Dexmedetomidine for adult cardiac surgery: a systematic review, meta-analysis and trial sequential analysis.

The effects of dexmedetomidine in adults undergoing cardiac surgery are inconsistent. We conducted a systematic review and meta-analysis to analyse the effects of peri-operative dexmedetomidine in adults undergoing cardiac surgery. We searched MEDLINE via Pubmed, EMBASE, Scopus and Cochrane for relevant randomised controlled trials between 1 January 1990 and 1 March 2022. We used the Joanna Briggs Institute methodology checklist to assess study quality and the GRADE approach to certainty of evidence. We assessed the sensitivity of results to false data. We used random-effects meta-analyses to analyse the primary outcomes: durations of intensive care and tracheal intubation. We included 48 trials of 6273 participants. Dexmedetomidine reduced the mean (95%CI) duration of intensive care by 5.0 (2.2-7.7) h, p = 0.001, and tracheal intubation by 1.6 (0.6-2.7) h, p = 0.003. The relative risk (95%CI) for postoperative delirium was 0.58 (0.43-0.78), p = 0.001; 0.76 (0.61-0.95) for atrial fibrillation, p = 0.015; and 0.49 (0.25-0.97) for short-term mortality, p = 0.041. Bradycardia and hypotension were not significantly affected. Trial sequential analysis was consistent with the primary meta-analysis. Adjustments for possible false data reduced the mean (95%CI) reduction in duration of intensive care and tracheal intubation by dexmedetomidine to 3.6 (1.8-5.4) h and 0.8 (0.2-1.4) h, respectively. Binary adjustment for methodological quality at a Joanna Briggs Institute score threshold of 10 did not alter the results significantly. In summary, peri-operative dexmedetomidine reduced the durations of intensive care and tracheal intubation and the incidence of short-term mortality after adult cardiac surgery. The reductions in intensive care stay and tracheal intubation may or may not be considered clinically useful, particularly after adjustment for possible false data.

Five-year experience with congenital cardiac surgery at National University Heart Centre, Singapore.

INTRODUCTION: Surgical procedures performed for congenital heart disease are usually complex and variable. The aims of this paper were to analyse patient demographics in a centre that caters to congenital cardiac surgery, compare departmental standards to international centres, and investigate the relationship between patient volume and clinical outcome. METHODS: A total of 163 patients who presented to the Cardiac, Thoracic and Vascular Surgery Department of the National University Hospital , Singapore between 2002 and 2006 were identified and studied retrospectively. Patient demographics were analysed. The mortality rates and patient volume were compared with those observed at international centres. RESULTS: The mean annual patient volume was 32.6 cases. The mean age of the patients was 15.7 years, with the oldest patient being 73 years old. 57.1 percent of the patients were Chinese, 23.3 percent were Malay and 19.6 percent were Indian and other races. Foreigners made up nearly half of the patient cohort (45.4 percent). Atrial septal defect was found to be the most common diagnosis (n is 64), with the secundum being most commonly involved (76.9 percent). The commonest postoperative morbidities encountered were arrhythmias and pleural effusions. Patient volume was not found to be a significant factor affecting clinical outcomes. CONCLUSION: With a growing population of adults with congenital heart disease and a significant number of foreign patients, improvements to our resources and infrastructure need to be considered in order to cope with the increasing demands. Despite having a low patient volume, the centre is still able to provide congenital heart surgery with good clinical outcomes that are comparable to those of international centres with similar or higher patient volumes.

Predictors of adverse neurological outcome following cardiac surgery.

