Validation of a new model of selective antegrade cerebral perfusion with circulatory arrest in rats.

BACKGROUND: Selective antegrade cerebral perfusion (SACP) is adopted as an alternative to deep hypothermic circulatory arrest (DHCA) during aortic arch surgery. However, there is still no preclinical evidence to support the use of SACP associated with moderate hypothermia (28-30°C) instead of DHCA (18-20°C). The present study aims to develop a reliable and reproducible preclinical model of cardiopulmonary bypass (CPB) with SACP applicable for assessing the best temperature management. MATERIALS AND METHODS: A central cannulation through the right jugular vein and the left carotid artery was performed, and CPB was instituted.Animals were randomized into two groups: normothermic circulatory arrest without or with cerebral perfusion (NCA vs SACP). EEG monitoring was maintained during CPB. After 10 min of circulatory arrest, rats underwent 60 min of reperfusion. After that, animals were sacrificed, and brains were collected for histology and molecular biology analysis. RESULTS: Power spectral analysis of the EEG signal showed decreased activity in both cortical regions and lateral thalamus in all rats during the circulatory arrest. Only SACP determined complete recovery of brain activity and higher power spectral signal compared to NCA (p < 0.05). Histological damage scores and western blot analysis of inflammatory and apoptotic proteins like caspase-3 and Poly-ADP ribose polymerase (PARP) were significantly lower in SACP compared to NCA. Vascular endothelial growth factor (VEGF) and RNA binding protein 3 (RBM3) involved in cell-protection mechanisms were higher in SACP, showing better neuroprotection (p < 0.05). CONCLUSIONS: SACP by cannulation of the left carotid artery guarantees good perfusion of the whole brain in this rat model of CPB with circulatory arrest. The present model of SACP is reliable, repeatable, and not expensive, and it could be used in the future to achieve preclinical evidence for the best temperature management and to define the best cerebral protection strategy during circulatory arrest.

Impact of Surgeon Experience and Centre Volume on Outcome After Off-Pump Coronary Artery Bypass Surgery: Results From the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) Registry.

AIM: The aim of this study was to assess the impact of surgeon experience and centre volume on early operative outcomes in patients undergoing off-pump coronary artery bypass (OPCAB) surgery. METHOD: Of 7,352 patients in the European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG) registry, 1,549 underwent OPCAB and were included in the present analysis. Using adjusted regression analysis, we compared major early adverse events after procedures performed by experienced OPCAB surgeons (i.e., ≥20 cases per year; n=1,201) to those performed by non-OPCAB surgeons (n=348). Furthermore, the same end points were compared between procedures performed by OPCAB surgeons in high OPCAB volume centres (off-pump technique used in >50% of cases; n=894) and low OPCAB volume centres (n=307). RESULTS: In the experienced OPCAB surgeon group, we observed shorter procedure times (ß -43.858, 95% confidence interval [CI] -53.322 to -34.393; p<0.001), a lower rate of conversion to cardiopulmonary bypass (odds ratio [OR] 0.284, 95% CI 0.147-0.551; p<0.001), a lower rate of prolonged inotrope or vasoconstrictor use (OR 0.492, 95% CI 0.371-0.653; p<0.001), a lower rate of early postprocedural percutaneous coronary interventions (OR 0.335, 95% CI 0.169-0.663; p=0.002), and lower 30-day mortality (OR 0.423, 95% CI 0.194-0.924; p=0.031). In high OPCAB volume centres, we found a lower rate of prolonged inotrope use (OR 0.584, 95% CI 0.419-0.814; p=0.002), a lower rate of postprocedural acute kidney injury (OR 0.382, 95% CI 0.198-0.738; p=0.004), shorter duration of intensive care unit (ß -1.752, 95% CI -2.240 to -1.264; p<0.001) and hospital (ß -1.967; 95% CI -2.717 to -1.216; p<0.001) stays, and lower 30-day mortality (OR 0.316, 95% CI 0.114-0.881; p=0.028). CONCLUSIONS: Surgeon experience and centre volume may play an important role on the early outcomes after OPCAB surgery.

Nerve growth factor transfer from cardiomyocytes to innervating sympathetic neurons activates TrkA receptors at the neuro-cardiac junction.

