bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of left ventricular segmental wall motion in hypertrophic cardiomyopathy with myocardial tagging.
Authors: Maier S E , Fischer S E , McKinnon G C , Hess O M , Krayenbuehl H P , Boesiger P 
Published: June 2012

BACKGROUND
Segmental wall motion was assessed noninvasively in eight patients with hypertrophic cardiomyopathy and six healthy volunteers by magnetic resonance myocardial tagging.

METHODS AND RESULTS
Localization scans were performed for determination of the true short-axis views of the left ventricle (double-angulated view). Spatial modulation of magnetization was used to produce a rectangular grid of landmarks. Distortion of the grid was assessed at end diastole, mid systole, and end systole with multiphase gradient echoes. Image sets were acquired at three different planes, namely, the base, the equator, and the apex. Quantitative evaluation was carried out by computer-assisted image analysis. Each individual grid crossing point was identified automatically and the displacement calculated. A polar coordinate system with the center of gravity as motion reference point was chosen to assess fractional rotation and radial displacement at the endocardial, midwall, and epicardial layers of the septal, anterior, posterior, and inferior regions. A wringing motion of the left ventricle with a clockwise rotation of 5.0 +/- 2.4 degrees at the base and a counterclockwise rotation of -9.6 +/- 2.9 degrees at the apex was observed in control subjects. An equal rotation of 5.0 +/- 2.5 degrees at the base and a slightly reduced rotation of -7.3 +/- 5.2 degrees at the apex was found in patients with hypertrophic cardiomyopathy. A transmural gradient in fractional rotation and radial displacement was observed, with the highest values in the endocardial layer. Rotation in patients with hypertrophic cardiomyopathy was significantly less than in normal volunteers in the posterior region of the equatorial and apical planes. Furthermore, radial displacement was significantly reduced in the septum and inferior wall. In the anterior and posterior wall segments, a reduction of the radial displacement was observed only in the epicardium and midwall layers.

CONCLUSIONS
Magnetic resonance myocardial tagging allows the noninvasive assessment of regional wall motion. Both in normal volunteers and in patients with hypertrophic cardiomyopathies, cardiac motion occurs in a complex mode, with the base and the apex rotating in opposite directions and the equatorial plane as a transitional zone (wringing motion). A reduced cardiac rotation can be observed in patients with hypertrophic cardiomyopathy mainly in the posterior region, whereas a reduced radial displacement is found in the inferior septal zone.
Response of nonreentrant catecholamine-mediated ventricular tachycardia to endogenous adenosine and acetylcholine. Evidence for myocardial receptor-mediated effects.
Authors: Lerman B B 
Published: June 2012

BACKGROUND
Reentrant ventricular tachycardia (VT) is known to be insensitive to the nucleoside adenosine. However, we have previously identified a form of nonreentrant, catecholamine-mediated VT that can be initiated with rapid pacing, demonstrates cycle length dependence, and is sensitive to exogenous adenosine as well as to the Valsalva maneuver. The mechanism of this tachycardia is thought to be due to a catecholamine-induced, cAMP-mediated increase in intracellular calcium, resulting in delayed afterdepolarizations and triggered activity. The antiarrhythmic effects of exogenous adenosine and Valsalva on this form of VT may be due to receptor-mediated inhibition of adenylate cyclase or to noncardiac receptor-mediated effects, i.e., exogenous adenosine may modulate VT through alterations in autonomic tone by activation of arterial chemoreceptors, and Valsalva has been shown to decrease venous return, resulting in a reduction in cardiac dimensions and myocardial stretch. To clarify this issue and circumvent both autonomic and noncardiac receptor effects, the response of nonreentrant catecholamine-mediated VT to endogenous adenosine and acetylcholine was evaluated.

