Stephen F. Davidson

Assessment of the lymphocyte response to silicone

The biocompatibility of silicone is once again the focus of increased interest. Long considered inert, silicone has now been reported to be responsible for macrophage inhibition in rats and to possibly cause adjuvant disease in humans, and the related compound silica has elicited an antibody response in mice. The present study evaluates lymphocytic response to silicone as expressed by the demonstration of immunologic memory, or changes in specific lymphocyte subpopulations. Thirty-six female Lewis rats (250 gm body weight) were used as test animals. Group 1 (n = 12) was injected subcutaneously with 2.5 ml Freunds Complete Adjuvant (FCA) alone. Group 2 (n = 12) was injected with 2.5 ml FCA sonicated with silicone gel. Group 3 (n = 6) was injected with 2.5 ml FCA, and at 4 weeks, gel-filled silicone implants were placed subcutaneously. Group 4 (n = 6) was injected with 2.5 ml FCA sonicated with silicone gel, and gel-filled silicone implants were placed at 4 weeks. An additional group of six rats (group 5) served as control for the experimental animals, and a group of four rats (group 6) served as naive control. Groups 1 and 2 were sacrificed at 4 weeks, and splenic lymphocytes were obtained for lymphocyte transformation assays performed against silicone. Assays also were run with the addition of the known mitogens Con A, PHA, LPS, and pokeweed. Cytofluorographic analysis of pan-T, T-helper, T-suppressor, and B-cell populations was performed. Groups 3, 4, 5, and 6 were harvested at 8 months, and splenic lymphocytes were subjected to lymphocyte transformation assay.(ABSTRACT TRUNCATED AT 250 WORDS)

The fate of free autogenous fascial grafts in the rabbit

Fascial grafts were taken from 34 New Zealand rabbits and implanted above and below the cranial periosteum in the same animal. They were placed as four-layered folded grafts and as single-layered grafts. When harvested from 6 to 14 months after transplantation, the multi-layered grafts and the single-layered grafts on bone had maintained their bulk but consisted histologically of only a retained collagen matrix with no viable cellular structure. The one-layered grafts on periosteum, however, retained their cellular make-up with normal vascularity and normal cellular structure when harvested at approximately the same intervals.

The role of various antithrombotic agents in microvascular surgery

The ultimate goal in microvascular surgery is to achieve improved patency rates while reducing complications of systemic antithrombotic agents. Using a described model of microarterial thrombosis, the antithrombotic effects of oral aspirin (ASA) were assessed in rats. ASA-treated animals (30 mg/kg orally) exhibited significantly prolonged mean bleeding times 1 h and 24 h after dosing when compared to controls (p < 0.01). Platelet aggregation profiles also displayed an inhibition of platelet aggregation in the ASA group relative to controls. In the thrombosis model, however, patency rates were significantly improved at 20 min, but all vessels were thrombosed at 24 h.

A functional model of microvascular thrombosis

A new model of microvascular thrombosis is presented, with the evaluation of single-dose heparin in the prevention of microvascular thrombosis. The technique, which involves arterial crushing and an arteriotomy with intimal abrasion, was performed on the superficial femoral artery of the rat. The model was applied to a series of 30 consecutive rat superficial femoral arteries. A 100 percent thrombosis rate was seen immediately and at 24 hours in 10 nonheparinized animals. An operator control group of 10 vessels without intimal abrasion had a patency rate of 100 percent immediately and at 24 hours. Ten vessels following single-dose heparin and intimal abrasion were all patent initially, with 7 remaining patent at 24 hours. Reproducibility of the model was documented by a second operator with similar results. Utilizing this model, single-dose heparin was effective in maintaining vessel patency.

Effects of ketorolac tromethamine (ToradolR) on a functional model of microvascular thrombosis

Ketorolac tromethamine (Toradol), a potent nonsteroidal anti-inflammatory drug used for postoperative pain, also strongly inhibits platelet aggregation. The anti-thrombotic effects of intramuscular ketorolac were assessed with a described rat model of microarterial thrombosis. After a single dose of ketorolac mean bleeding times were significantly prolonged (p < 0.01) and platelet aggregation was markedly reduced. Patency rates at 20 min were significantly higher in ketorolac groups compared to controls (p < 0.005). However, all vessels were thrombosed at 24 h. Scanning electron microscopy demonstrated decreased platelet aggregation and decreased thrombus formation in ketorolac treated animals at 20 min. The prolonged bleeding time and reduction in platelet aggregation add support to concerns of bleeding complications reported in patients treated with ketorolac perioperatively. Thus, ketorolac should probably not be used for pain relief in patients in whom postoperative haematoma formation is a particular concern. In addition, in this model, ketorolac as a single agent was ineffective for long-term prevention of microarterial thrombosis.

The effects of ultraviolet radiation on wound healing

The effects of prior ultraviolet light exposure on wound tensile strength and skin histology were evaluated in the hairless guinea pig model. Hairless guinea pigs (strain IAF/HA-HO) were irradiated with either UVA (80 J/cm2) or UVB (0.46 J/cm2) every other day for 16 weeks. Following cessation of treatment, a standard dorsal wound was made in each animal, allowed to heal, and mechanically tested to failure at 21 days. Serial 4 mm punch biopsies were obtained prior to the initial exposure and at 2, 4, 8, 12 and 16 weeks. Histological examination with haematoxylin and eosin, trichrome and elastin stains was performed. In comparison to the unexposed control group, wound tensile strength was significantly less in the UVA- and UVB-irradiated animals. Histological examination revealed a marked endothelial swelling and eosinophilic infiltration in the irradiated groups. These results indicate that repeated exposure to even moderate doses of non-ionising radiation alters normal skin structure and adversely affects subsequent wound tensile strength in this model.

