bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Model of Ventricular Plication: A Suturing Technique to Decrease Left Ventricular Dimensions, Improve Contractility, and Attenuate Ventricular Remodeling After Myocardial Infarction in the Rat Heart
Authors: Schwarz Ernst R. , Speakman Mark T. , Kloner Robert A. 
Published: November 2007

Background: The Batista procedure (cardioreduction) is a surgical technique in patients with dilated cardiomyopathy that results in improvement of ventricular function. The purpose of this study was to test a new suturing technique without resection for cardioreduction of myocardial infarct scars in rats. Methods and Results: Myocardial infarction (MI) was induced by occluding the left coronary artery 4 weeks before enrollment. Animals then were randomized to a control (n = 11) or treatment group (n = 11). A pursestring suture was placed within the border zones of the infarcted area and was either tightened (treated) or not (controls). Echocardiography was used to measure left ventricular diameters before, 1 hour, and 6 to 7 weeks after plication. Acutely after plication, end-diastolic length (EDL) decreased from 0.70 ± 0.03 cm to 0.53 ± 0.02 cm, P < .001; end-systolic length (ESL) decreased from 0.51 ± 0.03 cm to 0.23 ± 0.02 cm, P < .001; and fractional shortening (FS) increased from 27.6 ± 1.5% to 57.6 ± 2.3%, P < .001, whereas controls were unchanged. In control rats EDL increased from baseline at 0.73 ± 0.02 cm to 0.82 ± 0.04 cm at 6 weeks postsurgery, P < .05; ESL increased from 0.54 ± 0.02 cm to 0.66 ± 0.04 cm, P < .005; and FS decreased from 26.9 ± 1.1% to 19.2 ± 1.2% at 6 weeks, P < .05. In contrast, at 6 weeks in plicated animals, EDL was significantly less than controls at 0.64 ± 0.02 cm, P < .005; ESL was significantly less than controls at 0.39 ± 0.03 cm, P < .005, and FS was significantly better than controls at 40.5 ± 2.2%, P < .005. Conclusion: The progressive LV enlargement between 4 and 10 weeks after MI reflects late ventricular remodeling. Plication by suturing infarcted tissue acutely decreases diameters and improves function. At 6 weeks, function remains improved over untreated animals.
Electrophysiologic Effects of Beta-blocking Agent, Tilisolol; on Isolated Guinea Pig Ventricular Myocytes
Authors: Sakai Fumio , Kawano Seiko , Hiraoka Masayasu 
Published: November 2007

Background: Electrophysiologic effects of a beta-blocking agent, tilisolol, were studied with isolated guinea pig ventricular myocytes using the whole cell patch clamp technique. Methods and Results:. Tilisolol at 10 μM or higher concentrations prolonged action poten tial duration (APD) at 90% repolarization (APD90) and at 100 μM or higher concentrations shortened APD at 20% repolarization (APD20) without changes in resting membrane poten tial. At 10 μM concentration tilisolol prolonged APD90 from 236.6 ± 55.3 ms in the control to 253.4 ± 52.4 ms (n = 16; P < .0 L), while APD20 was unaffected. At 100 μM tilisolol, APD20 was shortened from 143.6 ± 15.7 ms in the control to 133.7 ± 22.6 ms (n = 8; P < .05). Under voltage clamp, tilisolol decreased the delayed rectifier K+ current (IK), while the drug little affected the inward rectified K+ current (IKI). Applications of 10 μM and 100 μM tilisolol reduced the maximal conductance of IK by 35.7 ± 3.5% and 47.4 ± 3.5% of the control, respectively, without changes in voltage dependence (n = 10). Tilisolol at 100 μM decreased the L-type Ca2+, current (I Ca.L) by 22.0 ± 9.8% (n = 6) of the control, and the inactivation curve was shifted to a hyperpolarizing direction. Conclusions: Tilisolol has a direct membrane action to depress IK and ICa.L, in addition to its beta-receptor blocking action.
Urinary Nitrotyrosine Content as a Marker of Peroxynitrite-induced Tolerance to Organic Nitrates
Authors: Skatchkov M. , Larina L.L. , Larin A.A. , Fink N. , Bassenge E. 
Published: November 2007