Sympathetic neurons densely innervate the myocardium with non-random topology and establish structured contacts (i.e. neuro-cardiac junctions, NCJ) with cardiomyocytes, allowing synaptic intercellular communication. Establishment of heart innervation is regulated by molecular mediators released by myocardial cells. The mechanisms underlying maintenance of cardiac innervation in the fully developed heart, are, however, less clear. Notably, several cardiac diseases, primarily affecting cardiomyocytes, are associated with sympathetic denervation, supporting the hypothesis that retrograde 'cardiomyocyte-to-sympathetic neuron' communication is essential for heart cellular homeostasis. We aimed to determine whether cardiomyocytes provide nerve growth factor (NGF) to sympathetic neurons, and the role of the NCJ in supporting such retrograde neurotrophic signalling. Immunofluorescence on murine and human heart slices shows that NGF and its receptor, tropomyosin-receptor-kinase-A, accumulate, respectively, in the pre- and post-junctional sides of the NCJ. Confocal immunofluorescence, scanning ion conductance microscopy and molecular analyses, in co-cultures, demonstrate that cardiomyocytes feed NGF to sympathetic neurons, and that this mechanism requires a stable intercellular contact at the NCJ. Consistently, cardiac fibroblasts, devoid of NCJ, are unable to sustain SN viability. ELISA assay and competition binding experiments suggest that this depends on the NCJ being an insulated microenvironment, characterized by high [NGF]. In further support, real-time imaging of tropomyosin-receptor-kinase-A vesicle movements demonstrate that efficiency of neurotrophic signalling parallels the maturation of such structured intercellular contacts. Altogether, our results demonstrate the mechanisms which link sympathetic neuron survival to neurotrophin release by directly innervated cardiomyocytes, conceptualizing sympathetic neurons as cardiomyocyte-driven heart drivers. KEY POINTS: CMs are the cell source of nerve growth factor (NGF), required to sustain innervating cardiac SNs; NCJ is the place of the intimate liaison, between SNs and CMs, allowing on the one hand neurons to peremptorily control CM activity, and on the other, CMs to adequately sustain the contacting, ever-changing, neuronal actuators; alterations in NCJ integrity may compromise the efficiency of 'CM-to-SN' signalling, thus representing a potentially novel mechanism of sympathetic denervation in cardiac diseases.

Coronary Artery Bypass Grafting in Patients With High Risk of Bleeding.

BACKGROUND: Postoperative bleeding after cardiac surgery is associated with increased morbidity and mortality. We tested the hypothesis that patients with a preoperatively estimated high risk of severe perioperative bleeding may have impaired early outcome after on-pump versus off-pump coronary artery bypass grafting (CABG). METHOD: Data from 7,352 consecutive patients who underwent isolated CABG from January 2015 to May 2017 were included in the multicentre European Coronary Artery Bypass Grafting registry. The postoperative bleeding risk was estimated using the WILL-BLEED risk score. Of all included patients, 3,548 had an increased risk of severe perioperative bleeding (defined as a WILL-BLEED score ≥4) and were the subjects of this analysis. We compared the early outcomes between patients who underwent on-pump or off-pump CABG using a multivariate mixed model for risk-adjusted analysis. RESULTS: Off-pump surgery was performed in 721 patients (20.3%). On-pump patients received more packed red blood cell units (on-pump: 1.41 [95% confidence interval {CI} 0.99-1.86]; off-pump: 0.86 [95% CI 0.64-1.08]; p<0.001), had a longer stay in the intensive care unit (on-pump: 4.4 [95% CI 3.6-8.1] days; off-pump: 3.2 [95% CI 2.0-4.4] days; p=0.049), and a higher rate of postoperative atrial fibrillation (on-pump: 46.5% [95% CI 34.9-58.1]; off-pump: 31.3% [95% CI 21.7-40.9]; p=0.025). Furthermore, on-pump patients showed a trend towards a higher rate of postoperative stroke (on-pump: 2.4% [95% CI 0.9-4.1]; off-pump: 1.1 [95% CI 0.2-2.7]; p=0.094). CONCLUSION: Our data suggest that in patients with an increased risk of bleeding, the use of cardiopulmonary bypass is associated with higher morbidity. These patients may benefit from off-pump surgery if complete revascularisation can be ensured.

Hybrid treatment of aortic aneurism, type-A dissection, and aortic valve stenosis.

