Marcin Misterski

Predictive factors of late venous aortocoronary graft failure: ultrastructural studies.

Background Venous aortocoronary graft arterialization may precede a preterm occlusion in some coronary artery bypass grafting (CABG) patients. The aim of the present study was to identify ultrastructural variations in the saphenous vein wall that may have an impact on the development of venous graft disease in CABG patients. Methods The study involved 365 consecutive patients with a mean age of 62.9±9.4 years who underwent isolated CABG. The thickness and area of the whole venous wall, the tunica intima, the tunica media and the adventitia and the number and shape (length, thickness and length/thickness ratio) of the nuclei in the medial smooth muscle cells nuclei in the distal saphenous vein segments were evaluated by ultrastructural studies. Patients were followed up for 41 to 50 months (mean 45.1±5.1). Saphenous vein graft patency was assessed by follow-up coronary angiography. Logistic regression models were used to identify independent risk factors for late graft failure. Results In 71 patients significant lesions in the saphenous vein grafts were observed. The whole venous wall thickness (437.5 µm vs. 405.5 µm), tunica media thickness (257.2 µm vs. 211.5 µm), whole venous wall area (2.23 mm2 vs. 2.02 mm2) and tunica media area (1.09 mm2 vs. 0.93 mm2) were significantly larger for this group of patients than for those without graft disease. In the latter group more elongated smooth muscle cell nuclei (higher length/thickness ratio) were found in the tunica media of the saphenous vein segments. Thickening of the saphenous vein tunica media and chunky smooth muscle cell nuclei were identified as independent risk factors for graft disease development. Conclusions Saphenous vein tunica media hypertrophy (resulting in wall thickening) and chunky smooth muscle cell nuclei might predict the development of venous graft disease.

Endothelial integrity of radial artery grafts harvested by minimally invasive surgery — immunohistochemical studies of CD31 and endothelial nitric oxide synthase expressions: a randomized controlled trial

OBJECTIVE To compare the endothelial integrity of radial artery grafts harvested by minimally invasive surgery and arteries harvested conventionally for coronary artery bypass surgery (CABG) in 200 participants, who were assigned to interventions by using random allocation. METHODS An immunohistochemical procedure with monoclonal antibodies was employed to estimate CD31 antigen and endothelial nitric oxide synthase (eNOS) expressions - markers defining endothelial integrity. RESULTS The CD31 immunostaining revealed that the endothelial cell integrity of the minimally invasive harvested arteries was preserved in 76.1±7.4% of the circumference of luminal endothelium, which was similar to results obtained in conventionally harvested grafts (77.2±9.8%; not significant). On the other hand, eNOS immunostaining indicated that the endothelial integrity of the minimally invasive harvested grafts was preserved in 75.4±10.5% while in conventionally harvested grafts it was reduced to 42.4±14.5% of the total luminal endothelium circumference (P<0.05). CONCLUSIONS The endothelial integrity of radial artery grafts harvested by minimally invasive surgery is better preserved than in the grafts obtained by the conventional manner. This could play an important role in improving graft patency and might represent a preliminary condition of stable functioning in coronary arterial bypasses.

Preexisting High Expression of Matrix Metalloproteinase-2 in Tunica Media of Saphenous Vein Conduits Is Associated with Unfavorable Long-Term Outcomes after Coronary Artery Bypass Grafting

Introduction. Migration of the smooth muscle cells (SMCs) to the tunica media in the saphenous vein (SV) transplants is facilitated by matrix metalloproteinases (MMPs). The aim of this study was to identify any associations between expression of MMP-2 or endogenous tissue inhibitors (TIMP-2 and TIMP-3) in the SV segments and late failure of the SV grafts. Methods. Two hundred consecutive patients with a mean age of 63.1 ± 8.9 years who underwent primary isolated venous CABG were examined. Patients were retrospectively split into two subgroups, with the SV graft disease (SVGD (+); n = 47) or without it (SVGD (−); n = 153). In the SV segments, immunohistochemical analysis of the expression of the MMP-2, TIMP-2, and -3 was performed. Results. In the SVGD (+) patients, tissue expression of MMP-2 was stronger, whereas that of both TIMPs was weaker than in the SVGD (−) patients. In majority of the SV segments obtained from the SVGD (−) individuals, a balance in MMP and TIMP expressions was found, whereas an upregulation of MMP-2 expression was usually noted in the SVGD (+) subjects. Conclusion. The strong expression of MMP-2 accompanied by reduced immunostaining of both TIMPs is associated with the development of the SV graft disease and unfavorable CABG outcomes.

