The use of urokinase in ischemic replanted extremities in rats

We compared the efficacy of intra-arterial infusion of urokinase, a fibrinolytic agent, with that of intra-arterial infusion of nitrendipine, a peripheral calcium-channel blocking agent, in preventing the no-reflow phenomenon in rats after prolonged ischemia at room temperature. Urokinase increased the survival of the limbs after both four and five hours of ischemia at room temperature to 100 per cent compared with 50 and 20 per cent, respectively, in untreated controls. Nitrendipine significantly increased the blood flow but failed to significantly increase the survival of the limb. Scanning electron microscopy was used to assist in the evaluation of the endothelium of the vessels. The etiological mechanism of the no-reflow phenomenon appears to be that ischemia damages the endothelial cells, causing impairment of the fibrinolytic system, retraction of the endothelial membrane, exposure of the subintimal collagen, and fibrin-platelet deposition. Thrombosis of the vessels ensues, resulting in the no-reflow phenomenon. Clinical Relevance: Experimentally, intra-arterial infusion of urokinase increased the survival of the limb in replanted extremities that were subjected to ischemia. This effectively lengthened the safe limit of ischemia at room temperature before microsurgical replantation or elective free-tissue transfer. Clinical trials of the use of intra-arterial fibrinolytic agents for the treatment of revascularized tissue are indicated.     

An experimental study of the effect of fluorocarbon perfusion for amputated limb preservation. The effect of inhibition for replantation toxemia and muscle tissue destruction

In replantation surgery, it is widely accepted that replantation toxemia or muscle destruction in replanted limbs might occur after a long time of ischemia. Their possibilities are particularly high after replantation of the amputated limbs which contain more muscle tissue than tendon and bones. The present study was performed to investigate the efficacy of fluorocarbon (FC: artificial blood) perfusion to the amputated limbs in preventing these problems after replantation. The hind limbs of dogs were completely amputated at mid-thigh. Amputated limbs were divided into two groups. One was stored in ice water and the other at room temperature for six hours. Each group was furthermore divided into four subgroups. The amputated limbs were perfused with oxygenated FC or Hartmann's solution before replantation and remaining limbs were not perfused. All of them were replanted under an operating microscope. The results were as follows: Perfusion with FC had an inhibiting effect on the anaerobic metabolism in an amputated limb and also decreased the rate of death due to replantation toxemia. Perfusion with FC was effective for inhibiting leakage of creatine phosphokinase from the replanted limb and preventing muscle destruction. Both these effects were detected biochemically and histologically. The reactive hyperemia of the replanted limb usually occurred after replantation. This rate, however, was significantly decreased after replantation of the amputated limb perfusion with FC. These effects described above were more remarkable when the amputated limb was perfused continuously rather than intermittently. It is therefore reasonable to conclude that for prevention of systemic ill effect after replantation and for preservation of function of the amputated limb, continuous perfusion with FC in ice water is more effective than ice water cooling alone.     

Improved survival in a replantation model containing ischemic muscle

The effectiveness of superoxide dismutase and allopurinol was evaluated in preventing reperfusion injury in Sprague-Dawley rats utilizing a limb replantation model after 6 hours of warm ischemia. Immediately prior to reperfusion of the replanted limb the animals received (intravenously) either a single bolus of superoxide dismutase (16,000 units/kg), a single bolus of allopurinol (45 mg/kg), both agents, or only control solutions. In the rats that received only control solutions, 30% of the limbs survived the ischemic insult. The group that received both superoxide dismutase and allopurinol had a 75% limb survival (P = 0.005). The animals that had only superoxide dismutase or allopurinol had 58% and 60% of the replanted limbs survive, respectively. This study suggests that the administration of superoxide dismutase and allopurinol may be helpful in the prevention of reperfusion injury in skeletal muscle in an acute injury setting (without pretreatment) and may thereby improve limb salvage after a significant ischemic period.     