Hybrid multidisciplinary interventions are attractive care options for heart valve and vascular diseases in high-risk patients. We describe the feasibility of staged hybrid aortic arch repair to treat a type Ia endoleak and transcatheter aortic valve replacement to treat an aortic valve stenosis, achieving an escape strategy to treat an unexpected type-A aortic dissection.

Carotid Endarterectomy with Modified Eversion Technique: Results of a Single Center.

BACKGROUND: Carotid endarterectomy (CEA) has a wide range of approaches based on personal expertise and preference. We evaluated our outcome with CEA with modified eversion technique (meCEA) under local anesthesia and whether the surgeon's experience could influence it. METHODS: at our Institution, 837 patients underwent CEA across 8 years. Although the surgical technique was standardized, 2 groups were considered further: meCEA performed by a single Senior Operator (Group A) and meCEA performed by 4 young Consultants (Group B). RESULTS: A selective shunting policy was needed in 5.1%, together with general anesthesia. Overall operative time was 63.9 ± 15.1 minutes (61.4 ± 12.5 and 66 ± 16.9 minutes in Group A and Group B respectively; P < 0.001) and cross-clamp time 19.3 ± 2.9 minutes (19.0 ± 3.2 vs. 19.5 ± 2.8, P = 0.009). At 30 days, 0.7% TIA and 0.8% strokes were recorded. No differences (p = N.S.) between the 2 study groups in terms of postoperative neurological complications, with postoperative ipsilateral strokes always < 1%. At a median imaging follow-up of 22.5 months, the overall percentage of restenosis was 3.7%, with no difference between the 2 groups (P = 0.954). Twenty-two patients (2.6%) underwent reintervention for significant restenosis, and none of them had an ipsilateral stroke or TIA. Freedom from reintervention for restenosis at 24 months was 97.9% in Group A and 95.9% in Group B, with no between-group difference (P = 0.14). At the median survival follow-up of 37 months, the overall survival rate at 24 months was 97.9%in Group A, and 97.9% in Group B, with no between-group difference (P = 0.070). CONCLUSIONS: In our experience, CEA with a modified technique is safe and achieves comparable outcomes to those of other established techniques. The reported short cross-clamp time, also in less experienced hands, is an additional strength.

Impact on Renal Function and Hospital Outcomes of an Individualized Management of Cardiopulmonary Bypass in Congenital Heart Surgery: A Pilot Study.

During cardiopulmonary bypass (CPB), high flows can allow an adequate perfusion to kidneys, but, on the other hand, they could cause emboli production, increased vascular pressure, and a more intense inflammatory response, which are in turn causes of renal damage. Along with demographic variables, other intra-operative management and post-operative events, this might lead to Acute kidney injury (AKI) in infants undergoing cardiac surgery. The aim of our study was to investigate if a CPB strategy with flow requirements based on monitoring of continuous metabolic and hemodynamic parameters could have an impact on outcomes, with a focus on renal damage. Thirty-four consecutive infants and young children undergoing surgery requiring CPB, comparable as for demographic and patho-physiological profile, were included. In Group A, 16 patients underwent, for a variable period of 20 min, CPB aiming for the minimal flow that could maintain values of MVO2 > 70% and frontal NIRS (both left and right) > 45%, and renal NIRS > 65%. In Group B, 18 patients underwent nominal flows CPB. Tapered CPB allowed for a mean reduction of flows of 34%. No difference in terms of blood-gas analysis, spectroscopy trend, laboratory analyses, and hospital outcome were recorded. In patients developing AKI (20%), renal damage was correlated with demographic characteristics and with renal NIRS during the first 6 h in the ICU. A safe individualized strategy for conduction of CPB, which allows significant flow reduction while maintaining normal hemodynamic and metabolic parameters, does not impact on renal function and hospital outcomes.

Cerebral perfusion strategy in a challenge cerebral vessels debranching.

We present a case of antegrade cerebral perfusion based on a circuit with a centrifugal pump for general open-heart surgery to achieving cerebral protection during a challenging hybrid aortic arch repair.

Single-Cell Sequencing of Mouse Heart Immune Infiltrate in Pressure Overload-Driven Heart Failure Reveals Extent of Immune Activation.

