bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac noradrenergic nerve terminal abnormalities in dogs with experimental congestive heart failure.
Authors: Himura Y , Felten S Y , Kashiki M , Lewandowski T J , Delehanty J M , Liang C S 
Published: June 2012

BACKGROUND
We have shown previously that norepinephrine (NE) uptake activity is reduced in the failing right ventricle of animals with right heart failure (RHF) produced by tricuspid avulsion and progressive pulmonary constriction. However, it is unknown whether this defect in neuronal NE uptake is related to reduction of noradrenergic nerve terminals or whether these changes also occur in animals with left heart failure (LHF). It is also unknown whether increased NE release in heart failure contributes to the noradrenergic nerve abnormalities.

METHODS AND RESULTS
We measured myocardial NE content. NE uptake function, and noradrenergic nerve profiles in dogs with either RHF or LHF induced by rapid ventricular pacing. NE uptake activity was measured using [3H]NE, and noradrenergic nerve profiles were visualized by glyoxylic acid (SPG)-induced histofluorescence and tyrosine hydroxylase immunocytochemical staining. To study the effects of excess NE, we exposed normal dogs to 8 weeks of chronic NE infusion using subcutaneous osmotic minipumps. RHF and LHF animals exhibited reduced myocardial contractile function and congestive heart failure, as evidence by reduced cardiac output and elevated right atrial pressure. However, unlike that in LHF, left atrial pressure was not increased in RHF. The animals also showed an increase in plasma NE and a decrease in cardiac NE. In addition, SPG-induced histofluorescence correlated significantly with NE uptake activity (r = .712, P < .001) and tyrosine hydroxylase immunoreactive profiles (r = .569, P < .001) in the right ventricles of RHF dogs and in both ventricles of LHF dogs. The numbers of catecholaminergic profiles and tyrosine hydroxylase profiles significantly correlated with cardiac filling pressures. Chronic infusion of NE decreased heart rate in normal dogs but had no effect on either mean aortic pressure or left atrial pressure; like heart failure, it resulted in significant decreases in myocardial NE uptake activity and numbers of SPG-induced catecholaminergic histofluorescence and immunoreactive tyrosine hydroxylase profiles.

CONCLUSIONS
Myocardial NE uptake activity was reduced only in the failing ventricles with elevated filling pressure in RHF and LHF. These changes probably were caused by loss of noradrenergic nerve terminals in the failing ventricles, as evidenced by the reductions of catecholaminergic histofluorescence and tyrosine hydroxylase immunostained profiles. Furthermore, since similar reductions of myocardial NE uptake and noradrenergic nerve profiles could be produced by chronic NE infusion in normal dogs, elevated NE levels may play a role in the development of cardiac noradrenergic nerve abnormalities in congestive heart failure.
Coexistence of functioning beta 1- and beta 2-adrenoceptors in single myocytes from human ventricle.
Authors: del Monte F , Kaumann A J , Poole-Wilson P A , Wynne D G , Pepper J , Harding S E 
Published: June 2012

BACKGROUND
Both beta 1- and beta 2-adrenoceptors (beta 1 AR and beta 2 AR) are present in human ventricle. This study was designed to determine whether the two subtypes contribute to contraction in single myocytes from human heart.

METHODS AND RESULTS
(-)-Epinephrine increased the contraction amplitude and velocity of single myocytes isolated from the ventricles of failing and nonfailing human hearts. Concentration-response curves to (-)-epinephrine were constructed in the presence and absence of selective antagonists for beta 1 AR (CGP 20712A) and beta 2 AR (ICI 118,551). Responses to (-)-epinephrine were antagonized to a variable degree by the blockers, suggesting heterogeneous contribution of beta 1AR and beta 2AR among cells. The most common response in single myocytes was that ICI 118,551 (50 nmol/L) shifted the concentration-response curve less than 10-fold: this was lower than the 100-fold shift expected for a pure beta 2AR effect. Inclusion of CGP 20712A (300 nmol/L) with ICI 118,551 shifted the (-)-epinephrine curve still further. These observations suggest that both beta 1AR and beta 2AR contribute to the increase in contraction amplitude with (-)-epinephrine in this group of myocytes. When 300 nmol/L CGP 20712A was present as the sole antagonist, only a marginal shift of the concentration-response curve for (-)-epinephrine was usually observed, indicating that beta 1AR were not mediating the effect of these low concentrations of (-)-epinephrine. Both beta 1AR and beta 2AR mediated a considerable abbreviation of the time to peak contraction and time to 50% relaxation in the single cells.

