Optimizing Surgical Skills in Cardiac Surgery Residents with Cardiac Transplant in the High-Fidelity Porcine Model.

OBJECTIVES: Simulation is a pivotal tool within cardiac surgery to facilitate learner growth and skill acquisition. There are many methods of simulation and it is possible to develop and implement new curricula incorporating these modalities. The objective of this paper is to describe the feasibility of a high-fidelity cardiac transplant simulation curriculum for surgical residents. METHODS: Our simulation setting was the Animal Resource Center at the University of Calgary. It was set up with 4 separate operating rooms, 2 for donor heart retrievals and 2 for heart implantations. This was done to allow 2 learners to participate with each animal, replicating the true intraoperative environment. Our teaching sessions were facilitated by 2 surgeons experienced in cardiac transplantation. In addition, we had support staff including multiple perfusionists, nurses, and anesthesia technologists. RESULTS: The curriculum was evaluated from many perspectives in real time throughout the simulation as well as afterward in posttest qualitative interviews with all participants. The residents readily identified the acquisition of and increased proficiency in specifically targeted surgical skills. In addition, the residents were able to practice communication, collaboration, and management. Furthermore, the simulation session and our debriefings contributed significantly to fostering a team approach. CONCLUSIONS: The pig is an excellent preclinical model for acquiring and developing the skills necessary for human cardiac transplantation. The residents partaking in the curriculum were satisfied with the learning they received and saw value in the swine transplant curriculum. The overall curriculum was cost-effective, due to the low overall operating costs associated with it.

Clinical Trypanosoma cruzi Disease after Cardiac Transplantation in a Cynomolgus Macaque (Macaca fascicularis).

A cynomolgus macaque received a heterotopic cardiac allograft as part of a transplant study, with monoclonal antibodies targeted to specific immune costimulation molecules (CD154, CD28) but no traditional immunosuppressive therapy after surgery. Clinical anemia was detected on postoperative day (POD) 35 and had worsened (Hgb, 2.3 g/dL; Hct = 7.3%) by POD 47, despite type-matched whole-blood transfusions. After a total of 4 blood transfusions, hematologic parameters were improved (Hgb, 5.9 g/dL; Hct, 18.7%). On POD 50, a peripheral blood smear revealed trypomastigotes, and qualitative RT-PCR of whole blood identified the organism as Trypanosoma cruzi. Although clinically stable initially, the macaque soon developed sufficient weight loss to necessitate euthanasia on POD 64. The final diagnosis was clinical anemia due to T. cruzi infection. This study represents the first reported case of Chagas disease after heart transplant in a NHP.

Heterotopic Cervical Heart Transplantation in Mice.

The heterotopic cervical heart transplantation in mice is a valuable tool in transplant and cardiovascular research. The cuff technique greatly simplifies this model by avoiding challenging suture anastomoses of small vessels thereby reducing warm ischemia time. In comparison to abdominal graft implantation the cervical model is less invasive and the implanted graft is easily accessible for further follow-up examinations. Anastomoses are performed by pulling the ascending aorta of the graft over the cuff with the recipient's common carotid artery and by pulling the main pulmonary artery over the cuff with the external jugular vein. Selection of appropriate cuff size and complete mobilization of the vessels are important for successful revascularization. Ischemia-reperfusion (I/R) injury can be minimized by perfusing the graft with a cardioplegic solution and by hypothermia. In this article, we provide technical details for a simplified and improved cuff technique, which should allow surgeons with basic microsurgical skills to perform the procedure with a high success rate.

Rat Heterotopic Abdominal Heart/Single-lung Transplantation in a Volume-loaded Configuration.

Herein, we describe a novel technique for heterotopic abdominal heart-lung transplantation (HAHLT) in rats. The configuration of the transplant graft involves anastomosis of donor inferior vena cava (IVC) to recipient IVC, and donor ascending aorta (Ao) to recipient abdominal Ao. The right upper and middle lung lobes are preserved and function as conduits for blood flow from right heart to left heart. There are several advantages to using this technique, and it lends itself to a broad range of applications. Because the graft is transplanted in a configuration that allows for dyamic volume-loading, cardiac function may be directly assessed in vivo. The use of pressure-volume conductance catheters permits characterization of load-dependent and load-independent hemodynamic parameters. The graft may be converted to a loaded configuration by applying a clamp to the recipient's infra-hepatic IVC. We describe modified surgical techniques for both donor and recipient operations, and an ideal myocardial protection strategy. Depending on the experimental aim, this model may be adapted for use in both acute and chronic studies of graft function, immunologic status, and variable ventricular loading conditions. The conducting airways to the transplanted lung are preserved, and allow for acute lung re-ventilation. This facilitates analysis of the effects of the mixed venous and arterial blood providing coronary perfusion to the graft. A limitation of this model is its technical complexity. There is a significant learning curve for new operators, who should ideally be mentored in the technique. A surgical training background is advantageous for those wishing to apply this model. Despite its complexity, we aim to present the model in a clear and easily applicable format. Because of the physiologic similarity of this model to orthotopic transplantation, and its broad range of study applications, the effort invested in learning the technique is likely to be worthwhile.