Histological evaluation of age-related variations in saphenous vein grafts used for coronary artery bypass grafting.

Introduction Venous coronary artery bypass grafts (CABG) might undergo a process of arterialization resulting in neointimal formation and medial hypertrophy. It is often followed by critical occlusion of the graft lumen. The aim of the study was to assess histological representative features of saphenous vein reconstruction in aging as well as to establish optimal patients’ age limits applicable for optimal selection of grafts. Material and methods One hundred and ten patients undergoing venous CABG were divided into 4 age subgroups: (A) 50 years and less, (B) 51-60 years, (C) 61-70 years and (D) > 70 year-old subjects. Distal venous graft segments were saved for an adequate morphometric assay which was followed by suitable statistical analysis. Results The entire venous wall thickness as well as its tunica media were found to become significantly thinner between subgroups A and D. The number of smooth muscle cell (SMC) nuclei within the tunica media did not differ between study subgroups. The majority of these nuclei in subgroup D were found, however, to be more elongated than in subgroup A (SMC length/width index in subgroup D was found to be significantly higher than in subgroup A). Conclusions Progressive, age-related thinning of the venous wall and tunica media as well as SMC nucleus elongation might suggest impairment of SMCs’ migration and proliferation rate. Consequently, individuals aged 70 years and over may benefit clinically more from venous CABG than younger patients due to the lower risk of arterialization and occlusion of the graft lumen in the future.

Comparison of conventional tacrolimus versus prolong release formula as initial therapy in heart transplantation.

BACKGROUND A new formulation of tacrolimus that is characterized by prolonged release has been developed to facilitate treatment and patient compliance. Initial therapy with prolonged release formula in heart transplantation is not widely accepted. MATERIAL AND METHODS We enrolled 19 patients into a randomized analysis divided into 2 groups with different initial regimens. There were 8 patients with a mean age of 44 ± 13 years treated by Advagraf, and 11 patients with a mean age of 41 ± 9 years treated by Prograf. Serum concentration of immunosuppressive drug was followed by its oral dosage and endomyocardial biopsy results. Arterial hypertension, kidney function, and incidence of diabetes mellitus were recorded. RESULTS There were no perioperative deaths. The risk of acute rejection within 6 months following surgery was 1 (2%) in the Advagraf group and 1 (1.5%) in the Prograf group. Although the serum tacrolimus results were comparable between groups, the drugs daily dosages were different after 6 months of therapy (3 ± 1 mg in the Advagraf group and 6 ± 2 mg in the Prograf group (p<0.05). The low rate of adverse effects throughout the study was noted. CONCLUSIONS Prolonged-release tacrolimus formula is an efficient immunosuppressant in heart transplantation. Its initial application after surgery has low risk of adverse effects with similar results to conventional formula.

Cytokeratin 8 in venous grafts: A factor of unfavorable long-term prognosis in coronary artery bypass grafting patients

BACKGROUND Smooth muscle cells, present in the saphenous vein (SV) tunica media, may contribute to late occlusion of venous aortocoronary grafts. The aim of present study was to evaluate expression of selected cytoskeletal proteins in tunica media of SV grafts obtained from patients undergoing coronary artery bypass grafting (CABG) and correlate procured results to late venous graft failure observed in these patients. METHODS The study involved 218 patients (mean age of 62.5 ± 8.7 years) who underwent primary isolated CABG with the use of at least one venous aortocoronary bypass graft. Expressions of alpha-smooth muscle actin, smooth muscle-myosin heavy chain, calponin and cytokeratin 8 in SV wall were estimated by means of immunohistochemistry. The primary clinical endpoint was defined as the presence of any coronary artery disease (CAD) progression symptom while angiographic one as significant stenosis in the venous graft. RESULTS Thirty-eight (18.1%) patients have reached the primary clinical endpoint. Freedom from clinical CAD deterioration was 0.95 ± 0.02, 0.87 ± 0.03 and 0.83 ± 0.04, for 12-, 24-,36-month follow-up, respectively. Forty-four study participants have reached the angiographic endpoint. Multivariate logistic regression analysis revealed an increased expression of cytokeratin 8 accompanied by calponin under expression in SV tunica media were independent risk factors for venous graft failure. CONCLUSIONS An increased expression of cytokeratin 8 and weak of calponin in tunica media of SV grafts might be useful markers of unfavorable long-term prognosis in CABG patients. In the future, assessment of their expression may enable to select the most appropriate candidates for SV grafts.