Background: Anti-ischemic therapy with nitrovasodilators as NO-donors is complicated by the induction of tolerance. When nitrovasodilators are metabolized to release NO there is a considerable coproduction of oxygen-derived radicals leading to a diminished cyclic GMP production and to impaired vasomotory responses. We analyzed in vivo the glyceroltrinitrate- induced generation of strong oxidative/nitrating compounds contributing to development of tolerance. Methods and Results: In 16 patients we studied the urinary nitrotyrosine excretion during either (1) placebo control conditions, (2) 2-day nonintermittent transdermal nitroglycerin administration (0.4 mg/h), (3) 2-day nonintermittent glyceroltrinitrate administration (0.4 mg/h) along with a continuous infusion of vitamin C (55 μg/kg/min) as an antioxidant, or (4) with vitamin C but without glyceroltrinitrate (diminished urinary nitrotyrosine content of 34 ± 18 μg/day observed). Glyceroltrinitrate administration augmented urinary nitrotyrosine from 56 ± 24 (basal) to 186 ± 32 μg/day (glyceroltrinitrate tolerance). Coadministration of vitamin C caused complete elimination of tolerance and a decrease in urinary nitrotyrosine to 130 ± 28 μg/day. Glyceroltrinitrate-induced formation of oxidants was confirmed in vitro comparing glyceroltrinitrate-induced and peroxynitrite-induced tachyphylaxis in isolated perfused rabbit hearts and analyzing tolerance-induced inactivation of soluble guanylyl cyclase in cultured aortic smooth muscle cells. Conclusions: Augmented urinary nitrotyrosine excretion during glyceroltrinitrate adminis tration reflects enhanced formation of peroxynitrite and of nitrotyrosine. Glyceroltrinitrate- induced tolerance is the result of oxidative stress and can be suppressed by additional antiox idant therapy aimed to prevent glyceroltrinitrate-induced formation and/or actions of peroxynitrite.
Alterations in β-Adrenoceptor Mechanisms in Hearts Perfused with Xanthine Plus Xanthine Oxidase
Authors: Persad Sujata , Takeda Satoshi , Dhalla Naranjan S. 
Published: November 2007

Background: Although β-adrenoceptors and adenylyl cyclase are known to be affected upon exposing cardiac membranes to some oxyradical generating systems, the results are conflict ing. Furthermore, functional significance of alterations in the β-adrenoceptor-adenylyl cyclase system in terms of changes in the inotropic responses to catecholamines is not clear. Methods and Results: The positive inotropic effect of isoproterenol was augmented on per fusing the isolated rat hearts with xanthine (X) plus xanthine oxidase (XO) for 5 minutes but was attenuated by perfusion for 15 minutes. The isoproterenol-stimulated adenylyl cyclase activity in cardiac membranes showed an increase at 10 minutes and a decrease at 30 minutes perfusion of hearts with X plus XO. The density of β-adrenoceptors in cardiac membranes was reduced after 10 minutes and 30 minutes of perfusion with X plus XO, whereas the affin ity of β-adrenoceptors was increased after 10 minutes and reduced after 30 minutes. Although β-adrenoceptors were unaltered by 10 minutes of perfusion with X plus XO, their affinity was increased and density was decreased by 30 minutes of perfusion. The agonist competition curves using isoproterenol indicated an increase in the number of coupled recep tors in the high affinity state on 10 minutes of perfusion and an increase in the low affinity state of coupled receptor due to 30 minutes of perfusion with X plus XO. The basal as well as forskolin-, NaF- and Gpp(NH)p-stimulated adenylyl cyclase activities in cardiac membranes exhibited an increase after 10 minutes and decrease after 30 minutes of perfusion with X plus XO. Although the presence of superoxide dismutase plus catalase in the perfusion medium prevented most of the alterations due to X plus XO, it did not alter the increased affinity of the β-adrenoceptor upon perfusing hearts for 10 minutes with X plus XO. Conclusions: The results in this study suggest the biphasic nature of the oxyradical-induced alterations in both the inotropic responses to catecholamines and the β-adrenoceptor-medi ated signal transduction mechanism in the heart.
Effects of Phentolamine on Responses to PAMP in the Hindquarters Vascular Bed of the Rat
Authors: Nossaman Bobby D. , Kaye Alan D. , Champion Hunter C. , Bin Kang  , Feng Chang J. , Kadowitz Philip J. 
Published: November 2007