BACKGROUND: Inflammation is a key component of cardiac disease, with macrophages and T lymphocytes mediating essential roles in the progression to heart failure. Nonetheless, little insight exists on other immune subsets involved in the cardiotoxic response. METHODS: Here, we used single-cell RNA sequencing to map the cardiac immune composition in the standard murine nonischemic, pressure-overload heart failure model. By focusing our analysis on CD45+ cells, we obtained a higher resolution identification of the immune cell subsets in the heart, at early and late stages of disease and in controls. We then integrated our findings using multiparameter flow cytometry, immunohistochemistry, and tissue clarification immunofluorescence in mouse and human. RESULTS: We found that most major immune cell subpopulations, including macrophages, B cells, T cells and regulatory T cells, dendritic cells, Natural Killer cells, neutrophils, and mast cells are present in both healthy and diseased hearts. Most cell subsets are found within the myocardium, whereas mast cells are found also in the epicardium. Upon induction of pressure overload, immune activation occurs across the entire range of immune cell types. Activation led to upregulation of key subset-specific molecules, such as oncostatin M in proinflammatory macrophages and PD-1 in regulatory T cells, that may help explain clinical findings such as the refractivity of patients with heart failure to anti-tumor necrosis factor therapy and cardiac toxicity during anti-PD-1 cancer immunotherapy, respectively. CONCLUSIONS: Despite the absence of infectious agents or an autoimmune trigger, induction of disease leads to immune activation that involves far more cell types than previously thought, including neutrophils, B cells, Natural Killer cells, and mast cells. This opens up the field of cardioimmunology to further investigation by using toolkits that have already been developed to study the aforementioned immune subsets. The subset-specific molecules that mediate their activation may thus become useful targets for the diagnostics or therapy of heart failure.

Aortic Valve Replacement for Aortic Stenosis in Low-, Intermediate-, and High-Risk Patients: Preliminary Results From a Prospective Multicenter Registry.

OBJECTIVE: To evaluate current results of surgical aortic valve replacement (SAVR) ± coronary artery bypass grafting surgery. DESIGN: Independent, multicenter, prospective registry. SETTING: Tertiary university hospitals. PARTICIPANTS: The study comprised 1,192 consecutive patients, stratified as low-, intermediate-, and high-risk according to EuroSCORE II (<4, 4-9, >9, respectively). INTERVENTIONS: SAVR ± coronary artery bypass grafting surgery. MEASUREMENTS AND MAIN RESULTS: Thirty-day mortality and major morbidity, 2-year actuarial survival and freedom from stroke, and independent predictors of mortality in each risk category were assessed. These data were considered in light of published randomized controlled trials. Thirty-day mortality was 1.0%, 3.0% and 2.1% in the low-, intermediate-, and high-risk patients, with a 2-year actuarial survival of 98.6%, 93.8%, and 94.0%, respectively. Preoperative atrial fibrillation (odds ratio [OR] 8.3), minithoracotomy access (OR 5.8), postoperative dialysis (OR 3.4), type V acute myocardial infarction (OR 20.4), and moderate aortic regurgitation (OR 28.8) predicted 30-day mortality in the low-risk group. Preoperative dialysis (OR 18.3), critical state (OR 36.7), postoperative transfusions of plasma (OR 1.9 per unit transfused), and de-novo dialysis (OR 6.2) predicted 30-day mortality in the intermediate-risk group. Prior cardiac surgery (OR 18.1), postoperative extracorporeal membrane oxygenation (OR 9.8), and gastrointestinal complications (OR 17.2) predicted 30-day mortality in the high-risk group. Although baseline differences existed, low-risk patients demonstrated low 30-day mortality and 30-day to 12-month stroke in light of the PARTNER 3 and EVOLUT Low Risk trial results. Intermediate-risk patients demonstrated low 30-day to 2-year mortality, when the PARTNER 2 trial was considered, and low 30-day to 2-year stroke, when the PARTNER 2 and SURTAVI trials were considered. High-risk patients showed low 30-day to 2-year mortality in light of the results of the PARTNER 1 and CoreValve US trials. CONCLUSIONS: SAVR is still a safe and effective surgery for aortic stenosis regardless of risk category.

Content of mitochondrial calcium uniporter (MCU) in cardiomyocytes is regulated by microRNA-1 in physiologic and pathologic hypertrophy.

