Advanced Preservation Rhinoplasty in the Era of Osteoplasty and Chondroplasty: How Have We Moved Beyond the Cottle Technique?

BACKGROUND: Over the last 10 years, many new papers on innovative strategies from different surgeons worldwide have elevated the philosophy of preservation rhinoplasty (PR) to a different level: advanced preservation rhinoplasty. OBJECTIVES: The goal of this article was to illustrate how 4 experienced surgeons approach important anatomical and functional issues related to PR. METHODS: M.G.F., A.M.K., B.S., and D.M.T. were asked about how they approach classical problems and relative contraindications for dorsal PR with different modern advanced preservation rhinoplasty techniques. RESULTS: The answers of each surgeon make clear a new reality in dorsal PR that did not exist in the recent past. These advances in dorsal PR techniques are due to many surgeons' contributions, leading this practice to a different level: advanced preservation rhinoplasty. CONCLUSIONS: Dorsal preservation is making a dramatic resurgence and is fueled by the many very talented surgeons who are demonstrating outstanding outcomes with preservation techniques. The authors believe that this trend will continue, and a mutual collaboration between structuralists and preservationists going forward will continue to advance rhinoplasty as a specialty.

Will cell therapies provide the solution for the shortage of transplantable organs?

PURPOSE OF REVIEW: The potential to regenerate ischemically damaged kidneys while being perfused ex-vivo offers the best near-term solution to increasing kidney allografts for transplantation. RECENT FINDINGS: There are a number of stem-cell sources including: stromal mesenchymal cells (MSC), induced adult pluripotent stem cells, fetal stem cells from placenta, membranes, amniotic fluid and umbilical cord and hematopoietic cells. MSC are increasingly the stem cell of choice and studies are primarily focused on novel induction immunosuppression to prevent rejection. Stem-cell therapies applied in vivo may be of limited benefit because the nonintegrating cells do not remain in the kidney and are not detectable in the body after several days. MSC therapies for transplantation have demonstrated early safety and feasibility. However, efficacy has not been clearly established. A more feasible application of a stem-cell therapy in transplantation is the administration of MSC to treat damaged renal allografts directly while being perfused ex vivo. Initial feasibility has been established demonstrating MSC-treatment results in statistically significant reduction of inflammatory responses, increased ATP and growth factor synthesis and mitosis. SUMMARY: The ability to regenerate renal tissue ex-vivo sufficiently to result in immediate function could revolutionize transplantation by solving the chronic organ shortage.

Minimally Invasive Strip Craniectomy Simplifies Anesthesia Practice in Patients With Isolated Sagittal Synostosis.

BACKGROUND: Traditional open corrective surgery for isolated sagittal synostosis entails significant blood loss, transfusion rates, morbidity, and a lengthy hospitalization. Minimally invasive strip craniectomy (MISC) was introduced to avoid the disadvantages of open techniques. OBJECTIVES: The aim of the study was, first, to compare the anesthesia practice in MISC and open extended strip craniectomy (OESC), and, second, to evaluate the incidence of perioperative complications in both surgical procedures. METHODS: A retrospective analysis was conducted for all consecutive patients receiving either OESC or MISC for nonsyndromic isolated sagittal synostosis between January 2006 and February 2014. The primary endpoints were the volume of blood loss, the volume of infused blood products, the duration of surgery, the anesthesia time, the intubation time, and the length of admission to high care units and the hospital. RESULTS: In MISC, the median duration of surgery (90 versus 178 min.), anesthesia time (178 versus 291 min), and intubation time (153 versus 294 min) were all significantly (P < 0.001) shorter than in OESC. Intraoperative blood loss was less in MISC than in OESC (3.8 versus 29.7 mL/kg, P < 0.001), requiring less crystalloids (33.3 versus 76.9 mL/kg, P < 0.001) as well as less erythrocyte transfusions (0.0 versus 19.7 mL/kg, P < 0.001) in a smaller number of patients (2/20 versus 13/15). The improved hemodynamic stability in MISC allowed for placement of less arterial and central venous catheters. After OESC all 15 patients were admitted to high care units, compared with 9 of 20 in MISC. The overall median hospital stay was shorter in MISC than in OESC (4 versus 6 d, P < 0.001). Although the incidence of technical complications was similar in both techniques, patients in MISC were less affected by perioperative electrolyte and acid-base disturbances and postoperative pyrexia. CONCLUSIONS: Minimally invasive strip craniectomy simplifies anesthesia practice relative to OESC with shorter operative times, decreased needs for replacement fluids and blood products, lessened requirements for invasive monitoring, and reduced demands for postoperative high care beds.

