bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of beta-adrenergic stimulation with dobutamine on isovolumic relaxation in the normal and failing human left ventricle.
Authors: Parker J D , Landzberg J S , Bittl J A , Mirsky I , Colucci W S 
Published: June 2012

BACKGROUND
We tested the hypothesis that beta-adrenergic receptor-stimulated acceleration of left ventricular (LV) isovolumic relaxation (i.e., positive lusitropic response) is attenuated in patients with severe congestive heart failure (CHF) compared with patients without LV dysfunction or CHF.

METHODS AND RESULTS
The beta-adrenergic agonist dobutamine was infused by the intracoronary route in 14 subjects (normal group, six; CHF patients, eight) and by the intravenous route in a second group of 14 subjects (normal group, four; CHF patients, 10). The positive inotropic response to intracoronary or intravenous dobutamine was substantially and significantly reduced in the patients with CHF. LV isovolumic relaxation rate was determined by the methods of Weiss (TL), Mirsky (T1/2), and by a nonlinear regression technique (TNL). LV isovolumic relaxation assessed by all three methods was significantly prolonged in CHF patients compared with normal subjects. Intracoronary and intravenous infusions of dobutamine caused significant acceleration of LV isovolumic relaxation in both normal subjects and patients with CHF. The magnitude of the dobutamine-stimulated acceleration of isovolumic relaxation in patients with CHF was comparable with that in normal subjects.

CONCLUSIONS
These data demonstrate that beta-adrenergic receptor stimulation causes significant acceleration of LV isovolumic relaxation in both normal subjects and patients with severe CHF. Coronary to our hypothesis, the lusitropic response to beta-adrenergic stimulation is well preserved in patients with severe CHF despite substantial attenuation of the beta-adrenergic positive inotropic response. These findings have potentially important implications regarding the physiology and pharmacology of adrenergically mediated LV relaxation in humans.
Regional three-dimensional geometry and function of left ventricles with fibrous aneurysms. A cine-computed tomography study.
Authors: Lessick J , Sideman S , Azhari H , Marcus M , Grenadier E , Beyar R 
Published: June 2012

BACKGROUND
To assess the extent and nature of the dysfunction surrounding aneurysms of the left ventricle (LV), we examined the parameters of local and global three-dimensional shape, size, and function of LVs of eight patients with histologically confirmed anterior fibrous aneurysms.

METHODS AND RESULTS
Three-dimensional reconstructions of each LV were made from 10-12 short-axis fast cine-angiographic computed tomography (cine-CT) slices encompassing the entire heart at end diastole and end systole. Regional three-dimensional wall thickness, thickening, motion, curvature, and stress index were calculated for 84 elements encompassing the entire LV. The aneurysmal border was defined by a sharp decrease in end-diastolic wall thickness and separated the LV into an aneurysmal zone and a normal zone that was further divided into adjacent normal (AN) and remote normal (RN) zones. As expected, thickening was negligible in both the aneurysmal and the border zones. Although both the AN and the RN zones had normal wall thickness (1.05 +/- 0.20 and 1.09 +/- 0.20 cm, respectively), thickening was depressed in the AN (0.22 +/- 0.08 cm) but not the RN (0.44 +/- 0.19 cm) zones. The size of the dysfunction zone (defined as less than 2 mm thickening) was found to be considerably greater than the anatomic size of the aneurysm (60.9 +/- 13.7% versus 33.6 +/- 7.6% of the left ventricular endocardial area, respectively; p less than 0.001). In addition, the AN zone had a smaller curvature and a higher stress index than the RN zone.

CONCLUSIONS
LVs with fibrous aneurysms are characterized by a relatively large region of nonfunction that encompasses the thin aneurysmal area and its transitional border zone, a normally functioning remote zone, and an intermediate region of normal wall thickness but with reduced function, which may be attributed to its low curvature and high stress index.
Relation of risk factor levels in young adulthood to parental history of disease. The CARDIA study.
Authors: Burke G L , Savage P J , Sprafka J M , Selby J V , Jacobs D R , Perkins L L , Roseman J M , Hughes G H , Fabsitz R R 
Published: June 2012

BACKGROUND
The relation between self-reported parental disease and risk factor levels was examined in 2,637 black and 2,478 white men and women aged 18-30 years at the Coronary Artery Risk Development in Young Adults (CARDIA) Study baseline examination (1985-1986).