METHODS AND RESULTS
Group 1 (n = 8): Dipyridamole (0.56 mg/kg i.v.), a nucleoside transport blocker that potentiates the effects of endogenous adenosine, reproducibly abolished sustained nonreentrant, nonautomatic, catecholamine-mediated VT in the five patients in whom it was evaluated. VT recurred with the addition of aminophylline, a competitive adenosine A1-receptor antagonist. Edrophonium (10 mg i.v.), a cholinesterase inhibitor that potentiates the effects of acetylcholine at the muscarinic cholinergic receptor, terminated VT in four of four patients, an effect that was reversed by atropine. Group 2 (n = 6): In patients with reentrant VT, dipyridamole and edrophonium had no effect on VT cycle length or duration. Group 3 (n = 4): Adenosine and vagal maneuvers had no effect on catecholamine-mediated VT caused by automaticity in three of four patients tested. In one patient, adenosine transiently suppressed VT (< 5 seconds), after which it spontaneously resumed.

CONCLUSIONS
The results of this study further delineate the mechanism of a newly recognized form of clinical VT. It can be identified by termination of the tachycardia in response to activation of the adenosine A1 or muscarinic cholinergic receptor, which results in inhibition of adenylate cyclase. These receptor-mediated effects appear to be specific for identifying nonreentrant, nonautomatic, catecholamine-mediated VT.
Hemodynamic and autonomic nervous system responses to mixed meal ingestion in healthy young and old subjects and dysautonomic patients with postprandial hypotension.
Authors: Lipsitz L A , Ryan S M , Parker J A , Freeman R , Wei J Y , Goldberger A L 
Published: June 2012

BACKGROUND
Although postprandial hypotension is a common cause of falls and syncope in elderly persons and in patients with autonomic insufficiency, the pathophysiology of this disorder remains unknown.

METHODS AND RESULTS
We examined the hemodynamic, splanchnic blood pool, plasma norepinephrine (NE), and heart rate (HR) power spectra responses to a standardized 400-kcal mixed meal in 11 healthy young (age, 26 +/- 5 years) and nine healthy elderly (age, 80 +/- 5 years) subjects and 10 dysautonomic patients with symptomatic postprandial hypotension (age, 65 +/- 16 years). Cardiac and splanchnic blood pools were determined noninvasively by radionuclide scans, and forearm vascular resistance was determined using venous occlusion plethysmography. In healthy young and old subjects, splanchnic blood volume increased, but supine blood pressure remained unchanged after the meal. In both groups, HR increased and systemic vascular resistance remained stable. Forearm vascular resistance and cardiac index increased after the meal in elderly subjects, whereas these responses were highly variable and of smaller magnitude in the young. Young subjects demonstrated postprandial increases in low-frequency HR spectral power, representing cardiac sympatho-excitation, but plasma NE remained unchanged. In elderly subjects, plasma NE increased after the meal but without changes in the HR power spectrum. Patients with dysautonomia had a large postprandial decline in blood pressure associated with no change in forearm vascular resistance, a fall in systemic vascular resistance, and reduction in left ventricular end diastolic volume index. HR increased in these patients but without changes in plasma NE or the HR power spectrum.

CONCLUSIONS
1) In healthy elderly subjects, the maintenance of blood pressure homeostasis after food ingestion is associated with an increase in HR, forearm vascular resistance, cardiac index, and plasma NE. In both young and old, systemic vascular resistance is maintained. 2) Dysautonomic patients with postprandial hypotension fail to maintain systemic vascular resistance after a meal. This impairment in vascular response to meal ingestion may underlie the development of postprandial hypotension. 3) The measurement of mean HR or plasma NE does not adequately characterize autonomic cardiac control. Power spectral analysis suggests an impairment in the postprandial autonomic modulation of HR in healthy elderly and dysautonomic subjects, possibly predisposing to hypotension when vascular compensation is inadequate.
Evaluation of the role of polymorphonuclear leukocytes on contractile function in myocardial reperfusion injury. Evidence for plasma-mediated leukocyte activation.
Authors: Shandelya S M , Kuppusamy P , Weisfeldt M L , Zweier J L 
Published: June 2012

BACKGROUND
It has been hypothesized that chemotaxis and activation of polymorphonuclear leukocytes (PMNs) occur upon reperfusion of ischemic myocardium. Questions remain, however, regarding the mechanisms by which PMNs are chemotaxed and activated and how this process causes contractile failure.