CONCLUSIONS
beta 1AR and beta 2AR coexist and function on human ventricular myocytes. At low (-)-epinephrine concentrations, contractile responses are predominantly mediated by beta 2AR rather than beta 1AR in myocytes from failing hearts.
Electrocardiographic diagnosis of postinfarction regional pericarditis. Ancillary observations regarding the effect of reperfusion on the rapidity and amplitude of T wave inversion after acute myocardial infarction.
Authors: Oliva P B , Hammill S C , Edwards W D 
Published: June 2012

BACKGROUND
The ECG recognition of diffuse pericarditis following acute myocardial infarction has been based on changes of the ST segment and, to a lesser extent, alterations of the PQ segment. No ECG criteria exist for the diagnosis of postinfarction regional pericarditis. Recently, it was observed that the T wave evolution follows an atypical pattern before fatal free wall rupture and that this pattern is due to the associated pericarditis. Therefore, this study was conducted on 200 patients with acute myocardial infarction to further elucidate the sensitivity and specificity of the atypical T wave changes in patients with regional postinfarction pericarditis without rupture and to assess the affect of lytic treatment on the rapidity and amplitude of postinfarction T wave evolution.

METHODS AND RESULTS
An analysis of the clinical courses and serial ECGs of 200 consecutive patients with acute myocardial infarction was performed. Among 43 patients with postinfarction pericarditis, the pattern of T wave evolution consistently differed from the customary postinfarction pattern of T wave evolution. This unusual evolutionary course was expressed as either persistently positive T waves 48 or more hours after infarction (67%) or premature, gradual reversal of inverted T waves to positive deflections (33%). The sensitivity and specificity of these T wave alterations were 100% and 77%, respectively. The only other processes identified that caused this type of postinfarction T wave evolution were cardiopulmonary resuscitation, reinfarction, and very small infarcts. Both reperfusion, as judged by the creatine kinase-MB curve, and patency, as assessed by the angiogram, were correlated with the rapidity and depth of T wave inversion. Ninety percent of patients with reperfusion attained a maximum T wave negativity of 3 mm or more within 48 hours after the onset of chest pain in the lead that initially displayed the greatest ST segment elevation. Seventy-six percent of patients without reperfusion attained a maximum negativity of 2 mm or less within 72 hours. Thus, like the ST segment, accelerated evolution and deepening of the T wave may be noninvasive markers of reperfusion.

CONCLUSIONS
First, premature reconcordancy of the ST segment and T wave after acute myocardial infarction is a sensitive, reasonably specific, and easily recognizable ECG manifestation of postinfarction regional pericarditis. Second, reperfusion is associated with accelerated evolution and deepening of the T waves following acute myocardial infarction.
Slow conduction in the infarcted human heart. 'Zigzag' course of activation.
Authors: de Bakker J M , van Capelle F J , Janse M J , Tasseron S , Vermeulen J T , de Jonge N , Lahpor J R 
Published: June 2012

BACKGROUND
Ventricular tachycardias occurring in the chronic phase of myocardial infarction are caused by reentry. Areas of slow conduction, facilitating reentry, are often found in the infarcted zone. The purpose of this study was to elucidate the mechanism of slow conduction in the chronic infarcted human heart.

METHODS AND RESULTS
Spread of activation was studied in infarcted papillary muscles from hearts of patients who underwent heart transplantation because of infarction. Recordings were carried out on 10 papillary muscles that were superfused in a tissue bath. High-resolution mapping was performed in areas revealing slow conduction. Activation delay between sites perpendicular to the fiber direction and 1.4 mm apart could be as long as 45 milliseconds. Analysis of activation times revealed that activation spread in tracts parallel to the fiber direction. Conduction velocity in the tracts was between 0.6 and 1 m/s. Although tracts were separated from each other over distances up to 8 mm, they often connected with each other at one or more sites, forming a complex network of connected tracts. In this network, wave fronts could travel perpendicular to the fiber direction. Separation of tracts was due to collagenous septa. At sites where tracts were interconnected, the collagenous barriers were interrupted.