METHODS AND RESULTS
The prevalence of parental disease (at least one parent) in white versus black participants was 44% and 56% for hypertension, 47% and 44% for obesity, 16% and 13% for myocardial infarction, 11% and 17% for diabetes, and 6% and 10% for stroke, respectively. Among these young adults, parental hypertension was associated with higher sex- and age-adjusted systolic and diastolic blood pressure levels. Parental myocardial infarction was associated with higher plasma cholesterol, higher blood pressure levels, and lower high density lipoprotein cholesterol levels in white participants. Parental diabetes was associated with higher fasting blood glucose and insulin levels in all race-sex groups and with higher triglycerides and lower high density lipoprotein cholesterol in black participants only. Parental history of obesity was related to less favorable age- and sex-adjusted lipid levels in white participants and higher blood pressure levels in black participants. Parental history of stroke was associated with higher systolic blood pressure levels in black participants. In general, these differences across family history were predicted only in part by obesity. The prevalence of more than one disease reported in parents occurred more frequently than would have been expected due to chance alone.

CONCLUSIONS
These associations between parental disease and risk factors in their adult children probably reflects the impact of both environmental and genetic factors. Parental history may be a useful marker for high risk individuals.
Reentrant excitation around a fixed obstacle in uniform anisotropic ventricular myocardium.
Authors: Brugada J , Boersma L , Kirchhof C J , Heynen V V , Allessie M A 
Published: June 2012

BACKGROUND
The purpose of this study was to investigate the role of tissue anisotropy and dispersion of refractoriness on initiation of reentrant ventricular tachycardia (VT).

METHODS AND RESULTS
A ring of perfused uniform anisotropic ventricular epicardium in Langendorff-perfused rabbit hearts was created by an endocardial freezing technique. High-resolution mapping (248 channels) was used to analyze epicardial activation of the left ventricle. One to three premature beats were induced at a total of 272 points in 17 experiments (16 different points around the ring in each experiment). Reentrant VT could be initiated at 43 of the 272 points tested. The cycle length of VT was stable and ranged from 128 to 198 msec (mean, 161 +/- 19 msec). Correlation between conduction velocity and the angle between the circulating activation wave and epicardial fiber orientation showed that in segments of the ring where conduction was perpendicular to the fiber axis, mean conduction velocity was 25 +/- 5 cm/sec compared with 60 +/- 7 cm/sec when conduction was parallel to the fiber orientation. Analysis of the site of unidirectional conduction block showed that in 41 of 43 cases, block occurred while the impulse was propagating parallel to the fiber orientation. Measurement of the refractory periods at either side of the line of unidirectional block showed that only in 12 of 43 cases did block occur while the impulse was propagating into an area with a longer (more than 10 msec) refractory period.

CONCLUSIONS
In uniform anisotropic ventricular myocardium, reentrant VT is initiated because lowering the stimulating efficacy of the depolarization wave by premature beats leads to preferential conduction block parallel to the fiber orientation.
Proarrhythmic response to sodium channel blockade. Theoretical model and numerical experiments.
Authors: Starmer C F , Lastra A A , Nesterenko V V , Grant A O 
Published: June 2012

BACKGROUND
The use of flecainide and encainide was terminated in the Cardiac Arrhythmia Suppression Trial because of an excess of sudden cardiac deaths in the active treatment group. Such events might arise from reentrant rhythms initiated by premature stimulation in the presence of anisotropic sodium channel availability. Drugs that bind to sodium channels increase the functional dispersion of refractoriness by slowing (a result of the drug-unbinding process) the transition from an inexcitable state to an excitable state. It is interesting that encainide and flecainide unbind slowly (15-20 seconds), whereas lidocaine and moricizine unbind rapidly (0.2-1.3 seconds).

METHODS AND RESULTS
With a computer representation of a cable with Beeler-Reuter membrane properties, we found a small (6 msec) vulnerable window that occurred 338 msec after the last drive stimulus. Premature stimuli falling within the vulnerable window resulted in unidirectional block and reentrant activation. In the presence of a slowly unbinding drug, the window was delayed an additional 341 msec, and its duration was extended to 38 msec. The delay (antiarrhythmic effect) before the onset of the vulnerable window and its duration (proarrhythmic effect) were both dependent on the sodium channel availability and the recovery process. Both effects were also prolonged when sodium channel availability was reduced by membrane depolarization. Defining the proarrhythmic potential as the duration of the vulnerable window, we found that hypothetical use-dependent class I drugs have a greater proarrhythmic potential than non-use-dependent drugs.

