Mild membrane depolarization in neurons induces immediate early gene transcription and acutely subdues responses to a successive stimulus.

Immediate early genes (IEGs) are transcribed in response to neuronal activity from sensory stimulation during multiple adaptive processes in the brain. The transcriptional profile of IEGs is indicative of the duration of neuronal activity, but its sensitivity to the strength of depolarization remains unknown. Also unknown is whether activity history of graded potential changes influence future neuronal activity. In this work with dissociated rat cortical neurons, we found that mild depolarization-mediated by elevated extracellular potassium (K+)-induces a wide array of rapid IEGs and transiently depresses transcriptional and signaling responses to a successive stimulus. This latter effect was independent of de novo transcription, translation, and signaling via calcineurin or mitogen-activated protein kinase. Furthermore, as measured by multiple electrode arrays and calcium imaging, mild depolarization acutely subdues subsequent spontaneous and bicuculline-evoked activity via calcium- and N-methyl-d-aspartate receptor-dependent mechanisms. Collectively, this work suggests that a recent history of graded potential changes acutely depress neuronal intrinsic properties and subsequent responses. Such effects may have several potential downstream implications, including reducing signal-to-noise ratio during synaptic plasticity processes.

New Insurance Product Needed for Physicians: Coverage for Sham Peer Review and Hospital Immunity.

This commentary article highlights the need for an insurance product for hospital-employed physicians that provides coverage against sham peer review and a complete defense against wrongful hospital allegations of incompetent, whistleblowing, or disruptive behavior.

Certain ortho-hydroxylated brominated ethers are promiscuous kinase inhibitors that impair neuronal signaling and neurodevelopmental processes.

The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH-BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH-BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK-ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand-protein docking suggested that 6-OH-BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH-BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH-BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body ß-lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK-ERK signaling, and axonal guidance.

Early and Midterm Clinical Outcomes of Transcatheter Valve-in-Valve Implantation Versus Redo Surgical Aortic Valve Replacement for Aortic Bioprosthetic Valve Degeneration: Two Faces of the Same Medal.

OBJECTIVE: To compare early and midterm outcomes of transcatheter valve-in-valve implantation (ViV-TAVI) and redo surgical aortic valve replacement (re-SAVR) for aortic bioprosthetic valve degeneration. DESIGN: Patients who underwent ViV-TAVI and re-SAVR for aortic bioprosthetic valve degeneration between January 2010 and October 2018 were retrospectively analyzed. Mean follow-up was 3.0 years. SETTING: In-hospital, early, and mid-term outcomes. PARTICIPANTS: Eighty-eight patients were included in the analysis. INTERVENTIONS: Thirty-one patients (37.3%) had ViV-TAVI, and 57 patients (62.7%) had re-SAVR. MEASUREMENTS AND MAIN RESULTS: In the ViV-TAVI group, patients were older (79.1 ± 7.4 v 67.2 ± 14.1, p < 0.01). The total operative time, intubation time, intensive care unit length of stay, total hospital length of stay, inotropes infusion, intubation >24 hours, total amount of chest tube losses, red blood cell transfusions, plasma transfusions, and reoperation for bleeding were significantly higher in the re-SAVR cohort (p < 0.01). There was no difference regarding in-hospital permanent pacemaker implantation (ViV-TAVI = 3.2% v re-SAVR = 8.8%, p = 0.27), patient-prosthesis mismatch (ViV-TAVI = 12 patients [mean 0.53 ± 0.07] and re-SAVR = ten patients [mean 0.56 ± 0.08], p = 0.4), stroke (ViV-TAVI = 3.2% v re-SAVR = 7%, p = 0.43), acute kidney injury (ViV-TAVI = 9.7% v re-SAVR = 15.8%, p = 0.1), and all-cause infections (ViV-TAVI = 0% v re-SAVR = 8.8%, p = 0.02), between the two groups. In-hospital mortality was 0% and 7% for ViV-TAVI and re-SAVR, respectively (p = 0.08). At three-years' follow-up, the incidence of pacemaker implantation was higher in the re-SAVR group (ViV-TAVI = 0 v re-SAVR = 13.4%, p < 0.01). There were no differences in reintervention (ViV-TAVI = 3.8% v re-SAVR = 0%, p = 0.32) and survival (ViV-TAVI = 83.9% v re-SAVR = 93%, p = 0.10) between the two cohorts. CONCLUSIONS: ViV-TAVI is a safe, feasible, and reliable procedure.