The mitochondrial Ca2+ uniporter complex (MCUC) is a multimeric ion channel which, by tuning Ca2+ influx into the mitochondrial matrix, finely regulates metabolic energy production. In the heart, this dynamic control of mitochondrial Ca2+ uptake is fundamental for cardiomyocytes to adapt to either physiologic or pathologic stresses. Mitochondrial calcium uniporter (MCU), which is the core channel subunit of MCUC, has been shown to play a critical role in the response to ß-adrenoreceptor stimulation occurring during acute exercise. The molecular mechanisms underlying the regulation of MCU, in conditions requiring chronic increase in energy production, such as physiologic or pathologic cardiac growth, remain elusive. Here, we show that microRNA-1 (miR-1), a member of the muscle-specific microRNA (myomiR) family, is responsible for direct and selective targeting of MCU and inhibition of its translation, thereby affecting the capacity of the mitochondrial Ca2+ uptake machinery. Consistent with the role of miR-1 in heart development and cardiomyocyte hypertrophic remodeling, we additionally found that MCU levels are inversely related with the myomiR content, in murine and, remarkably, human hearts from both physiologic (i.e., postnatal development and exercise) and pathologic (i.e., pressure overload) myocardial hypertrophy. Interestingly, the persistent activation of ß-adrenoreceptors is likely one of the upstream repressors of miR-1 as treatment with ß-blockers in pressure-overloaded mouse hearts prevented its down-regulation and the consequent increase in MCU content. Altogether, these findings identify the miR-1/MCU axis as a factor in the dynamic adaptation of cardiac cells to hypertrophy.

Mitral valvuloplasty complicated by catheter perforation of the right atrium and the aortic root.

According to latest guidelines, percutaneous mitral commissurotomy (PMC) represents the first-line treatment for symptomatic severe mitral valve stenosis with favorable morphology. We report successful surgical treatment of a potential life-threatening complication occurred during PMC. Heart-team discussion and closed collaboration with centers are crucial for decision-making and cardiac surgery onsite should be ensured for high-risk procedures.

Transapical mitral valve-in-valve procedure with elective venoarterial ECMO in a patient with severe kyphoscoliosis.

Transcatheter mitral valve-in-valve replacement (TMVR) is a feasible alternative in high-risk patients requiring reoperation for failing mitral bioprosthesis. Such patients may present with hemodynamic instability or sudden complications, which may jeopardize the outcomes. We report a successful transapical TMVR in a patient, with severe kyphoscoliosis and on prolonged mechanical ventilation, with prophylactic extracorporeal membrane oxygenator support. This combined procedure may be helpful to reduce the complications of TMVR in critically ill subjects.

Intraventricular entrapment of a Sapien-3 balloon in transapical TAVR: A near missed catastrophe.

Balloon rupture is an uncommon complication during balloon-expandable transcatheter aortic valve replacement (TAVR). We describe a balloon rupture and tearing with intraventricular entrapment complicating transapical-TAVR, as well as our bailout retrieval of the failed device.

Novel, digital, chest drainage system in cardiac surgery.

BACKGROUND: A new, self-contained, digital, continuous pump-driven chest drainage system is compared in a randomized control trial to a traditional wall-suction system in cardiac surgery. METHODS: One hundred and twenty adult elective cardiac patients undergoing coronary artery bypass graft and/or valve surgery were randomized to the study or control group. Both groups had similar pre/intra-operative demographics: age 67.8 vs 67.0 years, Euroscore 2.3 vs 2.2, and body surface area 1.92 vs 1.91 m2 . Additionally, a satisfaction assessment score (0-10) was performed by 52 staff members. RESULTS: Given homogenous intra-operative variables, total chest-tube drainage was comparable among groups (566 vs 640 mL; ns), but the study group showed more efficient fluid collection during the early postoperative phase due to continuous suction (P = .01). Blood, cell saver transfusions and postoperative hemoglobin values were similar in both groups. The study group experienced drain removal after 29.8 vs 38.4 hours in the control group (ns). Seven crossovers from the Study to the Control group were registered but no patient had drain-related complications. The Personnel Satisfaction Assessment scored above 5 for all questions asked. CONCLUSIONS: The new, digital, chest drainage system showed better early drainage of the chest cavity and was as reliable as conventional systems. Quicker drain removal might impact on intensive care unit (ICU) stay and reduce costs. Additional advantages are portable size, battery operation, patient mobility, noiseless function, digital indications and alarms. The satisfaction assessment of the new system by the staff revealed a higher score when compared to the traditional wall suction chest drainage system.

