bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of human apolipoprotein A-I on endotoxin-induced leukocyte adhesion on endothelial cells in vivo and on the growth of Escherichia coli in vitro
Authors: Thaveeratitham Premtip , Plengpanich Wanee , Naen-Udorn Worakamol , Patumraj Suthiluk , Khovidhunkit Weerapan 
Published: June 2007

Background: High-density lipoprotein (HDL) has been shown to inhibit leukocyte adhesion to endothelial cells induced by endotoxin in vivo and suppress the growth of bacteria in vitro; however, the components responsible for these effects, either lipids or proteins, are not yet defined. In this study, we examined the effects of apolipoprotein (apo) A-I, the major protein of HDL, on ameliorating the effect of endotoxin and inhibiting the growth of bacteria. Materials and Methods: Apo A-I, purified from normal human HDL, was incubated with endotoxin. Leukocyte adhesion to endothelial cells of rat mesenteric venules was assessed using intravital fluorescence microscopy. Ability of apo A-I to inhibit the growth of Escherichia coli was assessed using a spread plate method. Results: Purified, lipid-free apo A-I could inhibit endotoxin-induced leukocyte adhesion to endothelial cells in vivo in a dose-dependent manner. In addition, apoA-I was able to suppress the growth of Escherichia coli in vitro. Conclusions: These data suggest that apo A-I of HDL can directly interact with endotoxin, ameliorating its effect and that apo A-I may have a direct toxic effect on whole bacteria. Therefore, therapeutic use of apo A-I in septicemia and bacterial infection should be further explored.
Fenoldopam Infusion Associated with Preserving Renal Function After Aortic Cross-Clamping for Aneurysm Repair
Authors: Gilbert Timothy B. , Hasnain Jawad U. , Flinn William R. , Lilly Michael P. , Benjamin Marshall E. 
Published: June 2007

Background: Cross-clamping of the descending aorta during operative repairs causes sudden, significant reductions in renal function that may persist well beyond arterial clamp release. Commonly used agents, such as dopamine and mannitol, have not consistently affected renal outcome in these high-risk patients. Fenoldopam mesylate is a novel, highly selective dopamine type-I agonist that preferentially dilates the renal and splanchnic vasculature, but has not been investigated in patients undergoing prolonged aortic clamping for whom adverse renal outcomes should be more likely. Methods and Results: Twenty-two adult patients without significant pre-existing renal dysfunction and presenting for elective repairs of abdominal aortic aneurysms were studied. Fenoldopain mesylate was infused after obtaining baseline values ranging from 0.1 to 1.0 pg/kg/min for the first 24 hours postoperatively to maintain mean arterial pressure ±25% baseline. Serial renal function indices, including creatinine clearance and electrolyte fractional excretions, were measured at baseline, at aortic clamping and unclamping, and post-clamp release, and were estimated through hospital discharge. Creatinine clearance fell during abdominal exploration and clamping, reaching a nadir with clamp removal. Partial recovery occurred by 2 hours after clamp removal, and returned to baseline values by postoperative day 1 and thereafter. Fractional excretions rose rapidly throughout the operative phase. Total fenoldopam dose was directly related to the baseline creatinine clearance; after clamp removal, creatinine clearance was directly related to the mean arterial pressure at the lowest dose of fenoldopam, and inversely related to the mean arterial pressure at clamp release. Conclusions: In elderly patients with severe vascular disease undergoing aneurysmal repairs, the use of a fenoldopam infusion in this open-label, uncontrolled trial was associated with a relatively rapid return of renal function to baseline values, despite profound decreases during aortic cross-clamping. Further studies will be necessary to investigate how fenoldopam infusions compare with traditional therapies.
Renal Artery Stenosis in Minority Patients Undergoing Diagnostic Cardiac Catheterization: Prevalence and Risk Factors
Authors: Alhaddad Imad A. , Blum Steve , Heller Eliot N. , Beato Milton A. , Bhalodkar Narendra C. , Keriaky Ghassan E. , Brown Edward J. 
Published: June 2007