Characterization of a Vesivirus Associated with an Outbreak of Acute Hemorrhagic Gastroenteritis in Domestic Dogs.

Four of eleven affected dogs died despite aggressive treatment during a 2015 focal outbreak of hemorrhagic gastroenteritis following a stay in a pet housing facility. Routine diagnostic investigations failed to identify a specific cause. Virus isolation from fresh necropsy tissues yielded a calicivirus with sequence homology to a vesivirus within the group colloquially known as the vesivirus 2117 strains that were originally identified as contaminants in CHO cell bioreactors. In situ hybridization and reverse transcription-PCR assays of tissues from the four deceased dogs confirmed the presence of canine vesivirus (CaVV) nucleic acids that localized to endothelial cells of arterial and capillary blood vessels. CaVV nucleic acid corresponded to areas of necrosis and hemorrhage primarily in the intestinal tract, but also in the brain of one dog with nonsuppurative meningoencephalitis. This is the first report of an atypical disease association with a putative hypervirulent vesivirus strain in dogs, as all other known strains of CaVV appear to cause nonclinical infections or relatively mild disease. After identification of the CU-296 vesivirus strain from this outbreak, four additional CaVV strains were amplified from unrelated fecal specimens and archived stocks provided by other laboratories. Broader questions include the origins, reservoir(s), and potential for reemergence and spread of these related CaVVs.

Conformal piezoelectric energy harvesting and storage from motions of the heart, lung, and diaphragm.

Here, we report advanced materials and devices that enable high-efficiency mechanical-to-electrical energy conversion from the natural contractile and relaxation motions of the heart, lung, and diaphragm, demonstrated in several different animal models, each of which has organs with sizes that approach human scales. A cointegrated collection of such energy-harvesting elements with rectifiers and microbatteries provides an entire flexible system, capable of viable integration with the beating heart via medical sutures and operation with efficiencies of ∼2%. Additional experiments, computational models, and results in multilayer configurations capture the key behaviors, illuminate essential design aspects, and offer sufficient power outputs for operation of pacemakers, with or without battery assist.

A Novel Hemostatic Patch That Stops Bleeding in Cardiovascular and Peripheral Vascular Procedures.

BACKGROUND: Achieving hemostasis during surgery is a common challenge across surgical specialties and procedures, including cardiovascular and peripheral vascular procedures. Although several hemostatic agents are available, they all become less effective as bleeding becomes more vigorous. Veriset™ hemostatic patch is a topical hemostatic agent that has been approved for use on solid organs and in soft tissue. The primary aim of these studies was to assess the safety of Veriset hemostatic patch during cardiovascular and peripheral vascular procedures. METHODS: Adult domestic swine were given intraoperative anticoagulation and systemic antiplatelet therapy, and then underwent a variety of cardiovascular coronary artery bypass graft (CABG anastomosis and aortotomy closure) and peripheral vascular (carotid arteriotomy with patch angioplasty) procedures. Bleeding was identified or created from each anastomotic site and was brisk in many cases. Veriset hemostatic patch, Surgicel(®) Nu-Knit(®) absorbable hemostat, or standard of care treatment was applied topically to the site of bleeding, and time to hemostasis was monitored for each animal. Animals were assessed during and after the surgical procedure to determine the effects of treatment on vessel diameter, clinical laboratory parameters, and host tissue response and/or tissue integration. RESULTS: Application of Veriset hemostatic patch had no effect on vessel diameter, similar to Surgicel Nu-Knit absorbable hemostat and standard of care treatment. Approximately 28 days after application, Veriset hemostatic patch and Surgicel Nu-Knit absorbable hemostat were completely absorbed, with no impact on serum chemistry profiles. Furthermore, Veriset hemostatic patch was as effective or more effective than Surgicel Nu-Knit absorbable hemostat when applied during carotid arteriotomy (30.0 ± 0.0 sec vs. 163.6 ± 86.9 sec, P < 0.001) and CABG anastomosis (91.9 ± 66.0 sec vs. 207.5 ± 159.2 sec, P = 0.053). CONCLUSIONS: Veriset hemostatic patch exhibits similar safety as Surgicel Nu-Knit absorbable hemostat, with effectiveness against cardiovascular and peripheral vascular bleeding. If these preclinical results are confirmed in clinical trials, this highly effective patch with a topical application requiring less than 30 seconds is likely to prove useful in many clinical settings.