METHODS AND RESULTS
Studies were performed in an isolated rat heart model in which the effects of isolated cellular or humoral factors could be studied. Isolated rat hearts were perfused by the method of Langendorff, subjected to 20 minutes of global ischemia, and reperfused with perfusate alone or with perfusate containing PMNs, plasma, PMNs plus plasma, or PMNs plus inactivated plasma (preheated to 56 degrees C for 30 minutes to denature complement) (n = 10 in each group). Left ventricular developed pressure (LVDP) was measured during 1 minute of preischemic control infusion and on reflow after a 20-minute period of global ischemia. Additional measurements of free-radical generation were also performed on the coronary effluent by electron paramagnetic resonance spectroscopy (EPR) with the spin trap 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO). During control infusion, no significant alterations in LVDP were observed, and there was no measurable free-radical generation. Reperfusion with plasma or PMNs alone did not alter postischemic LVDP, whereas plasma and PMNs together caused marked injury. LVDP after 45 minutes of reflow with PMNs plus plasma was 31.9 +/- 6.1% of control compared with 60.6 +/- 9.9% with plasma, 64.5 +/- 8.8% with PMNs, and 63.6 +/- 7.2% with perfusate alone (p < 0.01). With plasma, which was preheated to deplete complement, this injury was not seen; LVDP was 70.8 +/- 10.9%. EPR measurements with the spin trap DMPO in the absence of PMNs demonstrated that oxygen free-radical generation is observed only during the first 1-2 minutes of reflow. Upon reperfusion with PMNs and plasma, however, radical generation persisted for more than 10 minutes. Increased neutrophil accumulation was observed in the postischemic heart in the absence of plasma; however, plasma factors were required for neutrophil-mediated contractile failure. C5a alone did not cause significant injury, but in the presence of PMNs it effectively substituted for plasma, causing marked injury.

CONCLUSIONS
Thus, plasma factors, most likely complement, are required for neutrophil activation with oxygen free-radical generation and secondary contractile dysfunction.
Flecainide-induced arrhythmia in canine ventricular epicardium. Phase 2 reentry?
Authors: Krishnan S C , Antzelevitch C 
Published: June 2012

BACKGROUND
We recently reported that sodium channel block can produce opposite effects on action potential duration (APD) and refractoriness in epicardial versus endocardial tissues of the canine ventricle. In addition, strong sodium channel current inhibition was found to cause loss of the action potential dome in epicardium but not endocardium, thus inducing a marked dispersion of repolarization and refractoriness between epicardium and endocardium as well as among neighboring epicardial sites. The marked heterogeneity that evolves under these conditions provides a substrate for the development of arrhythmias. Flecainide was found to induce extrasystolic activity more readily than other sodium blockers. The present study contrasts the electrophysiological actions of flecainide in canine ventricular epicardium and endocardium and examines the characteristics of flecainide-induced arrhythmias in epicardial sheets of canine ventricle.

METHODS AND RESULTS
Standard microelectrode techniques were used. Flecainide (10-20 microM) produced either prolongation or marked abbreviation of APD in epicardium but only minor changes in the APD of endocardium. Marked abbreviation of APD in epicardium was due to loss of the action potential dome (plateau phase). Arrhythmias displaying characteristics of reentry could be readily induced in flecainide-treated preparations either by increasing the stimulation rate or by introduction of extrastimuli. Flecainide-induced slowing of conduction, more accentuated at the faster stimulation rates, appeared to act synergistically with the drug-induced dispersion of repolarization to generate reentry in these relatively small sheets of epicardium. 4-Aminopyridine, a transient outward current (Ito) blocker, reversed the flecainide-induced marked abbreviation of APD in epicardium and abolished reentrant activity in all cases. Flecainide failed to induce reentry in preparations pretreated with 4-aminopyridine.

CONCLUSIONS
Our data suggest that the presence of a prominent Ito in epicardium contributes the development of marked electrical heterogeneity in the ventricle after exposure to flecainide. Flecainide-induced dispersion of repolarization, especially when accompanied by prominent conduction delays, results in extrasystolic activity via a mechanism that we have termed "phase 2 reentry." Our results also suggest a role for Ito blockers in the treatment of reentrant arrhythmias.
Interaction between thromboxane A2 and 5-hydroxytryptamine receptor subtypes in human coronary arteries.
Authors: Chester A H , Allen S P , Tadjkarimi S , Yacoub M H 
Published: June 2012

BACKGROUND
Platelets release two powerful vasoconstrictors--thromboxane A2 (TXA2) and 5-hydroxytryptamine (5-HT). Animal studies have suggested that these two substances may act in a synergistic fashion to stimulate platelet activity and smooth muscle vasoconstriction.