A modified method for heterotopic mouse heart transplantion.

Mice are often used as heart transplant donors and recipients in studies of transplant immunology due to the wide range of transgenic mice and reagents available. A difficulty is presented due to the small size of the animal and the considerable technical challenges of the microsurgery involved in heart transplantation. In particular, a high rate of technical failure early after transplantation may result from recipient death and post-operative complications such as hind limb paralysis or a non-beating heart. Here, the complete technique for heterotopic mouse heart transplantation is demonstrated, involving harvesting the donor heart and its subsequent implantation into a recipient mouse. The donor heart is harvested immediately following in situ perfusion with cold heparinized saline and transection of the ascending aorta and pulmonary artery. The recipient operation involves preparation of the abdominal aorta and inferior vena cava (IVC), followed by end-to-side anastomosis of the donor aorta with the recipient aorta using a single running 10-0 microsuture and a similar anastomosis of the donor pulmonary artery with the recipient IVC. Following the operation the animal is injected with 0.6 ml normal saline subcutaneously and allowed to recover on a 37 ° C heating pad. The results from 227 mouse heart transplants are summarized with a success rate at 48 hr of 86.8%. Of the 13.2% failures within 48 hr, 5 (2.2%) experienced hind limb paralysis, 10 (4.4%) had a non-beating heart due to graft ischemic injury and/or thrombosis, while 15 (6.6%) died within 48 hr.

Effects of antegrade and retrograde machine perfusion preservation on cardiac function after transplantation in canines.

INTRODUCTION: Most studies investigating machine perfusion preservation for heart transplantation perfuse through the aortic root (antegrade), but the coronary sinus (retrograde) is a potential option. We hypothesized that retrograde machine perfusion provides better functional protection than static storage, while avoiding the potential irregular perfusion seen when aortic insufficiency occurs with antegrade perfusion. MATERIALS AND METHODS: Eighteen canine donor hearts were arrested, procured, and stored in modified Celsior solution for 4 hours by using either static storage at 0°C to 4°C (n = 6) or machine perfusion preservation at 5°C via the aortic root (antegrade, n = 6) or coronary sinus (retrograde, n = 6). Lactate and myocardial oxygen consumption were measured in perfused hearts. Hearts were reimplanted and reperfused for 6 hours with hourly function calculated by using the preload recruitable stroke work (PRSW) relation. Myocardial water content was determined at the end of the experiment. RESULTS: Storage lactate levels and myocardial oxygen consumption were comparable in both perfused groups. The PRSW was increased immediately after bypass in the antegrade group (120.6 ± 19.1 mm Hg) compared with the retrograde (75.0 ± 11.3 mm Hg) and static (78.1 ± 10.5 mm Hg) storage groups (P < .05). At the end of reperfusion, PRSW was higher in the retrograde group (69.8 ± 7.4 mm Hg) compared with the antegrade (40.1 ± 6.8 mm Hg) and static (39.9 ± 10.9 mm Hg) storage groups (P < .05). Myocardial water content was similar among groups. CONCLUSIONS: Both antegrade and retrograde perfusion demonstrated excellent functional preservation, at least equivalent to static storage. Initial function was superior in the antegrade group, but the retrograde hearts displayed better function late after reperfusion. Neither perfused group developed significant edema. Machine perfusion preservation is a promising technique for improving results of cardiac transplantation.

Ultrastructural findings in porcine hearts after extracorporeal long-term preservation with a modified Langendorff perfusion system.

Preserved ultrastructure is an important precondition for functional regeneration after heart transplantation. We investigated the effectiveness of a newly developed modified Langendorff system in extracorporeal heart perfusion. (Experiment I) Cardioplegia and cold ischaemia were performed in six pigs. Hearts were connected to a modified Langendorff system, and perfused with leucocyte depleted autologous blood. (Experiment II) The untreated hearts of three healthy pigs served as controls. Forty-seven myocardial biopsies at different timepoints (I: n = 29, II: n = 18) were investigated by transmission electronmicroscopy. Cardioplegia/hypothermia (I) induced mild-to-moderate mitochondrial swelling, mild myofibrillar degeneration in cardiomyocytes and moderate endothelial oedema. After 4 h reperfusion cardiomyocytes showed moderate myofibrillar and mild sarcolemmal damage. Moderate endothelial degeneration, mild interstitial oedema and haemorrhages appeared. Untreated hearts (II) showed severely damaged mitochondria and nuclei after 30 min while the myofibrillar structure remained unaffected until 4 h later. This is a promising model for extracorporeal heart perfusion. However, ultrastructural findings indicated that some necessary modifications to prevent cellular damages during reperfusion were needed.

