Excellent Restoration of Left Ventricular Compliance After Prolonged Del Nido Single-Dose Cardioplegia in an In Vivo Piglet Model

%LV compliance was preserved after ischemia with an acceptable reduction in contractility.

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Hypothermic Liver Machine Perfusion With EKPS-1 Solution vs Aqix RS-I Solution: In Vivo Feasibility Study in a Pig Transplantation Model

Objective

Hypothermic machine perfusion (HMP) is superior to simple cold storage for kidney preservation. We previous observed in a porcine liver transplantation model increased tumor necrosis factor-α (TNF-α) production eventually leading to poor recipient survival after HMP using standard kidney perfusion solution (KPS-1) compared with simple cold storage. We compared two solutions for HMP preservation of the liver: enriched KPS-1 (EKPS-1) and Aqix RS-I.

Methods

Pig livers were obtained after cold flushing with histidine-tryptophan-ketoglutarate solution. Subsequently, the livers were subjected to dual-vessel perfusion with two preservation solutions: EKPS-1 (n = 6) and Aqix RS-I (n = 3). After HMP preservation and transplantation, graft and recipient survival, hepatocellular damage (aspartate aminotransferase concentration), TNF-α production, and endothelial cell damage (hyaluronic acid clearance) were recorded.

Results

No primary graft nonfunction was observed. Recipient survival at postoperative day 3 was similar in both groups (33%). Aspartate aminotransferase concentration measured in serum samples after reperfusion was similar in both groups. After reperfusion, TNF-α concentration was higher and hyaluronic acid clearance was lower in the EKPS-1 group vs the Aqix RS-I group at 60, 120, and 180 minutes (all P < .05).

Conclusion

Hypothermic machine perfusion provided adequate longer term graft survival. After reperfusion, TNF-α production seems to be reduced, and endothelial cell dysfunction remains pronounced with Aqix RS-1 solution compared with EKPS-1 solution.     

In Vivo Gene Transfer of Hepatocyte Growth Factor to Skeletal Muscle Prevents Changes in Rat Kidneys After 5/6 Nephrectomy

Hepatocyte growth factor (HGF) has been reported to be a renal regeneration factor. We previously reported that HGF acts as a renotropic factor, inducing cell recovery from ischemic injury or drug toxicity. Gene transfer by electroporation, which uses plasmid DNA as the vector, has several advantages over the conventional gene transfer method using viral vectors, inducing the ability to perform repeated transfers without apparent immunologic responses to the DNA vector. We recently demonstrated that electroporation of the HGF gene into skeletal muscle was an effective treatment for liver injury in an animal model. We presently investigated prevention of development of chronic renal disease by repetitive HGF gene transfer in rats with 5/6 nephrectomy. Hepatocyte growth factor gene transfer-treated rats showed better growth in body weight than untreated rats. Histologic changes such as glomerulosclerosis and interstitial fibrosis were significantly ameliorated by HGF gene transfer compared with untreated rats. Hepatocyte growth factor gene transfer by electroporation into skeletal muscle is feasible and effective against morphologic injury in subtotally nephrectomized rats.     

Rabbit Tibial Periosteum and Saphenous Arteriovenous Vascular Bundle as an In Vivo Bioreactor to Construct Vascularized Tissue‐Engineered Bone: A Feasibility Study

The aim of this project was to construct vascularized tissue‐engineered living bone with an autologous vascular network by means of a rabbit bioreactor in vivo. The key components of the in vivo bioreactor for bone formation were the vascularized tibial periosteum and the saphenous vascular bundle. Beta‐tricalcium phosphate (β‐TCP) scaffolds were implanted into the in vivo bioreactor (vascular pedicle implantation and vascularized periosteum encapsulation). At 4 weeks postsurgery, new bone formation was mainly “cartilage‐bone inducing” in the inner periosteum, and was primarily seen in the outer aspects of the scaffold with some amount in the middle part as well. Microvascular infusion showed that direct revascularization of β‐TCP was obtained by means of vascular implantation. Triple staining results showed a large amount of blue collagen fibers. Vascular endothelial growth factor immunohistochemical staining displayed endothelial cells of new blood vessels in bone tissue. The bioreactor established in this study can be used to prepare tissue‐engineered bone with a vascular network.     

Reducing Persistent Postoperative Pain and Disability 1 Year After Breast Cancer Surgery: A Randomized,Controlled Trial Comparing Thoracic Paravertebral Block to Local Anesthetic Infiltration

Background

The objective of this study was to compare the effect of thoracic paravertebral block (TPVB) and local anesthetic (LA) on persistent postoperative pain (PPP) 1 year following breast cancer surgery. Secondary objectives were to compare the effect on arm morbidity and quality of life.