METHODS AND RESULTS
To assess the interaction between TXA2 and 5-HT at the individual 5-HT receptor subtypes reported to mediate contraction, the effect of the amine was determined in the presence of differing concentrations of the thromboxane mimetic U46619. A total of 168 vessel segments were removed from 20 recipient hearts of patients undergoing cardiac transplantation. Segments were set up in isolated organ baths and tested for their response to 5-HT in the presence of an EC10, EC30, or EC50 concentration of U46619 (n = 4). A synergistic response was only seen in a small number of the segments tested under these conditions. However, in the presence of ketanserin (10(-6) M) to block 5-HT2 receptors, there was a significant increase in the response to 10(-6) M 5-HT in the presence of both the EC30 (p < 0.025) and EC50 (p < 0.05) concentrations of U46619 (n = 4). The potentiation of non-5-HT2 receptor mediated responses to 5-HT, in the presence of U46619 (EC30), could be prevented by 10(-7) M methiothepin, a nonselective 5-HT1-like/5-HT2 receptor antagonist.

CONCLUSIONS
These data indicate that TXA2 receptor activation can increase the response of 5-HT mediated by 5-HT1-like receptors in human coronary arteries. 5-HT1-like receptors have been shown to mediate the contractile effect of 5-HT in patients with variant and chronic stable angina. Thus, platelet contents may act together at specific receptor subtypes in the induction of myocardial ischemia.
Loss of myocardial protection after preconditioning correlates with the time course of glycogen recovery within the preconditioned segment.
Authors: Wolfe C L , Sievers R E , Visseren F L , Donnelly T J 
Published: June 2012

BACKGROUND
Although previous investigators have demonstrated that myocardial preconditioning reduces infarct size, the mechanisms of cardioprotection associated with preconditioning are not completely understood.

METHODS AND RESULTS
To test the hypothesis that preconditioning (four 5-minute episodes of ischemia each followed by 5 minutes of reperfusion) reduces infarct size by depleting cardiac glycogen stores and attenuating the degree of intracellular acidosis during subsequent prolonged left coronary artery occlusion, preconditioned and control rats were subjected to 45 minutes of left coronary artery occlusion and 120 minutes of reflow immediately after preconditioning (groups 1P and 1C, respectively) or after 30 minutes (groups 2P+30m and 2C), 1 hour (groups 3P+60m and 3C), or 6 hours (groups 4P+360m and 4C) of nonischemic recovery after preconditioning but before prolonged ischemia. In each group, cardiectomy was performed in selected rats immediately before prolonged ischemia for cardiac glycogen assay. In selected animals, 31P magnetic resonance spectroscopy was performed to monitor intracellular pH and measure high-energy phosphate levels during ischemia and reperfusion. Group 1P rats demonstrated marked glycogen depletion after preconditioning compared with controls (0.72 +/- 0.39 [n = 9] versus 5.67 +/- 1.73 [n = 12] mg glucose/g wet wt; p < 0.001 versus group 1C) that was associated with attenuation of intracellular acidosis during ischemia, as measured by 31P magnetic resonance spectroscopy (6.8 +/- 0.3 [n = 11] versus 6.2 +/- 0.3 [n = 9] pH units; p < 0.01), and marked infarct size reduction (0.3 +/- 0.6% [n = 7] versus 38.1 +/- 11.3% [n = 7], infarct size divided by risk area; p < 0.0001). During ischemia, there were no differences in myocardial ATP or phosphocreatine levels or in any hemodynamic determinant of myocardial oxygen demand between groups 1P and 1C. In preconditioned rats that were allowed to recover before ischemia (groups 2P+30m, 3P+60m, and 4P+360m), the time course of glycogen repletion paralleled the loss of protection from ischemic injury.