INTRODUCTION: Stroke is a debilitating complication of cardiac surgery. Many intraoperative and postoperative factors predict the likelihood of post-cardiac surgery stroke. We evaluated preoperative parameters, seeking correlations with adverse neurological outcome following cardiac surgery. We investigated the possibility of preoperative carotid ultrasonography to select patients for carotid endarterectomy pre- or intraoperatively. METHODS: We conducted a retrospective analysis of 61 patients who suffered stroke post-cardiac surgery from 2003 to 2006. Data was collected for patient and disease characteristics, preoperative status, intraoperative events and postoperative course. Postoperative neurological complications were subdivided into three groups: mild/temporary events, moderate events such as seizures, and severe events such as stroke. A mild/temporary event was defined as a focal neurological deficit of less than 24 hours in duration. RESULTS: A total of 2,226 cardiac cases were retrospectively evaluated. The frequency of stroke was 61 patients (2.7 percent). The mean age of these patients was 63.7 +/- 7.4 years, and 40 (65.6 percent) were males. Logistic EuroSCORE, left ventricular ejection fraction (as determined by two-dimensional echocardiogram) and aortic cross-clamp time were significantly correlated with postoperative neurological complications, with a p-value of less than 0.05 for all subgroups. There was a significant correlation between the presence of preoperative carotid disease (as proven by pre- and postoperative carotid ultrasonography) and postoperative neurological events (p-value equals 0.033). However, atrial fibrillation did not correlate with postoperative stroke. CONCLUSION: The stage of cardiac disease (risk factor level, ejection fraction and presence of carotid stenosis) correlates with stroke and may predict an adverse neurological outcome.

The minimized extracorporeal circulation system causes less inflammation and organ damage.

The minimized extracorporeal circulation system (MECC) is being used to reduce priming volume and blood/polymer contact during cardiac procedures. In this study, we evaluated the efficacy and potential advantages of the system in coronary artery bypass graft (CABG) patients. We included two groups of patients destined for CABG in a prospective, randomized study: Group A was operated on the usual pump (n = 30) while Group B was operated using the MECC (n = 50). Pre-operative demographics, intra-operative times and values as well as a series of post-operative outcome data (blood loss, transfusion requirements, ventilation time, ICU and hospital stay) were recorded. CK, CK-MB, troponin-T, IL-6 and IL-8 were measured. Pre-operative and post-operative lung function were assessed. In the MECC-operated group, patients developed less post-operative troponin-T (0.2 +/- 0.3 vs. 0.5 +/- 0.5 ng/mL, p=0.031) and less IL-8 (13.8 +/- 5 vs. 22.5 +/- 0.5 microg/L, p = 0.05). While blood loss was comparable in both groups, packed red blood cells and fresh frozen plasma were given less frequently in the MECC group (p = 0.015 resp. 0.022). The one-tailed Student's t-test revealed shorter bypass time in the MECC group (74 +/- 17 vs. 82 +/- 24 min). There was no difference in ventilation and ICU-time (patients were not treated in a fast-track fashion). The FEV1 was better in the MECC group (relative values: 70.1 +/- 18.2% vs. 61.1 +/- 12.3%, p = 0.02). Utilization of the MECC may cause less cytokine (IL-8) liberation, owing to less blood/tubing contact, as well as less red blood cell and fresh frozen plasma demand. It may also be the circuit in patients with chronic obstructive pulmonary disease (COPD).

Aortic prosthesis re-replacement due to concealed stenosing subvalvular pannus ring.

In a patient with mechanical aortic valve prosthesis, a high transvalvular gradient was detected 16 years following the procedure, without echocardiographic clues for the underlying etiology. Intraoperatively, a stenosing pannus ring was found and excised. This pathological entity should be considered in cases of unclear transprosthetic gradient and early operation should be encouraged in symptomatic patients.

[Tissue engineering: in vitro creation of tissue substitutes]. / Tissue-Engineering ist mehr als nur Gewebezüchtung.

Tissue engineering is a young, multidisciplinary scientific field which aims at generating bioartificial tissues in vitro to restore diseased human organs. This fledgling sector of biosciences emerged few years ago but draws scientific and public attention increasingly, as the recent accomplishments are impressive and promise alternative therapeutic concepts to replace or enhance failing human organs. Tissue engineering using either polymers or decellularized native allogeneic or xenogeneic matrices may provide the techniques to develop the ideal graft. The matrix scaffold can be seeded with cells that organise and develop into tissue prior to or following implantation. This review surveys upon recent developments in the field of in vitro tissue engineering (skin, heart, heart valves, blood vessels, liver, kidney, urogenital, and nerves), without claiming completeness, thus providing an insight into what has been attempted and what may be possible in the near future.