Methods

Women scheduled for elective breast cancer surgery were randomly assigned to either TPVB or LA followed by general anesthesia. An NRS value of >3 at rest or with movement 1 year following surgery defined PPP. Blinded interim analysis suggested rates of PPP much lower than anticipated, making detection of the specified 20 % absolute reduction in the primary outcome impossible. Recruitment was stopped, and all enrolled patients were followed to 1 year.

Results

A total of 145 participants were recruited; 65 were randomized to TPVB and 64 to LA. Groups were similar with respect to demographic and treatment characteristics. Only 9 patients (8 %; 95 % CI 4–14 %) met criteria for PPP 1 year following surgery; 5 were in the TPVB and 4 in the LA group. Brief Pain Inventory severity and interference scores were low in both groups. Arm morbidity and quality of life were similar in both groups. The 9 patients with PPP reported shoulder-arm morbidity and reduced quality of life.

Conclusions

This study reports a low incidence of chronic pain 1 year following major breast cancer surgery. Although PPP was uncommon at 1 year, it had a large impact on the affected patients’ arm morbidity and quality of life.     

A New Technique for the Surgical Creation of Aneurysms in an In Vivo Tortuous Vessel Model to Test Neurovascular Devices

The purpose of this study was to develop an aneurysm model that mimics the tortuous anatomy of the cerebrovasculature for the evaluation of endovascular devices. This model is an adaptation of the carotid siphon model of Georganos et al. The common carotid artery trunks in 10 swine were surgically elongated using an EXXCEL Soft ePTFE vascular graft and then sutured into position to form an S-curve, with each bend having a 5- to 10-mm radius. Following a 3- to 4-week healing period, aneurysms were surgically created from jugular vein grafts along or distal to the tortuous segment and immediately embolized with coils. In a subset (n = 6) of the arteries, a stent was also placed across the aneurysm neck. Animals were allowed to survive for 30 days. Clinical relevance and utility of the model were evaluated based on comparison to human angiographic images, physician feedback, and histopathological assessment. Tortuous anatomy was successfully created in all 10 animals, and aneurysms were added at various locations within or distal to the tortuous segment in a subset of 8 animals, creating 11 aneurysms in total. At 30 days, 18/20 vessels were patent and the bend radius was maintained. Endovascular access to aneurysms and placement of embolization coils and/or stents was successful in 10 of 11 attempts. Physician feedback indicated this tortuous model was more clinically relevant in terms of endovascular device delivery and deployment compared to established, nontortuous aneurysm models.     

Physiologic Changes in the Heart Following Cessation of Mechanical Ventilation in a Porcine Model of Donation After Circulatory Death: Implications for Cardiac Transplantation

Hearts donated following circulatory death (DCD) may represent an additional source of organs for transplantation; however, the impact of donor extubation on the DCD heart has not been well characterized. We sought to describe the physiologic changes that occur following withdrawal of life‐sustaining therapy (WLST) in a porcine model of DCD. Physiologic changes were monitored continuously for 20 min following WLST. Ventricular pressure, volume, and function were recorded using a conductance catheter placed into the right (N = 8) and left (N = 8) ventricles, and using magnetic resonance imaging (MRI, N = 3). Hypoxic pulmonary vasoconstriction occurred following WLST, and was associated with distension of the right ventricle (RV) and reduced cardiac output. A 120‐fold increase in epinephrine was subsequently observed that produced a transient hyperdynamic phase; however, progressive RV distension developed during this time. Circulatory arrest occurred 7.6±0.3 min following WLST, at which time MRI demonstrated an 18±7% increase in RV volume and a 12±9% decrease in left ventricular volume compared to baseline. We conclude that hypoxic pulmonary vasoconstriction and a profound catecholamine surge occur following WLST that result in distension of the RV. These changes have important implications on the resuscitation, preservation, and evaluation of DCD hearts prior to transplantation.     