CONCLUSIONS
Glycogen depletion and the attenuation of intracellular acidosis during ischemia appear to be important factors in delaying irreversible injury and reducing infarct size in this animal model of myocardial preconditioning.
Overdrive stimulation of functional reentrant circuits causing ventricular tachycardia in the infarcted canine heart. Resetting and entrainment.
Authors: Waldecker B , Coromilas J , Saltman A E , Dillon S M , Wit A L 
Published: June 2012

BACKGROUND
Clinical electrophysiology studies have used, for the most part, models of anatomic reentrant circuits to explain entrainment of ventricular tachycardia. Our studies use activation maps to directly determine mechanisms of entrainment of functional circuits that cause tachycardia.

METHODS AND RESULTS
Electrograms were recorded from 192 sites on reentrant circuits in the epicardial border zone of canine myocardial infarcts during sustained ventricular tachycardia. Overdrive stimulation from different sites and at different cycle lengths was investigated. The reentrant circuits were shown to be functional, yet stimulated impulses could enter and repetitively reset the circuits (entrainment), demonstrating the presence of an excitable gap. Entrainment could occur from different stimulation sites with the stimulated impulses from each site activating the circuit with a different pattern. Entrainment, however, did not occur when the stimulated wave fronts obliterated the lines of functional block in the circuit. Fusion on the ECG occurred during entrainment when the stimulated impulses activated the ventricles concurrently with a previous stimulated impulse leaving the reentrant circuit at a different site. The first postpacing QRS was captured but not fused because it was caused by the last stimulated impulse emerging from the circuit. The first postpacing cycle length on the ECG was either equal to or longer than the overdrive cycle length depending on whether there was a fusion QRS during overdrive. The first postpacing cycle length at sites in the reentrant circuit equaled the pacing cycle length. At an appropriately short overdrive cycle length, stimulated impulses blocked in the circuit to terminate reentry.

CONCLUSIONS
Functional reentrant circuits causing ventricular tachycardia can be reset and entrained. Activation maps directly show the mechanisms.
Morphological determinants of echocardiographic patterns of mitral valve systolic anterior motion in obstructive hypertrophic cardiomyopathy.
Authors: Klues H G , Roberts W C , Maron B J 
Published: June 2012

BACKGROUND
The morphological determinants of mitral valve systolic anterior motion (SAM) and obstruction to left ventricular outflow in patients within the broad clinical spectrum of hypertrophic cardiomyopathy (HCM) are not completely understood, particularly the contribution of mitral leaflet length and size.

METHODS AND RESULTS
To clarify this issue, mitral valve specimens from 43 patients with HCM and basal outflow obstruction were used to relate morphometric measurements of leaflet area to certain morphological and functional assessments of left ventricular outflow tract geometry and valvular motion obtained from echocardiograms in the same patients. Twenty-four patients (56%) had mitral valves of normal size (leaflet area < 12.0 cm2) and 19 patients (44%) had enlarged and elongated valves (area > or = 12.0 cm2). Compared with normal-sized mitral valves, the enlarged valves were situated more posteriorly in a larger left ventricular outflow tract (cross-sectional area, 3.3 +/- 1.0 versus 1.9 +/- 0.7 cm2 for normal-sized valves; p < 0.001) and also had greater systolic excursion of the anterior leaflet (16.2 +/- 4.5 versus 13.3 +/- 3.3 mm, p < 0.02), usually with a distinctive sharp-angled bend and localized contact of the leaflet tip with ventricular septum ("typical" SAM); this pattern of SAM was possible because the central and distal portions of the leaflet were relatively free of fibrous thickening. In contrast, normal-sized mitral valves were situated more anteriorally in a smaller left ventricular outflow tract and frequently showed a different mechanism of SAM and subaortic obstruction with relatively limited leaflet motion, absence of a sharp bend, and septal contact involving more substantial portions of the anterior leaflet and contiguous chordae ("atypical" SAM); mitral-septal apposition was effected in large measure by posterior ventricular septal motion. This pattern of SAM was invariably associated with a more diffuse pattern of fibrous thickening.

CONCLUSIONS
Patients with obstructive HCM show patterns of mitral valve SAM that are diverse and determined largely by the interrelation of left ventricular outflow tract geometry, the size and mobility of the mitral leaflets, and the presence and distribution of fibrous thickening.