Background: Responses to proadrenomedullin NH2-terminal 20 peptide (PAMP), a novel hypotensive peptide formed from preproadrenomedullin, and the effects of inhibition of adrenergic vasomotor tone with the α-receptor antagonist, phentolamine, on responses to PAMP were investigated in the systemic and hindquarters vascular bed of the rat. Methods and Results: Intravenous injections of PAMP decreased systemic arterial pressure and in the hindquarters vascular bed of the rat under conditions of controlled hindquarters blood flow, intra-arterial injections of PAMP decreased perfusion pressure in a dose-related manner. Following administration of the alpha receptor blocking agent, phentolamine, sys temic depressor and hindquarters vasodilator responses to PAMP were not significantly decreased, whereas phentolamine significantly decreased systemic and hindquarters pressor responses to norepinephrine. Phentolamine had no significant effect on vasodilator responses to bradykinin, albuterol, or to nitroglycerin. Conelusions: The present data show that PAMP has significant systemic vasodepressor and vasodilator activity in the hindquarters vascular bed of the rat and suggest that vasodepressor and hindquarters vasodilator responses to PAMP are not dependent upon the presence of adrenergic vasomotor tone.
Pinacidil's Effects on Defibrillation Outcomes: Role of Increased Potassium Conductance Via the KATP Channel
Authors: Winecoff Allison P. , Sims J. Jason , Markel Michael L. , Ujhelyi Michael R. 
Published: November 2007

Background: It has been shown that the inhibition of potassium ion conductance decreases defibrillation threshold. We postulated that if potassium conductance is a primary mechanism affecting defibrillation threshold values, then increasing potassium ion conductance will increase defibrillation values. The primary objective of this study was to determine if the ATP-dependent potassium (KATP) channel opener pinacidil would increase defibrillation threshold values. The second objective was to prove that the observed changes were due to potassium conductance by using the KATP inhibitor, glyburide, to reverse the electrophysio logic actions of pinacidil. The third objective was to determine if the electrophysiology actions of pinacidil correlate with changes in defibrillation threshold value. Methods and Results: Domestic farm swine (n = 14) were anesthetized and intubated. Subsequently, they were instrumented with monophasic action potential catheters and epi cardial defibrillation patches. Defibrillation threshold values, action potential duration, effective refractory period, and ventricular fibrillation cycle length were determined at base line and during treatment phase 1 and treatment phase 2. Pigs were randomized into 2 groups: group 1 (n = 6) received D5W in treatment phase one followed by D5W in treatment phase 2 and group 2 (n = 8) received pinacidil in treatment phase one followed by the addi tion of glyburide in treatment phase two. DFTED50 did not change at baseline, treatment phase one or treatment phase two for group 1 (10.5 ± 2, 11.1 ± 1.7, 10.5 ± 1.0 J) or for group 2 (10.1 ± 2.2, 11.4 ± 4.2, 11.4 ± 3.0 J). Electrophysiologic parameters (QRS, effec tive refractory period, action potential duration 90, and ventricular fibrillation cycle length) were not significantly changed from baseline in group 1. In contrast, effective refractory period, action potential duration90, and ventricular fibrillation cycle length significantly decreased at all recorded sites after the administration of pinacidil in group 2 (range of 7-13%, 6-9%, and 12-17%, respectively). However, pinacidil did not change the basal level of dispersion in effective refractory period, action potential duration, and ventricular fibrillation cycle length during paced rhythm or ventricular fibrillation. Glyburide reversed pinacidil's electrophysiologic actions. Conclusions: Pinacidil does not alter defibrillation threshold, but it reduces effective refractory period, action potential duration, and ventricular fibrillation cycle length and does not increase electrical heterogeneity. Therefore, changes in potassium channel conductance as well as short ening repolarization are unlikely primary mechanisms for elevating defibrillation threshold.
Electrophysiologic Effects of the New Class III Antiarrhythmic Drug Dofetilide in an Experimental Canine Model of Pacing-induced Atrial Fibrillation
Authors: Feld Gregory K. , Yongmei Cha  
Published: November 2007