三种灌注液对断指再植组织再灌注损伤保护作用的研究

目的 研究三种不同灌注液对断肢再植后缺血再灌注损伤的保护作用。方法 建立大鼠后肢的断肢再植模型，应用3种不同灌注液（A组肝素钠组，B组肝素钠＋利多卡因组，C组肝素钠＋地塞米松组）对离断肢体进行灌注，然后进行再植。分别于缺血前、缺血6h、通血60min取材，测定断肢皮肤中丙二醛（MDA）、透射电镜观察缺血6h后再通血60min血管内膜的改变。结果 3组再植肢体成活率相当，B组灌注前后MDA差值明显低于A组，差异有统计学意义。B组、C组血管内膜改变较A组轻微。结论 断肢再植前应用含利多卡因、地塞米松灌注液对离断指进行灌注，可以减轻再植肢体的缺血再灌注损伤，且对血管内膜有保护作用。     

Arterial shunting as an adjunct to major limb revascularization.

Temporary arterial and venous shunting has been employed to reduce warm ischemia in major limb replantation and revascularization on eight occasions. This has allowed identification of vital structures, thorough debridement, and rigid internal or external skeletal fixation prior to definitive arterial repair. Arterial shunting has not been associated with any significant complications and has improved our operative technique in these severe vascular injuries.     

Crossover replantation of the foot after bilateral traumatic lower extremity amputation

BACKGROUND: Bilateral traumatic amputation and limb-threatening injury of the lower extremities is more challenging than the unilateral amputation. Successful replantation of both lower extremities has been reported previously. However, orthotopic implantations may not be possible when amputation of both lower limbs with different levels of section and degrees of damage to surrounding tissues occurs. It was reported that the crossover replanted foot in combination with prosthetic limb is better than 2 artificial limbs. Hence, crossover replantation should be considered when anatomic replantation of both lower extremities is not possible as a result of bilateral total or subtotal amputation. To our knowledge, there are few reports about the crossover replantation of the lower extremity in the literature. CASE REPORT: A 30-year-old engineer being run over by the train had crushed the bilateral lower limbs in different anatomic levels. We decided to perform the crossover replantation of the right foot to the stump of the left leg to provide the patient with at least 1 weight-bearing sensate extremity. At the latest follow-up examination, 30 months after the operation, he had mild pain, especially in toes of the replanted foot. There was no ulceration in both the replanted extremity and the right amputation stump. The sole has maintained complete protective sensation. The patient described the functional result of the reimplanted leg as satisfying and better than the prosthesis that has caused much more problems than the replanted extremity. He had no complaint about the cosmetic result. He stated that he would have the crossover replantation again under the same condition. He was able to return to his previous job. Moreover, he affirmed that he is able to carry on his all social activities as he had done before the accident except for playing football. In conclusion, the possibility of the crossover replantation should be considered while evaluating the patient with bilateral lower limb injuries to allow the patient to stand on their own foot and still touch ground.     

A case of replantation of a completely amputated digit after 26 hours of warm ischemia

A seven-year-old-boy received a digit replantation after 26 hours of warm ischemia and showed good recovery of motor and sensory functions. In the case reported, replantation was performed after a much longer ischemic time than had been considered an indication for the procedure in previous reports. Successful replantation and revascularization can thus be achieved, even in cases of extensive warm ischemia.     

Can indications for lower limb replantation and revascularization be expanded with simultaneous free-flap transfer for limb salvage?

High-energy trauma from road accidents and work-related injuries is the most common cause of lower-limb traumatic amputations. Many of these cases require extensive debridement and substantial bone shortening for primary closure because of crushing and/or avulsion of the involved parts. Since 1998, the authors have replanted or revascularized five lower limbs in five patients. Free tissue transfers have been used to cover soft-tissue defects during replantation and revascularization in all patients. The numbers and kinds of free flaps include one latissimus dorsi muscle, two transverse rectus abdominis musculocutaneous (TRAM), and two anterolateral thigh fasciocutaneous flaps. Survival of the replanted and revascularized limbs and transferred flaps was obtained in four patients. Below-knee amputation was performed because of flap necrosis and extensive infection in one patient. Simultaneous free-tissue transfers may be used simultaneously with lower limb replantation or revascularization to obtain functional extremities in appropriately selected patients. The indications for lower limb salvage may be enhanced and successful results may be obtained in one stage, with low complication rates and shorter hospital stays. The authors report their experience with simultaneous free tissue transfers and lower limb replantation or revascularization.     