Factors influencing blood loss and allogeneic blood transfusion practice in craniosynostosis surgery.

OBJECTIVE/AIMS: To identify factors influencing perioperative blood loss and transfusion practice in craniosynostotic corrections. BACKGROUND: Craniosynostotic corrections are associated with large amounts of blood loss and high transfusion rates. METHODS: A retrospective analysis was performed of all pediatric craniosynostotic corrections during the period from January 2003 to October 2009. The primary endpoint was the receipt of an allogeneic blood transfusion (ABT) during or after surgery. Pre-, intra-, and postoperative data were acquired using the electronic hospital registration systems and patients' charts. RESULTS: Forty-four patients were operated using open surgical techniques. The mean estimated blood loss during surgery was 55 ml·kg(-1). In 42 patients, red blood cells were administered during or after surgery with a mean of 38 ml·kg(-1). In 23 patients, fresh frozen plasma was administered with a mean of 28 ml·kg(-1). A median of two different donors per recipient was found. Longer duration of surgery and lower bodyweight were associated with significantly more blood loss and red blood cell transfusions. Higher perioperative blood loss and surgery at an early age were correlated with a longer duration of admission. CONCLUSIONS: In this study, craniosynostotic corrections were associated with large amounts of blood loss and high ABT rates. The amount of ABT could possibly be reduced by appointing a dedicated team of physicians, by using new less-invasive surgical techniques, and by adjusting anesthetic techniques.

Predictive value of weight gain and airway obstruction in isolated Robin sequence.

OBJECTIVE: Treatment of airway obstruction and feeding difficulties among newborns with isolated Robin sequence is challenging. The lack of clear guidelines may lead to prolonged hospital stays and delays in treatment. Appropriate risk stratification can facilitate treatment planning. We aim to identify factors that prognosticate prolonged hospital stay in children with isolated Robin sequence. SETTING: We used a retrospective multivariate analysis of 46 patients admitted with isolated Robin sequence at the Hospital for Sick Children, in Toronto, between 2000 and 2007. During the initial 4 weeks following admission, data regarding duration of hospital stay, management of airway obstruction, respiratory rate, management of feeding difficulties, and reflux therapy were collected. RESULTS: Correlation between length of hospital stay, airway management, and weight gain during the initial 4 weeks was noted. No correlation was found between length of hospital stay and respiratory rate, supplemental oxygen requirement, or reflux therapy. CONCLUSIONS: Risk stratification is possible in children with isolated Robin sequence. Delayed weight gain in Robin sequence correlates with the degree of airway obstruction. The need for a nasopharyngeal tube and weight gain during the initial 4 weeks of life in newborns with Robin sequence reliably predict length of hospital stay. These prognosticators should contribute to parent and physician expectations, as well as assist in treatment and discharge planning.

Potentiating Renal Regeneration Using Mesenchymal Stem Cells.

BACKGROUND: The potential of a mesenchymal stem cell (MSC) therapy to accelerate the repair of ischemically damaged human kidneys during 24 hours of warm perfusion was evaluated. The hypothesis was that by administering MSC directly to the renal tissue, there would be an improved opportunity for cellular repair mediated by intrarenal paracrine effects. METHODS: Studies were performed using the exsanguinous metabolic support (EMS) tissue-engineering platform. Five pairs of human kidney allografts from donation after circulatory death donors were studied. One human kidney was EMS perfused for 24 hours (control), whereas its paired kidney was EMS perfused with MSC (1 × 10). The kidneys were evaluated for DNA synthesis, cytokine/chemokine synthesis, cytoskeletal regeneration, and mitosis. RESULTS: Treatment with MSC resulted in reduced inflammatory cytokines synthesized by the kidneys. Mesenchymal stem cell treatment led to a significant increase in the synthesis of adenosine triphosphate and growth factors resulting in normalization of metabolism and the cytoskeleton. Toluidine Blue staining of MSC-treated kidneys demonstrated a significant increase in the number of renal cells undergoing mitosis (26%) compared with EMS perfusion alone. CONCLUSIONS: To our knowledge, our work is the first to have demonstrated actual renal regeneration while ischemically damaged human kidneys are perfused ex vivo for 24 hours. The observed regeneration entails: increased synthesis of adenosine triphosphate, a reduced inflammatory response, increased synthesis of growth factors, normalization of the cytoskeleton and mitosis. The ability to regenerate renal tissue ex vivo sufficiently to result in immediate function could revolutionize transplantation by solving the chronic organ shortage.

