Antigenicity of fresh and cryopreserved rat valve allografts.

Aortic valve allografts have demonstrated excellent clinical performance, but the importance of antigenic differences between donor and recipient is largely unknown. To determine the antigenicity of aortic valve grafts, rat aortic valves with a short portion of thoracic aorta were transplanted into the abdominal aorta of recipient rats. Valves were used immediately after harvest (fresh) or following cryopreservation. Three weeks after this procedure, the recipient rats received a skin graft from a rat of a strain syngeneic to that of the aortic valve donor. Additional groups of rats were subjected to sham operation (sham) followed three weeks later by skin grafting. Recipient rats were of the Lewis strain. Donor rats were of the Lewis, F344 (weakly allogeneic, RT1-compatible, non-RT1-incompatible), LBN F1 (moderately allogeneic, one-haplotype-identical and one-haplotype-incompatible at both the RT1 and non-RT1 loci), or BN (strongly allogeneic, RT1 and non-RT1-incompatible) strain. Time to skin graft rejection was measured. Among rats receiving the F344 grafts, the time to skin graft rejection (mean +/- SD) was sham: 9.1 +/- 1.0 days, fresh: 7.1 +/- 1.2 days, cryopreserved: 6.9 +/- 0.7 days. Among rats receiving the LBN F1 grafts, the corresponding times were sham: 7.8 +/- 0.8 days, fresh: 5.6 +/- 0.5 days, cryopreserved: 5.4 +/- 0.5 days. Among rats receiving the BN grafts, the corresponding times were sham: 7.1 +/- 0.3, fresh: 4.5 +/- 1.0 days, and cryopreserved: 4.3 +/- 0.7 days. Significant differences (P less than 0.05) existed between sham and fresh and between sham and cryopreserved, but not between fresh and cryopreserved. Significant differences (P less than 0.05) also existed between each histocompatibility grouping. It is concluded that aortic valve allografts in rats are antigenic and produce recipient sensitization. Cryopreservation does not diminish this sensitization. The degree of antigenicity is related to the degree of histoincompatibility between donor and recipient. Both RT1 and non-RT1 antigens appear to play a role in this process.

Allograft vein patency in a canine model. Additive effects of cryopreservation and cyclosporine.

Autogenous saphenous vein is the preferred conduit for many cardiovascular operations. Attempts to use allograft veins for arterial reconstruction have had poor results. To define circumstances under which allograft veins might prove to be acceptable vascular conduits, dogs underwent femoral artery bypass using reversed saphenous veins. Veins were transplanted fresh or after cryopreservation. Group I dogs received a fresh autograft to replace one femoral artery (group I F) and a cryopreserved (CP) autograft (group I C) to replace the other. Group II dogs received fresh allograft veins, and group III received CP allograft veins, neither group receiving additional treatment. Group IV received fresh allograft veins and Group V received CP allograft veins; both groups received cyclosporine 15 mg/kg. Animals were maintained until grafts occluded or until six months elapsed. Patency was observed in all group I F grafts throughout the observation period. Six-month patency rates in the other groups were: group I C, 9/10 (P = NS vs. group I F); group II, 0/10 (P less than 0.01), group III, 0/10 (P less than 0.01), group IV, 1/10 (P less than 0.01), group V, 7/11 (P = NS). In a separate series of observations 10 cryopreserved allograft veins were implanted in 10 dogs that received CsA for 30 days. CsA was then discontinued. All of these grafts occluded within 30 days of discontinuing the CsA. Long-term patency of saphenous vein allografts was achieved only with the combination of cryopreservation and immunosuppression with continued CsA.

Production of endothelium-dependent relaxation responses by saphenous vein grafts in the canine arterial circulation.

To determine if venous endothelium can acquire the ability to elicit endothelium-dependent relaxation responses, five dogs underwent femoral artery bypass with autogenous saphenous vein. The veins were harvested 15 to 17 months later. Endothelium-dependent relaxation was determined by measuring tension of deendothelialized coronary arteries mounted on a tensiometer and superfused with the effluent of the vein grafts. These grafts were perfused with acetylcholine and calcium ionophore A23187, which cause case vascular smooth muscle relaxation by means of endothelium-dependent relaxing factor production. Control arteries and veins were obtained from other dogs for comparison. In response to acetylcholine from 10(-9) to 10(-4) mol/L, the final cumulative relaxation produced in the detector coronary artery (mean +/- SD) was 64.2% +/- 25.7% by the control arteries, 14.2% +/- 5.5% by the vein bypass graft, and 5.3% +/- 5.6% by the control veins. In response to A23187 from 10(-8) to 10(-4) mol/L, the final cumulative relaxation was 66.2% +/- 19.0% by the control arteries, 30.6% +/- 8.9% by the vein bypass grafts, and 5.3% +/- 5.6% by the control veins. The differences were significant between the vein bypass grafts and the control arteries (p less than 0.04 for acetylcholine; p less than 0.04 for A23187) and the control veins (p less than 0.03 for acetylcholine; p less than 0.02 for A23187). Perfusion of saphenous veins used as chronic arterial bypass grafts with either acetylcholine or A23187 produced detector vessel relaxation, consistent with endothelium-dependent relaxing factor production. The magnitude of the relaxation response did not approach that from perfusion of control arteries.