Restoration of venous outflow by simultaneous creation of an arteriovenous shunt and pedicle flap using a rat model of foot replantation.

Replantation of amputated rat feet utilizing an efferent arteriovenous shunt constructed between the distal posterior tibial artery and the proximal posterior tibial vein, in the absence of all other venous drainage, provides an alternative pathway to the normal venous drainage in a replanted rat foot. However, this substitute venous drainage was insufficient to prevent progressive ischemia and necrosis of some or all of a replanted rat foot. When a cutaneous pedicle flap supplemented the arteriovenous shunt, venous drainage was much improved, tissue hypoxia and edema began to subside on the third day, severe tissue necrosis was prevented, and seven of eight feet replanted by this technique survived. These observations may be useful in replantation in humans when veins in the amputated part are too small to be used or so damaged that they cannot be repaired or reconstructed by a vein graft, but arteries can still provide a means of returning blood from the amputated part. Constructing an alternative pathway to the normal venous drainage pattern may allow severely damaged parts to survive after replantation.     

Effects of transient ischemia on nutrient flow and arteriovenous shunting in canine hindlimb.

A canine model was developed to simulate use of a pneumatic tourniquet in the clinical setting in order to study the acute and delayed effects of transient ischemia on limb and tissue blood flow, using radioactive microspheres and electromagnetic flow probes. Experimental femoral artery flow rose markedly after tourniquet ischemia, and remained significantly elevated for 24 hours (p less than 0.01). Blood flow to the rectus femoris and anterior tibial muscles rose significantly (p less than 0.05) immediately after tourniquet ischemia, and the latter remained significantly elevated at 24 hours (p less than 0.05). Blood flow to the skin of the experimental limbs was elevated significantly (p less than 0.05), immediately ater tourniquet ischemia, and at no other time. Blood flow to the nerves did not increase to its maximum until 15 minutes after tourniquet deflation, and by 24 hours was normal. Tibial and femoral marrow blood flow remained significantly lower in the experimental limb throughout the 24-hour period. Ater tourniquet ischemia (300 mmhg; 2 hours), greatly increased femoral artery flow was related to reactive hyperemia in skin, muscle, and nerve. Twenty-four hours after tourniquet deflation, there was a significant increase in femoral artery and anterior tibial muscle blood flow, and significant arteriovenous shunting from the experimental limb. These data suggest that the hemodynamic response to a transient ischemic injury is more prolonged and of greater magnitude than previously believed.     

Major limb replantation in children

This retrospective study evaluated patients under 18 years of age who underwent major limb replantation between 1976 and 1989 at Louisville Hand Surgery. The age of the 15 patients followed for between 1 and 8.5 years (mean 4.2 years) ranged from 2 to 17 years (mean 9.8). Of amputations, 40% were guillotine, 40% were limited crush-avulsions, 7% were extended crushing, and eight were of an upper extremity and seven of a lower extremity. Average warm/total ischemia times were 4.8/14.8 hr in failures and 1.1/7.5 hours in successful replantation. Overall limb survival was 87%. Among the patients, 93% felt that their replanted limb functioned and looked better than a prosthesis; 87% of patients had a sensory recovery of more than S2+ in the lower extremity or S3 in the upper extremity; and 38% of upper extremity replantation patients had two-point discrimination of less than 15 mm.     

Experimental evaluation of oxygen free radical scavengers in the prevention of reperfusion injury to skeletal muscle

A prolonged preoperative ischemic interval decreases the chances for successful replantation of an amputated limb. Skeletal muscle is especially sensitive to periods of prolonged ischemia. It is now hypothesized that significant tissue injury occurs during reperfusion, when oxygen-rich blood contacts anaerobic metabolites forming toxic oxygen free radicals. A replantation model, using the rabbit hind limb tibialis anterior muscle, was developed to assess muscle function and histological appearance following ischemic intervals of five and eight hours. Muscle strength five weeks after injury was used as a functional measurement of tissue damage. The effects of the superoxide free radical scavenger superoxide dismutase (SOD) and the hydroxyl radical scavenger dimethylsulfoxide (DMSO), administered systemically just before reperfusion, were studied. Muscle treated with SOD following five hours of ischemia had essentially normal strength and histological appearance; however, there was no protective effect after eight hours. DMSO treatment had no beneficial effects after five hours of ischemia, but after eight hours DMSO-treated muscle had significantly better function than untreated muscle. Histological examination confirmed the functional results. Clinical treatment of ischemic limbs with free radical scavengers before revascularization may aid in avoiding reperfusion injury and may improve survival and later muscle function.     