Background: Dofetilide is a new class III antiarrhythmic drug currently under investigation for the treatment of supraventricular arrhythmias in humans. Dofetilide have been previously shown to be highly effective in terminating and suppressing reentrant atrial flutter in the experimental canine crush-injury model, in which its antiarrhythmic efficacy was correlated with prolongation of wavelength and reduction in dispersion of refractoriness, effects not produced by the class IA antiarrhythmic drug quinidine. The purpose of this study was to evaluate the antiarrhythmic efficacy and mechanisms of action of dofetilide in an experimen tal model of atrial fibrillation. Methods and Results: Dofetilide was administered intravenously to seven open-chest dogs with acute sustained atrial fibrillation induced by rapid atrial pacing for up to 4 hours. Mean atrial effective refractory period (ERP), dispersion of ERP, conduction velocity and wave length were determined by multipoint right atrial programmed stimulation and activation mapping using a 56-electrode mapping plaque on the right atrial free wall. Dofetilide pro longed average ERP by 22% from 104 ± 13 to 127 ± 15 ms ( P < .001), prolonged maximum ERP by 11% from 129 ± 7 to 143 ± 10 ( P < .003), had no effect on conduction velocity at 200 ms pacing cycle length, slowed conduction velocity by 16% from 0.89 ± 12 to 0.75 ± .17 ms at 150 ms pacing cycle length ( P < .001), increased wavelength by 20% from 93 ± 7 to 112 ± 9 mm ( P < .01), reduced dispersion of ERP by 24% from 11.4 ± 2.9 to 8.7 ± 2.3 ( P = .016), and reduced the number of adjacent electrodes with ERP difference ≥20 ms by 67% from 18.4 ± 7.1 to 6.1 ± 4.2 ( P < .001). Dofetilide reduced the number of excitation wavelets (total over three beats) entering the region of the mapping plaque by 38% from 5.0 ± .8 to 3.1 ± .4 ( P < .002). Dofetilide terminated atrial fibrillation in all seven dogs at a mean of 3.4 ± 2.2 minutes into the loading infusion and prevented reinduction of atrial fibrillation in all seven dogs after completion of the loading infusion, while on maintenance infusion. Time to termination of atrial fibrillation correlated closely with change in ERP ( r = 0.78, P = .036). Conclusions: Dofetilide was highly effective in terminating and suppressing sustained pac ing induced atrial fibrillation in this canine model. Time to termination of atrial fibrillation correlated with the degree of change in ERP produced by dofetilide. The mechanism of ter mination of atrial fibrillation by dofetilide appeared to be a progressive reduction and even tual extinction of re-entrant wavelets. The predominant electrophysiologic effects of dofetilide were prolongation of ERP and wavelength and a reduction in dispersion of refrac toriness. Dofetilide had little effect on conduction velocity in this model, except at very short pacing cycle lengths.
Intravenous Propafenone for Conversion of Atrial Fibrillation or Flutter to Sinus Rhythm: A Randomized, Placebo-controlled, Crossover Study
Authors: Serdar Fak Ali , Tezcan Hakan , Caymaz Oguz , Tokay Sena , Oktay Şule , Oktay Ahmet 
Published: November 2007

Background: Propafenone has been claimed to be effective in converting atrial fibrillation and flutter to sinus rhythm; however, controlled clinical trials have reported variable results, and data about the safety of propafenone in the setting of heart failure are lacking. The aim of the present study was to evaluate the efficacy and safety of intravenous propafenone in con verting atrial fibrillation and flutter to sinus rhythm. Methods: Sixty patients with acute (< 72 h) or chronic atrial fibrillation or flutter were included in a randomized, placebo-controlled, conditional cross-over study. Twenty eight patients, of whom 12 were in New York Heart Association class III and IV, had heart failure. Patients received intravenous propafenone (2 mg/kg in 10 minutes) and placebo subsequently at 1 hour intervals if sinus rhythm was not achieved. The patients' rhythms were continuously monitored for 1 hour and a 12-lead electrocardiogram, a 1-minute continuous rhythm strip and vital signs were recorded at baseline and at 15, 30, 45, and 60 minutes after the adminis tration of each drug. Results: Twenty of the 59 patients (34%) treated with propafenone converted to sinus rhythm, while only 4 of the 50 patients (8%) treated with placebo converted (P < .001). Propafenone was more effective in patients with acute (< 72 h) atrial fibrillation (64.5%). The conversion rate with propafenone was not significantly different from placebo in patients with atrial flutter and chronic atrial fibrillation (> 72 h). Propafenone significantly decreased ( P < .005 vs placebo) mean ventricular rate in nonresponders with a baseline heart rate of more than 100 beats/min. No clinically significant adverse effect occurred. Conclusions: We conclude that intravenous propafenone treatment is effective for converting acute atrial fibrillation; however, it seems unlikely to be beneficial in atrial flutter and chronic atrial fiorillation. Propafenone decreases ventricular rate in nonresponders, and a single dose of propafenone is relatively safe even in moderate-to-severe heart failure.
Comparative Study of the Effects of Erythromycin and Roxithromycin on Action Potential Duration and Potassium Currents in Canine Purkinje Fibers and Rabbit Myocardium
Authors: West Paul D. , Martin Donald K. , Bursill Jane A. , Wyse Kenneth R. , Campbell Terence J. 
Published: November 2007