Effect of storage at 4 degrees C in a nutrient medium on antigenic properties of rat aortic valve allografts.

The effects of prolonged storage at 4 degrees C in nutrient medium on the antigenic properties of aortic valve allografts are unknown. Lewis rats received heterotopic aortic valve allografts from Brown Norway donors. Valves were transplanted immediately after harvest (fresh), or after antibiotic sterilization and storage in a nutrient medium at 4 degrees C for 3, 7, 14, or 21 days. Additional rats underwent sham laparotomy (sham). All recipient rats received Brown Norway skin grafts 3 weeks after valve transplant or sham procedure. Time to skin graft rejection for all groups was as follows: fresh (n = 10), 4.5 +/- 0.9 days; sham (n = 10), 7.1 +/- 0.3 days; 3-day (n = 10), 4.9 +/- 0.3 days; 7-day (n = 10), 5.2 +/- 0.4 days; 14-day (n = 10), 6.1 +/- 0.7 days; and 21-day (n = 10), 6.0 +/- 0.6 days. Significant differences existed between the sham group and each of the transplanted groups. No significant differences existed between the fresh group and either the 3-day or 7-day groups. The difference between the fresh group and the 14-day group approached significance (0.05 less than p less than 0.10), and the difference between the fresh and 21-day groups was significant (p less than 0.05). Additional valves not used for transplantation were studied with scanning electron microscopy. The valves preserved in nutrient medium exhibited a progressive loss of endothelium as compared with fresh valves. Storage of aortic valve allografts in a nutrient medium at 4 degrees C is associated with a progressive attenuation of antigenic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Island adipofascial flap for resurfacing of the Achilles tendon.

Satisfactory replacement of soft-tissue defects over the Achilles tendon remains a difficult challenge for plastic surgeons. Flap coverage is vital to preserve an exposed tendon as well as to supply a gliding surface. Ten patients were selected for this study who had sustained exposed Achilles tendons either after trauma or after excision of burn scar. The island adipofascial flap was used based on the most distal two to three septocutaneous perforators of the posterior tibial artery that are located 3.7 to 5.5 cm proximal to the tip of the medial malleolus, as confirmed by my anatomic study. The island adipofascial flap provides a durable and thin coverage for the Achilles tendon, as well as a good vascularized bed for skin grafting.

Island fasciocutaneous flap based on the proximal perforators of the radial artery for resurfacing of burned cubital fossa.

In the vast majority of burned patients, the injury is limited to the skin and superficial subcutaneous tissue, and the vasculature of the deeper fascia is spared. This fact encouraged me to design a flap in which the burned scar tissue is employed. The island fasciocutaneous flap is based only on the proximal septocutaneous perforators of the radial artery. The flap is used to resurface the anterior as well as the lateral burned cubital fossa after excision of the scar tissue and release of contracture. An anatomic study as well as clinical approach has been conducted.

Adipofascial turn-over flap based on perforators of the dorsalis pedis for resurfacing forefoot defects: an anatomic and clinical approach.

The aim of this study is to stress the possibility of harvesting a more sizable adipofascial turn-over flap based on the perforators of the dorsalis pedis artery than previously described. This flap can resurface the most distal dorsal defects of the forefoot, and the posttraumatic distal amputation of the forefoot, as a new indication. A detailed anatomic dissection of the flap was carried out on 12 fresh lower extremities together with injection study to determine flap pedicle location, flap dimensions, and its area of reach in the distal forefoot. The anatomic findings encouraged the author to elevate an adipofascial turn-over flap based on the perforators of the dorsalis pedis artery, where the largest flap size was 13 x 7 cm, and the base area to flap area ratio ranged from 1:3.5 to 1:6.5. An experience with 11 flaps was quite successful on eight patients with severe crushing and avulsion injuries of the forefoot and on three patients with unstable and ulcerating distal grafted amputated stumps secondary to trauma.