Customization of a patient simulator for ECMO training

Background: Poland is setting up its first regional ECMO program and relies heavily on the use of simulation in testing processes and training clinicians.1 As ECMO is a complex and expensive procedure, we developed an advanced ECMO simulator for high-fidelity medical simulation training.2–6 It can be used to modify any type of full-body patient simulator and allows for the creation of an unlimited number of scenarios. Methods: The system is equipped with an electronic core control unit (CCU) (Figure 1), a set of synthetic valves, pressure sensors, and hydraulic pumps. The major functions of the CCU are to stabilize the hydraulic system (flow of simulated blood, differential pressures in the arterial and venous lines), providing instant information about the system to the user via a display. Electric valves and sensors provide ‘on-the-fly’ information to the CCU about the actual systems status and it can be made to respond to specific instructions imitating the physiological circulatory system and simulating several scenarios (i.e. bleeding, low pressure, occlusion, reaction to proper and incorrect pharmacological treatment). It can be connected to an ECMO machine to act like the human body during ECMO run. Silicone tubes (modified polyethylene) that can be realistically cannulated using ultrasound imaging represent the artificial vessels. The CCU is made of electronic components that can be integrated to customize any mannequin as shown in Figure 1. The hardware includes both digital and analogue components that are controlled by a software run on a computer connected to the CCU via a serial port (RS232) (Figure 2). The software allows for the visualization of measurements obtained from the sensors and the control of the pumps and valves via electronic controllers. The controllers affect the ECMO circuit simulated blood flow, and hence the readings from the ECMO machine sensors, to recreate various clinical scenarios.Figure 1. The modified patient simulator with circulatory loop prepared for VA ECMO cannulation and CCU (core control unit) for high-fidelity simulations. Figure 2. The ECMO simulator architecture. Results: Every component used can be easily replaced. The total cost of the simulator modification, excluding the cost of the computer or future mobile device, is approximately 200 USD, and the consumable parts cost about 20 USD. It has been used to help simulate successfully a range of scenarios.1 Although the system is currently tethered, the next prototype will include a wireless controller so that the system can be controlled from a mobile application. Conclusions: This advanced simulator allows for unlimited possibilities with regard to creating clinical scenarios. Our ambition is to become a reference ECMO training center in Poland so that our high-fidelity ECMO simulator can be used to its full potential and for the benefit of more clinicians and their patients around Poland.

Induction therapy, tacrolimus plasma concentration, and duration if intensive care unit stay are risk factors for peripheral leucopenia following heart transplantation.

BACKGROUND Although survival among heart recipients has increased, a limiting factor is chronic adverse effects of immunosuppression therapy. MATERIAL AND METHODS We performed a retrospective analysis of 22 patients (19 men and 3 women) with a mean age of 48 ± 12 years who underwent orthotropic heart transplantation. There were 20 (91%) patients who received induction therapy (basiliximab, Simulect, Novartis Europharm Limited). All patients were treated with standard triple immunosuppressive regimen (tacrolimus, mycophenolate mofetil, and steroids). RESULTS Patients were divided into 2 groups according to postoperative peripheral cytopenia diagnosis. There were 16 (73%) in the cytopenic group and 6 (27%) in the non-cytopenic group. Mean time of peripheral leucopenia detection was 65 ± 13 days following surgery. The blood leucocyte count was 0.98 ± 0.2 × 10(3)/mm(3) vs. 5.85 ± 0.9 × 10(3)/mm(3) in patients with peripheral cytopenia compared to non-cytopenic patients (p<0.01). There was a statistically important difference in duration of intensive care unit stay between the 2 groups (p<0.01). A correlation between tacrolimus serum concentration and risk for leucopenia was also detected (p<0.05). CONCLUSIONS Basiliximab administration as induction therapy, tacrolimus serum concentration, and duration of intensive care unit stay are risk factors for leucopenia.

