bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oleamide: A Fatty Acid Amide Signaling Molecule in the Cardiovascular System?
Authors: Hiley C. Robin , Hoi Pui Man 
Published: August 2010

ABSTRACTOleamide (cis‐9,10‐octadecenoamide), a fatty acid primary amide discovered in the cerebrospinal fluid of sleep‐deprived cats, has a variety of actions that give it potential as a signaling molecule, although these actions have not been extensively investigated in the cardiovascular system. The synthetic pathway probably involves synthesis of oleoylglycine and then conversion to oleamide by peptidylglycine α−amidating monooxygenase (PAM); breakdown of oleamide is by fatty acid amide hydrolase (FAAH). Oleamide interacts with voltage‐gated Na+channels and allosterically with GABAAand 5‐HT7receptors as well as having cannabinoid‐like actions. The latter have been suggested to be due to potentiation of the effects of endocannabinoids such as anandamide by inhibiting FAAH‐mediated hydrolysis. This might underlie an “entourage effect” whereby co‐released endogenous nonagonist congeners of endocannabinoids protect the active molecule from hydrolysis by FAAH. However, oleamide has direct agonist actions at CB1cannabinoid receptors and also activates the TRPV1 vanilloid receptor. Other actions include inhibition of gap‐junctional communication, and this might give oleamide a role in myocardial development. Many of these actions are absent from thetransisomer of 9,10‐octadecenoamide. One of the most potent actions of oleamide is vasodilation. In rat small mesenteric artery the response does not involve CB1cannabinoid receptors but another pertussis toxin‐sensitive, G protein–coupled receptor, as yet unidentified. This receptor is sensitive to rimonabant and O‐1918, an antagonist at the putative “abnormal‐cannabidiol” or endothelial “anandamide” receptors. Vasodilation is mediated by endothelium‐derived nitric oxide, endothelium‐dependent hyperpolarization, and also through activation of TRPV1 receptors. A physiological role for oleamide in the heart and circulation has yet to be demonstrated, as has production by cells of the cardiovascular system, but this molecule has a range of actions that could give it considerable modulatory power.
N‐(p‐Amylcinnamoyl)anthranilic Acid (ACA): A Phospholipase A2Inhibitor and TRP Channel Blocker
Authors: Harteneck Christian , Frenzel Henning , Kraft Robert 
Published: August 2010

ABSTRACTPhospholipase A2enzymes display a superfamily of structurally different enzymes classified in at least nine subfamilies by biochemical and structural properties.N‐(p‐amylcinnamoyl)anthranilic acid commonly referred to as ACA is often used as a broad‐spectrum inhibitor for the characterization of phospholipase A2–mediated pathways. Compounds like ACA and ACA‐like structures have been described to block the receptor‐induced release of arachidonic acid and subsequent signaling cascades in the pancreas and the cardiovascular system. We showed that ACA directly blocks several transient receptor potential (TRP) channels (TRPC6, TRPM2, TRP and TRPM8). With respect to the published data of ACA in the phospholipase A2field, the finding that ACA blocks diacylglycerol‐activated TRP channels is of specific interest as it offers the opportunity to interfere with receptor‐induced calcium‐dependent signaling processes in platelets and vascular smooth muscle cells. Overall,N‐phenylcinnamides, as a new pharmaceutical lead structure, form the first class of synthetic TRP channel blockers and represent a promising start for the development of small organic TRP channel–specific blockers.
Perhexiline
Authors: Ashrafian Houman , Horowitz John D. , Frenneaux Michael P. 
Published: August 2010

ABSTRACTPerhexiline, 2‐(2,2‐dicyclohexylethyl)piperidine, was originally developed as an anti‐anginal drug in the 1970s. Despite its success, its use diminished due to the occurrence of poorly understood side effects including neurotoxicity and hepatotoxicity in a small proportion of patients. Recently, perhexiline's mechanism of action and the molecular basis of its toxicity have been elucidated. Perhexiline reduces fatty acid metabolism through the inhibition of carnitine palmitoyltransferase, the enzyme responsible for mitochondrial uptake of long‐chain fatty acids. The corresponding shift to greater carbohydrate utilization increases myocardial efficiency (work done per unit oxygen consumption) and this oxygen‐sparing effect explains its antianginal efficacy. Perhexiline's side effects are attributable to high plasma concentrations occurring with standard doses in patients with impaired metabolism due to CYP2D6 mutations. Accordingly, dose modification in these poorly metabolizing patients identified through therapeutic plasma monitoring can eliminate any significant side effects. Herein we detail perhexiline's pharmacology with particular emphasis on its mechanism of action and its side effects. We discuss how therapeutic plasma monitoring has led to perhexiline's safe reintroduction into clinical practice and how recent clinical data attesting to its safety and remarkable efficacy led to a renaissance in its use in both refractory angina and chronic heart failure. Finally, we discuss the application of pharmacogenetics in combination with therapeutic plasma monitoring to potentially broaden perhexiline's use in heart failure, aortic stenosis, and other cardiac conditions.
A Multiple Ion Channel Blocker, NIP‐142, for the Treatment of Atrial Fibrillation
Authors: Tanaka Hikaru , Hashimoto Norio 
Published: August 2010