CONCLUSIONS
The antiarrhythmic and proarrhythmic properties of pure sodium channel antagonists are both dependent on sodium channel availability. Consequently, the price for increased antiarrhythmic efficacy (suppressed premature ventricular contractions) is an increased proarrhythmic vulnerability to unsuppressed premature ventricular contractions.
Left ventricular regional relaxation and its nonuniformity in hypertrophic nonobstructive cardiomyopathy.
Authors: Hayashida W , Kumada T , Kohno F , Noda M , Ishikawa N , Kojima J , Himura Y , Kawai C 
Published: June 2012

BACKGROUND
Regional nonuniformity has been suggested to be closely related to left ventricular (LV) relaxation in diseased heart. The purpose of the present study was to assess LV global and regional relaxation in patients with nonobstructive hypertrophic cardiomyopathy (HCM).

METHODS AND RESULTS
Left ventriculography was conducted simultaneously with pressure micromanometry in 10 normal control subjects and 11 patients with nonobstructive HCM. LV silhouettes in the right anterior oblique projection were divided into eight regions, and regional wall stress during isovolumic relaxation was computed for six regions from the midventricle to the apex. In HCM patients, isovolumic relaxation time (IRT) and the time constant of LV pressure decrease (Tp) were greater than in control subjects (IRT, 84 +/- 13 versus 66 +/- 6 msec; Tp, 51 +/- 8 versus 36 +/- 5 msec, respectively; p less than 0.01). In HCM patients, the (-)dP/dt upstroke pattern was convex-downward, and dP/dt(20/60), the ratio of dP/dt values 20 and 60 msec after peak (-)dP/dt, was less than in control subjects (1.46 +/- 0.16 versus 2.15 +/- 0.14, p less than 0.01). These findings suggest that there is impaired LV relaxation in HCM patients. End-systolic regional wall stress was lower, and the time constant of regional stress decrease (Tst) was prolonged for each region in HCM patients compared with control subjects. In the HCM group, Tst tended to be more prolonged in regions with increased wall thickness than in regions with normal wall thickness (60 +/- 15 versus 50 +/- 11 msec, p less than 0.01). The coefficient of variation for Tst values in six areas of the left ventricle was calculated in each subject and was greater in HCM patients than in control subjects (13 +/- 7% versus 7 +/- 3%, p less than 0.05), indicating regional nonuniformity in Tst during isovolumic relaxation in HCM patients.

CONCLUSIONS
Significant correlations existed between the coefficients of variation for Tst and Tp (r = 0.80, p less than 0.01), IRT (r = 0.79, p less than 0.01), and dP/dt(20/60) (r = -0.67, p less than 0.05) in the HCM group. Thus, regional nonuniformity is closely related to the impairment of LV relaxation in HCM.
Body surface distribution of abnormally low QRST areas in patients with left ventricular hypertrophy. An index of repolarization abnormalities.
Authors: Hirai M , Hayashi H , Ichihara Y , Adachi M , Kondo K , Suzuki A , Saito H 
Published: June 2012

BACKGROUND
QRST isointegral maps (I-maps) have been useful in detecting repolarization abnormalities. We investigated the body surface distribution of abnormally low QRST areas in patients with left ventricular hypertrophy (LVH) and the relation of the abnormalities in I-map to the severity of LVH as assessed by echocardiography.

METHODS AND RESULTS
QRST area departure maps were constructed from electrocardiographic (ECG) data recorded in patients with LVH and precordial negative T waves resulting from aortic stenosis (AS) (10 patients), aortic regurgitation (AR) (12 patients), or hypertrophic cardiomyopathy (HCM) with asymmetric septal hypertrophy (22 patients). Fifty normal subjects served as controls. The I-map was constructed from 87 body surface electrocardiograms recorded simultaneously at a sampling interval of 1 msec. The area where the QRST area was smaller than normal limits (mean -2 SD) was designated the "-2 SD area." The echocardiographic left ventricular (LV) mass was calculated by Devereux's method. Patients with large LV masses due to AS or AR had 2 SD areas located over the left anterior chest or the midanterior chest, respectively. The 2 SD area was located over the left shoulder and left anterior chest and had a lingual shape in patients with HCM. The sum of QRST area values less than the normal range (sigma QRST) was significantly correlated with LV mass in patients with AS or AR (r = 0.83 and r = 0.69, p less than 0.01 and p less than 0.05). However, there was no significant correlation between sigma QRST and the severity of LVH in patients with HCM. sigma QRST divided by the number of electrodes in the 2 SD area was significantly greater in patients with HCM than in those with AS or AR.

