Unraveling the role of resistin, retinol-binding protein 4 and adiponectin produced by epicardial adipose tissue in cardiac structure and function: evidence of a paracrine effect.

PURPOSE: Adipokines produced by adipose tissue have been found to be involved in the pathophysiology of metabolic and cardiovascular diseases. We aimed to investigate the relationships of resistin, retinol-binding protein 4 (RBP4) and adiponectin produced by epicardial adipose tissue with coronary artery disease (CAD) and cardiac structure and function. METHODS: Forty-one non-diabetic males scheduled for cardiothoracic surgery were examined. Anthropometric measurements, echocardiography, coronary angiography, and blood analysis were performed preoperatively. We measured the serum levels of resistin, RBP4, and adiponectin and their mRNA expression in thoracic subcutaneous adipose tissue and two epicardial adipose tissue samples, one close to left anterior descending artery (LAD) (resistin-LAD, RBP4-LAD, adiponectin-LAD), and another close to the right coronary artery (RCA) (resistin-RCA, RBP4-RCA, adiponectin-RCA). RESULTS: Left ventricular (LV) ejection fraction correlated negatively with adiponectin-LAD (rho = - 0.390, p = 0.025). The ratio of early to late diastolic transmitral flow velocity, as an index of LV diastolic function, correlated negatively with resistin-LAD (rho = - 0.529, p = 0.024) and RBP4-LAD (rho = - 0.458, p = 0.049). There was no difference in epicardial adipose tissue mRNA expression of resistin, RBP4, and adiponectin between individuals with CAD and those without CAD. When we compared the individuals with CAD in the LAD with those without CAD in the LAD, there was no difference in resistin-LAD, RBP4-LAD, and adiponectin-LAD. There was no difference in resistin-RCA, RBP4-RCA, and adiponectin-RCA between the individuals with CAD in the RCA and those without CAD in the RCA. CONCLUSION: Elevation of epicardial adipose tissue mRNA expression of adiponectin was associated with LV systolic dysfunction, while that of both resistin and RBP4 was linked to LV diastolic dysfunction.

The Effect of Cell Salvage on Bleeding and Transfusion Needs in Cardiac Surgery.

Introduction: Cell salvaging is well established in the blood management of cardiac patients, but there remain some concerns about its effects on perioperative bleeding and transfusion variables. This randomized controlled study investigated the potential effects of the centrifuged end-product on bleeding, transfusion rates, and other transfusion-related variables in adult cardiac surgery patients submitted to extracorporeal circulation. Materials and Methods: Patients were randomly chosen to receive (cell-salvage group, 99 patients) or not to receive (control group, 110 patients) the centrifuged product of a cell salvage apparatus. Bleeding and transfusion rates according to the universal definition of perioperative bleeding (UDPB) classification, postoperative hemoglobin, coagulation, and oxygenation indices were recorded and compared between the groups. Results: Both groups had almost identical bleeding and transfusion rates (median value: 2 units of red blood cells (RBC) and no units of fresh frozen plasma (FFP) and platelets (PLT) for both groups, p > 0.05). Patients in the cell-salvage group presented slightly higher hemoglobin concentrations (10.6 ± 1.1 vs. 10.1 ± 1.7 g/dL, p < 0.05, respectively) and a tendency towards better oxygenation indices (PaO2/FiO2: 241 ± 94 vs. 207 ± 84, p=0.013) in the postoperative period albeit with a tendency for prolongation of prothrombin time (INR: 1.31 ± 0.18 vs. 1.26 ± 0.12, p=0.008). Conclusion: Within the study's constraints, the perioperative use of the cell salvage concentrate does not seem to affect bleeding or transfusion variables, although it could probably ameliorate postoperative oxygenation in adult cardiac surgery patients. A tendency to promote coagulation disturbances was detected.

The Coadministration of Levosimendan and Exenatide Offers a Significant Cardioprotective Effect to Isolated Rat Hearts against Ischemia/Reperfusion Injury.