ABSTRACTAtrial fibrillation (AF) is one of the most frequent cardiac arrhythmia and is associated with increased cardiovascular morbidity and mortality, and the risk of stroke. Although currently available antiarrhythmic drugs are moderately effective in restoring normal sinus rhythm in patients with AF, excessive delay of ventricular repolarization by these agents may be associated with increased risk of proarrhythmia. Therefore, selective blockers of cardiac ion channel(s) that are exclusively present in the atria are highly desirable.NIP‐142 is a novel benzopyrane derivative, which blocks potassium, calcium, and sodium channels and shows atrial specific action potential duration prolongation. NIP‐142 preferentially blocks the ultrarapid delayed rectifier potassium current (IKur) and the acetylcholine‐activated potassium current (IKACh). Since IKurand IKAChhave been shown to be expressed more abundantly in the atrial than in the ventricular myocardium, the atrial‐specific repolarization prolonging effect of NIP‐142 is considered to be due to the blockade of these potassium currents. In canine models, NIP‐142 was shown to terminate the microreentry type AF induced by vagal nerve stimulation and the macroreentry type atrial flutter induced by an intercaval crush. These effects of NIP‐142 have been attributed to the prolongation of atrial effective refractory period (ERP), because this compound prolonged atrial ERP without affecting intraatrial and interatrial conduction times in these models. The ERP prolongation by NIP‐142 was greater in the atrium than in the ventricle. NIP‐142 also terminated the focal activity type AF induced by aconitine. In addition, NIP‐142 reversed the atrial ERP shortening and the loss of rate adaptation induced by short‐term rapid atrial pacing in anesthetized dogs. Thus, although clinical trials are required to provide evidence for its efficacy and safety, the novel multiple ion channel blocker, NIP‐142, appears to be a useful agent for the treatment of several types of AF with a low risk of proarrhythmic activity.
Granulocyte–colony‐stimulatory factor: a strong inhibitor of natural killer cell function
Authors: Schlahsa Laura , Jaimes Yarúa , Blasczyk Rainer , Figueiredo Constança 
Published: August 2010

BACKGROUND: The human cytokine granulocyte–colony stimulatory factor (G‐CSF) has found widespread application in the medical treatment of neutropenia and to mobilize hematopoietic stem cells used for transplantation. So far, the effect of G‐CSF on natural killer (NK) cells has not been fully investigated.STUDY DESIGN AND METHODS: The effect of G‐CSF on the phenotype, cytokine secretion profile, and cytotoxicity of NK cells was assessed. NK cells incubated in vitro in presence of G‐CSF for 48 hours as well as NK cells isolated from peripheral blood of G‐CSF–mobilized stem cell donors (in vivo) were used.RESULTS: In vitro, G‐CSF caused a strongly altered phenotype in NK cells with 49% down regulation of NKp44 frequency. Furthermore, the expression of the activating receptors NKp46 and NKG2D decreased 40 and 64%, respectively. The expression of KIR2DL1 and KIR2DL2 decreased by 46% each. In cytotoxicity assays, the lytic capacity of G‐CSF–exposed NK cells is reduced by up to 68% in vitro and up to 83% in vivo. Accordingly, granzyme B levels of in vivo G‐CSF–exposed NK cells were reduced by up to 87% in comparison to nonstimulated NK cells. Cytokine production of in vitro and in vivo incubated NK cells was strongly decreased for interferon‐γ, tumor necrosis factor‐α, and granulocyte macrophage colony‐stimulating factor as well as interleukin (IL)‐6 and IL‐8. Furthermore, we observed a reduction in proliferation and a positive feedback loop that increased the expression of the G‐CSF receptor.CONCLUSION: G‐CSF was demonstrated to be a strong inhibitor of NK cells activity and may prevent their graft‐versus‐leukemia effect after transplantation.
Hemostatic function of buffy coat platelets in additive solution treated with pathogen reduction technology
Authors: Ostrowski Sisse R. , Bochsen Louise , Windeløv Nis A. , Salado‐Jimena José A. , Reynaerts Inge , Goodrich Raymond P. , Johansson Pär I. 
Published: August 2010