A nationwide survey on perception, experience, and expectations of hybrid coronary revascularization among top-ranked US hospitals.

BACKGROUND: Hybrid coronary revascularization (HCR) combines a surgical and percutaneous approach for treatment of multivessel coronary artery disease. METHODS: A survey was conducted among 200 cardiologists and cardiac surgeons from 100 top-ranked US hospitals. Questions were asked involving the perception, experience, and future expectations of HCR. RESULTS: Of physicians invited to the survey, 90 completed the survey (45.5%). Relative to nonresponders, responders were more often affiliated with an academic institution (80.0% vs 61.8%, P=.005), with higher patient volumes, and with the availability of a hybrid operating room (90.0% vs 67.3%, P<.001). Survey responders felt that HCR should be considered in an older and relatively healthy patient population without complex lesions. Cardiac surgeons were more favorable to use HCR in patients with chronic lung disease (42.0% vs 10.0%, P<.001) or renal failure (28.0% vs 15.0%, P=.06). Among responders with HCR experience (n=54), 94% reported good to excellent results, and the learning curve differed depending on the surgical technique used. Inappropriate patient selection (41.2%) was the most common cause for complications. Three-quarter of responders believe that the future role for HCR will expand in the next decade. Important determinants of greater HCR use in the future were collaborative associations between cardiac surgeons and cardiologists (86.7%), appropriate patient selection (67.8%), and the outcomes of ongoing clinical trials (57.8%). CONCLUSION: In this nationwide survey, cardiologists and cardiac surgeons felt that HCR is a reasonable alternative technique for coronary revascularization among suitable patients. Most felt that use of HCR would increase in the next decade.

Simulation trainer for practicing emergent open thoracotomy procedures.

BACKGROUND: An emergent open thoracotomy (OT) is a high-risk, low-frequency procedure uniquely suited for simulation training. We developed a cost-effective Cardiothoracic (CT) Surgery trainer and assessed its potential for improving technical and interprofessional skills during an emergent simulated OT. MATERIALS AND METHODS: We modified a commercially available mannequin torso with artificial tissue models to create a custom CT Surgery trainer. The trainer's feasibility for simulating emergent OT was tested using a multidisciplinary CT team in three consecutive in situ simulations. Five discretely observable milestones were identified as requisite steps in carrying out an emergent OT; namely (1) diagnosis and declaration of a code situation, (2) arrival of the code cart, (3) arrival of the thoracotomy tray, (4) initiation of the thoracotomy incision, and (5) defibrillation of a simulated heart. The time required for a team to achieve each discrete step was measured by an independent observer over the course of each OT simulation trial and compared. RESULTS: Over the course of the three OT simulation trials conducted in the coronary care unit, there was an average reduction of 29.5% (P < 0.05) in the times required to achieve the five critical milestones. The time required to complete the whole OT procedure improved by 7 min and 31 s from the initial to the final trial-an overall improvement of 40%. CONCLUSIONS: In our preliminary evaluation, the CT Surgery trainer appears to be useful for improving team performance during a simulated emergent bedside OT in the coronary care unit.