Mesothelial/monocytic incidental cardiac excrescence in autoimmune disease.

Mesothelial/monocytic incidental cardiac excrescence (MICE) is a rare benign finding made of mesothelial cells, histiocytes, and fibrin, usually found during heart valve surgery. The clinical relevance resides in the potential misdiagnosis as metastatic carcinoma or arterial embolism. The pathogenesis remains uncertain, with artifactual and reactive hypotheses. Here we present a case of MICE with paradigmatic clinical, imaging, and histological features in a 28-year-old woman with undifferentiated connective tissue disease without previous cardiac catheterization with possible pathogenesis, highlighting the importance of awareness of the existence of this lesion in patients with autoimmune disease.

An observational, prospective study on surgical treatment of secondary mitral regurgitation: The SMR study. Rationale, purposes, and protocol.

The natural history of secondary mitral regurgitation (MR) is unfavorable. Nevertheless, there are no evidence that its correction can improve the outcome. If from one side the original cause of secondary MR can be such to limit the possibilities of improvement, from the other side it is possible that the surgical technique widely applied to repair, restrictive mitral annuloplasty, is not adequate to correct the regurgitation. The addition of valvular and/or subvalvular techniques has been considered a possible technical solution. However, we do not know the prevalence of each technique, how many times mitral replacement is used to correct secondary MR. This aspect is of particular importance, as we know that a successful mitral repair causes a better left ventricular systolic remodeling than a unsuccessful repair or replacement. This study is a prospective, observational registry, conceived to understand what is done in the real world. Any surgeon will use the technique he thinks the most suitable for the patient. Every year, for 5 years, patients will have a clinical and echocardiographic follow-up, to evaluate the risk factors for a worse result (death, rehospitalization for heart failure, reoperation for MR return, moderate, or more MR return). This knowledge will give us the possibility to understand which is the technique, or the strategy, more efficient to treat this disease and the real efficacy of the surgical treatment.

Hospital Volume and Outcome after Bilateral Internal Mammary Artery Grafting.

BACKGROUND: Bilateral internal mammary artery (BIMA) grafting largely is underutilized in patients undergoing coronary artery bypass grafting (CABG), partly because of the perceived increased complexity of the procedure. AIMS: In this study, we evaluated whether BIMA grafting can safely be performed also in centers, where this revascularization strategy infrequently is adopted. METHODS: Out of 6,783 patients from the prospective multicenter E-CABG study, who underwent isolated non- emergent CABG from January 2015 to December 2016, 2,457 underwent BIMA grafting and their outcome was evaluated in this analysis. RESULTS: The mean number of BIMA grafting per center was 82 cases/year and hospitals were defined as high or low volume, according to this cutoff value. Six hospitals were considered as centers with a high volume of BIMA grafting (no. of procedures ranging from 120 to 267/year; overall: 2,156; prevalence: 62.2%) and nine hospitals as centers with a low volume of BIMA grafting (no. of procedures ranging from 2 to 39/year; overall: 301; prevalence: 9.1%). Multilevel mixed-effects regression analysis showed that the low- and high-volume cohorts had similar outcomes. Propensity score one-to-one matching analysis of 292 pairs showed that the low-volume cohort had a significantly shorter intensive care unit stay (2.2 ± 2.3 versus 2.9 ± 4.8 days, P = .020). The rates of in-hospital death (1.0% versus 0.3%, P = .625), deep sternal wound infection/mediastinitis (3.8% versus 3.1%, P = .824), and 1-year survival (98.1% versus 99.7%, P = .180) as well as other outcomes were similar between the high- and low-volume cohorts. CONCLUSIONS: BIMA grafting can be safely performed also in centers in which this revascularization strategy is infrequently performed.

Fingolimod (FTY720) Preserves High Energy Phosphates and Improves Cardiac Function in Heterotopic Heart Transplantation Model.