Background: Atherosclerotic renal artery stenosis (RAS) is a frequently overlooked clinical entity that can cause progressive renal failure and uncontrolled hypertension. Revascularization of a stenosed renal artery is associated with improved clinical outcomes including the prevention of renal failure. Thus, it is important to recognize all potential candidates for renal artery revascularization. In a general population referred for diagnostic cardiac catheterization, RAS of any severity was found in 30% of patients and significant stenosis (> 50% diameter narrowing) was found in 15% of patients. The number of minority groups is increasing in the US population, and RAS in this population is not well investigated. Our purpose was to determine the prevalence and risk factors associated with RAS in minority patients referred for diagnostic cardiac catheterization. Methods: Abdominal aortography was performed in 171 consecutive minority patients referred for diagnostic cardiac catheterization (hispanics = 115, African Americans = 56). The association of clinical and angiographic variables with RAS was examined using univariate and multivariate logistic regression analyses. Results: Renal artery stenosis of any severity was identified in 13.5% of patients (unilateral 7.7%, bilateral 5.8%). Significant RAS was found in 7.7% of patients (unilateral 4.8%, bilateral 2.9%). Independent predictors of RAS included age (mean ±SD, 68 ±0 vs 57 ± yr, P < 0.001, for patients with vs without RAS), coronary artery disease, and elevated serum creatinine levels (> 115,umolVL). Race/ethnicity (hispanics vs African Americans), sex, smoking, congestive heart failure, diabetes mellitus, peripheral vascular disease, and hyper-tension were not independent predictors. Conclusions: Renal artery stenosis in minority patients undergoing diagnostic cardiac catheterization is less common than reported in white patients, is similar in hispanics and African Americans, and is similar in women and men. The clinical and angiographic features are helpful in predicting its presence.
Electrophysiologic Effects of a Novel Selective Adenosine A1 Agonist (CVT-510) on Atrioventricular Nodal Conduction in Humans
Authors: Lerman Bruce B. , Ellenbogen Kenneth A. , Kadish Alan , Platia Edward , Stein Kenneth M. , Markowitz Steven M. , Mittal Suneet , Slotwiner David J. , Scheiner Marc , Iwai Sei , Belardinelli Luiz , Jerling Markus , Shreeniwas Revati , Wolff Andrew A. 
Published: June 2007

Background: CVT-510, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside, is a selective A,-adenosine receptor agonist with potential potent antiarrhythmic effects in tachycardias involving the atrioventricular (AV) node. This study, the first in humans, was designed to determine the effects of CVT-5 10 on AV nodal conduction and hemodynamics. Methods and Results: Patients in sinus rhythm with normal AV nodal function at electrophysiologic study (n = 32) received a single intravenous bolus of CVT-5 10. AH and HV intervals were measured during sinus rhythm and during atrial pacing at 1, 5, 10, 15, 20, 30, 45, and 60 minutes after the bolus. Increasing doses of CVT-510 (0.3 to 10 pg/kg) caused a dosedependent increase in the AH interval. At 1 minute, a dose of 10,ug/kg increased the AH interval during sinus rhythm from 93 ± 23 msec to 114 ± 37 msec, p = 0.01 and from 114 ± 31 msec to 146 ± 44 msec during atrial pacing at 600 msec, p = 0.003). The AH interval returned to baseline by 20 minutes. CVT-510 at doses of 0.3 to 10,ug/kg had no effect on sinus rate, HV interval, or systemic blood pressure, and was not associated with serious adverse effects. At doses of 15 and 30 pg/kg, CVT-510 produced transient second/third degree AV heart block in all four patients treated. One of these patients also had a prolonged sedative effect that was reversed with aminophylline. Conclusions: CVT-510 promptly prolongs AV nodal conduction and does not affect sinus rate or blood pressure. Selective stimulation of the A,-adenosine receptor by CVT-510 may be useful for immediate control of heart rate in atrial fibrillation/flutter and to convert paroxysmal supraventricular tachycardia to sinus rhythm, while avoiding vasodilatation mediated by the A2-adenosine receptor, as well as the vasodepressor and negative inotropic effects associated with 3-adrenergic receptor blockade and/or calcium channel blockers.
Female Gender Does Not Influence the Magnitude of Ibutilide-Induced Repolarization Delay and Incidence of Torsades de Pointes in an In Vivo Rabbit Model of the Acquired Long QT Syndrome
Authors: Johansson Marie , Carlsson Leif 
Published: June 2007