[In vivo detection of integration of grafted cells after myocardial transplantation]. / Bildgebende Verfahren zum In-vivo-Nachweis der Integration transplantierter Zellen im Myokard.

Myocardial transplantation of myocytes and bone marrow derived cells is currently under clinical evaluation as an alternative therapy of heart failure. One of the main problems of all clinical studies performed so far is the inability to track the fate of the transplanted cells. The aim of our study was the development of a potentially clinically applicable approach, which allows for detection of the transplanted cells without need for collection of tissue samples. Fetal canine cardiomyocytes were labelled with the non-toxic fluorescent membrane dye Vybrant CM-DiI and delivered into the free wall of the left ventricle of adult mongrel dogs. For subsequent tracking of the cellular graft, the dogs underwent a second operation in which an intra-vital microscope was mounted above the exposed heart within the thorax. A special computer software eliminated artefacts caused by myocardial contraction. Two months after transplantation, the fluorescent graft was macroscopically visible by intra-vital microscopy using a 10x magnification. Histological studies served as microscopic control and confirmed the existence of DiI-labelled cells at the site of injection. Connexin 43 immunoreactivity was visible at junctional complexes between donor and recipient cells, suggesting morphologic and functional coupling as a result of gap junction formation. Our results demonstrate that in vivo detection of transplanted cells in the heart is feasible. Further technical adjustments should allow for thoracoscopic/endoscopic application of this method, making it appropriate for use in other organs and in clinical studies.

Pulsatile perfusion and cardiomyocyte viability in a solid three-dimensional matrix.

BACKGROUND: The manufacture of full thickness three-dimensional myocardial grafts by means of tissue engineering is limited by the impeded cellular viability in unperfused in vitro systems. We introduce a novel concept of pulsatile tissue culture perfusion to promote ubiquitous cellular viability and metabolism. METHODS: In a novel bioreactor we established pulsatile flow through the embedded three-dimensional tissue culture. Fibrin glue served as the ground matrix wherein neonatal rat cardiomyocytes were inoculated. Fluor-Deoxy-Glucose-Positron-Emission-Tomography (FDG-PET) and life/dead assays were employed for comparative studies of glucose uptake resp. cell viability. RESULTS: A solid 8 mm thick structure resulted. Cellular viability significantly increased in the perfused chambers. We observed centripetal migration of the embedded cardiomyocytes to the site of the core vessel. However, cellular viability was high in the periphery of the tissue block too. FDG-PET revealed enhanced metabolic activity in perfused chambers. CONCLUSIONS: The present concept is highly effective in enhancing cellular viability and metabolism in a three-dimensional tissue culture environment. It could be utilized for various co-culture systems and the generation of viable tissue grafts.

[Ross procedure with combined replacement of the ascending aorta: impact on autograft root function and distensibility]. / Aorta ascendens-Ersatz und Ross-Operation: Einfluss auf die Distensibilität der Neo-Aortenwurzel.

BACKGROUND: The safety and effectiveness of combined aortic root autograft replacement in combination with ascending aorta replacement has been demonstrated recently. Replacement of the ascending aorta with a vascular prosthesis results in an increase in aortic root distension, and aortic root wall stress. In this study we aimed to assess the autograft root dimensions, distensibility, and autograft valve function in patients after Ross operation combined with replacement of the ascending aorta compared to patients who underwent Ross operation only. PATIENTS AND METHODS: Echocardiographic follow-up was performed on 28 patients after Ross operation with complete root replacement only (group R) and 12 patients who received an additional replacement of the ascending aorta (group R/A). The mean follow-up time was 24.9 +/- 17.2 months. Autograft root dimensions, root distensibility and valve function were assessed by echo-cardiography. The aortic root was measured at the level of the annulus, sinus of valsalva, and sinotubular junction. The distensibility was calculated as percent change of radius. RESULTS: The mean distensibility at the annulus level was higher in group R/A (18.4 +/- 6.8% vs 13.4 +/- 8.1%; p = 0.047); at the level of the sinus of valsalva and sinotubular junction no differences were observed. The autograft pressure gradient was within physiological limits in all patients. The majority of patients showed a competent autograft valve (group R: AI 0 degree; 83%, AI I degree; 14%, AI II degree; 3%; group R/A: AI 0 degree; 75%, AI I degree; 25%). CONCLUSIONS: Replacement of the ascending aorta with a non-compliant prosthesis does not effect root dimension, distensibility, and valve function.