Bleeding outcomes in patients given clopidogrel within 5 days of robotic coronary artery bypass graft procedure.

BACKGROUND: Current guidelines recommend that clopidogrel should be held for 5 days prior to coronary artery bypass graft (CABG) procedure. However, it is unknown if this recommendation should apply to robotic-assisted (rCABG), which is less invasive because it does not involve sternotomy and thus reduces the risk of bleeding. OBJECTIVE: To compare postoperative bleeding for rCABG patients who were taking clopidogrel within 5 days of the procedure with those who were not taking clopidogrel. METHODS: This was a retrospective cohort study conducted between January 1, 2012 and December 31, 2012 of consecutive patients undergoing rCABG. Patients were categorized into 2 groups based on whether or not clopidogrel was administered within 5 days prior to the date of surgery. The primary outcome measure was the occurrence of the Bleeding Academic Research Consortium (BARC) definition for CABG-related bleeding. The secondary outcome measure was a comparison of chest tube output during the first 24-hour postoperative period. RESULTS: A total of 136 rCABG patients were included in the final analyses. Of these, 39 (29%) received clopidogrel within 5 days of surgery. CABG-related bleeding using the BARC definition occurred in 26% of patients who received clopidogrel and 8% of patients who did not (P = .011). Median chest tube output during the first 24-hour postoperative period was also greater in patients who received clopidogrel (900 vs 735 mL, P = .002). CONCLUSIONS: The use of clopidogrel within 5 days of rCABG is associated with greater postoperative bleeding and chest tube output, as defined by the BARC criteria.

Cyclocreatine Phosphate: A Novel Bioenergetic/Anti-Inflammatory Drug That Resuscitates Poorly Functioning Hearts and Protects against Development of Heart Failure.

Irreversible myocardial injury causes the exhaustion of cellular adenosine triphosphate (ATP) contributing to heart failure (HF). Cyclocreatine phosphate (CCrP) was shown to preserve myocardial ATP during ischemia and maintain cardiac function in various animal models of ischemia/reperfusion. We tested whether CCrP administered prophylactically/therapeutically prevents HF secondary to ischemic injury in an isoproterenol (ISO) rat model. Thirty-nine rats were allocated into five groups: control/saline, control/CCrP, ISO/saline (85 and 170 mg/kg/day s.c. for 2 consecutive days), and ISO/CCrP (0.8 g/kg/day i.p.) either administrated 24 h or 1 h before ISO administration (prophylactic regimen) or 1 h after the last ISO injection (therapeutic regimen) and then daily for 2 weeks. CCrP protected against ISO-induced CK-MB elevation and ECG/ST changes when administered prophylactically or therapeutically. CCrP administered prophylactically decreased heart weight, hs-TnI, TNF-α, TGF-ß, and caspase-3, as well as increased EF%, eNOS, and connexin-43, and maintained physical activity. Histology indicated a marked decrease in cardiac remodeling (fibrin and collagen deposition) in the ISO/CCrP rats. Similarly, therapeutically administered CCrP showed normal EF% and physical activity, as well as normal serum levels of hs-TnI and BNP. In conclusion, the bioenergetic/anti-inflammatory CCrP is a promising safe drug against myocardial ischemic sequelae, including HF, promoting its clinical application to salvage poorly functioning hearts.

Managing port-site bleeding during less invasive coronary artery bypass grafting.