Background: Clinical and experimental in vitro observations indicate that female gender is associated with a higher risk of developing torsades de pointes with repolarizing-delaying agents. The present study addressed the question of gender difference in the susceptibility towards developing torsades de pointes in a rabbit model of the acquired long QT syndrome in vivo.Methods and Results: Female (F, n = 40) or male (M, n = 40) NZW rabbits, characterized as young (Y, n = 20) or adult (A, n = 20) were anesthetized with oc-chloralose and sensitized to developing torsades de pointes by a continuous infusion of methoxamine. The class III antiarrhythmic agent ibutilide was subsequently infused at a rate of 8 nmol/kg/min for 30 minutes maximum. Before commencement of drug infusion, no gender-related differences in the QT interval were observed (121 ± 1.9 msec and 126 ± 3.3 msec in FA and in MA and 116 ± 1.6 msec and 113 ± 1.7 msec in the FY and MY, respectively). Infusion of ibutilide was associated with a rapid and marked increase in the QT interval, which did not differ significantly between the groups. Hence, the maximal QT lengthening observed was 39 ± 3.1% in FA, 46 ± 5.7% in MA, 38 ± 3.9% in FY and 36 ± 3.4% in MY, respectively (p > 0.05 between gender). In the adults, the incidence of torsades de pointes in F was 70% and in M 90% (p = 0.235), whereas in the young, the incidence in F was 45% and in M 70% (p = 0.200). The cumulative doses of ibutilide causing torsades de pointes were not statistically significantly different between the four groups of rabbits (70 ± 15.5 nmol/kg in FA, 50 ± 5.3 nmol/kg in MA, 59 ± 17.2 nmol/kg in FY and 61 ± 15.9 nmol/kg in MY, respectively).Conclusions: In this in vivo rabbit model of the acquired long QT syndrome, female gender was not associated with a longer repolarization time (QT interval), an excessive change in the baseline QT interval or a higher incidence of torsades de pointes in response to ibutilide challenge.
Local Delivery of a Hydrophobic Heparin Reduces Neointimal Hyperplasia After Balloon Injury in Rat Carotid but not Pig Coronary Arteries
Authors: Sasseen Brett M. , Gray Brian D. , Gal Dov , Lorinc Robert , Carpenter Donald C. , Klugherz Bruce D. , Wilensky Robert L. 
Published: June 2007

Background: Intimal hyperplasia following percutaneous interventional vascular procedures is a major cause of restenosis. Although heparin inhibits intimal hyperplasia, it has not proven clinically useful in part due to an inadequate duration of intramural drug residence. This study was designed to evaluate the efficacy of local delivery of hydrophobic heparin (PTIR-RS-1), exhibiting increased intramural binding, on neointimal hyperplasia after angioplasty injury. Methods and Results: PTIR-RS-1 was delivered locally into rat carotid arteries at three doses: 0.1 mM (440 IU), 0.3 mM (1320 IU), or 1.0 mM (4400 IU). Animals were killed at 14 days. In the pig, the doses tested were the low dose in the rat and a high dose 1 log higher. Animals were killed 28 days later. Morphometric analysis was performed to evaluate the intima:media ratio in rats and the normalized neointimal area in pigs. In rats a significant reduction in neointimal to medial area ratio from 0.73 ± 0.15 for control vs 0.80 ± 0.27 for sodium heparin (P = NS) and 0.15 ± 0.07 for the 0.1 mM PTIR-RS-l dose (P < 0.008). In pigs, PTIR-RS-1 the high dose reduced the normalized neointimal area by 16%, a difference that was not statistically significant. Conclusions: Increased hydrophobicity of heparin reduced neointimal area following balloon overstretch injury in the rat carotid but not the pig coronary artery model. This study attests to the importance of performing studies evaluating the pharmacologic effect of local delivery of a medication in at least two animal models of restenosis.
Delta Opioid Receptors Inhibit Vagal Bradycardia in the Sinoatrial Node
Authors: Jackson Keith E. , Farias Martin , Stanfill Amber , Caffrey James L. 
Published: June 2007

Background: Methionine-enkephalin-arginine-phenylalanine (MEAP) is an endogenous opiate derived from the C-terminal sequence of the larger precursor molecule proenkephalin. This heptapeptide is abundant in the myocardium and has significant vagolytic activity when infused systemically. MEAP interrupted vagal bradycardia when it was delivered directly into the sinoatrial node by local microdialysis. This study was conducted to determine the opioid receptor responsible for the vagolytic effect of MEAP. Methods and Results: Microdialysis probes were placed in the sinoatrial node of mongrel dogs and perfused at 5 μL/min. Increasing doses of MEAP were included in the nodal perfusate and approximately two thirds of the vagal bradycardia was inhibited with a maximal effect at 0.3 nmoles/μ,L and a half-maximal response near 0.1 nmoles/,uL. When deltorphin II (a delta opioid receptor agonist) was infused into the sinoatrial node, more than 95% of the vagal bradycardia was eliminated at 0.3 nmoles/,uL with the half-maximal response near 0.1 nmoles/,L, indicating that deltorphin II was more efficacious than MEAP. The maximal deltorphin II and MEAP effects were both similarly reversed by the paired infusion of increasing doses of the 6 opiate receptor antagonist, naltrindole. Selected, μ (endomorphin, super DALDA) and κ (dynorphin, U50488) receptor agonists and,μ (CTAP) and κ (norBNI) receptor antagonists were completely ineffective in this system. Conclusions: These data suggest that the vagolytic effect of MEAP involves the activation of delta opiate receptors within the sinoatrial node.
HR (Paroven, Venoruton; 0-(β-hydroxyethyl)-rutosides) in Venous Hypertensive Microangiopathy: A Prospective, Placebo-Controlled, Randomized Trial
Authors: Incandela L. , Belcaro G. , Renton S. , DeSanctis M. T. , Cesarone M. R. , Bavera P. , Ippolito E. , Bucci M. , Griffin M. , Geroulakos G. , Dugall M. , Golden G. , Acerbi G. 
Published: June 2007