(1) Background: The present study aims to investigate the effect of administration of Levosimendan and Exenatide in various concentrations, as well as of the coadministration of those agents in an ischemia-reperfusion injury isolated heart model. (2) Methods: After 30 min of perfusion, the hearts underwent a 30 min period of regional ischemia followed by a 120 min period of reperfusion. All animals were randomly divided into 12 experimental groups of nine animals in each group: (1) Control, (2) Sham, (3) Digox (Negative control, Digoxin 1.67 µg/min), (4) Levo 1 (Levosimendan 0.01 µg/min), (5) Levo 2 (Levosimendan 0.03 µg/mL), (6) Levo 3 (Levosimendan 0.1 µg/min), (7) Levo 4 (Levosimendan 0.3 µg/min), (8) Levo 5 (Levosimendan 1 µg/min), (9) Exen 1 (Exenatide 0.001 µg/min), (10) Exen 2 (Exenatide 0.01 µg/min), (11) Exen 3 (Exenatide 0.1 µg/min) and (12) Combi (Levosimendan 0.1 µg/mL + Exenatide 0.001 µg/min). The hemodynamic parameters were recorded throughout the experiment. Arrhythmias and coronary flow were also evaluated. After every experiment the heart was suitably prepared and infarct size was measured. Markers of myocardial injury were also measured. Finally, oxidative stress was evaluated measuring reactive oxygen species. (3) Results: A dose-dependent improvement of the haemodynamic response was observed after the administration of both Levosimendan and Exenatide. The coadministration of both agents presented an even greater effect, improving the haemodynamic parameters further than the two agents separately. Levosimendan offered an increase of the coronary flow and both agents offered a reduction of arrhythmias. A dose-dependent reduction of the size of myocardial infarction and myocardial injury was observed after administration of Levosimendan and Exenatide. The coadministration of both agents offered a further improving the above parameters. Levosimendan also offered a significant reduction of oxidative stress. (4) Conclusions: The administration of Levosimendan and Exenatide offers a significant benefit by improving the haemodynamic response, increasing the coronary flow and reducing the occurrence of arrhythmias, the size of myocardial injury and myocardial oxidative stress in isolated rat hearts.

External flail chest stabilization; The simple, low-cost way.

Flail chest is a life-threatening clinical entity which can be complicated by respiratory insufficiency. Paradoxical motion of a part of chest wall is the basic cause to put the blame on. Consequently, stabilization of the chest wall is occasionally of paramount importance to achieve early extubation in a patient with post-trauma respiratory insufficiency. Hereby, a simple, low cost, harmless and effective approach of external stabilization is presented.

Cardioplegic storage solution: Is it the guardian of saphenous vein graft endothelium?

INTRODUCTION: Despite their suboptimal long-term patency, saphenous vein grafts are the most widely used conduits to achieve complete revascularization during coronary artery bypass grafting (CABG). Although vein storage critically impairs endothelial integrity, contradictory data concerning optimal storage solutions exist. The aim of this study is to explore any in vitro impact of cardioplegic solutions and temperature on vein grafts endothelial integrity during their storage. MATERIALS AND METHODS: A single-center, prospective trial including 40 consecutive patients was conducted. Eligibility criteria included patients submitted to CABG receiving at least one vein graft. An excess segment of the graft was harvested and divided into four different parts. Each one of them was stored under different conditions; either in a conventional heparin-enriched blood solution or in a cardioplegic solution, at room temperature (20°C-22°C) and in the refrigerator (5°C). Endothelial integrity was evaluated via immunohistochemistry using an antibody against CD31. RESULTS: Endothelial integrity (measured in a scale from 1-worst to 5-best) was significantly better after cardioplegic solution storage (2.83 ± 0.15 and 3.10 ± 0.13 in cold and room temperature, respectively) compared with storage in conventional solutions (2.23 ± 0.16 and 2.0 ± 0.15 in cold and room temperature, respectively). A significant effect of cardioplegic storage solution, as well as of cold temperature and cardioplegic solution interaction on endothelial preservation was reported, whereas storage temperature did not prove a significant factor by its own. CONCLUSIONS: Cardioplegic storage solutions result in significantly better endothelial preservation compared with conventional heparin-enriched blood solutions. The association with superior clinical outcomes remains to be proved.

Antegrade cardioplegia as a possible cause of acute saphenous vein endothelial damage in patients undergoing on pump coronary artery bypass surgery.