INTRODUCTION: Robotic-assisted coronary artery bypass grafting (r-CABG) requires the placement of ports bluntly through the chest wall. When removed, these ports create bleeding sites that can be difficult to detect and treat. This study evaluated whether a topical hemostatic agent placed locally within these sites helps to reduce bleeding and blood product requirements. METHODS: We retrospectively analyzed outcomes for r-CABG cases where 5 mL of a flowable hemostatic agent was injected locally within all port sites (hemostat group, n = 62) compared with patients whose port sites were untreated (controls, n = 131). Outcomes included chest tube output, red blood cell (RBC) transfusions, length of hospital stay, and the risk of reoperation for bleeding. Analyses were adjusted for risk factors known to influence bleeding and Society of Thoracic Surgeons (STS) risk score as a weighted composite of variables, which controls for patient and clinical variables. RESULTS: The 2 study groups had similar baseline characteristics and underwent the same r-CABG procedure. The hemostat group had significant reductions in RBC transfusion (24.2% versus 40.8% receiving blood; P = .026; 0.44 versus 1.39 U transfused postoperatively, P = .024). After adjustment for bleeding risks (using STS risk score), differences in transfusions remained significant. Reoperation rates for bleeding, length of stay, chest tube drainage, and intraoperative transfusions were not significantly different in the 2 groups. CONCLUSIONS: There was significantly reduced postoperative bleeding and less exposure to blood products in the hemostat group. These findings suggest that undetected bleeding from sites used for port access serves as an underappreciated source of morbidity after r-CABG.

Robotic surgery: would any other (more accurate) name smell as sweet?

The term we use to describe a surgical case that employs robotics influences how experts and laypeople think about this procedure. Robotic surgery is a misnomer because it implies more automation compared to what actually happens. A more realistic description is robot-assisted surgery and this term is likely to help promote more realistic understanding among stakeholders.

Is endoscopic harvesting bad for saphenous vein graft patency in coronary surgery?

PURPOSE OF REVIEW: Endoscopic vein harvest (EVH) has quickly been adopted as the standard-of-care for coronary artery bypass grafting (CABG). Despite clear advantages in terms of wound morbidity, healing, pain, and patient satisfaction, data from recent large clinical trials have called the safety of this technique into question. RECENT FINDINGS: Post-hoc analyses of a variety of prospective trials have suggested EVH is associated with decreased graft patency, higher rates of cardiovascular complications (e.g. myocardial infarction, need for repeat revascularization) and mortality. Imaging studies of veins procured by EVH have revealed retained clot and vascular injury, particularly during the 'learning curve' of the technician. These findings may alter the quality of the conduit and, therefore, the outcome of the bypass graft. Elucidating the mechanisms that underlie any differences in results produced by the open and endoscopic procedures would help better inform clinical practice and the development of targeted strategies to improve EVH. SUMMARY: Clear clinical advantages over traditional open vein harvest have allowed EVH to rapidly become the standard-of-care for harvesting of one or more vein grafts during CABG. The quality of these conduits, suggested to be equivalent by early studies, has come into question as groups with varying levels of experience have adopted the endoscopic technique. Elucidating the principles of 'best practice' for vein harvest will likely help shorten the learning curve and improve the safety of EVH.

Coronary computed tomography angiography following robotic coronary artery bypass grafting surgery: Systematic approach to image analysis and practical considerations.

Standard open chest Coronary Artery Bypass Grafting (CABG) has evolved over last couple of decades. With advancement in minimally invasive procedures, Robotic CABG (RCABG) is still in its evolution phase. There is dearth of experienced surgeons in this complicated field and lack of data to verify it clinical safety. in this review, we intend to describe the utility of Cardiac Computed Tomography Angiography (CCTA) in assessment of graft anatomy and quality, grafting strategy, distal graft anastomosis site evaluation and detection of complications associated with RCABG. CCTA appears to provide valuable information regarding the visualization of grafts, target coronary arteries and other cardiac and non-cardiac structures.

OR and ICU teams 'running in parallel' at the end of cardiothoracic surgery improves perceptions of handoff safety.