The aim of this study was to demonstrate whether HR (Paroven-Venoruton; 0-(β-hydroxyethyl)-rutosides), was effective in improving the microcirculation in venous hypertension and microangiopathy. Sixty patients with severe venous hypertension due to chronic venous insufficiency, ankle swelling, and lipodermatosclerosis were included. After informed consent, patients were randomized into a treatment group and a placebo group. Patients in the treatment group received oral HR (2 g/day for 8 weeks); those in the placebo group received a comparable placebo. Results: The two groups were comparable for age and sex distribution. The mean age was 45 years (SD 9) in the treatment group (31 patients) and 45.5 (SD 10) in the placebo group (29 patients). There were no differences between the placebo and treatment groups at inclusion. There was no change between inclusion and measurements at 8 weeks in the placebo group. A significant decrease (P < 0.05) in flux at rest and rate of ankle swelling was observed in the treatment group. The decrease in capillary filtration was associated with improvement in signs and symptoms (P < 0.05). The difference in flux, sign and symptoms, and filtration was clinically important at 8 weeks in the treatment group when compared with the placebo group. No adverse effects were observed. Conclusion: Venous microangiopathy was improved by HR treatment.
Downregulation of Immunodetectable Atrial Connexin4O in a Canine Model of Chronic Left Ventricular Myocardial Infarction: Implications to Atrial Fibrillation
Authors: Oahara Keiko , Miyauchi Yasushi , Ohara Toshihiko , Fishbein Michael C. , Zhou Shengmei , Lee Moon-Hyoung , Mandel William J. , Chen Peng-Sheng , Karagueuzian Hrayr S. 
Published: June 2007

Background: The substrate(s) for atrial fibrillation associated with chronic left ventricular myocardial infarction remain poorly defined. Since atrial connexin40 has a rapid turnover rate and may cause atrial fibrillation, we hypothesized that chronic left ventricular myocardial infarction downregulates atrial Connexin40 and increases atrial fibrillation vulnerability. Methods and Results: The left anterior descending coronary artery was occluded distal to the first diagonal branch in five dogs and studied 7 weeks later. Five dogs with no left anterior descending coronary artery occlusion served as control. Vulnerability to atrial fibrillation was tested by burst atrial stimulation (50 milliseconds for 3 seconds). Atrial fibrillation was induced in all myocardial infarction dogs, lasting from 20 seconds to several minutes. In contrast, only rapid repetitive activity and short-lasting atrial fibrillation (< 5 seconds) could be induced in control dogs. The mean refractory periods of epicardial RA and LA appendages were not significantly different in the two groups. Mean left ventricular myocardial infarction size was 17 ± 4% of the left ventricle. Histologic analyses showed no signs of atrial ischemic injury or interstitial fibrosis in either group. Atrial myocyte diameter measured at the level of the nuclei of longitudinally sectioned myocytes was not significantly different in the two groups (10.1 ± 1.2 pm vs. 10.2 ± 1.2 pm; P = 0.3). Atrial Connexin40 (both left and right atria) in the left ventricular myocardial infarction group was highly heterogeneous and had significantly smaller total area stained than in the control (0.48 ± 0.09% vs. 0.82 ± 0.13%; P < 0.01). Conclusions: Chronic left ventricular myocardial infarction downregulates immunodetectable atrial Connexin40, a property that might contribute to the increased atrial fibrillation vulnerability in this model.
Mechanism of the Positive Inotropic Effect of Lysophosphatidic Acid in Rat Heart
Authors: Xu Yan-Jun , Rathi Satyajeet S. , Zhang Ming , Bhugra Praveen , Dhalla Naranjan S. 
Published: June 2007