BACKGROUND: The administration of antegrade cardioplegia through vein grafts after the completion of each distal anastomosis is a common practice. However, the cardioplegic solution may disrupt the vein endothelium and contribute to late vein graft atherosclerotic disease. This study aimed at evaluating the possible impact of the cardioplegic solution on vein graft endothelium. METHODS: Total of 52 patients (16 women and 36 men) aged 68±8.5 years old that underwent on pump coronary revascularization with at least one vein graft were enrolled. Sections of grafts from the greater saphenous vein were obtained prior to and after delivery of potassium antegrade cardioplegic solution through them. These sections were then examined histologically with immunochemical stain and CD34 index. The endothelial damage and length of vein specimens of both graft sections were evaluated. RESULTS: The endothelial damage of vein specimens appeared to be increased significantly with exposure to antegrade cardioplegia in male and female patients (P from Wilcoxon tests <0.001, for both genders). The increase in the length of vein specimens was significant too (P from Wilcoxon test <0.001 for men and P=0.001 for women). CONCLUSIONS: Antegrade cardioplegia delivered through vein grafts causes substantial damage on vein endothelium. This may have an adverse effect on long-term graft patency.

Alexander the Great's Life-Threatening Thoracic Trauma.

Alexander the Great was a world-class leader with tremendous courage. He paid no heed to the dangers of the battlefield, so he was always in the front lines. However, his excessive courage put his life in danger. Herein, we present an analysis of the information contained in the chronicles about a very severe, life-threatening thoracic trauma that nearly killed the great stratelates. The detailed descriptions made by Arrianus allow us to conclude that Alexander the Great experienced a nearly fatal case of tension pneumothorax. Information on how he was managed is also presented.

Factors associated with early cardiac complications following transcatheter aortic valve implantation with transapical approach.

PURPOSE: To estimate the incidence of postprocedural early cardiac complications among patients undergoing transcatheter aortic valve implantation, through transapical approach (TA-TAVI), and to identify factors independently associated with the occurrence of them. PATIENTS AND METHODS: A retrospective cohort study of 90 patients, who had undergone TA-TAVI in a tertiary hospital of Liverpool, UK, during a 5-year period (September 2008-October 2013), was conducted. Data on patient demographics, periprocedural characteristics and cardiac complications presented within 30-day post TA-TAVI were collected, retrospectively, using the hospital's electronic database. RESULTS: The overall 30-day incidence of cardiac complications was estimated at 18.9% (n=17/90). The rate of new onset of atrial fibrillation (AF), atrioventricular block requiring permanent pacemaker implantation, shockable cardiac arrest rhythm and cardiac tamponade was 11.1%, 3.3%, 2.2% and 2.2%, respectively. Bivariate analysis found that absence of preoperative AF (p=0.01), receiving of oral inotropes preprocedurally (p=0.01), intravenous inotropic support postprocedurally (p=0.01) and requirement for postprocedural tracheal intubation (p=0.001) were the main factors associated with increased probability for patient cardiac morbidity. CONCLUSION: It seems that patients with absence of AF and oral inotropic support preprocedurally and those with post TA-TAVI mechanical ventilatory and intravenous inotropic support have greater probability to develop cardiac complications. This knowledge allows the early identification of high-risk patients and supports clinicians to apply both preventive and therapeutic interventions for the optimum patient management and care. In addition, administrators could allocate the health care system resources effectively.

Predictors of length of stay and duration of tracheal intubation after transcatheter aortic valve implantation.

BACKGROUND: While short-term outcomes for patients undergoing transcatheter aortic valve implantation (TAVI) have long been studied, there is very little data on their predictors. We aimed to identify the predictors of outcomes, such as intensive care unit (ICU) and in-hospital length of stay (LOS), duration of postoperative intubation and in-hospital mortality, after TAVI procedures. METHODS: We conducted a retrospective cohort study of 162 consecutive patients with aortic valve disease, who were admitted to a tertiary hospital of Liverpool for TAVI, during a five-year period. The data was collected using of the hospital's structured database on November 2014. RESULTS: By using a multivariate analysis we found that any postoperative bleeding [odds ratio (OR) 2.71; 95% confidence interval (CI): 1.41-5.24] was the independent predictor of prolonged ICU-LOS, while older age (OR 1.11; 95% CI: 1.05-1.17) and transapical TAVI (OR 4.11; 95% CI: 1.94-8.71) were the predictors of prolonged in-hospital LOS. Additionally, patients treated with oral inotropic agents, preoperatively (OR 5.77; 95% CI: 2.21-15.01), non-diabetics (OR 3.07; 95% CI: 1.12-8.42) and those with any postoperative bleeding (OR 3.53; 95% CI: 1.68-7.43) had a significantly greater probability in remaining intubated postoperatively. The multivariate analysis did not reveal any predictor of in-hospital mortality. CONCLUSIONS: The above predictors permit the early identification of TAVI patients at high risk for longer hospitalization and increased mechanical ventilation. This piece of information is crucial for clinicians and administrators contributing to more efficient patient care planning and better allocation of healthcare resources.