Background: Erythromycin and roxithromycin are macrolide antibiotics in common clini cal use. Erythromycin occasionally produces life-threatening arrhythmias ( torsades de pointes) by blocking the outward potassium current responsible for repolarization of the cardiac action potential. Methods and Results: We used standard cellular electrophysiological and whole-cell patch- clamping techniques to compare the relative efficacy of erythromycin and roxithromycin in prolonging cardiac action potential in canine Purkinje fibers and in blocking individual out ward potassium currents in isolated rabbit ventricular myocytes. We demonstrated signifi cant prolongation of action potential duration in canine Purkinje fibers by erythromycin but not roxithromycin at a concentration of 100 μM. The delayed rectifier, the outward potas sium current thought to be most sensitive to modulation by drugs, was significantly depressed by both agents at concentrations of ≥30 μM in isolated rabbit ventricular myo cytes. Both drugs had similar potencies (26% and 21 % reduction by 30 μM erythromycin and roxithromycin, respectively, and 50% and 36% reduction by 100 μM erythromycin and roxithromycin). Neither agent significantly blocked other potassium currents (including the transient outward current). Conclusions: Taking into account normally observed peak blood concentrations of these agents in clinical use and the fact that roxithromycin is not normally administered intrave nously, we conclude that the risk of proarrhythmia during normal clinical use of oral roxithromycin is extremely remote.
Lysophosphatidylcholine and Cellular Potassium Loss in Isolated Rabbit Ventricle
Authors: Goldhaber Joshua I. , Deutsch Nicholas , Alexander Laura D. , Weiss James N. 
Published: November 2007

Background: Lysophospholipids such as lysophosphatidylcholine (LPC) have many direct electrophysiological effects on cardiac muscle and have been implicated as a cause of lethal ventricular arrhythmias during acute myocardial ischemia. Because extracellular K + accu mulation is also a key arrhythmogenic factor during acute ischemia, we examined the effects of LPC on cellular K+ balance, including its interaction with adenosine triphosphate- sensitive K+ (KATP) channels. Methods and Results : Isolated rabbit interventricular septa paced at 75 beats/min were loaded with 42K+ to measure unidirectional K+ efflux rate (in 42K- washout experiments) or tissue K + content (in 42K+ uptake experiments) and action potential duration (APD) during exposure to 20 μM LPC for 30 minutes. LPC caused tissue K+ content to decrease by 15 ± 2% (n = 4) at a steady rate over 30 minutes, associated with gradual APD shortening and a delayed increase in unidirectional K+ efflux rate. Pretreatment with 12 μM cromakalim to selectively activate KATP channels shortened APD by 44 ± 66% and had no effect on net tis sue K+ content during control aerobic perfusion. However, cromakalim increased net K+ loss during exposure to LPC to 22 ± 4%, a 47% increase. Conclusions: LPC induced net K loss in heart, which was potentiated by the KATP channel agonist cromakalim. This ATP finding suggests that if LPC accumulates to similar levels during myocardial ischemia and hypoxia, it may be an important mechanism in net K+ loss.
A Multicenter, Placebo-Controlled, Dose-Ranging Study of Atorvastatin
Authors: Schrott Helmut , Fereshetian Anita Gmerek , Knopp Robert H. , Bays Harold , Jones Peter H. , Littlejohn Thomas W. , McLain Richard , Black Donald M. 
Published: November 2007

Background: Coronary heart disease (CHD) is the number one cause of death in Western societies. Elevated levels of plasma low-density lipoprotein (LDL) cholesterol and triglycer ides (TG) increase the risk for CHD. 3-Hydroxy-3-methylglutaryl conenzyme A (HMG- CoA) reductase inhibitors effectively reduce plasma cholesterol levels in patients with hypercholesterolemia. This study assesses the safety and dose-related effects of atorvastatin calcium on lipoprotein fractions in patients with LDL cholesterol levels between 160 mg/dL (4.1 mM) and 250 mg/dL (6.5 mM) or less and TG levels of 400 mg/dL (4.5 mM) or less. Methods and Results: Sixty-five patients were enrolled in a 6-week, randomized, placebo- controlled, parallel-group study. Patients received placebo or atorvastatin 10, 20, 40, 60, or 80 mg once daily. Adjusted mean decreases in LDL cholesterol for patients receiving ator vastatin 10, 20, 40, 60, and 80 mg were 37%, 42%, 50%, 52%, and 59%, respectively, com pared with a mean increase of 0.3% for patients receiving placebo; the differences between each of the atorvastatin dose groups and placebo were statistically significant ( P = .0001). Total cholesterol, triglycerides, and apolipoprotein B were significantly reduced in atorva statin groups ( P = .0001). Adverse events were similar in the placebo and atorvastatin treat ment groups. No patient had a serious adverse event or withdrew because of an adverse event during this study. Conclusions: Atorvastatin effectively lowered plasma LDL cholesterol, triglycerides, and apoB levels in a dose-related manner. Atorvastatin was well tolerated in hyperlipidemic patients over a 6-week period.