Clinically established hemostatic scaffold (tissue fleece) as biomatrix in tissue- and organ-engineering research.

Various types of three-dimensional matrices have been used as basic scaffolds in myocardial tissue engineering. Many of those are limited by insufficient mechanical function, availability, or biocompatibility. We present a clinically established collagen scaffold for the development of bioartificial myocardial tissue. Neonatal rat cardiomyocytes were seeded into Tissue Fleece (Baxter Deutschland, Heidelberg, Germany). Histological and ultrastructural examinations were performed by DAPI and DiOC(18) staining and electron microscopy, respectively. Force measurements from the spontaneously beating construct were obtained. The constructs were stimulated with agents such as adrenalin and calcium, and by stretching. Passive stretch curves were obtained. Spontaneous contractions of solid bioartificial myocardial tissue (BMT), 20 x 15 x 2 mm, resulted. Contractions continued to week 12 (40% of BMTs) in culture. Histology revealed intercellular and also cell-fibril junctions. Elasticity was similar to that of native rat myocardium. Contractile force increased after topical administration of Ca(2+) and adrenaline. Stretch led to the highest levels of contractile force. In summary, bioartificial myocardial tissue with significant in vitro longevity, spontaneous contractility, and homogeneous cell distribution was produced using Tissue Fleece. Tissue Fleece constitutes an effective scaffold to engineer solid organ structures, which could be used for repair of congenital defects or replacement of diseased tissue.

Carboxyfluorescein diacetate succinimidyl ester facilitates cell tracing and colocalization studies in bioartificial organ engineering.

BACKGROUND: We demonstrate a method that includes colocalization studies to analyze cell suspensions after isolation and to characterize 3-dimensional grafts consisting of cells and matrix in vitro and in vivo. MATERIALS AND METHODS: Neonatal rat cardiomyocytes were labelled by CFDA-SE after harvest. Cells in the isolated cell suspension, the embodied cells in the seeded scaffolds were characterized measuring features such as viability and distribution of the cell types. RESULTS: Selective cell count revealed high yields of viable cardiomyocytes. After seeding cells in collagen matrix, viability of the cells decreased gradually in the time process in vitro. Histology of implanted bioartificial myocardial tissue detected viable cardiomyocytes within the graft. CONCLUSION: Using colocalization histology we could label and track cells within the bioartificial myocardial tissue graft in vitro and post implant and assess viability and distribution.

Traveling after heart transplantation.

BACKGROUND: With evolving medical techniques and post-operative care, the quality of life after cardiac transplantation is improving over the recent years. However, the need for continuous immunosuppressive therapy may result in restrictions from some social and recreational activities, including traveling. The aim of this study was to analyze traveling activities and complications in a large cohort of heart transplant recipients, with the intention to develop adequate safety and behavioral guidelines. METHODS: Using a standardized questionnaire, 103 consecutive patients (pts) were asked to report about time and destination of their traveling activities, predominant activities, as well as potential travel-related complications. Documented rejection episodes as well as laboratory data are listed. RESULTS: Feedback was 97% (of 103 pts asked). Out of 100 pts who responded, [82 males, 18 females, mean age 52.3 +/- 12.4 yr, 6.9 +/- 3.8 yr post-heart transplantation (HTX)] 95 reported on traveling activities (95%). Concomitant disease was present in form of diabetes (n=8), renal insufficiency (n=5) and cardiac allograft vasculopathy (n=12). Mean cumulative traveling time was 120 +/- 125 d (3-560 d). Except from domestic journeys, 79 pts chose destinations within Europe, and 29 to overseas countries. Complications were reported by 15 of 95 pts (15.8%), being mostly small accidents and febrile episodes. Rejection episodes or other life threatening events were not observed. There was no significant correlation between observed complications and gender, age, time post-HTX, immunosuppression or comorbidities. CONCLUSIONS: Traveling after HTX appears to be safe and favorably improves quality of life, if certain precautions are met.