Transplante experimental cardíaco heterotópico e cutâneo em camundongos / Experimental heterotopic cardiac and cutaneous transplantation in mice

OBJETIVO: Estudo experimental com o objetivo de desenvolver e avaliar a viabilidade das técnicas de transplante experimental cardíaco heterotópico abdominal vascularizado e cutâneo em camundongos, criando um instrumento para investigação da eficácia de soluções de preservação, novas drogas imunossupressoras, agentes biológicos, terapia gênica e indução de tolerância imunológica. MÉTODO: Para este estudo, as técnicas utilizadas foram descritas previamente por Corry et al. e Billingham et al. RESULTADOS: O tempo cirúrgico total para a realização dos transplantes cardíacos (n=20) foi, em média, 60,3±6,3 minutos e para os transplantes cutâneos (n=20), 17,75±0,71 minutos. A média de sobrevida dos aloenxertos cutâneos (n=34) e cardíacos (n=24) foi, respectivamente, 7 e 11 dias, enquanto que os isoenxertos sobreviveram por mais de 100 dias. CONCLUSÕES: Ambas as técnicas se caracterizaram pela fácil reprodutibilidade dos modelos experimentais. As diferenças entre as técnicas não se limitaram às peculiaridades metodológicas ou ao tempo de sobrevida e vascularização, mas principalmente à sua imunogenicidade e suscetibilidade à rejeição.

Provision of anaesthesia for porcine cardiac transplantation at the veterinary school in Trinidad and Tobago.

A successful heterotopic cardiac transplantation was performed between sibling female Yorkshire Juvenile swine. Adequate pre-medication with azaperone and a smooth induction were ensured for both pigs, which were anaesthetized simultaneously with sodium thiopentone followed by endotracheal intubation and intermittent positive pressure ventilation. Inhalation anaesthetic agents were used for maintenance, neuromuscular blockade was achieved with cisatracurium and both fentanyl and tramadol were used to provide analgesia. Invasive monitoring was used in both the donor and recipient. Central venous pressure (CVP) was maintained at > 10 cm H2O and mean arterial pressure (MAP) > 60 mmHg. Heparin was injected during the surgical dissection of the heart in the donor to prevent coronary thrombosis and prior to aortic side clamping for end-to-side anastomosis of the donor heart in the recipient abdomen. After transplantation, the cardiovascular parameters of the recipient showed a MAP of 85-105 mmHg and a CVP of 8-10 cm H2O while echocardiography of the transplanted heart confirmed an ejection fraction (EF) of 80%. A functional anaesthetic team was assembled and trained to provide anaesthesia for porcine cardiac transplantation. The transplanted heart suffered pump failure after 69 days and was excised for performance of tissue analysis.

Provision of anaesthesia for porcine cardiac transplantation at the veterinary school in Trinidad and Tobago

A successful heterotopic cardiac transplantation was performed between sibling female Yorkshire Juvenile swine. Adequate pre-medication with azaperone and a smooth induction were ensured for both pigs, which were anaesthetized simultaneously with sodium thiopentone followed by endotracheal intubation and intermittent positive pressure ventilation. Inhalation anaesthetic agents were used for maintenance, neuromuscular blockade was achieved with cisatracurium and both fentanyl and tramadol were used to provide analgesia. Invasive monitoring was used in both the donor and recipient. Central venous pressure (CVP) was maintained at > 10 cm H2O and mean arterial pressure (MAP) > 60 mmHg. Heparin was injected during the surgical dissection of the heart in the donor to prevent coronary thrombosis and prior to aortic side clamping for end-to-side anastomosis of the donor heart in the recipient abdomen. After transplantation, the cardiovascular parameters of the recipient showed a MAP of 85-105 mmHg and a CVP of 8-10 cm H2O while echocardiography of the transplanted heart confirmed an ejection fraction (EF) of 80. A functional anaesthetic team was assembled and trained to provide anaesthesia for porcine cardiac transplantation. The transplanted heart suffered pump failure after 69 days and was excised for performance of tissue analysis

Anaesthetic management of baboons undergoing heterotopic porcine cardiac xenotransplantation.