Myocardial revascularization without extracorporeal circulation; Why hasn't it convinced yet?

Extracorporeal circulation has led to a great development in cardiovascular surgery during the last five decades. Its time-proven efficacy and safety have made on-pump coronary artery bypass grafting (CABG) the gold standard method of surgical revascularization. However, coronary revascularization on cardiopulmonary bypass and the accompanying aortic manipulation are related to plenty of deleterious complications. Therefore, off-pump CABG surgery was established to avoid complications. Nevertheless, despite the initial enthusiasm on this technique, only 20% of myocardial revascularization procedures worldwide are performed off-pump. Not only are off-pump cardiac procedures more technically difficult but also they do not provide better results in terms of graft patency, completeness of revascularization, repeat revascularization requirement, cost, and quality of life. Completeness of revascularization and anastomotic quality should not be compromised to avoid cardiopulmonary bypass.

Lazaroid U-74389G for cardioplegia-related ischemia-reperfusion injury: an experimental study.

BACKGROUND: The adverse effects of myocardial ischemia and reperfusion during cardiopulmonary bypass (CPB) have been thoroughly described. Lazaroid U-74389G, a 21 aminosteroid, has been shown to attenuate ischemia and reperfusion injury and improve recovery in a variety of experimental models. METHODS: Sixteen male swine were randomly divided in two groups. All animals underwent 45 min of ischemic cardioplegic arrest, with U-74389G addition to the standard cardioplegic solution, whereas controls underwent the same procedure without U-74389G. Creatine kinase-MB isoenzyme (CK-MB) and cardiac troponin T levels were measured immediately before CPB (time point 0), during the ischemic period (time point 1) and 30 (time point 2), 60 (time point 3), and 120 (time point 4) min after reperfusion. Myocardial biopsies were obtained at time points 0 and 4. RESULTS: CK-MB levels (in U/L) at time points 0-4 were 205 (186-235) versus 219 (196-269; P = 0.72), 215 (167-248) versus 253 (193-339; P = 0.23), 234 (198-255) versus 338 (249-441; P = 0.02), 244 (217-272) versus 354 (269-496; P = 0.01), and 285 (230-321) versus 439 (432-530; P < 0.01) in lazaroid-treated animals versus controls, respectively. Cardiac troponin T levels (in ng/L) at time points 0-4 were 58 (26-287) versus 237 (26-395; P = 0.72), 129 (61-405) versus 265 (145-525; P = 0.23), 261 (123-467) versus 474 (427-1604; P = 0.04), 417 (204-750) versus 841 (584-1818; P = 0.11), and 643 (353-1259) versus 1600 (1378-2313; P < 0.01), respectively. Necrosis grades at time point 4 were 0.0 (0.0-1.0) versus 1.5 (1.0-2.0; P < 0.01) in lazaroid-treated animals versus controls, respectively. CONCLUSIONS: The present study, in addition to reconfirming the well-described adverse effects of CPB, demonstrates the efficacy of the newer generation lazaroid U-74389G in alleviating these effects.

Novel no touch technique of saphenous vein harvesting: Is great graft patency rate provided?

Coronary artery bypass grafting surgery effectively relieves signs and symptoms of myocardial ischemia. The left internal thoracic artery (LITA) graft is the gold standard having 90-95% patency rate at 10 years, whereas only 50% of saphenous vein (SV) grafts are patent at 10 years. However, there is a novel "no touch" technique in order to harvest an SV complete with its cushion of surrounding tissue, thus maintaining its endothelium-intact. Significantly superior short- and long-term graft patency rates comparable to LITA grafts can be achieved. Consequently, the SV may be revived as an important conduit in coronary artery bypass surgery.