CONCLUSIONS
Slow conduction perpendicular to the fiber direction in infarcted myocardial tissue is caused by a "zigzag" course of activation at high speed. Activation proceeds along pathways lengthened by branching and merging bundles of surviving myocytes ensheathed by collagenous septa.
Height and incidence of cardiovascular disease in male physicians.
Authors: Hebert P R , Rich-Edwards J W , Manson J E , Ridker P M , Cook N R , O'Connor G T , Buring J E , Hennekens C H 
Published: June 2012

BACKGROUND
An inverse association between height and risk of coronary heart disease (CHD) has been reported in several case-control and cohort studies, but the reasons for the association remain uncertain. We evaluated this association among 22,071 male physicians, a population homogeneous for high educational attainment and socioeconomic status in adulthood.

METHODS AND RESULTS
The study population was comprised of participants in the Physicians' Health Study, a randomized, double-blind, placebo-controlled trial of low-dose aspirin and beta-carotene in the primary prevention of cardiovascular disease and cancer among US male physicians, aged 40 to 84 years, in 1982. Participants were classified into five height categories at study entry, from shortest to tallest, and were followed an average of 60.2 months to determine the incidence of myocardial infarction (MI), stroke, and death from cardiovascular disease. Men in the tallest (> or = 73 in. or 185.4 cm) compared with the shortest (< or = 67 in. or 170.2 cm) height category had a 35% lower risk of MI (relative risk, 0.65; 95% confidence interval, 0.44 to 0.99; P = .04), after adjusting for known cardiovascular risk factors. Further, a marginally significant inverse trend (P trend = .05) across the height categories was observed. Although the relationship was not strictly linear, for every inch of added height, there was an approximate 2% to 3% decline in risk of MI. In contrast, men in the tallest compared with the shortest height category had only small and nonsignificant decreases in risk of stroke and cardiovascular death. While no significant trend in risks of these end points across the height categories was observed, the numbers of events for these end points were far less than for MI, and thus the confidence intervals were wide.

CONCLUSIONS
These data indicate that height is inversely associated with subsequent risk of MI. At this time, a few mechanisms are plausible, but none are convincing. Other epidemiological and basic research efforts are needed to explore a variety of physiological correlates of height that may be responsible for mediating the height-MI association. In the meantime, while height is not modifiable, it is easy to measure and may be useful to evaluate CHD disease risk profiles and target lifestyle interventions.
Angiographic-pathologic correlations after elective percutaneous transluminal coronary angioplasty.
Authors: Naruko T , Ueda M , Becker A E , Tojo O , Teragaki M , Takeuchi K , Takeda T 
Published: June 2012

BACKGROUND
The local effect of coronary angioplasty is evaluated on the basis of postangioplasty angiograms. Smooth-walled dilation is considered to represent minimal or no injury, whereas intraluminal haziness corresponds with wall laceration. This study correlates the preangioplasty and postangioplasty angiograms with the histopathology of the target sites.

METHODS AND RESULTS
The study includes 12 patients, each undergoing an elective procedure, and covers 19 angioplasty sites. Smooth-walled dilation and intraluminal haziness were not mutually exclusive. The angiograms were interpreted as smooth-walled dilation (n = 3), smooth-walled dilation with intraluminal haziness (n = 4), intraluminal and extraluminal haziness (n = 5), extraluminal dissection (n = 5), spiraltype dissection (n = 1), and aneurysm (n = 1). The histology of the arterial segments revealed wall laceration in all. Smooth-walled dilation without intraluminal haziness correlated with laceration limited to the intima in two, but with medial injury in one. Smooth-walled dilation with intraluminal haziness correlated with laceration limited to the intima in two and with medial injury in two. Intraluminal and extraluminal haziness corresponded with extensive laceration with deep involvement of the media in each. Extraluminal dissection correlated with a dissection along the shoulder area of the plaque, creating a broad-based flap. The spiral-type dissection corresponded with a true dissection into the plaque-free media. The aneurysm correlated with partial washout of an atherosclerotic plaque.