BACKGROUND: Pathogen reduction technologies (PRTs) may influence the hemostatic potential of stored platelet (PLT) concentrates. To investigate this, buffy coat PLTs (BCPs) stored in PLT additive solution (SSP+) with or without Mirasol PRT treatment (CaridianBCT Biotechnologies) were compared by functional hemostatic assays.STUDY DESIGN AND METHODS: We performed in vitro comparison of PRT (PRT‐BCP) and control pooled‐and‐split BCPs (CON‐BCP) after 2, 3, 6, 7, and 8 days' storage. Hemostatic function was evaluated with thrombelastography (TEG) and impedance aggregometry (Multiplate), the latter also in a sample matrix (Day 2) with or without addition of red blood cells (RBCs), control plasma, and/or PRT‐treated plasma.RESULTS: PRT treatment of 8‐day‐stored BCPs influenced clot formation (TEG) minimally, with reductions in maximum clot strength (maximum amplitude, p = 0.014) but unchanged initial fibrin formation (R), clot growth rate (α), and fibrinolysis resistance. In the absence of RBCs and plasma, PRT impaired aggregation (Multiplate) in stored BCPs, with reduced aggregation against thrombin receptor activating peptide‐6 (p < 0.001), collagen (p = 0.014), adenosine 5′‐diphosphate (p = 0.007), and arachidonic acid (p = 0.070). Addition of RBCs and PRT‐treated or untreated plasma to PRT‐BCP and CON‐BCP, respectively, enhanced aggregation in both groups.CONCLUSIONS: Mirasol PRT treatment of BCPs had a minimal influence on clot formation, whereas aggregation in the absence of RBCs and plasma was significantly reduced. Addition of RBCs and plasma increased agonist‐induced responses resulting in comparable aggregation between PRT‐BCP and CON‐BCP. The clinical relevance for PLT function in vivo of these findings will be investigated in a clinical trial.
Factors affecting banking quality of umbilical cord blood for transplantation
Authors: Yang Hongyou , Loutfy Mona R. , Mayerhofer Stephanie , Shuen Paul 
Published: August 2010

BACKGROUND: The most important objective for cord blood banks is to store cord blood units of high quality, which is determined by total nucleated cells (TNCs) and CD34+ cells. Determining the factors affecting the stored life‐saving cells would be beneficial to the field.STUDY DESIGN AND METHODS: A total of 4930 cord blood units were collected between January 2007 and October 2009 and processed using a double extraction technique to sediment red blood cells with variable centrifugation time determined by the formula CT = KL – M, where CT is centrifuge time, K is 7.7227, M is 29.742, and L is ln (volume of cord blood with anticoagulant). The recovery rate of TNCs and other relevant factors affecting banking quality were analyzed.RESULTS: The mean recovery rate of TNCs was 97.7 ± 2.5% with 0.04% (2/4930) units below 80% and 10.8% (532/4930) units below 95%. The TNCs per unit was affected by gestation duration (p < 0.01), sex of infant (p < 0.01), mode of delivery (p < 0.01), collection method (p < 0.01), and ethnicity (p < 0.001). The number of postprocessing CD34+ cells was affected only by sex of the infant (p < 0.05). The viability of nucleated cells after processing was 94.8 ± 4.8% and was affected by the number of hours between collection and processing (p < 0.01). In contrast, the viability of CD34+ cells was 99.5 ± 1.0% (n = 30) when samples with low viability of TNCs were assessed. The results did not reveal a significant correlation (r = 0.07, p = 0.38).CONCLUSION: The double extraction technique provides a high and consistent recovery of TNCs, which ensures that more life‐saving cells will be banked for transplants.
Mechanisms of Phrenic Nerve Injury During Radiofrequency Ablation at the Pulmonary Vein Orifice
Authors: BUNCH T. JARED , BRUCE G. KEITH , MAHAPATRA SRIJOY , JOHNSON SUSAN B. , MILLER DYLAN V. , SARABANDA ALVARO V. , MILTON MARK A. , PACKER DOUGLAS L. 
Published: August 2010