A minimally invasive endovascular rabbit model for experimental induction of progressive myocardial hypertrophy.

The purpose of this paper is to describe a novel minimally invasive endovascular model of progressive myocardial hypertrophy in rabbits as an experimental protocol of hypertrophic cardiomyopathy. Nine New Zealand White rabbits underwent transauricular aortic catheterization. Under fluoroscopy a bare metal stent was partially deployed in the descending thoracic aorta (balloon length/stent length=1/2) so as to produce a funnel-shaped thoracic stent. Another nine animals underwent a sham procedure without stent placement (control). Follow-up computed tomography imaging was performed to exclude aortic occlusion. Subjects were killed after 3 months and their hearts were harvested and weighed. Cardiac hypertrophy was assessed with the heart weight-to-body weight (HW/BW) ratio and post-mortem histology was performed. We also used immunohistochemical staining for myogenin to compare the thickness of the wall between the two groups. The stents were polymer embedded for histomorphometry. Expressions of vascular endothelial growth factor (VEGF) and pleiotrophin (PTN) were analyzed by western blot analysis of total protein heart extracts. Computerized image analysis of CD34 and VEGF immunoreactivity was used to quantify myocardial angiogenesis. After 3 months, cross-sectional microscopic analysis of the harvested aortas showed total stent occlusion of the distal underdeployed area and some evidence of thrombus formation at the transitional zone toward the fully deployed stent in all cases. There was a nearly +10% increase of the adjusted HW/BW ratio compared with controls (absolute ratio difference was 0.02±0.01%; P=0.02). VEGF and CD34 expression was significantly suppressed, but expression of PTN was significantly increased in case of myocardial hypertrophy (stent group). Cardiac hypertrophy was evidenced using immunohistochemical staining for myogenin by significantly increased cardiomyocyte cross-sectional area (+38.4%; P<0.0001) compared with the control animals. In conclusion, this minimally invasive novel technique of transauricular funnel-shaped stent insertion in the descending thoracic aorta may achieve progressive myocardial hypertrophy in rabbits.

Inhibition of Atherosclerosis Progression, Intimal Hyperplasia, and Oxidative Stress by Simvastatin and Ivabradine May Reduce Thoracic Aorta's Stiffness in Hypercholesterolemic Rabbits.

AIMS: This study aims to evaluate atherosclerosis, oxidative stress, and arterial stiffness attenuation by simvastatin and ivabradine in hyperlipidemic rabbits. METHODS AND RESULTS: Forty rabbits were randomly divided into 4 groups: atherogenic diet (group C), atherogenic diet plus simvastatin (group S), atherogenic diet plus ivabradine (group I), and atherogenic diet plus simvastatin and ivabradine (group S + I). After 9 weeks, rabbits were euthanized and descending aortas excised for mechanical testing. Atherogenic diet induced the development of significant atherosclerotic lesions in group C animals but in none of groups S, I, and S + I. RAM-11 and HHF-35-positive cells were significantly reduced in groups S, I, and S + I compared with group C (P < .001). A significant neointimal hyperplasia and intima-media ratio reduction was demonstrated in groups S (P = .015 and P < .001), I (P = .021 and P < .001), and S + I (P = .019 and P < .001) compared with group C. Protein nitrotyrosine levels were significantly decreased in group S compared with group C (P = .009), and reactive oxygen species levels were decreased in group I compared with group C (P = .011). Aortic stiffness was significantly reduced in groups S, I, and S + I compared with group C (P = .003, P = .011, and P = .029). CONCLUSION: Simvastatin and ivabradine significantly inhibited intimal hyperplasia and oxidative stress contributing to aortic stiffness reduction in hyperlipidemic rabbits.

Cardiac tumors: a retrospective multicenter institutional study.