A Dose-Related Curve of Wound Tensile Strength Following Ultraviolet Irradiation in the Hairless Guinea Pig

A dose-related curve of wound tensile strength was derived following exposure to three doses of predominantly UVA (Ultraviolet A) radiation (98.3% between 315 nm and 400 nm, 1.7% less than 315 nm). Forty female hairless guinea pigs were divided into four equal groups: Group 1 (controls); Group 2 (40 J[Joules]/cm2/day); Group 3 (80 J/cm2); and Group 4 (160 J/cm2). Preoperatively, the experimental groups were irradiated on alternate days for 16 weeks. Serial dorsal punch biopsies (4 mm) were taken prior to the initial exposure and subsequently at 2, 4, 8, 12, and 16 weeks and examined histologically and microscopically. Then, standard 6 cm midline dorsal surgical wounds were made and allowed to heal for 21 days. Wounds were excised and wound tensile strength was assessed. Significant decreases (p less than .05) were noted in wound tensile strength of Groups 2, 3, and 4 compared to the controls, with the decrease being directly related to the dose received. Dermal changes were noted in all irradiated groups as early as four weeks after initial UVA/B exposure. Electron microscopy revealed elastosis and disruption of collagen fibers. Prolonged exposure to radiation, predominantly in the UVA range, appears to impede wound healing in a dose-related fashion and elicits elastosis and collagen disruption.

The effects of ultraviolet irradiation on wound contraction in the hairless guinea pig

Ultraviolet radiation has been shown to alter wound tensile strength and evoke a number of intracellular changes in fibroblasts. We examined the effects of relatively high doses of ultraviolet radiation on subsequent wound contraction of circular wounds in the hairless guinea pig model. Female hairless guinea pigs were divided into two experimental groups receiving 80 J/cm2 or 480 J/cm2 every other day for 16 weeks. Age-matched unirradiated animals were used as controls. After exposure, all animals had either a 4 mm punch biopsy (80 J/cm2) or a 2.4 cm diameter ((480 J/cm2) Groups 3 and 4) circular area excised from the dorsum. The extent of wound enlargement immediately following wounding of the irradiated animals was decreased as compared to the controls. The rate of wound contraction was significantly lower during early stages of wound contraction in each group of irradiated animals, and wound contraction was significantly slower overall in both groups of irradiated animals compared to controls.

Comparison of single-dose antithrombotic agents in the prevention of microvascular thrombosis

A model of thrombosis was used to evaluate the efficacy of single-dose heparin, hemodilution, and 40,000 milliwatts dextran in the prevention of microvascular thrombosis. Forty Lewis rats (275 gm body weight) were divided into four groups (n = 10): hemodilution (6 ml NS), single-dose heparin (1 mu/gm), 40,000 mw dextran (0.3 gm/100 gm), and control (0.275 ml NS). After exposure of the superficial femoral arteries, a model of arterial crush with arteriotomy followed by an intimal abrasion was used. The animals randomly received one of the four solutions above. Experimental results included patency rates of 90% at 20 minutes and 10% at 24 hours in the hemodilution group, 100% at 20 minutes, and 70% at 24 hours in the single-dose heparin group, and 100% at both 20 minutes and 24 hours in the dextran group. A 100% thrombosis rate was observed in the control group at 20 minutes and 24 hours. Single-dose heparin and dextran significantly improved patency in comparison to both the control and hemodilution groups at 24 hours (p less than 0.01). Scanning electron microscopy of the vessels revealed thrombus deposition consistent with these findings. These results indicate that single-dose heparin and single-dose dextran reduce thrombosis in this model of microvascular injury.

Wound tensile strength in the hairless guinea pig following irradiation with pure ultraviolet—A light

Ultraviolet light in the wavelength range of 315-400 nm (UVA) is known to penetrate the epidermis more readily than UVB and to result in significant dermal damage. Fibroblasts within the dermis are responsible for the production of collagen, which is the chief determinant of wound tensile strength during the third week of wound healing. The present study assesses the effects of UV radiation limited to the UVA wavelength on wound tensile strength in the hairless guinea pig. Twenty female hairless guinea pigs were randomly divided into two equal groups (n = 10). Group 1 animals served as controls. Group 2 animals were irradiated with 120 J/cm2 from a pure UVA fluorescent light source every other day for a period of 21.3 weeks (cumulative dose = 8960 J/cm2). Upon completion of the irradiation schedule, a standard 6 cm linear full-thickness surgical wound was created on the dorsum of all animals and allowed to heal for 21 days. The wounds were excised and wound tensile strength was assessed by determining breaking strength and dividing by the breaking-point surface area. Wound tensile strength was significantly lower (p less than 0.0017) in irradiated animals (0.99 +/- 0.12) than in controls (1.54 +/- 0.08). Therefore, UVA at this dose significantly decreased wound tensile strength in this model and raises further concern regarding exposure to this wavelength of ultraviolet radiation.