A detailed anaesthetic technique for baboons (Papio anubis) undergoing heterotopic abdominal cardiac xenotransplantation is described. Twenty-two baboons served as transplant recipients. Donors were either crossbred farm pigs (Sus scrofa) (n = 4) or transgenic pigs (Sus scroefa) (n = 18) expressing human complement regulatory proteins on the endothelium. Intra-operative management was complicated by the physiological consequences of infrarenal. abdominal aortic cross-clamping, in addition to the immunological sequelae related to cross-species transplantation. In choosing anaesthetics for this procedure, we considered the need for maximal cardiac stability throughout a long surgical procedure that required abdominal aortic cross-clamping to facilitate the implantation of an oversized porcine cardiac graft. Baboons received a balanced anaesthetic consisting of inhaled isoflurane in oxygen, intravenous fentanyl and intravenous pancuronium. The pharmacological techniques employed were found to be safe and reliable and were well tolerated by our recipients without any significant side-effects.

Comparison of methods to evaluate acute rejection in heterotopic heart transplantation in rats.

We compared palpation and electrocardiograms (ECG) as methods of evaluation of acute rejections, and also studied the mode of expression of rejection from histological findings by means of a cervical heart transplantation model in LEW strain rats with (LEW x BN) F1 rats as donors. Evaluation by palpation mainly involved changes in the intensity of the beat of the transplanted heart. With this method, it was also possible to observe changes in the size of the graft, and to investigate these changes over time. Unlike with abdominal heart transplants, the time of cardiac arrest can be clearly determined without any influence from the heart rate of the recipient. But with the ECG evaluation method, it was possible to distinguish clearly between the waveforms of the graft and the recipient waveforms unlike with the conventional lead method. In histological findings, the time of transfer of infiltrating cells into the graft and the time of appearance of CD8 positive cells matched the times when changes occur in the intensity of the beat and in the heart rate seen with palpation. Unlike the palpation and ECG methods, however, these findings are not suitable for evaluation of the time of cardiac arrest of the graft. The graft survival time was 6.1 +/- 0.6 days (n = 73) by palpation and 8.5 +/- 1.8 days (n = 73) by ECG. Since the graft survival time was significantly longer in the ECG evaluation than in the evaluation by palpation (P < 0.001), it appeared better to use these methods independently rather than concurrently in consideration of their features. Histological examination appeared to be useful in experimental systems for clarification of the mode of expression of the acute rejection after its has occurred.

New assist method for orthotopic heart transplantation in the dog.

We used cross circulation as an assist method for orthotopic heart transplantation in eight dogs. Seven of the eight dogs could be extubated on the first to third postoperative day and were able to eat and walk several hours after extubation. The survival times and the causes of death in these eight dogs were as follows: 436 days (alive), 5 days (sudden death), 17 days (rejection), 17 days (pyothorax), 3 days (accidental death), 59 days (rejection), 19 days (pneumothorax), and 188 days (alive). None of the dogs died of any problems related to the use of cross circulation. Hematologic and biochemical studies revealed that the CK, CK-MB, LDH, GOT, GPT, and lactate levels increased shortly after the operation and returned to the preoperative values within 14 days. The blood urea nitrogen, creatinine, amylase, hematocrit, and total protein levels remained almost unchanged. No free hemoglobin was detected. These findings indicated that no severe damage occurred to the recipient's organs. The key factors for performing successful cross circulation are as follows: (1) The body weight of the support dog should be at least three times that of the recipient. (2) The systolic pressure of the support dog and the pressure gradient between the support and the recipient should be kept above 150 mm Hg and 50 mm Hg, respectively. (3) The flow rate in the arterial tube should be maintained at between 30% and 50% of the basal cardiac output of the recipient. In conclusion, cross circulation is a suitable assist method for orthotopic heart transplantation in the dog.

Heart transplantation in the rat: experience with a modified technique of heterotopic grafting.

Heart transplantation in the rat is a frequently used model to study immunological problems of primary, vascularized allografts. A modified technique of heterotopic grafting is described in detail. The donor heart is transplanted heterotopically into the recipient with the brachiocephalic artery anastomosed to the renal artery with 10 single sutures, and the pulmonary artery to the renal vein with 2 continuous, semicircular sutures which were left untied. Both anastomoses were done end-to-end with 10-0 Ethilon. The experience with 187 rat heart transplants are reported. The time needed for one transplantation ranged from 25 to 35 min (mean 30 min). Complications like bleeding, thrombosis and primary no-function did occur in 12 out of 187 transplants (6.4%). In conclusion, this modified technique of heterotopic heart transplantation in the rat is less time consuming and highly successful.