Background: The phrenic nerve can be injured with radiofrequency energy delivery. Nevertheless, the mechanisms of injury are unknown. This study was undertaken to examine phrenic nerve tissue temperatures during ablation at the pulmonary vein (PV) orifice, assess the temperature dependence of injury, and to delineate the possible mechanisms of untoward nerve effects. Methods: Ten dogs underwent ablation at the right superior PV (RSPV) orifice. Phrenic nerve temperatures were assessed with implanted thermocouples overlying the endocardial ablation site. Using an 8‐mm ablation catheter tip, energy was titrated to 50°C and incremented by 5°C for 120 seconds. Results: Phrenic nerve capture was achieved in nine (90%) dogs after thermocouple implantation. A RSPV orifice tissue temperature >60°C occurred in 32 (84%) of energy deliveries with a power of 34 ± 22 W. In three (33%) dogs, this resulted in nerve dysfunction (maximum nerve temperature: 41°C, 41°C, and 91°C) with histology consistent with acute thermal injury. In four additional dogs, 17 energy deliveries were made directly to the phrenic nerve using a novel in situ model. In 5 (29%) energy deliveries, nerve function was impacted immediately by the generated current, with resolution simultaneous with discontinuing radiofrequency. Transient phrenic nerve injury occurred in all dogs at a temperature of 47 ± 3°C (range: 43–53°C) after 38 ± 32 seconds (range: 20–120 seconds). After termination of the energy delivery, nerve function returned in 15(88%) during 30 seconds of postablation pacing. In two (12%) ablation attempts, nerve recovery was delayed (>3 minutes). Permanent injury occurred in all dogs after 92 ± 83 seconds (range: 20–280 seconds) of additional energy delivery at a temperature of 51 ± 6°C (range: 45–65°C). Conclusion: Phrenic nerve injury can be more common than anticipated with RF ablation at the RSPV orifice. Relatively low tissue temperatures can injure the nerve. Immediate nerve effects suggest a second mechanism of nerve dysfunction related to electrical current. Transient nerve effects occur prior to permanent damage, providing an opportunity to discontinue energy delivery before permanent injury.
Clinical Predictors of Noninducibility of Sustained Atrial Fibrillation After Pulmonary Vein Isolation
Authors: ROTTER MARTIN , JAÏS PIERRE , GARRIGUE STEPHANE , SANDERS PRASHANTHAN , HOCINI MÉLÈZE , HSU LI‐FERN , TAKAHASHI YOSHIHIDE , ROSTOCK THOMAS , SACHER FRÉDERIC , CLEMENTY JACQUES , HAÏSSAGUERRE MICHEL 
Published: August 2010

Background: Noninducibility of sustained atrial fibrillation (AF) after pulmonary vein isolation (PVI) has been shown to be associated with a better clinical outcome. We evaluated the role of clinical variables that could predict noninducibility of sustained AF after PVI. Methods and Results: Data were collected prospectively from 181 patients (153 male; age 54 ± 9 years) referred for ablation of drug‐refractory symptomatic paroxysmal AF (duration ≤7 days). Clinical variables were evaluated with regard to their ability of predicting noninducibility of sustained AF (≤10 minutes) after PVI. Univariate analysis was performed on all collected variables followed by multivariate analysis for variables showing a P value <0.1. After PVI, sustained AF was noninducible in 97 (54%) patients. The following clinical variables showed a significant difference between the groups: body weight, longest AF episode, duration of AF history, presence or absence of structural heart disease, left ventricular (LV) hypertrophy, prior cardioversion, left atrial (LA) parasternal, and longitudinal diameters and LV diameters. On multivariate analysis, three independent predictors of noninducibility were identified: a shorter duration of AF episodes (AF <12 hours: RR 0.01 (0.002–0.06), P < 0.001; AF 12–48 hours: RR 0.07 (0.01–0.37), P = 0.001); LA longitudinal diameter <57 mm (RR 0.33 (0.13–0.82), P = 0.016); and absence of LV hypertrophy (RR 0.15 (0.04–0.63), P = 0.01). Conclusions: Shorter AF episodes, smaller LA longitudinal diameter, and absence of LV hypertrophy are independent predictors of noninducibility of sustained AF after PVI.
Endocardial Implantation of a Cardioverter Defibrillator in Early Childhood
Authors: GASPARINI MAURIZIO , REGOLI FRANÇOIS , GALIMBERTI PAOLA , PRIORI SILVIA G. 
Published: August 2010