CONCLUSIONS
These findings suggest that abnormalities in patients with HCM are manifest even in mild LVH and that there is a greater disparity of repolarization in hypertrophied left ventricles due to HCM than in LVH due to aortic valve disease. QRST isointegral departure maps may provide ECG evidence of LV mass of patients with AS or AR and of susceptibility to malignant arrhythmias in patients with HCM.
Importance of two-dimensional echocardiographic assessment of left ventricular systolic function in patients presenting to the emergency room with cardiac-related symptoms.
Authors: Sabia P , Abbott R D , Afrookteh A , Keller M W , Touchstone D A , Kaul S 
Published: June 2012

BACKGROUND
This prospective study was designed to test the hypothesis that the assessment of left ventricular systolic function at the time of emergency room (ER) presentation provides valuable diagnostic and prognostic information in patients with cardiac-related symptoms.

METHODS AND RESULTS
The study is based on a 2-year follow-up of 171 consecutive patients evaluated in the ER for such symptoms. In the course of follow-up, one third of the patients (55 of 171) suffered a major cardiac event. For those with left ventricular systolic dysfunction (LVSD), the age-adjusted rate of early events (occurring within 48 hours of presentation) was more than eight times higher than for those without LVSD (26.9% versus 3.3%, p less than 0.01). For events occurring after 48 hours of ER presentation, LVSD was associated with a nearly fourfold excess of cardiac events (23.9% versus 6.4%, p less than 0.01). Other than advanced age, the most important confounder for early events included an abnormal electrocardiogram diagnostic for acute myocardial infarction. Confounders for late events included advanced age and a history of hypertension. LVSD on two-dimensional echocardiography (2DE) was the only finding associated with early and late events after controlling for other risk factors. In addition, the prediction of these events derived from the combination of historical, clinical, electrocardiographic, and 2DE findings was significantly improved when accounting for the presence or absence of LVSD (p less than 0.01).

CONCLUSIONS
We conclude that the 2DE assessment of left ventricular systolic function provides valuable diagnostic and prognostic information in subjects presenting to the ER with cardiac-related symptoms.
Transvenous coronary ultrasound imaging. A novel approach to visualization of the coronary arteries.
Authors: Sudhir K , Fitzgerald P J , MacGregor J S , DeMarco T , Ports T A , Chatterjee K , Yock P G 
Published: June 2012

BACKGROUND
Catheter-based ultrasound is a new imaging modality to examine endovascular detail in the coronary circulation. This technique requires direct placement of the catheter in the arterial segment of interest.

METHODS AND RESULTS
We examined the feasibility of a less invasive approach by imaging the coronary arterial circulation by using a 5F (30 MHz) imaging catheter placed in the cardiac venous system. Using simultaneous fluoroscopy, we studied anesthetized closed-chest dogs (n = 6) and human subjects undergoing right heart catheterization (n = 11). After cannulation of the coronary sinus, the circumflex coronary artery (Cx) was visualized from the great cardiac vein (GCV), and on advancing the catheter into the anterior interventricular vein (AIV), the left anterior descending artery (LAD) was identified. Where artery and vein were parallel to each other, circular cross-sectional images of the coronary artery were obtained, whereas oblique and transverse orientation of artery to vein produced ellipsoid images or long-axis images. In the dogs, ultrasound-determined cross-sectional area of the coronary arteries (4.81 +/- 0.18 mm2) correlated closely with angiography (4.77 +/- 0.21 mm2) (r = 0.91, p less than 0.001). In humans, the Cx was readily visualized from the GCV in all subjects but because of anatomic variability, the LAD was seen less consistently from the AIV (73%). There was significant correlation between ultrasound-determined cross-sectional areas of the coronary arteries (8.25 +/- 0.34 mm2) with those from angiography (8.59 +/- 0.3 mm2) (r = 0.82, p = 0.001) in humans. In all subjects, the ultrasound transducer could be safely advanced into the AIV to the cardiac apex. Limitations of the technique include ultrasonic penetration problems, caused in part by the large size of human coronary veins and variability in artery-vein relations.

CONCLUSIONS
We conclude that transvenous imaging of coronary arteries with intravascular ultrasound is a less invasive, promising new approach to the study of structure and morphology in the coronary vasculature.
Response of relatively refractory canine myocardium to monophasic and biphasic shocks.
Authors: Daubert J P , Frazier D W , Wolf P D , Franz M R , Smith W M , Ideker R E 
Published: June 2012

BACKGROUND
Certain biphasic waveforms defibrillate at lower energies than monophasic waveforms, although the mechanism is unknown.