Using simulation to create a unique regional ECMO program for the Greater Poland region

Background: “ECMO for Greater Poland” is a program being developed to serve the 3.5 million inhabitants of the Greater Poland region (Wielkopolska) based on an approach already implemented in the USA1 or Qatar.2,3Method: The program is complex and takes full advantage of the ECMO perfusion therapy opportunities to save the life of patients in the Greater Poland region. The main implementation areas are: – treatment of patients with hypothermia;4 – treatment of reversible severe respiratory failure;5 – treatment of acute intoxication resulting in cardiorespiratory failure6 or other critical conditions resulting in heart failure; – in the absence of response to treatment and eventual death, and with donor authorization, there is possible organ transplantation from a non-heart beating donor (NHBD) to another patient.7 This led to the development of a program for donation after circulatory death (DCD). Study: The program will help to put in place a Medical Rescue System including ECMO (Figure 1). It requires training in specialized resuscitation, perfusion, and transplantation teams in the implementation of this “ECMO rescue chain”. The main strength of the program is the widespread use of extracorporeal perfusion. All program arms in the use of ECMO should be implemented in parallel to maximize its positive impact.Figure 1. Organizational model of “ECMO for Greater Poland” – “ECMO rescue chain” scheme divided into three stages: prehospital, hospital/perfusion, and transplantation. As this organizational model is complex and expensive, we used high-fidelity medical simulation to prepare for the real-life implementation of our ECMO program. During 4 months, we performed scenarios including: – “ECMO for DCD” which includes: prehospital identification, CPR ALS (cardiopulmonary resuscitation advanced life support), perfusion therapy (CPR-ECMO or DCD-ECMO), inclusion and exclusion criteria matching, mechanical chest compression, transport, DCD confirmation, and donor authorization, the veno-arterial (VA) cannulation of a mannequins artificial vessels, and starting on-scene organ perfusion.7 – “ECMO for INTOXICATION” which includes: hospital identification (Department of Toxicology), poisoning treatment, CPR ALS, mechanical chest compression, VA cannulation, for the implementation of ECMO therapy and transport to another hospital (Department of Cardiac Surgery).6 – “ECMO for RRF” (reversible respiratory failure) which includes: hospital identification (Regional Department of Intensive Care) – inclusion and exclusion criteria matching, ECMO team transport (80 km), therapy confirmation, veno-venous cannulation for the implementation of perfusion therapy, and return transport (80 km) with ECMO to another hospital in a provincial city (Clinical Department of Intensive Care), where the veno-venous (VV) ECMO therapy was continued for the next 48 hours.5 The training programs, in a short time, resulted in a team being appropriately trained to successfully undertake the complex procedures. Soon after these simulations, Maastricht category II DCD procedures were performed involving real patients and resulting in two double successful kidney transplantations, for the first time in Poland. One month later, we treated two hypothermia patients and, for the first time in the region, also treated on ECMO an adult patient with reversible respiratory failure. Conclusions: The “ECMO for Greater Poland” program will allow the use of perfusion therapy for the inhabitants of Wielkopolska in a comprehensive manner, covering all critical disease states, by what appears to be a unique regional program in Poland. The full-scale, high-fidelity simulation enabled standardized training and testing of new, commonly, and rarely used procedures, and facilitated clinicians’ skills development.

High-fidelity simulation — the first DCD-ECMO procedure in Poland

Mateusz Puslecki, Marcin Ligowski, Marek Dabrowski, Maciej Sip, Sebastian Stefaniak, Tomasz Klosiewicz, Lukasz Gasiorowski, Marek Karczewski, Tomasz Malkiewicz, Malgorzata Ladzinska, Marcin Zielinski, Aleksander Pawlak, Agata Dabrowska, Piotr Ziemak, Bartlomiej Perek, Marcin Misterski, Slawomir Katarzynski, Piotr Buczkowski, Wojciech Telec, Ilona Kiel-Puslecka, Michal Kiel, Michael Czekajlo, Marek Jemielity Poznan University of Medical Sciences, Department of Cardiac Surgery and Transplantology, Clinical Hospital SKPP, Poznan, Poland Poznan University of Medical Sciences, Department of Rescue and Disaster Medicine, Poznan, Poland Polish Society of Medical Simulation, Poland Poznan University of Medical Sciences, Center for Medical Simulation, Poznan, Poland Poznan University of Medical Sciences, Department of Intensive Care and Pain Treatment, Poznan, Poland Poznan University of Medical Sciences, Department of Transplantology, General, Vascular and Plastic Surgery, Poznan, Poland Poznan University of Medical Sciences, Department of Anesthesiology and Intensive Care, Clinical Hospital H. Święcickiego, Poznan, Poland Voivodeship Emergency Medical Services, Poznan, Poland Poznan University of Medical Sciences, Department of Palliative Medicine, Poznan, Poland ZF RTW, Częstochowa, Poland Hunter Holmes McGuire VA Medical Center, Department of Surgery, Richmond, United States of America Lublin Medical University, Lublin, Poland