CONCLUSIONS
The angiographic image of intraluminal and extraluminal haziness indicates extensive medial laceration. Smooth-walled dilation, with or without intraluminal haziness, is not a reliable indicator. The study emphasizes the need to reconsider the interpretations of postangioplasty coronary angiograms.
Alterations of heart rate and of heart rate variability after radiofrequency catheter ablation of supraventricular tachycardia. Delineation of parasympathetic pathways in the human heart.
Authors: Kocovic D Z , Harada T , Shea J B , Soroff D , Friedman P L 
Published: June 2012

BACKGROUND
Persistent inappropriate sinus tachycardia has been reported as a complication after radiofrequency (RF) ablation of the fast atrioventricular (AV) nodal pathway. The purpose of this study was to evaluate the prevalence of this complication and its mechanism using heart rate variability analysis.

METHODS AND RESULTS
Time and frequency domain analysis of heart rate was performed in the electrophysiology laboratory immediately before and immediately after RF ablation in 64 patients with supraventricular tachycardia. Ablation targets in these 64 patients included the fast AV nodal pathway (n = 3), the slow AV nodal pathway (n = 14), a posteroseptal accessory pathway (n = 23), and a left lateral accessory pathway (n = 24). A control group of 21 patients undergoing diagnostic study but not ablation underwent identical analysis immediately before and at the conclusion of their procedure. Patients undergoing ablation also had time and frequency domain analysis performed on ambulatory 24-hour Holter tapes recorded before ablation and at 1 day, 1 month, and 6 months after ablation. Compared with preablation values, time domain analysis immediately after ablation revealed a significant increase in mean heart rate and significant reductions in heart rate variability expressed as SD, MSSD, and PNN50 in patients undergoing AV nodal modification or posteroseptal accessory pathway ablation. Frequency domain analysis revealed marked attenuation of high frequency (0.15 to 0.40 Hz) components, indicating parasympathetic denervation. These acute changes were not seen after ablation of left lateral accessory pathways or after diagnostic study without ablation. Time and frequency domain analysis of 24-hour ambulatory Holter monitors performed serially after ablation revealed resolution of abnormalities of heart rate and of heart rate variability 1 to 6 months after ablation, with reappearance of the high frequency parasympathetic component suggestive of reinnervation.

CONCLUSIONS
RF ablation in the anterior, mid, and posterior regions of the low interatrial septum may disrupt preganglionic or postganglionic parasympathetic fibers located in these regions that are destined to innervate the sinus node. Such fibers become more scarce along the left AV groove with increasing distance from the posteroseptal space. Parasympathetic denervation may be one mechanism for persistent inappropriate sinus tachycardia after RF ablation.
Cellular electrophysiological effects of hyperthermia on isolated guinea pig papillary muscle. Implications for catheter ablation.
Authors: Nath S , Lynch C , Whayne J G , Haines D E 
Published: June 2012

BACKGROUND
The primary mechanism of tissue injury by radiofrequency catheter ablation is presumed to be thermally mediated. However, the myocardial cellular electrophysiological effects of hyperthermia are not well characterized. We used an in vitro model of isolated guinea pig right ventricular papillary muscle to investigate the acute cellular electrophysiological effects of hyperthermia.

METHODS AND RESULTS
Excised guinea pig right ventricular papillary muscles were pinned in a high-flow tissue bath and superfused with Tyrode's solution at 37.0 +/- 0.5 degrees C. The superfusate temperature was rapidly changed to 38.0 to 56.0 degrees C for 60 seconds and then returned to 37.0 degrees C. Conventional microelectrodes were used to measure membrane potential (Vm), maximum rate of rise of the action potential (dV/dtmax), and action potential (AP) amplitude and AP duration at 50% (APD50) and 90% (APD90) repolarization. Hyperthermia resulted in (1) a progressive depolarization of Vm at temperatures > or = 40.0 degrees C, which became more prominent at temperatures > or = 45.0 degrees C; (2) changes in the AP characterized by a temperature-dependent increase in dV/dtmax and a temperature-dependent decrease in AP amplitude, APD50, and APD90; (3) reversible loss of cellular excitability within a temperature range of 42.7 to 51.3 degrees C (median, 48.0 degrees C); (4) irreversible loss of cellular excitability and tissue injury at temperatures > or = 50.0 degrees C; and (5) the development of abnormal automaticity at temperatures > 45.0 degrees C.