Ketamine as an Adjunct to Postoperative Pain Management in Opioid Tolerant Patients After Spinal Fusions: A Prospective Randomized Trial

Management of acute postoperative pain is challenging, particularly in patients with preexisting narcotic dependency. Ketamine has been used at subanesthetic doses as a N-methyl d-aspartate (NMDA) receptor antagonist to block the processing of nociceptive input in chronic pain syndromes. This prospective randomized study was designed to assess the use of ketamine as an adjunct to acute pain management in narcotic tolerant patients after spinal fusions. Twenty-six patients for 1–2 level posterior lumbar fusions with segmental instrumentation were randomly assigned to receive ketamine or act as a control. Patients in the ketamine group received 0.2 mg/kg on induction of general anesthesia and then 2 mcg kg⁻¹ hour⁻¹ for the next 24 hours. Patients were extubated in the operating room and within 15 minutes of arriving in the Post Anesthesia Care Unit (PACU) were started on intravenous patient-controlled analgesia (PCA) hydromorphone without a basal infusion. Patients were assessed for pain (numerical rating scale [NRS]), narcotic use, level of sedation, delirium, and physical therapy milestones until discharge. The ketamine group had significantly less pain during their first postoperative hour in the PACU (NRS 4.8 vs 8.7) and continued to have less pain during the first postoperative day at rest (3.6 vs 5.5) and with physical therapy (5.6 vs 8.0). Three patients in the control group failed PCA pain management and were converted to intravenous ketamine infusions when their pain scores improved. Patients in the ketamine group required less hydromorphone than the control group, but the differences were not significant. Subanesthetic doses of ketamine reduced postoperative pain in narcotic tolerant patients undergoing posterior spine fusions. This work was funded by the Department of Anesthesia, Hospital for Special Surgery. This work was completed following IRB approval.     

Isolation and Ex Vivo Expansion of Bone Marrow-Derived Porcine Mesenchymal Stromal Cells: Potential for Application in an Experimental Model of Solid Organ Transplantation in Large Animals

Pharmacological aspecific immunosuppression, despite being widely used in solid organ transplantation recipients, is unable to completely prevent allograft rejection. It promotes the occurrence of sometimes life-threatening infections. Due to their immunosuppressive and anti- inflammatory properties, there is great interest in the therapeutic use of bone marrow (BM)-derived mesenchymal stromal cells (MSC). Large animal models play a crucial role to investigate the biological and functional properties of MSCs as novel cellular therapy. In the current study we sought to isolate expand ex vivo, and phenotypically characterize MSC derived from BM of 4 Large White 6-month-old piglets. Porcine MSC (pMSC) were characterized for their in vitro differentiation capacity. pMSC were successfully isolated from all BM samples. They showed spindle-shaped morphology and a stable doubling time on culture. They were positive for CD90, CD29, CD105, and negative for CD45 and CD11b. Furthermore, they differentiated, upon specific in vitro conditions toward adipogenic and osteogenic lineages. The optimization of methods for the isolation and characterization of pMSC may be useful to elucidate their biological and functional properties. The anatomy and physiology of the pig, which is similar to humans, make this animal model more attractive than small animals to test the safety and efficacy of MSC in the context of solid organ transplantation.     

Hypothermic Machine Perfusion as an Alternative to Biopsy Assessment in Transplantation of Kidneys Donated After Cardiocirculatory Death: A Pilot Study

BackgroundTransplantation of kidneys from donation after cardiocirculatory death (DCD) donors is becoming an ever-increasing reality. So far, biopsy histologic assessment is the main parameter for evaluation of graft suitability, but it has several drawbacks and has poor reliability. The aim of this study is to verify if real-time renal resistance (RR) measurement during hypothermic machine perfusion (HMP) can be used as a reliable parameter to evaluate the quality of grafts from DCD and extracorporeal membrane oxygenation (ECMO) donors.MethodsFrom January 2015 to September 2018, HMP has been systematically applied to all organs from DCD and ECMO donors. All grafts underwent preimplantation biopsy histologic assessment with Karpinski’s score. Single kidney transplants (SKTs) or double kidney transplants (DKTs) were performed according to biopsy score results. Kidneys were considered suitable for transplant if RR reached ≤ 1.0 within 3 hours of perfusion. RR trend and postoperative outcome were analyzed considering biopsy score and donor type.ResultsA total of 30 kidneys (15 from DCD and 15 from ECMO donors) were used to perform 26 transplants (22 SKTs and 4 DKTs). Considering RR trend, all grafts were considered suitable for transplant within 1 hour of perfusion. Biopsy confirmed this result in all cases, and median score was 3 (range, 0-7). SKT score kidneys had lower starting RR than DKT ones (1.88 vs 2.88; P = .04) but identical final RR (0.58 vs 0.57; P = .76). DKT recipients had faster postoperative creatinine reduction than SKT recipients but similar postoperative day 30 value (1.42 vs 1.15 mg/dL; P = .20). No differences were found between DCD and ECMO grafts in terms of RR trend and postoperative outcome.ConclusionsHMP can be an alternative to histologic biopsy assessment for evaluation of transplant suitability of DCD and ECMO kidneys. If acceptability threshold is reached, SKT can be performed in all cases. ECMO donors should be considered like DCD donors.