Replantation of a crush amputation of distal tibia followed by lengthening with Ilizarov circular external fixator: two-year follow-up

A 20-year-old male sustained a severe crush injury to his left leg, resulting in amputation of the foot at the level of the distal tibia. Despite 12-h warm ischemia, replantation was attempted after radical debridement, bone shortening, and proximal fasciotomies. The replanted part survived totally. Four months later, a 13-cm shortness of the extremity was managed by 10-cm lengthening with distraction osteogenesis, using Ilizarov's circular external fixator and by means of a special shoe. Two-year follow-up of the patient revealed acceptable functional and sensorial recovery. Success of replantation despite the excessive warm-ischemia time was attributed to the sparse muscle content of the distal tibia and foot. Fasciotomies performed on the proximal segment of the leg ensured the patency of anastomoses by maintaining adequate blood flow distally despite increasing edema after the crush injury. Debridement and bone shortening at the proximal stump eliminated the vein and nerve grafts to bridge the gap. In conclusion, considering the functional outcome of our case, replantation of distal parts of a lower extremity should be attempted first, even if the nature of the injury is unfavorable and the ischemia time is longer than the documented ischemia-tolerance.     

Gustilo ⅢC型股骨开放性骨折保肢成功病例分析

目的介绍股骨热缺血时间大于10 h的GustiloⅢC型开放性骨折成功保肢的治疗经验。方法回顾性分析2016年2月至2017年4月太原长城骨伤手外科医院收治的2例股骨热缺血时间大于10 h的GustiloⅢC型开放性骨折患者的临床资料。均为男性,年龄分别为42、27岁;清创术后分别短缩8.0、10.0 cm再植。骨折端-端相对钢板加压固定,股动脉直接吻合,肌肉端-端吻合。再植成活4个月后,行二期截骨术,单边重建外固定支架固定。术后1周开始进行肢体延长。根据Paley等提出的标准评定疗效。结果2例患者小腿肌群均出现散在不规则坏死,经4次清创,40 d后减张切口经植皮愈合。2例成功保肢并延长至与对侧肢体等长,分别延长8.0、10.0 cm,延长时间为3.0、3.5个月,单边重建外固定支架佩戴时间为29、24个月。足底部感觉均于术后1年恢复至S4。拆除外固定支架6个月随访时,根据Paley等提出的标准评定疗效:骨性结果均为优,功能结果均为良。结论综合掌握保肢适应证的前提下,应用一期彻底清创骨折钢板固定短缩再植、二期单边重建外固定支架进行肢体延长用于股骨热缺血时间大于10 h的GustiloⅢC型开放性骨折的保肢是一种实用、有效的方法。     

Successful replantation of the lower leg after 42-hour ischemia: case report.

A case of right lower-leg replantation after 42-hr ischemia is presented. Revascularization of the other foot with circulatory decompensation after 36-hr ischemia was carried out simultaneously. The replanted lower leg survived. Following its shortening in replantation by 12 cm, right lower-leg lengthening by 8 cm was carried out 1.5 years after replantation with the aid of a distraction apparatus. The locomotor function in both lower extremities recovered.     