Background: Lysophosphatidic acid, a bioactive phospholipid, is mainly released from the activated platelets. The concentration of lysophosphatidic acid in serum is elevated under conditions such as ischemia, hypertension, and thrombosis; however, its effect on cardiac function, as well as the mechanisms of its action, have not been fully understood. Methods and Results: Cardiovascular effects of lysophosphatidic acid were studied in vivo in rats as well as in vitro by using the isolated perfused heart and cardiomyocyte preparations. Intravenous injection of lysophosphatidic acid (2.8 to 14 μgI/00 g body wt) increased the left ventricular systolic and diastolic pressures, rate of pressure development, and rate of pressure decay in rats. The positive inotropic effect of lysophosphatidic acid in vivo was not affected by the blockers of angiotensin II, endothelin-1, or adrenergic receptors, but this action was abolished by pretreatment with neurokinin type I receptor antagonist (L703606) as well as Ca2+-channel antagonist (verapamil). In the isolated heart, lysophosphatidic acid (1-10 μM) had no significant effect on cardiac function but higher concentrations (20-50 μM) elevated the left ventricular end diastolic pressure, significantly. Lysophosphatidic acid (1-30 μM) neither showed any effect on the basal intracellular concentration of free Ca2+ nor modified the KCl-induced increase in [Ca2+]i in freshly isolated cardiomyocytes. Conclusions: These results indicate that lysophosphatidic acid stimulated heart function under in vivo but not in vitro conditions. The positive inotropic effect of lysophosphatidic acid in vivo may be indirectly mediated by the activation of neurokinin type 1 receptors.
Comparison of Verapamil and Ibutilide for the Suppression of Immediate Recurrences of Atrial Fibrillation after Transthoracic Cardioversion
Authors: Sticherling Christian , Ozaydin Mehmet , Tada Hiroshi , Oral Hakan , Pelosi Frank , Knight Bradley P. , Strickberger S. Adam , Morady Fred 
Published: June 2007

Background: Verapamil and ibutilide blunt the atrial fibrillation-induced shortening of atrial refractoriness that may predispose to an immediate recurrence of atrial fibrillation after cardioversion. This study compared the efficacy of verapamil and ibutilide in preventing an immediate recurrence of atrial fibrillation. Methods and Results: Transthoracic cardioversion was performed in 223 patients with atrial fibrillation. Atrial fibrillation recurred within 10 minutes after cardioversion on two occasions in 21 patients (9.4%). Twenty of these patients were randomly assigned to receive an infusion of either 0. 15 mg/kg of verapamil at a rate of 2 mg/min (11 patients), or 1 mg of ibutilide over 10 minutes (9 patients). Eight patients (73%) had another episode of immediate recurrence of atrial fibrillation after verapamil, compared to two patients (22%) after ibutilide (P<0.05). Including the results after crossover, immediate recurrence of atrial fibrillation occurred in 8 of 12 patients (67%) who received verapamil, compared to 3 of 16 patients (19%) who received ibutilide (P=0.02). Verapamil and/or ibutilide successfully prevented immediate recurrence of atrial fibrillation in 17 of 20 patients (85%). After 700 days of follow-up, there was no significant difference in the recurrence rate of atrial fibrillation between the patients in whom immediate recurrence of atrial fibrillation was prevented by verapamil and/or ibutilide and the patients who were successfully converted to sinus rhythm and did not have immediate recurrence of atrial fibrillation. Conclusions: Ibutilide is more effective than verapamil in preventing immediate recurrence of atrial fibrillation. Suppression of immediate recurrence of atrial fibrillation by ibutilide and/or verapamil may allow for long-term maintenance of sinus rhythm postcardioversion as often as in patients who do not experience immediate recurrence of atrial fibrillation.
Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) Induced by Amiodarone: A Report on Two Cases
Authors: Ikegami Haruhiko , Shiga Tsuyoshi , Tsushima Toshio , Nirei Takashi , Kasanuki Hiroshi 
Published: June 2007

Background: Amiodarone is an effective antiarrhythmic agent for life-threatening arrhythmias but has some noncardiac toxicity. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by amiodarone during long-term therapy seems to be rare among adverse effects. Subjects and Results: We report on two elderly cases that developed hyponatremia caused by SIADH occurring during the initial loading period of amiodarone therapy. Both cases improved within 3 weeks after reduction of the dose, although amiodarone was continued. Conclusions: Amiodarone-induced SIADH may occur during the initial loading period, and it may be improved by reduction of the dose without discontinuation of the drug.