In vitro engineering of heart muscle: artificial myocardial tissue.

INTRODUCTION: Myocardial infarction followed by heart failure represents one of the major causes of morbidity and mortality, particularly in industrialized countries. Engineering and subsequent transplantation of contractile artificial myocardial tissue and, consequently, the replacement of ischemic and infarcted areas of the heart provides a potential therapeutic alternative to whole organ transplantation. METHODS: Artificial myocardial tissue samples were engineered by seeding neonatal rat cardiomyocytes with a commercially available 3-dimensional collagen matrix. The cellular engraftment within the artificial myocardial tissues was examined microscopically. Force development was analyzed in spontaneously beating artificial myocardial tissues, after stretching, and after pharmacologic stimulation. Moreover, electrocardiograms were recorded. RESULTS: Artificial myocardial tissues showed continuous, rhythmic, and synchronized contractions for up to 13 weeks. Embedded cardiomyocytes were distributed equally within the 3-dimensional matrix. Application of Ca(2+) and epinephrine, as well as electrical stimulation or stretching, resulted in enhanced force development. Electrocardiographic recording was possible on spontaneously beating artificial myocardial tissue samples and revealed physiologic patterns. CONCLUSIONS: Using a clinically well-established collagen matrix, contractile myocardial tissue can be engineered in vitro successfully. Mechanical and biologic properties of artificial myocardial tissue resemble native cardiac tissue. Use of artificial myocardial tissues might be a promising approach to reconstitute degenerated or failing cardiac tissue in many disease states and therefore provide a reasonable alternative to whole organ transplantation.

Restoration of blood flow and evaluation of corresponding angiogenic events by scanning electron microscopy after a single dose of VEGF in a model of peripheral vascular disease.

The angiogenic effect of vascular endothelial growth factor (VEGF) has typically been assessed by indirect methods, including microsphere injection and angiography. Here, we use 3-D scanning electron microscopy (SEM) to directly visualize patterns of angiogenesis after a single bolus administration of VEGF in a model of peripheral vascular ischemia. Hind limb ischemia was induced by subcutaneous turniquet implantation in adult Wistar rats. The control group (group A, n = 10) was left untreated, group B (n = 10) received a single dose of VEGF (50 microg) injected in the peroneus muscle. LASER Doppler was applied for blood flow measurements. Animals were sacrificed on day 14 after ischemia induction and vascular casting was performed. Angiogenetic events such as 'tiny lateral sprouts', arcus formations', confluences and the angle of sprouting were assessed by SEM. Significant capillary sprouting was observed in both groups. VEGF-treated limbs demonstrated higher degrees of capillary growth (P = 0.01) and flow recovery (P = 0.028). 3-D-SEM showed sprouts to be more frequent in group B. Tiny lateral sprouts, which always left the mother vessel at an angle of 90 degrees and which were of small diameter and lacked imprints of endothelial cell nuclei, were more frequent in the VEGF-treated group (P = 0.018). Arcus formation was significantly higher in the treated group (P = 0.02). We have developed a simple and effective experimental model of ischemia. For the study of angiogenic phenomena, 3-D imaging of the microvasculature offers a direct and conclusive method for the study of angiogenic events.

Impact of vascular branching sites on focal progression of allograft vasculopathy in transplanted hearts.