Improving outcome in meningococcal disease: don't forget compartment syndrome!

OBJECTIVE: To advocate a surgical intervention that can prevent the loss of limbs in patients with meningococcal disease. DESIGN: Case report. SETTING: Pediatric intensive care unit. PATIENT: A 4-month-old male infant presenting with acute circulatory failure due to meningococcal disease. INTERVENTIONS: Measurements of compartment pressures of all extremities and echo-Doppler of peripheral arteries were performed at regular intervals, starting at admittance to the pediatric intensive care unit. After compartment syndrome in the lower extremities was diagnosed, emergency surgical intervention (fasciotomy and arteriolysis) was performed in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: During surgery, the compartments initially revealed pale, poorly perfused tissue. After decompression, immediate bulging of the muscles and restoration of microcirculation were seen. All digits were spared, and muscle compartments remained vital with exception of the tibialis anterior and extensor hallucis longus muscles in the left leg. Several ecchymoses and purpura of the lower extremities caused skin necrosis, necessitating skin transplants. No other surgical intervention was required. CONCLUSIONS: In meningococcal disease, compartment syndrome can occur within hours after initial presentation due to massive capillary leakage and circulatory failure. Immediate surgical intervention is the gold standard in treatment, making early recognition vital. In all patients presenting with meningococcal disease, compartment syndrome should be considered and early monitoring included in the initial evaluation.

Underlying Mechanisms of Protection Involved in Immunocloak.

BACKGROUND: We have previously reported on a novel organ-specific immunomodifying therapy that provides protection from early allograft rejection in the absence of systemic immunosuppressive drugs. This novel therapy is a nanobarrier membrane called ImmunoCloak, consisting of a matrix of laminin, proteoglycans, fibronectin, and collagens. The membrane "immunocloaks" the luminal surfaces within the renal vasculature by covering the point of contact between donor vascular endothelial cells and the recipient's immune cells, without adversely affecting renal function. The resulting nonthrombogenic and nonimmunogenic apical surface significantly delays the onset of rejection fivefold over untreated controls. Currently, our focus is to elucidate the mechanisms of protection provided by placement of the membrane. METHODS: The mechanisms underlying the protective effect of the ImmunoCloak treatment was evaluated using human peripheral blood mononuclear cells and by testing for antigen presentation by cytokine/chemokine analysis using the Luminex platform, T cell allogeneic responses were measured by flow cytometry, and diapedesis was assessed using transwell plates. RESULTS: We now report that ImmunoCloak interrupts antigen presentation thereby preventing early T cell activation and interferes with diapedesis. There was significant inhibition in the synthesis of proinflammatory cytokines with a concordant blockade of T cell-mediated responses. The placement of the ImmunoCloak also significantly reduced leukocyte migration through the endothelial cell layer by 93%. CONCLUSIONS: Eliminating the need for nephrotoxic immunosuppressive drugs during the early posttransplant period could help to ameliorate the severity of delayed graft function and could provide a path to using more ischemically damaged renal allografts.

Induction of heme oxygenase-1 in kidneys during ex vivo warm perfusion.

BACKGROUND: Reperfusion injury plays a pivotal role in the occurrence of delayed graft function and chronic rejection. Heme oxygenase-1 (HO-1), an inducible heat shock protein, is known to have cytoprotective effects against reperfusion injury. We report on the potential for ex vivo induction of HO-1 expression during acellular warm perfusion of canine kidneys, using cobalt protoporphyrin (CoPP) as an HO-1 inducer and zinc protoporphyrin as an HO-1 inhibitor. METHODS: Canine kidneys were used to evaluate HO-1 increase after exposure to warm ischemia (WI), hypothermic perfusion (mechanical perfusion [MP], 4 degrees C), warm perfusion (exsanguineous metabolic support [EMS], 32 degrees C), or various combinations. RESULTS: WI alone, MP, or EMS with or without WI, had no effect on HO-1 activity. However, the presence of CoPP during EMS perfusion resulted in a significant increase in kidney HO-1 activity, whereas zinc protoporphyrin reduced HO-1 activity. The presence of CoPP during MP did not induce elevated HO-1 expression. The results of our study demonstrate that sufficient metabolism supporting new protein synthesis resulting in the expression of the protective gene, HO-1, can be accomplished during an acellular near-normothermic perfusion using CoPP. Most importantly, the time required for ex vivo HO-1 induction with this method is compatible with the current time frame for which organs are preserved clinically. CONCLUSIONS: The ability to induce HO-1 expression ex vivo eliminates the need for donor therapy to induce HO-1 increase before retrieving organs and also prevents the potential of decreasing HO-1 enzyme activity that is known to occur with temperature-mediated inhibition of oxidative metabolism during hypothermic organ storage.