During heart transplantation, donor heart leads to reduced oxygen supply resulting in low level of high energy phosphate (HEP) reserves in cardiomyocyte. Lower HEP is one of the underlying reasons of cell death due to ischemia. In this study we investigated the role of Fingolimod (FTY720) in heart transplantation ischemia. Eight groups of Sprague-Dawley rats (n = 5 for each subgroup) were made, A1 and C1 were given FTY720 1 mg/kg while B1 and D1 were given normal saline. The hearts were implanted into another set of similar rats after preservation period of 1 h at 4-8 °C. Significantly higher Left ventricular systolic pressure (LVSP), dP/dT maximum (p < 0.05), dP/dT minimum (p < 0.05) were recorded in the FTY720 treated group after 24 h of reperfusion while after 1 h of reperfusion, there were no significant differences in LVSP, maximum and negative dP/dT, and Left ventricular end diastolic pressure (LVEDP) between the control and the FTY720-treated transplant groups. Coronary blood flow (CBF) was enhanced (p < 0.05) in the FTY720 treated group after 1 and 24 h. ATP p < 0.001, p < 0.05 at 1 and 24 h, ADP p < 0.001, p > 0.05 at 1 and 24 h, and phosphocreatine p < 0.05, p > 0.05 at 1 and 24 h were better preserved by FTY720 treatment as compared to control group. The study concluded that pretreatment of grafted hearts with FTY720 improved hemodynamics, CBF, high energy phosphate reserves, reduces the peroxynitrite level and poly (ADP ribose) polymerase (PARP) inhibition that prevents ischemia-reperfusion injury.

Impact of preoperative thrombocytopenia on the outcome after coronary artery bypass grafting.

The impact of thrombocytopenia on postoperative bleeding and other major adverse events after cardiac surgery is unclear. This issue was investigated in a series of patients who underwent isolated coronary artery bypass grafting (CABG) from the prospective, multicenter E-CABG registry. Preoperative thrombocytopenia was defined as preoperative platelet count <150 × 109/L and it was considered moderate-severe when preoperative platelet count was <100 × 109/L. Multilevel mixed-effects regression analysis was performed to adjust the effect of thrombocytopenia on outcomes for baseline and operative covariates as well as for interinstitutional differences in patient-blood management. Among 7189 patients included in this analysis, 599 (8.3%) had preoperative thrombocytopenia. Patient with preoperative thrombocytopenia had an increased chest drainage output at 12 h (mean, 519 vs. 456 mL, adjusted coeff. 39, 95%CI 18-60) and rates of severe-massive bleeding (Universal Definition of Perioperative Bleeding (UDPB) severity grades 3-4: 12.7% vs. 8.1%, adjusted OR 1.47, 95%CI 1.11-1.93; E-CABG bleeding severity grades 2-3: 10.4% vs. 6.1%, adjusted OR 1.78, 95%CI 1.30-2.43). Thrombocytopenia was associated with an increased risk of hospital/30-day death (3.2% vs. 1.9%, adjusted OR 2.02, 95%CI 1.20-3.42), 1-year death (5.7% vs. 3.4%, adjusted HR 1.68, 95%CI 1.16-2.44), deep sternal wound infection (3.5% vs. 2.4%, adjusted OR 1.65, 95%CI 1.02-2.66), acute kidney injury (28.1% vs. 22.2%, OR 1.45, 1.18-1.78), and prolonged stay in the intensive care unit (mean, 3.6 vs 2.8 days, adjusted coeff. 0.74, 95%CI 0.40-1.09). Similar results were observed in a subset of patients with moderate-severe thrombocytopenia (51 patients, 0.7%). In particular, these patients had a markedly higher rate of acute kidney injury (40%, adjusted OR, 1.94, 95%CI 1.05-3.57), resternotomy for bleeding (7.8%, adjusted OR 3.49, 95%CI 1.20-10.21), and severe-massive bleeding (UDPB severity grades 3-4: 23.5%, adjusted OR 3.08, 95%CI 1.52-6.22; E-CABG bleeding severity grades 2-3: 23.5%, adjusted OR 4.43, 95%CI 2.15-9.15) compared to patients with normal preoperative platelet count. Mild preoperative thrombocytopenia is associated with increased risk of severe-massive bleeding, mortality, and other major adverse events after CABG. Such risks are markedly increased in patients with moderate-severe preoperative thrombocytopenia.