Farm-related limb amputations in children

The purpose of this study was to review results for children sustaining traumatic farm-related limb amputations. Farm machinery accidents were responsible for 12 limb amputations among 260 consecutive childhood traumatic amputations. All amputations resulted in open, grade III-C fractures. Treatment consisted of operative debridement, antibiotics, possible replantation, and delayed wound closure. Mean follow-up was 8 years (range 1-20). Wound closure was achieved at a mean of 22 days (range 2-88) after an average of seven operative procedures (range, 2-11 operations). Skin grafting was necessary for 9 of the 12 limbs. Blood replacement was necessary for all but one patient. Initial wound cultures revealed polymicrobial contamination in all patients. Clinical infections developed exclusively and in all (6/6) patients who underwent attempted replantation. Replantation was considered in all cases and was attempted for six limbs but was successful in only two patients. Failure of replantation in four limbs was due to vascular insufficiency and infection. The surviving replanted limbs have continued to grow and have regained protective sensation. Prosthetic use ranges from excellent to intermittent among the 10 patients with permanent amputation. Farm-related limb amputations are among the most severe orthopaedic injuries sustained by children. Despite massive contamination, infection occurred only in replanted limbs. Because of the mutilating nature of these amputations, less than 20% can be successfully replanted.     

Salvage of replanted upper extremities with major soft-tissue complications.

Soft-tissue complications in the replantation wound, either septic or non-septic, are the main cause of failure in major extremity replantations. In the presence of necrosis or infection, vascular errosion or thrombosis readily develops and can lead to limb loss. Very aggressive surgical treatment has been recommended to salvage the replanted limb in these highly unstable clinical situations. Over a 10-year period, 423 amputated parts were replanted, 56 of which were replants proximal to the wrist. The experience of the author in treating 11 cases of critical soft-tissue necrosis (four septic and seven non-septic) after major replantation of the upper extremity with aggressive debridement and flap coverage, is reported. All flaps and limbs survived.     

Effect of fluorocarbon perfusion upon the preservation of amputated limbs. An experimental study

The present study was undertaken to investigate the effect of fluorocarbon on the preservation of an amputated limb. The hind limbs of dogs were completely amputated through the mid-thigh; some were perfused with fluorocarbon, others with lactated Ringer's solution and some were not perfused at all. After six hours of ischaemia, all the limbs were replanted. Perfusion with fluorocarbon had an inhibitory effect on the anaerobic metabolism of an amputated limb, thus increasing the survival rate. Leakage of creatine phosphokinase from the replanted limb also was inhibited by perfusion with fluorocarbon. These effects were more striking when the amputated limb was perfused continuously rather than intermittently and when it was preserved in iced water rather than at room temperature; these measures helped to prevent replantation toxaemia and to preserve muscle function.     

Effect of high-energy phosphates and free radical scavengers on replant survival in an ischemic extremity model

In replantation surgery, preoperative and intraoperative ischemia can lead to irreversible changes that prevent reperfusion during the subsequent re-establishment of circulation. These changes are termed the no-reflow phenomenon. Ischemic phase damage was addressed by comparing the dose-response effects of controls vs. five different high-energy phosphate compounds on replanted limb survival. Reperfusion damage was evaluated via comparisons of controls with superoxide dismutase (SOD). Ischemic hindlimbs treated with high-energy phosphates displayed improved survival compared with controls. Limbs treated with SOD demonstrated no change in survival at 4 hours and improved survival at 8 hours. Combining adenosine and SOD had no improved effect on survival. Adenosine was the most effective high-energy phosphate in limiting ischemic damage. The free radical scavenger (SOD) was beneficial only at the later stages of ischemia. In this experimental model, there appears to be a role for both phosphates and free radical scavengers in enhancing ischemic tissue survival © 1997 Wiley-Liss, Inc MICROSURGERY 17:481–486 1996     

Energy metabolism and histomorphological findings in replanted rat hind limbs using various conservation methods

Using various storage and conservation methods, we examined amputated and subsequently replanted limbs for their ischaemia tolerance level by investigating the changes in the adenylphosphocreatine system and glycolysis cycle. After replantation, amputated limbs that had been stored at room temperature (21.0 ± 1.5°C) for 2 hours were examined 14 days after operation. The adenosine triphosphate level of the skeletal muscle was reduced to 51% and the creatine phosphate to 77% of that of the control group. The glycogen was 13% of the normal value. The biochemical findings correlate with the histomorphological findings. After 2 hours ischaemia, the cross striations of the skeletal muscle and nuclear staining remained intact. There is a breakdown of the biochemical systems after 4 hours of ischaemia. They are no longer intact and the ischaemic limb does not recover. Histologically, muscle necrosis can be observed.