Overcoming severe renal ischemia: the role of ex vivo warm perfusion.

BACKGROUND: The ability to effectively utilize kidneys damaged by severe (2 hr) warm ischemia (WI) could provide increased numbers of kidneys for transplantation. The present study was designed to examine the effect of restoring renal metabolism after severe WI insult during ex vivo warm perfusion using an acellular technology. After warm perfusion for 18 hr, kidneys were reimplanted and evaluated for graft function. METHODS: Using a canine autotransplant model, kidneys were exposed to 120 min of WI. They were then either reimplanted immediately, hypothermically machine perfused (4 degrees C) for 18 hr with Belzer's solution, or transitioned to 18 hr of warm perfusion (32 degrees C) with an acellular perfusate before implantation. RESULTS: Warm perfused kidneys with 120 min of WI provided life-sustaining function after transplantation, whereas the control kidneys immediately reimplanted or with hypothermic machine perfusion did not. The mean peak serum creatinine in the warm perfused kidneys was 3.7 mg/dl, with the mean peak occurring on day 2 and normalizing on day 9 posttransplant. CONCLUSIONS: These results indicate that 18 hr of ex vivo warm perfusion of kidneys is feasible. Furthermore, recovery of renal function during warm perfusion is demonstrated, resulting in immediate function after transplantation. The use of ex vivo warm perfusion to recover function in severe ischemically damaged kidneys could provide the basis for increasing the number of transplantable kidneys.

Solving the organ shortage: potential strategies and the likelihood of success.

The discrepancy between the demand and supply of organs for clinical transplantation remains a major problem. The current incidence of end-stage renal disease results in a patient population that doubles every decade. However, there have been no advancements in developing a comparable increase in the number of available allografts. There are three potential approaches to solving the shortage. In the near-term, the development of technology to access the pool of warm ischemically damaged organs may represent a solution. To achieve this goal, it will be necessary to develop technology that mimics the physiologic processes of wound repair. Alternatively, it has been proposed that an increased supply of organs can be developed with xenografts. To make xenotransplantation a clinical reality, it will be necessary to overcome the barriers that exist in nature between the species. Recent work in the area of stem cell research has provided evidence supporting the potential of generating biohybrid organs. A major undertaking of this emerging field will be to develop the ability to define and control the differentiation processes involved in organ specificity. The following is a review of the current status and relative issues involved with these three potential approaches to solving the organ shortage.

Bioengineered skin allografts: a new method to prevent humoral response.

We previously reported that a bioengineered interface consisting of a nano-barrier membrane (NB-LVF4) used as an artificial interface between skin allografts and wound surfaces significantly prolonged graft survival without immunosuppression. We now evaluated whether NB-LVF4 could serve as a targeted drug delivery system to further improve outcomes. Fibroblast growth factor-1 (FGF-1) was selected for its known function as a wound hormone. Full-thickness 8-mm skin grafts were cross-transplanted between out-bred mice. Controls were transplanted without treatment. In test groups, the NB-LVF4, with or without FGF-1, was applied to both basolateral skin and wound surfaces with polymerization resulting in a tridimensional transparent membrane. The mice were evaluated for T-cell activation and development of donor-specific antibody. Rejection occurred in controls by 7 days. NB-LVF4 treatment, with or without FGF-1, was found to significantly prolong allograft survival (27 and 28 days, respectively [p < 0.05]). Untreated controls stimulated 10-fold shift in the number of circulating CD4+ cells while test groups exhibited substantially reduced shifts in CD4+ cells. The group treated with FGF-1 did not develop donor-specific antibody. Treatment with the NB-LVF4 membrane delays the onset of allograft rejection in the absence of systemic immunosuppression. FGF-1 appears to prevent the development of a humoral response by preventing B cell activation.

Pretransplant kidney-specific treatment to eliminate the need for systemic immunosuppression.