Prefabricated temporalis fascia pedicled flap for previously skin-grafted contracted eye socket.

The use of free skin, mucous membrane, or dermis-fat grafts in eye socket reconstruction proved to be unsatisfactory in long-term follow-up because of the progressive contraction of the socket. For achieving eye socket expansion of proper size and shape and a good vascularized lining that can last despite eventual fibrosis, a prefabricated temporalis fascia flap pedicled on the superficial temporal bundle is described in this report. In this technique, a split-thickness skin graft is applied over the termporalis fascia to create a sort of prefabricated flap, on which the proper dimensions of the socket can be fabricated on the grafted temporalis fascia. This study was conducted on 17 patients who had previously undergone eye socket reconstruction with skin graft after posttraumatic enucleation. All patients presented with a contracted eye socket, which manifested clinically by extrusion and migration of the ocular prosthesis. The procedure was performed in two stages. The purpose of prefabrication was to provide the proper shape and size of the newly created socket after release of skin-graft contracture to get a proper fit of the prosthesis, because the flap is thin and can be shaped well. The follow-up period ranged between 1 and 5 years, and the results were good.

Reliability of inferior pedicle reduction mammaplasty in burned oversized breasts.

Heavy pendulous breasts cause physical and psychological trauma. Postburn deformity of breasts results in significant asymmetry, displacement of nipple-areola complex, due to burn scar contracture, and significant scarring; these factors add more psychological discomfort and subsequent behavioral changes. The use of the inferior pedicle procedure in burned breasts can solve many problems. The technique reduces the size of the large breast, eliminates the scar tissue by excising both medial and lateral flaps, and brings the mal-located nipple and areola to a normal position. This study stresses the possibility of harvesting the inferior dermal pedicle flap from within the postburn scar tissue without necrosis of the nipple and areola, because of the excellent flap circulation. Acceptable aesthetic appearance and retainment of nipple viability and sensitivity can be achieved with the inferior pedicle technique even with postburn deformity of the breast. The study was conducted on 11 women, all of whom had sustained deep thermal burns to the breasts and anterior torso and whose breasts were hypertrophied and pendulous.

Island adipofascial flap based on distal perforators of the radial artery: an anatomic and clinical investigation.

Reconstruction of soft-tissue defects of the hand with exposed tendons, joints, and bone represents a challenge to the plastic surgeon, and such defects necessitate flap coverage to preserve hand function and to protect its vital structures. Reported here is the study of an island adipofascial flap based solely on the distal five to eight septocutaneous perforators of the radial artery and their venae comitantes. Designing the flap in the form of an island with skeletonization of the distal perforators of the radial artery ensures its vascular pattern from these perforators alone with no connection to the ulnar artery perforators or posterior interosseous artery perforators, as is the case with fascial pedicled flaps. Furthermore, designing the flap as an island facilitates the arc of rotation and avoids the pedicle kink when the flap is turned 180 degrees. Preservation of the radial artery, as well as the mild thickness of the flap are further advantages. The drawbacks of such a flap include temporary impaired sensation at the donor site, the obvious scar in the forearm, and loss of hair. Eleven fresh and fixed cadaver upper extremities were dissected to delineate the vascular pattern and to define the arc of rotation of the flap. Also, a clinical approach was conducted on two patients who sustained extension scar contracture with tendon adhesions of the dorsum of the hands, on two patients who sustained first web space contracture, and on two patients who had full-thickness soft-tissue loss over the palm; and finally on two patients who sustained traumatic soft-tissue loss over the dorsum of their hands with exposed tendons and metacarpal bones.

Time course of cytokine release and complement activation after implantation of the HeartMate left ventricular assist device.

Pro-inflammatory mediators, including interleukin-6 (IL-6), IL-8, and complement C3a, are released after cardiac surgery as part of the inflammatory response related to blood-biomaterial interaction in the cardiopulmonary bypass circuit. Post operative time course data for these mediators are not fully defined in patients receiving left ventricular assist device (LVAD) support. The authors performed enzyme linked immunosorbent assays for concentrations of IL-6, IL-8, and C3a in plasma in six HeartMate LVAD recipients at the following times: pre operatively; 4, 8, 16, 24, 36, and 48 hr post operatively; daily through the first week; and weekly thereafter for 6 weeks. All patients survived without major complications during the study. Pre operative concentrations of IL-6 and C3a in plasma were significantly increased compared with age matched controls. Post operatively, the concentrations of IL-6 and IL-8 in plasma took longer to return to baseline values after insertion of the LVAD than the trends reported in the literature after routine cardiopulmonary bypass alone. Concentrations of IL-6 and complement C3a continued to decrease to lower than baseline post operatively, reaching statistical significance after 6 weeks of LVAD support. The authors conclude that the presence of the HeartMate LVAD delays the return of pro-inflammatory mediator concentrations back to baseline values compared with routine cardiopulmonary bypass alone, but the device does not appear to be an ongoing source of cytokine release or complement activation.