BACKGROUND: Cardiac allograft vascular disease (CAVD) represents one of the most accelerated progressing coronary syndromes in the human heart. A variety of risk factors have been identified over recent years; however, little is known about the influence of physical forces. As a model for differences in focal blood flow dynamics, we analyzed progression of intimal hyperplasia at vascular bifurcational sites using intravascular ultrasound (IVUS). METHODS: The most diseased vascular sites ("worst sites") in 59 coronary arteries were assessed (30 MHz, motorized pull back) in 25 consecutive heart transplant recipients at baseline (52.8+/-15.3 days postoperatively) and after 1 year of follow up (360.5+/-24.9 days). Progression of intimal hyperplasia was compared between branching and non-branching lesions as well as in focal relation to the position of the flow divider. RESULTS: A total of 41 (69.5%) worst sites were identified at branching locations. Progression of intimal hyperplasia was found to be significantly more severe at bifurcational sites with an increase in plaque area by 1.5+/-1.8 mm(2) in branching versus 0.4+/-0.6 mm(2) in non-branching lesions (P=0.015). The highest rate in focal progression was found at the opposite site of the flow divider with an increase in maximal intimal thickness by 0.3+/-0.23 mm (180 degrees ) as compared to 0.11+/-0.15 mm (90 degrees, P<0.001) and 0.15+/-0.15 mm (P=0.014) at 270 degrees. CONCLUSIONS: Using serial intravascular ultrasound examinations, vascular branching sites could be identified to be predisposing locations not only for a donor related arteriosclerosis, but also for progression of intimal hyperplasia within transplanted hearts. The highest regional increase in intimal thickness was found at the outer wall of the flow divider, suggesting focal shear or wall stress to be involved in pathogenesis.

Hemoptysis following left ventricular aneurysm repair: a misleading clinical sign.

We report on a 66-year-old man with severe hemoptysis following coronary artery bypass grafting and repair of a left ventricular septal defect after acute myocardial infarction. Initial diagnosis was delayed by misleading clinical symptoms and radiologic studies. Due to subfebrile temperature and sputum culture positive for Pseudomonas aeruginosa, he had been treated with antibiotics before reoperation. At reoperation, replacement of all foreign material and reconstruction of the ventricular repair with bovine pericardium resulted in reinfection with the same organism despite prolonged antibiotic therapy after 6 months. Removal of the pericardial tissue with direct suture closure of the ventricles and interposition of omentum led to complete healing of the infection without reoccurrence after 2 years.

Minimally invasive coronary artery revascularization on the beating heart.

BACKGROUND: The quality of surgical beating heart revascularization is frequently questioned, especially when the surgical access is limited. Nevertheless, the number of off-pump coronary procedures is expanding worldwide. METHODS: Since getting started with minimally invasive direct coronary artery bypass to anterior myocardial vessels in June 1996, 306 patients received left internal mammary artery grafting through an anterior minithoracotomy. Risk increasing comorbidities were present in 168 of them. Particular attention was paid to early postoperative angiographic results and complications. RESULTS: The 30-day mortality summed up at 1.0% and was limited to patients with additional risks for conventional bypass grafting. Early postoperative control angiographies in 232 patients confirmed a global patency rate of 97.8%, revealing in addition four unexpected malinsertions to diagonal branches. In surviving patients major complications like myocardial infarction, stroke, or multiorgan failure were completely absent. CONCLUSIONS: Minimally invasive direct coronary artery bypass grafting appears to allow for a safe and effective revascularization of the left anterior descending artery by use of the left internal mammary artery. Especially patients with risk increasing comorbidities should benefit from this approach, provided the surgical indication based on a dominating left anterior descending artery lesion. Angiographic minimally invasive direct coronary artery bypass results seem to fulfill the expectations generated by results obtained in conventional left internal mammary artery grafting and appear to be superior to interventional means.

Transthoracic fistula with erosion of the ascending aorta along an IMA-protecting graft.

Internal mammary artery (IMA) graft protection with nonbiodegradable material, such as polytetrafluorethylene (PTFE), is recognized as an effective means for preventing overexuberant adhesion development as well as injury of retrosternally crossing arterial grafts in the event of resternotomy and should enable better identification of the IMA graft. It is still uncertain whether the use of PTFE material is suitable for diabetic patients with complete arterial revascularization due to potential infectious complications. We report on a young diabetic patient after arterial T-grafting due to severe coronary disease and readmission with wound infection and retrosternal fistula formation 8 months after operation.