Introduction: Experience in endovascular/endocardial techniques for implanting implantable cardioverter defibrillators in early childhood is limited. Potentially, this type of approach could limit the surgical risk, while increasing ICD therapy efficacy. The safety and feasibility of adopting a complete endovascular/endocardial approach for implanting ICDs is assessed by considering the cases of two young children. Methods and Results: Two boys, aged 3 and 6 years, were implanted with ICD for a history of syncope and documented ventricular tachycardia (VT). A complete endovascular/endocardial approach was adopted consisting of positioning a bipolar pacing and sensing lead in the right ventricular (RV) apex with intravascular redundancy forming a loop in the inferior vena cava (IVC), and a caval coil placed in the IVC. Sensing values (7–8 mV), pacing threshold (0.5–0.6 V/0.5 msec), and defibrillation testing (case 1 = 10 J, case 2 = 20 J) were all acceptable. During follow‐up, in both cases ICD intervened correctly. In one case, 16 months after implantation, because of change in the IVC coil‐active can vector, the IVC coil was effectively repositioned to a more distal position. Conclusion: A complete endovascular/endocardial ICD implantation technique in early childhood is both feasible and safe. This approach avoids thoracotomy and ensures ICD therapy efficacy.
Hemodynamic Effects of Atrial Septal Pacing in Cardiac Resynchronization Therapy Patients
Authors: DI PEDE FRANCESCO , GASPARINI GIANNI , DE PICCOLI BRUNO , YU YINGHONG , CUESTA FRANCISCA , RAVIELE ANTONIO 
Published: August 2010

Introduction: Spontaneous or pacing‐induced interatrial conduction delay may affect the outcome of heart failure patients treated with cardiac resynchronization therapy (CRT). The objective of this study was to evaluate the impact of the atrial pacing site (right atrial appendage, RAA; and low interatrial septum, LIS) during biventricular (BV) pacing on the left ventricular (LV) systolic function in candidates for CRT. Methods and Results: Fifteen heart failure patients with left bundle branch block and LV ejection fraction ≤35% were enrolled. Electrodes were placed at the RAA, LIS, right ventricular apex, and LV free wall. A DDD protocol was tested, which consisted of 50 beats in AAI mode from the RAA followed by 50 beats in BV DDD mode with atrial pacing at the RAA (DDD_RAA) or at the LIS (DDD_LIS) at four AV delays. The average (±SD)%LV+dP/dtmax increase during DDD_RAA and DDD_LIS pacing with respect to baseline was 24 ± 16% and 21 ± 15%, respectively (P < 0.01), and average percentage change in aortic pulse pressure during DDD_RAA and DDD_LIS with respect to baseline (%PP) was 13 ± 8% and 13 ± 7% (ns). Conclusions: Our results show a significant hemodynamic improvement with both DDD_RAA and DDD_LIS biventricular pacing compared to AAI pacing. However DDD_LIS pacing was not superior to DDD_RAA pacing in acute hemodynamic responses.
Isolation of Pulmonary Veins Using a Transvenous Curvilinear Cryoablation Catheter: Feasibility, Initial Experience, and Analysis of Recurrences
Authors: SKANES ALLAN C. , JENSEN STEEN M. , PAPP ROBERT , LI JULIANA , YEE RAYMOND , KRAHN ANDREW D. , KLEIN GEORGE J. 
Published: August 2010

Introduction: Pulmonary vein isolation (PVI) using focal cryothermal catheters is safe and moderately effective, but associated with long procedure times. We hypothesized that a linear freezing segment could shorten fluoroscopic and procedure times. We report our initial experience with a novel circular cryothermal catheter. Methods and Results: Complete PV isolation (PVI) was achieved in 41 of 45 PVs by cryoablation (91%) in 18 patients who underwent Lasso‐guided cryothermal using a novel 7 F circular catheter (2.5 ± 0.7 veins per patient). A mean of 27.2 ± 11 applications per patient (9.2 ± 4.7 per vein) with a mean temperature −79.8 ± 4°C were delivered. Recorded temperatures did not predict complete or incomplete isolation. Focal cryothermal ablation using a 7 F 4‐mm tip was required in the remainder for isolation. During 14.8 ± 6.2 month follow‐up, 4 (22%) had no recurrence of AF, and 7/18 (39%) had >90% reduction in symptoms without antiarrhythmic agents (AAA). Computed tomography scans at 3 months showed no stenosis (14.1 ± 2.5 mm, 13.9 ± 2.4 mm; P = 0.2). Eight patients underwent repeat ablation. Mapping demonstrated 13 of 14 (93%) previously isolated veins had recovery of over 64 ± 24% of the ostium. All were successfully isolated with RF and 7 of 8 were arrhythmia free 6.0 ± 2.9 months after ablation. Overall, 14 of 18 (78%) patients had their arrhythmia clinically controlled without drugs after one or two procedures. Conclusions: Our initial experience demonstrates safety and feasibility of circular cryothermal ablation with less fluoroscopic and procedure times as compared to focal cryothermy. As with RF, complete and permanent isolation of the PVs is not easily achieved. Reducing heat load due to PV flow may improve results.