The transfer of a cardiac surgery patient from the operating room (OR) to the intensive care unit (ICU) is both a challenging process and a critical period for outcomes. Information transferred between these two teams-known as the 'handoff'-has been a focus of efforts to improve patient safety. At our institution, staff have poor perceptions of handoff safety, as measured by low positive response rates to questions found in the Agency for Health Care Research and Quality (AHRQ) Hospital Survey on Patient Safety Culture (HSOPS). In this quality improvement project, we developed a novel handoff protocol after cardiac surgery where we invited the ICU nurse and intensivist into the OR to receive a face-to-face handoff from the circulating nurse, observe the final 30 min of the case, and participate in the end-of-case debrief discussions. Our aim was to increase the positive response rates to handoff safety questions to meet or surpass the reported AHRQ national averages. We used plan, do, study, act cycles over the course of 123 surgical cases to test how our handoff protocol was leading to changes in perceptions of safety. After a 10-month period, we achieved our aim for four out of the five HSOPS questions assessing safety of handoff. Our results suggest that having an ICU team 'run in parallel' with the cardiac surgical team positively impacts safety culture.

Evaluating 21-day doxycycline and azithromycin treatments for experimental Chlamydophila psittaci infection in cockatiels (Nymphicus hollandicus).

To determine the efficacy of 21-day therapy with azithromycin and doxycycline in the treatment of experimental infection with Chlamydophila psittaci in cockatiels (Nymphicus hollandicus), 30 birds randomly assigned to 3 treatment groups and 1 control group were inoculated with C psittaci by combined intranasal and ocular routes. Morbidity, mortality, and results of polymerase chain reaction testing confirmed that infection was successful. Birds in group 1 (n = 8) received azithromycin at 40 mg/kg PO q48h for 21 days; in group 2 (n = 8), doxycycline at 35 mg/kg PO q24h for 21 days; in group 3 (n = 8), doxycycline at 35 mg/kg PO q24h for 45 days; and, in group 4 (controls; n = 6), no treatment. Six birds died either before or within 2 days of initiating treatment: 4 in the 3 treatment groups and 2 in the control group. Clinical signs resolved and mortality ceased 2-6 days after treatment was initiated in all treatment groups, whereas birds in the control group exhibited clinical signs for the duration of the study. Plasma doxycycline concentrations were measured during the treatment period and exceeded 1 microg/mL at all time points. The absence of clinical signs and mortality in the treatment groups, even after inducing an immunocompromised state with dexamethasone (3 mg/kg IM q24h for 5 days), starting on day 70 postinoculation, suggested that treatment resulted in elimination of the pathogen. After euthanasia of the remaining 24 birds, 23 of the carcasses were submitted for necropsy. Spleen and liver samples from the birds in all treatment and control groups were polymerase chain reaction negative for C psittaci nucleic acid, and organisms were not detected by Gimenez stain. No gross or histologic differences were observed in the livers and spleens of treated and untreated infected birds. Lesions consistent with avian chlamydiosis (hystiocytosis) were seen in all birds and were considered residual. In this study, a 21-day course of either doxycycline or azithromycin was effective in eliminating C psittaci infection in experimentally inoculated cockatiels. Additional studies are necessary to evaluate the efficacy of these treatments in naturally infected cockatiels as well as other species of birds.

Merits and Limitations of Studying Neuronal Depolarization-Dependent Processes Using Elevated External Potassium.

Elevated extracellular potassium chloride is widely used to achieve membrane depolarization of cultured neurons. This technique has illuminated mechanisms of calcium influx through L-type voltage sensitive calcium channels, activity-regulated signaling, downstream transcriptional events, and many other intracellular responses to depolarization. However, there is enormous variability in these treatments, including durations from seconds to days and concentrations from 3mM to 150 mM KCl. Differential effects of these variable protocols on neuronal activity and transcriptional programs are underexplored. Furthermore, potassium chloride treatments in vitro are criticized for being poor representatives of in vivo phenomena and are questioned for their effects on cell viability. In this review, we discuss the intracellular consequences of elevated extracellular potassium chloride treatment in vitro, the variability of such treatments in the literature, the strengths and limitations of this tool, and relevance of these studies to brain functions and dysfunctions.