BACKGROUND: Despite significant side effects, chronic systemic immunosuppression remains the backbone of clinical transplantation. We investigated the feasibility of preventing early allorecognition in canine renal allografts using a nonsystemic pretreatment. METHODS: The renal vasculature was treated with a bioengineered interface consisting of a nano-barrier membrane during 3 hr of ex vivo warm perfusion. RESULTS: Preliminary feasibility of the immunocloaking technology was established by the following criteria: it is possible to achieve approximately 90% coverage of the vasculature with nano-barrier membrane after 3 hr of ex vivo warm perfusion; covering the luminal surfaces prevents allorecognition as determined by mixed lymphocyte-vascular endothelial reaction; covering the luminal surfaces does not negatively affect renal function as determined by autotransplant outcomes; and graft rejection is significantly postponed in canine kidneys treated with the immunocloaking technology. In the absence of systemic immunosuppression, untreated control dogs experienced a mean onset of rejection on day 6, whereas in the treated dogs with modified renal vascular luminal surfaces, the mean onset of rejection was significantly delayed until day 30. CONCLUSIONS: The ability to postpone, or eventually eliminate, the allorecognition that occurs immediately on reperfusion could provide a new window of opportunity to introduce adjunct therapies to support tolerance induction. To our knowledge, this is the first time significantly prolonged canine renal allograft survival has been achieved in the absence of systemic immunosuppression or immunologic manipulation of the recipient.

Delayed skin allograft rejection following matrix membrane pretreatment.

INTRODUCTION: No solution has been offered to induce long-term skin allograft survival in burn patients. We investigated whether transplant acceptance could be improved by a nonsystemic pretreatment of the graft and recipient wound surfaces with a bioengineered interface consisting of an acellular matrix membrane. METHODS: Group 1 (n=30): Crosstransplants of untreated skin grafts between BALB/c and C57BL/6 mice. Group 2 (n=30): Crosstransplants of matrix-treated skin grafts between BALB/c and C57BL/6 mice. Group 3 (n=30): Retransplantation of skin grafts from the original donor on to the sensitised recipients. Sensitisation was accomplished by prior transplantation of an untreated skin allograft from the same donor (Group 1 mice). Two skin grafts were transplanted: one treated and one untreated. RESULTS: Rejection occurred in the untreated group after a mean of 6.8 days (+/-1.5 days). In contrast, treatment with the bioengineered matrix membrane was found to substantially prolong allograft survival with a mean of 28 days (+/-3.8 days). Graft survival between the two groups reached statistical significance (P<0.05). In the sensitised mice, the untreated skin regrafts were all rejected in an accelerated fashion with an onset of less than 4 days (mean+/-1 days). However, the matrix membrane-treated skin regrafts were maintained for a mean of 18 days (+/-3 days). CONCLUSION: These results show that treatment with the bioengineered matrix membrane greatly delays the onset of acute allograft rejection. The described topical application to the wound surfaces of both the graft and the recipient may offer a new and readily available source of wound coverage in patients with extensive burns.

The modified Honig velopharyngoplasty - a new technique to treat hypernasality by palatal lengthening.

BACKGROUND: Palatal lengthening by pushback with a pharyngeal flap is a commonly used operative technique for the treatment of velopharyngeal insufficiency. The conventional Honig velopharyngoplasty uses full thickness mucoperiosteal flaps for the oral lining of the defect. PURPOSE: A modification is described using only mucosal flaps, thus preserving the periosteum and the palatine arteries. Vascularisation of the hard palate is preserved and bone is not exposed, avoiding potential detrimental scar formation overlying the hard palate, which may affect normal outgrowth of the maxilla. STUDY DESIGN: Eight patients with persisting hypernasality were included. Velopharyngeal closure was evaluated by nasendoscopy, nasometry and a Dutch speech test for cleft patients. RESULTS: Hypernasality was corrected in all cases. One patient developed a light hyponasality. In four patients the overall speech normalised and in the remaining four cases small errors persisted, but speech was well understandable. CONCLUSION: The procedure yields satisfactory speech results in this preliminary study, comparable to the conventional Honig velopharyngeaplasty. Long term follow up regarding maxillary growth and comparative studies with other operative techniques are now warranted.

Outcome of velopharyngoplasty in patients with velocardiofacial syndrome.