PURPOSE: Primary cardiac tumors are uncommon but not extremely rare. Cardiac tumors, mostly intracavitary, include benign and malignant tumors that arise from the endocardium, heart valves or myocardium. This retrospective study summarizes the experience of the Cardiac Surgery Departments of three tertiary Hospitals in this field, and particularly in cardiac myxomas, over the last 29 years. Herein, we present the results of cardiac tumors excision in relation to postoperative morbidity and mortality. METHODS: Between 1985 and 2014, 117 patients, aged from 16 to 82 years, underwent resection of a cardiac tumor. RESULTS: Ninety one of the tumors (77.78%) were myxomas, 15 of them (12.82%) were other primary cardiac tumors, 7 of them (5.98%) were infra-diaphragmatic tumors and the remaining 4 tumors (3.42%) were benign intracavitary masses (thrombi). Patients operated on for a cardiac tumor had a 30-day mortality rate of 3.29%. Atrial fibrillation appeared in 21 out of 91 patients (23.07%) operated on for cardiac myxoma, while neurological complications were observed in 3 patients (3.29%). Re-exploration for bleeding was performed in 5 out of 91 cases (5.49%) and recurrence occurred in 4.39% of myxomas. CONCLUSIONS: Despite being rare, primary cardiac tumors require open heart intervention soon after their diagnosis in order to prevent complications and achieve low mortality rates.

Intensive care unit-related generalized neuromuscular weakness due to critical illness polyneuropathy/myopathy in critically ill patients.

Thirty to fifty percent of critically ill patients admitted to the intensive care unit suffer from generalized neuromuscular weakness due to critical illness polyneuropathy, critical illness myopathy, or a combination of them, thus prolonging mechanical ventilation and their intensive care unit stay. A distinction between these syndromes and other neuromuscular abnormalities beginning either before or after ICU admission is necessary. These intensive care unit-related diseases are associated with both elevated mortality rates and increased morbidity rates. Generally, over 50 % of patients will completely recover. Most of them recover after 4-12 weeks, but some patients have been reported to keep on suffering from muscle weakness for at least 4 months. Prevention has a key role in the management of critical illness neuromuscular disorders, as no specific therapy has been suggested. Either prevention or aggressive treatment of sepsis can prevent critical illness polyneuropathy and critical illness myopathy. The dose and duration of the administration of neuromuscular blocking drugs should be limited, and their concurrent administration with corticosteroids should be avoided. Intensive insulin therapy has also been proven to reduce their incidence. Finally, early mobilization via active exercise or electrical muscle stimulation plays a significant role in their prevention.

Simultaneous occurrence of coronary artery disease and lung cancer: what is the best surgical treatment strategy?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether combined surgical procedures in one or two stages are the best surgical treatment strategy in patients with simultaneous coronary artery disease and lung cancer. Altogether, 264 papers were found using the reported search; of which, 15 represented the best evidence to answer the clinical question. The authors, journal, date, country of publication, patient group, study type, outcomes and results of papers are tabulated. The outcomes of the reported studies provided interesting results. All the studies were retrospective. Ten papers reported the results of combined and staged operations. The operative mortality rate of combined procedures was 0-20.8% and of staged procedures was 0-10%. The reoperation rate for bleeding of combined procedures was 0-11% and of staged procedures was 0%. The survival rate of combined procedures at 1 year was 79-100%, at 5 years was 34.9-85% and at 7 years was 61%. The survival rate of staged procedures at 1 year was 72.7% and at 5 years was 53%. Five studies reported the results of off-pump coronary artery bypass grafting (OPCABG) and lung surgery versus on-pump and lung surgery. The operative mortality rate of OPCABG and lung surgery was 0-6.6%. The 2-year survival rate of OPCABG and lung surgery was 47% and the 5-year survival rate was 13-68%. The re-exploration rate for bleeding of OPCABG was 4%. Simultaneous lung surgery and CABG could be safely performed with adequate cancer-free survival in patients with Stage I or II lung cancer. Lung surgery is better performed before institution of cardiopulmonary bypass, avoiding the complications of such a technique. Long-term survival after combined treatment is mostly related to the predicted survival after lung resection. This depends on the T stage and mostly on the patient's nodal status. In certain high-risk groups (if the cardiac procedure is difficult or if the patient is unstable), separate staged procedures (CABG as the first and lung resection as the second procedure) might be the most prudent action (3-6 weeks apart). There is also another option: OPCABG and lung resection, which could be a safe and effective treatment when unstable coronary heart disease and lung cancer coexist.