The influence of fat thickness on the human epicardial bipolar electrogram characteristics: measurements on patients undergoing open-heart surgery.

AIMS: Reference values exist for endocardial but not for epicardial (EPI) substrate mapping in cases of cardiomyopathy-associated ventricular tachycardia. We sought to establish such values for EPI electrogram voltage, including areas with overlying fat. METHODS AND RESULTS: Ten patients (six males) undergoing cardiac surgery were studied. After opening the pericardium, the distal bipole of an electrophysiology catheter was placed tangential to the EPI surface to obtain an electrogram recording. The bipole was tangentially rotated 90 degrees and the higher of the two amplitudes (mV) was taken as the local amplitude. Recordings were taken from normal left and right ventricular myocardium (n = 26 data points each), over thick (> or = 0.5 cm) fat at both ventricular bases (n = 16) and thin (<0.5 cm) fat at the mid-ventricular level (n = 32). A total of 100 recordings (mean 10/patient) were analysed. Four patients underwent valvular surgery, three bypass surgery, and three combined procedures. Mean age was 61.7 +/- 10.4 years and mean left ventricular ejection fraction was 46 +/- 12%. Electrogram amplitude was inversely related to EPI fat thickness. Over thick fat, 31% of recordings were <0.5 mV. CONCLUSION: Human EPI electrogram amplitude varies by ventricular chamber and significantly by EPI fat thickness. A cut-off of 0.5 mV to define 'scar' will include normal areas with thick overlying fat. EPI substrate maps should include data on EPI fat thickness for higher specificity.

A randomized clinical trial investigating the relationship between aprotinin and hypercoagulability in off-pump coronary surgery.

BACKGROUND: Off-pump coronary artery bypass (OPCAB) surgery is associated with a hypercoagulable state in which the platelet thrombin receptor, protease-activated receptor-1 (PAR-1), helps propagate a thrombin burst within saphenous vein grafts. Aprotinin, used in cardiothoracic surgery mainly for its antifibrinolytic properties, also spares platelet PAR-1 activation due to thrombin. We hypothesized that this PAR-1 antagonistic property provides an antithrombotic benefit during OPCAB surgery. METHODS: Patients were randomly assigned to receive saline (n = 38) or a modified full-dose regimen of aprotinin (n = 37) IV during OPCAB surgery. Blood sampled perioperatively from the coronary sinus, skin wounds, and systemic circulation was analyzed to test coagulation and platelet function. Major adverse cardiovascular events were monitored by obtaining troponin I at 24 h (myocardial infarction), predischarge computed tomography angiography (vein graft thrombosis), and by clinical examination for stroke. RESULTS: Coronary sinus blood obtained immediately after OPCAB surgery showed significantly less activation in the aprotinin group, as judged by reduced formation of platelet-leukocyte conjugates (P < 0.02) and platelet-derived microparticles (P < 0.05). The aprotinin group showed inhibition of platelet aggregation induced by thrombin (P = 0.007) but not adenosine diphosphate. Thrombin generation, defined by F1.2 levels, was significantly reduced by aprotinin in the coronary sinus but not in skin wound incisions. Major adverse cardiovascular events were significantly reduced in aprotinin-treated patients (5.4% vs 29.7%, P < 0.05). Aprotinin also demonstrated antifibrinolytic properties through diminished red blood cell transfusion (P < 0.04) and reduced blood loss postoperatively (603 +/- 330 vs 810 +/- 415 mL, P < 0.004). CONCLUSION: This study demonstrates that aprotinin protects patients undergoing OPCAB surgery from a hypercoagulable state by diminishing thrombin-induced platelet activation and thrombin generation within saphenous vein grafts, while maintaining systemic hemostatic and antifibrinolytic benefits. These results support further investigation of aprotinin and other PAR-1 antagonists in OPCAB surgery.