoxicity of doxorubicin is potentiated by HBO therapy. The elevated levels of MDA suggest a direct additive cytotoxic effect by increased membrane lipid peroxidation. HBO therapy, therefore, might be deleterious in the early (preulcer) stage of doxorubicin extravasation.

Augmentation of skin flap survival with allopurinol.

Although allopurinol is primarily known as an effective medication for gout, it has been shown to enhance tissue survival in a wide range of ischemic conditions. The study reported here investigated the effects of allopurinol on flap survival in a dorsal rat model. In a preliminary study, animals were given varying doses of allopurinol (0 to 400 mg per kilogram). A clinically efficacious dose was established upon conclusion of the test period by laboratory determinations and necropsy data. Other animals were divided into 3 groups: 1 (saline control), N = 11; 2 (50 mg per kilogram of allopurinol daily), N = 10; 3 (100 mg per kilogram of allopurinol qd), N = 11. Flaps were raised and necrosis assessed at 8 days. Flaps treated with allopurinol 100 mg per kilogram had significantly better survival than the controls (p < 0.001) and 50 mg per kilogram (p < 0.01). Allopurinol 50 mg per kilogram had no effect on flap survival.

The use of high-frequency ultrasound for the dissection of small-diameter blood vessels and nerves

The Cavition ultrasonic surgical aspirator has been successfully used in general surgery and neurosurgery. We have explored its use in the dissection of small-diameter blood vessels and nerves (1-2 mm) in a rat model. Our results seem to indicate that this technique may be useful in isolating blood vessels surrounded by fatty tissue without damage to the vessel itself. In this study, however, high-frequency ultrasound did cause significant damage to peripheral nerves.

REGRESSION OF LOCAL AND DISTANT TUMOR GROWTH BY TISSUE EXPANSION : AN EXPERIMENTAL STUDY OF MAMMARY CARCINOMA 13762 IN RATS. DISCUSSION

Soft-tissue expansion is most often used to correct a preexisting deformity or tissue deficit. More recently, tissue expansion has been used prior to creation of the tissue defect to facilitate closure of large defects with better cosmetic results, e.g., free-flap donor sites. Surgical excision of some malignant skin lesions results in difficult-to-close skin defects. Can a soft-tissue expander be used directly beneath a tumor prior to excision? If so, what effect does the tissue expansion have on tumor growth? To study this in the experimental animal, Fischer rats were injected intradermally with 13762 mammary carcinoma cells and assigned at random to one of four groups: group I (n = 24), nonoperated control; group II (n = 22), creation of a sham pocket beneath the tumor group III (n = 21), expander placed beneath the tumor bed, unexpanded; and group IV (n = 22), a tissue expander placed beneath the tumor bed, expanded. Three weeks following injection, the tumors were excised and weighed, and animals were sacrificed and autopsied. Tumor weights in various groups were as follows: group 1, 8.73 ω 1.2 gm; group II, 9.51 ω 1.3 gm; group III, 1.91 ω 0.4 gm; and group IV, 0.83 ω 0.2 gm. The tumor weight of the control (group I) and sham (group II) animals was greater than in the nonexpanded (group III) and expanded (group IV) animals (p < 0.0001). Thirteen of 24 animals (54 percent) in group I, 9 of 22 (41 percent) in group II, 5 of 21 (24 percent) in group III, and 2 of 22 (9 percent) in group IV demonstrated visceral metastases. We conclude that growth of the intradermal 13762 breast tumor in Fischer rats is substantially retarded by placement of a tissue expander beneath the tumor, and this is further diminished by tissue expansion. The tissue expander, in addition, acts as a barrier to visceral spread.

Magnetic ports in tissue expanders―A caution for MRI

Although a great deal is known about the potential hazards of ferromagnetic materials relative to MRI, little has been written about the safety of tissue panders. Recently a new modification of the existing ports has been made available by incorporating a magnet for ease of identification of the injection site. Despite its low mass, the intrinsic magnetic field presents a contra-indicating factor due to the potential for torque and movement in the presence of the strong magnetic field found in the clinical MR imagers. With any evidence of tissue expander prosthesis obtained in the history, a careful questioning about the possibility of a magnetic port should be carried out.

Evaluation of facial fat distribution using magnetic resonance imaging.

Magnetic resonance imaging (MRI) provides noninvasive images of facial and neck fat for a variety of conditions. It accurately maps the soft tissues pre- and postoperatively, enabling surgeons to precisely and objectively assess results of soft tissue facial contouring and fat transplantation. The risks of MRI are few. It has the potential to provide aesthetic surgeons with a more “scientific” means of comparing various techniques of fat contouring.

Studies on the nature of the flap/bed interaction in rodents--Part I: Flap survival under varying conditions.

A flap needs close contact with its bed for optimal flap survival. Using a rat dorsal flap model, flap/bed contact times were varied by use of a sterile polyethylene film. In addition, the flap was modified either by removing the panniculus carnosus or by converting the distal flap into a skin graft. Finally, the effect of using a dressing was assessed. Several observations were made: (1) The initial 6 to 12 hours of a flaps interaction with its bed is critical for optimal survival; (2) fluorescein accurately predicted flap survival upon polyethylene removal; (3) removing the panniculus carnosus increased flap and skin graft survival; (4) dressing allowed flaps and skin grafts to better withstand bed deprivation; and (5) distal flaps and skin grafts under various conditions responded differently to bed deprivation.