METHODS AND RESULTS
The relative ability of monophasic and biphasic shocks to stimulate partially refractory myocardium was compared because defibrillation is thought to involve stimulating relatively refractory myocardial tissue. Shocks of 25-125 V were given during regularly paced rhythm in 11 open-chest dogs. Computerized recordings of shock potentials, and of activations before and after the shocks, were made at 117 epicardial sites. To quantify the shock field strength, the shock potential gradients were calculated at the electrode sites. Monophasic action potential (MAP) electrode recordings, obtained in five dogs, confirmed direct myocardial excitation by the shock, that is, activations beginning during the shock. Tissue was directly excited up to 4 cm from the shocking electrode, and the area directly excited increased as the shock was made stronger or given less prematurely. In six dogs, strength-interval curves for direct excitation were determined from plots of potential gradient versus refractoriness at each electrode site. The biphasic curves were located to the right of the monophasic curves by 8 +/- 4 msec, indicating a lesser ability to excite refractory myocardium. When the gradient at the directly excited border was at least 3.8 +/- 1 V/cm, conduction failed to propagate away from the directly excited zone after the shock, and MAP recordings made near the border showed a shock-induced graded response. This graded response, which prolonged repolarization, may have been responsible for the failure of conduction from the directly excited zone. Although better for defibrillating, the biphasic waveform was thus less effective than the monophasic one in exciting relatively refractory myocardium.

CONCLUSIONS
These results indicated that waveform selection for defibrillation should not be guided solely by the ability of the waveform to stimulate tissue, as these two properties can be discordant.
Desensitization of myocardial beta-adrenergic receptors during cardiopulmonary bypass. Evidence for early uncoupling and late downregulation.
Authors: Schwinn D A , Leone B J , Spahn D R , Chesnut L C , Page S O , McRae R L , Liggett S B 
Published: June 2012

BACKGROUND
Cardiopulmonary bypass (CPB), a process routinely used during cardiac surgery, is a potent stimulant to the release of endogenous catecholamines. Hence, we tested the hypothesis that CPB results in myocardial beta-adrenergic receptor (beta AR) desensitization.

METHODS AND RESULTS
We obtained canine transmyocardial left ventricular biopsies before, during (155 minutes), and after CPB (pre-CPB, CPB, and post-CPB, respectively) and determined beta AR density, proportion of beta 1AR to beta 2AR, and beta AR coupling capacity to adenylyl cyclase. Beta AR density was stable at 112 +/- 14 fmol/mg (pre-CPB) and 103 +/- 9 fmol/mg (CPB) but decreased post-CPB to 84 +/- 7 fmol/mg. The ratio of beta 1AR to beta 2AR (determined by two-site fit for [125I]-iodocyanopindolol competition binding with the beta 1AR selective antagonist ICI89.406) remained constant throughout (60 +/- 3: 40 +/- 3 pre-CPB, 55 +/- 3: 44 +/- 3 CPB, and 61 +/- 2: 39 +/- 2 post-CPB), revealing that both beta 1AR and beta 2AR subtypes were downregulated. A different pattern was noted in the functional properties of these receptors during CPB. Decreased maximal isoproterenol-stimulated adenylyl cyclase activity (252 +/- 14 to 216 +/- 12 pmol/30 min/mg), submaximal isoproterenol-stimulated adenylyl cyclase activity (183 +/- 10 to 157 +/- 11 pmol/30 min/mg), and zinterol-stimulated adenylyl cyclase activity (187 +/- 11 to 159 +/- 11 pmol/30 min/mg, a measure of beta 2AR subtype activation) were noted during CPB, at the time when weaning from CPB takes place. However, this desensitized pattern was found to be completely reversed by 30 minutes post-CPB, with adenylyl cyclase activities returning to pre-CPB levels or slightly higher. Control dogs that did not receive CPB showed no change in beta AR density or adenylyl cyclase activity.

CONCLUSIONS
These data suggest that myocardial beta AR desensitization does occur during CPB in healthy, nonischemic canine myocardium and that this pattern is reversed 30 minutes after discontinuation of CPB. In addition, a slower process of beta AR downregulation persists after discontinuation of CPB. Because successful weaning from CPB is a critical process during myocardial surgery, these findings have potentially important implications in the management of such patients.