CONCLUSIONS
Hyperthermia causes significant changes in myocardial cellular electrophysiological properties that include membrane depolarization, reversible and irreversible loss of excitability, and abnormal automaticity. There appear to be specific temperature ranges for reversible and irreversible electrophysiological changes. These observations may have important implications for tissue temperature monitoring during radiofrequency catheter ablation.
Electrophysiological mechanisms in a canine model of erythromycin-associated long QT syndrome.
Authors: Rubart M , Pressler M L , Pride H P , Zipes D P 
Published: June 2012

BACKGROUND
Erythromycin is known to prolong ventricular repolarization and has been associated with the occurrence of torsades de pointes. In this study, we have investigated potential mechanisms in vivo and in vitro for induction of an acquired long QT syndrome by erythromycin.

METHODS AND RESULTS
Ventricular electrograms and endocardial monophasic action potentials were recorded in anesthetized open-chest dogs before and after administration of 40 to 120 mg/kg of erythromycin lactobionate. Conventional microelectrode techniques were used to record transmembrane action potentials in isolated dog Purkinje fibers and papillary muscles. Erythromycin at concentrations > 20 mg/L prolonged action potential duration. At higher concentrations (100 to 200 mg/L), erythromycin induced phase 2 and phase 3 early afterdepolarizations (EADs) both in vivo and in vitro. The effects of erythromycin on repolarization were more marked in Purkinje fibers than in papillary muscle. Pretreatment of Purkinje fibers with erythromycin antagonized the effects of dofetilide, a selective delayed-rectifier potassium channel (IK) blocker. Pretreatment with prazosin or tetrodotoxin had no effect on erythromycin-induced changes in action potential duration.

CONCLUSIONS
These pharmacological studies suggest that erythromycin prolongs repolarization to a large extent by block of IK. In turn, prolongation of action potential duration resulting from erythromycin's actions on IK may promote the development of EADs. The induction of ventricular arrhythmias observed clinically after exposure to erythromycin may be related to the development of EADs. The rarity of occurrence of ventricular arrhythmias suggests that other predisposing factors contribute to the acquired long QT syndrome associated with erythromycin.
Diminished contractile response to increased heart rate in intact human left ventricular hypertrophy. Systolic versus diastolic determinants.
Authors: Liu C P , Ting C T , Lawrence W , Maughan W L , Chang M S , Kass D A 
Published: June 2012

BACKGROUND
Experimental studies indicate that in addition to diastolic dysfunction, hypertrophied myocardium can display depressed contractile responses, particularly at rapid heart rates, compounding reserve limitations. This study tests whether such abnormalities exist in intact human subjects at physiological paced rates and, if so, whether they are linked to simultaneous rate-dependent deterioration in diastolic function.

METHODS AND RESULTS
Ten subjects with left ventricular hypertrophy (LVH) and 8 normal control subjects were studied. Most LVH patients presented with dyspnea and/or pulmonary edema and had concentric hypertrophy. Since rapid pacing simultaneously alters cardiac filling volumes and pressures, pressure-volume relation analysis was used to better define changes in contractile response. Patients were instrumented with a conductance catheter and micromanometer for pressure-volume data recording and a balloon occluder at the right atrial-inferior vena caval junction to vary filling and thus generate function relations. Data were obtained at baseline and at three atrial pacing rates (100, 120, 150 min-1). In addition, single-beat force-interval data were used to indirectly examine calcium cycling kinetics. LVH subjects demonstrated baseline diastolic abnormalities, including prolonged relaxation, elevated end-diastolic pressure, and reduced chamber compliance. However, systolic function was similar to that in control subjects. With rapid pacing, normal subjects displayed a positive contractile response, whereas this was markedly diminished in LVH subjects. With abrupt termination of pacing and return to slower sinus rhythm, LVH subjects displayed greater initial potentiation followed by a more rapid decline than control subjects, suggesting abnormalities of calcium handling. Despite contractile abnormalities, diastolic function did not further deteriorate with rapid pacing and thus did not appear to be tightly linked to the systolic changes.

CONCLUSIONS
Pacing stress in intact human LVH can result in systolic impairment superimposed on preexisting but not worsened diastolic dysfunction. Abnormal calcium handling probably contributes prominently to this response.