Aldehyde-treated porcine skin versus biobrane as biosynthetic skin substitutes for excised burn wounds: case series and review of the literature.

Background. The use of skin substitutes as temporary or permanent coverings has been a subject of research and study since 1500 BC. Temporary coverage of the burn wound can decrease the metabolic rate, fluid loss, pain, and colonization. The aim of this study is to review clinical experience with Biobrane and aldehyde-treated porcine skin (E.Z. Derm) as biosynthetic skin substitutes for the treatment of excised burn wounds. Methods. Fifty-two patients (42 males and 10 females) with deep dermal and full-thickness burns were selected for this retrospective study. Half of these patients were treated with Biobrane (this part of the study covered the period Jan. 1995/Dec. 1999) and the other half were treated with E.Z. Derm (Jan. 2000/Dec. 2005). The mean total body surface area (TBSA) burned was 30%. The excisional therapy was carried out in stages, each procedure being limited to 7-15% TBSA. All the patients underwent either tangential excision or excision down to the muscle fascia. The male/female ratio was 3:1 and the patients' ages ranged between 5 and 67 yr (mean, 35 yr). Data collection included: initial observation (age, sex extent of burn, depth of burn, photograph), skin substitute observation (adherence, presence of fluid collection, rejection, infection, photograph), and follow-up wound evaluation. Results. Both Biobrane and E.Z. Derm reduced pain, decreased evaporative water and heat loss, and limited bacterial growth. Both decreased exudative protein loss, protected the underlying vessels and nerves, and enhanced the healing of partial-thickness wounds. Both promoted the development of granulation tissues to be ready for autografting, and neither presented antigenicity or transmitted diseases. Porcine skin showed limited wound adhesion and limited control of infection compared to Biobrane. Conclusion. Biobrane and E.Z. Derm protected excised burn wounds from bacterial contamination and dehydration. It can be concluded that Biobrane has the potential for long-term adherence (10 days). Aldehyde-treated porcine skin (E.Z. Derm) is a reliable tool for short-term use and should not remain on the wound more than 3-4 days.

Clinical experiences with the extended first dorsal metacarpal artery island flap for thumb reconstruction.

A single surgical procedure was created to provide composite resurfacing of total volar or dorsal defects of a thumb with normal length. The procedure involved a flap that included the dorsal skin from both the proximal and middle phalanges of the index finger. The flap included the first dorsal metacarpal artery as well as more than 1 dorsal vein (located at the vicinity of the flap pedicle) and terminal dorsal branches of the radial nerve. Harvesting the dorsal skin of both the proximal and middle phalanges of the index finger is considered a modified version of the first dorsal metacarpal artery flap.

Immunogenicity, antigenicity, and endothelial viability of aortic valves preserved at 4 degrees C in a nutrient medium.

In patients undergoing aortic valve replacement, allograft valves stored at 4 degrees C in a nutrient medium have been associated with excellent immediate and long-term results. The effects of this method of prolonged storage on the antigenic, immunological and cellular characteristics of these grafts are incompletely understood. This study was designed to study these phenomena in rat aortic valves subjected to antibiotic sterilization and stored for up to 3 weeks in RPMI containing 10% fetal calf serum. Selected valves from Brown Norway rats were implanted heterotopically into the abdominal aorta of Lewis rats. Other valves were studied prior to transplantation. Antigenicity was determined by immunocytochemical staining using monoclonal mouse antibodies directed at Class I and Class II rat antigens. Immunogenicity was determined by duration of second-set skin graft survival following heterotopic aortic valve implant. Endothelial cell viability was determined by flow cytometric analysis of endothelial cells harvested from aortic valve allografts by collagenase digestion. Only fresh valves and valves stored for 1 day were positive for Class I antigens; no valves were positive for Class II antigens. Duration of skin graft survival was prolonged with greater duration of storage, but grafts remained immunogenic after 21 days of storage. Endothelial cell viability declined from 95% in the fresh valves to 64% after 21 days of storage. With prolonged duration of allograft valve storage at 4 degrees C, there is an attenuation of antigenicity, immunogenicity, and endothelial cell viability. Loss of endothelial cells may contribute to the changes in immunological responses to the valve allografts. The expression of antigens on the endothelial surface is not a reliable predictor of immunological response.