OBJECTIVE: To compare the outcomes of surgical correction of velopharyngeal insufficiency (VPI) in patients with velocardiofacial syndrome (VCFS) and a non-VCFS group. DESIGN: Twenty-five patients with VCFS (16 girls and 9 boys) underwent palatal lengthening for VPI between 1986 and 2001. The mean age at surgery was 6.4 years. Revision was defined as the need for secondary sphincter pharyngoplasty as determined by speech investigation, nasal endoscopy, and acoustic nasometry. A comparison was made to a control group made up of a randomized group of patients without VCFS who underwent palatal lengthening for VPI (32 patients: 10 girls and 22 boys). SETTING: Wilhelmina Children's Hospital, a tertiary referral center in Utrecht, the Netheralands. PATIENTS: A total of 57 patients who underwent palatal lengthening for VPI, 25 with VCFS and 32 without VCFS. INTERVENTIONS: Primary surgery consisted of a palatal lengthening technique. If revision was needed, a sphincter pharyngoplasty was carried out. MAIN OUTCOME MEASURES: Pharyngeal function was assessed using perceptual speech investigation, nasal endoscopy, and acoustic nasometry. RESULTS: In the VCFS group, 16% of the patients required surgical revision (4 of 25). These patients were slightly older at the time of primary surgery than those who did not require surgical revision (mean age, 6 vs 5.5 years). In the control group, no patients required revision. Preoperative speech analysis showed a more pronounced VPI in the VCFS group than in the control group. Outcomes of endoscopy and speech hypernasality improved significantly more in the control group than in the VCFS group. Improvement in the results of acoustic nasometry did not differ significantly between the 2 groups. CONCLUSIONS: Treatment of VPI using palatal lengthening in children with VCFS is both safe and effective. The discrepancy in improvement between the speech analysis and the nasal endoscopy results within the VCFS group indicates that mechanical improvement does not necessarily correspond to an improvement in speech and emphasizes the complexity of speech disorders found in VCFS.

Use of tissue expanders in adult postpneumonectomy syndrome.

OBJECTIVE: Mediastinal shift and rotation after pneumonectomy can lead to severe symptomatic airway compression. Historically, a variety of treatments, such as muscle-flap transposition, pericardial fixation, and plombage, have been used. In this study we retrospectively evaluated the effectiveness of intrathoracic tissue expansion in postpneumonectomy syndrome. METHODS: Since 1990, our center has used tissue expanders as plombage in patients with postpneumonectomy syndrome. Between 1990 and 2005, a total of 20 patients were treated. The outcome was evaluated by using preoperative, perioperative, and postoperative bronchoscopy and imaging studies. Patient satisfaction was determined with a validated questionnaire. RESULTS: In 19 of the 20 patients, up to 3 tissue expanders were placed and filled within the pleural cavity. Access to the pleural cavity could not be obtained in 1 patient because of adhesions. Perioperative and postoperative bronchoscopic scans demonstrated decompression of the left main bronchus in 16 (84%) of 19 patients. On discharge, all patients reported improvement of their respiratory symptoms. Six (32%) patients required reoperation because of herniation (n = 2), luxation (n = 1), inadequate positioning (n = 2), and leakage of the tissue expander (n = 4). In 4 patients additional filling was performed in the outpatient clinic, with immediate improvement of respiratory distress. CONCLUSION: Use of tissue expanders in adults with postpneumonectomy syndrome is an effective means of decompressing the remaining bronchus, thereby leading to a significant improvement in respiratory symptoms. Although 32% of patients required reoperation for complications, each complication was readily correctable.

Repair of damaged organs in vitro.

Treatments that can be performed ex vivo following ischemia to accelerate cellular recovery and ameliorate reperfusion injury could have major impact. An acellular, near-normothermic perfusion was employed to deliver growth factors to ischemically damaged kidneys. During the treatment oxidative metabolism was sufficiently restored to support up-regulation of cellular processes with the potential to modulate both injury and repair proteins in damaged kidneys. The results suggest that growth factor administration, without concomitant inflammation, triggers pathways for new synthesis leading to cellular recovery rather than cell death.

NOS: the underlying mechanism preserving vascular integrity and during ex vivo warm kidney perfusion.

Research involving metabolically active and functioning organs, maintained ex vivo in culture-like conditions, could provide numerous opportunities for medical innovations and research. We report successful perfusion of isolated canine and human kidneys ex vivo at near physiologic temperature for 48 h. During the perfusions parameters of metabolism and function remained stable. Nitric oxide synthase (NOS) was identified as the underlying mechanism preserving vascular integrity. Most importantly, when the canine kidneys were reimplanted there was immediate normal renal function. This report highlights the potential significance of whole organ culture using a warm temperature ex vivo perfusion and discusses medical applications that could be developed.