bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of regional myocardial blood flow with multiple colored microspheres.
Authors: Kowallik P , Schulz R , Guth B D , Schade A , Paffhausen W , Gross R , Heusch G 
Published: June 2012

BACKGROUND
The use of radioactive microspheres (RM) for the measurement of regional myocardial blood flow (RMBF) is limited and inaccessible to many investigators due to radiation safety concerns and radioactive waste disposal problems. Therefore, a new method for the measurement of RMBF using colored microspheres (CM) was developed.

METHODS AND RESULTS
Polystyrene spheres (diameter, 15 +/- 0.1 [SD] micron; density, 1.09 g/ml) were dyed with one of five colors. With the injection of CM into the left atrium or into a coronary perfusion line, RMBF and its distribution can be determined. CM are extracted from the myocardium and blood by digestion with potassium hydroxide and subsequent microfiltration. The dyes are then recovered from the CM within a defined volume of a solvent, and their concentrations are determined by spectrophotometry. The separation of composite absorbance spectra by spectrophotometry with the CM technique was as good as the separation of energy spectra by a gamma-counter using the RM technique. Leaching of dye from the CM was less than 0.1% during a 2-month period in vitro. Significant leaching of dye from the microspheres also did not occur during 8 hours in the blood and myocardium of four anesthetized dogs in vivo. For further validation of this method, pairs of CM and RM (15.5 +/- 0.1 [SD] microns) were simultaneously injected under five different RMBF conditions (range, 0-10 ml/[min.g]) into the left anterior descending coronary artery of four anesthetized pigs, with coronary inflow as a flow reference, or into the left atrium of four anesthetized dogs using aortic blood withdrawal as a reference. The relation between RMBF determined by CM and RM was CM = 0.01 + 1.00.RM (r = 0.98, n = 1,080 data points) in the pigs, and CM = -0.19 + 0.92.RM (r = 0.97, n = 1,813 data points) in the dogs.

CONCLUSIONS
Measurement of RMBF with CM yields values very similar to those of RM. Their use is less expensive and avoids all the disadvantages related to radioactivity, thus offering an alternative method for as many as five RMBF measurements in a single experiment.
Linking in accessory pathways. Functional loss of antegrade preexcitation.
Authors: Gonzalez M D , Greenspon A J , Kidwell G A 
Published: June 2012

BACKGROUND
Concealed retrograde activation has been proposed as a mechanism for antegrade conduction block in the bundle branches and atrioventricular accessory pathways. We studied this hypothesis (linking) in 10 patients with the Wolff-Parkinson-White syndrome in whom antegrade preexcitation could be persistently blocked by overdrive atrial pacing.

METHODS AND RESULTS
An atrial pacing protocol, with a decremental ramp followed by an incremental ramp, defined a range of atrial paced cycle lengths (linking window) associated with both persistent conduction and block in the accessory pathway. Within the limits of the linking window, the ability of an atrial impulse to conduct over the accessory pathway was dependent on the preceding state (i.e., conduction or block). The observed linking window ranged from 70 to 290 msec (mean, 185 +/- 68 msec) and closely approximated the measured delay in retrograde activation of the accessory pathway during persistent antegrade block. The mean antegrade effective refractory period of the accessory pathways was long (486 +/- 156 msec), and in each case, it exceeded the antegrade refractory period of the normal atrioventricular pathway. Critically timed premature ventricular extrastimuli, delivered while linking was maintained in the accessory pathway, were able to interrupt the linking and restore antegrade accessory pathway conduction.

CONCLUSIONS
These observations suggest that accessory pathway linking is associated with bidirectional block in the accessory pathway. The ability to initiate linking (and the stability of the phenomenon) depends on a critical relation between antegrade accessory pathway refractoriness and the magnitude of retrograde accessory pathway activation delay.
Prevention of nitrate tolerance with angiotension converting enzyme inhibitors.
Authors: Katz R J , Levy W S , Buff L , Wasserman A G 
Published: June 2012

BACKGROUND
Activation of neurohumoral hormones or sulfhydryl group depletion may contribute to the development of nitroglycerin tolerance. In an attempt to prevent nitrate tolerance, this study evaluated the interaction of nitroglycerin with angiotensin converting enzyme (ACE) inhibitors with and without a sulfhydryl group.

METHODS AND RESULTS
Thirty-four subjects were randomized to a 7-day regimen of enalapril 10 mg b.i.d., captopril 25 mg t.i.d., or placebo. Venodilator response to nitroglycerin was assessed with forearm plethysmography by measuring the change in venous volume after administration of 0.4 mg sublingual nitroglycerin. Plethysmographic measurements were obtained serially 1) at baseline, 2) after 4 days of ACE inhibitor or placebo, 3) 2 hours after application of a 10 mg/24 hr nitroglycerin patch, and 4) 74 hours after continuous nitropatch application. ACE inhibition alone caused no significant change in the response to sublingual nitroglycerin. Nitrate response remained unchanged after 2 hours ("acute") of nitropatch exposure in all three groups. After 74 hours ("chronic") of continuous nitropatch application, the venodilator response to sublingual nitroglycerin was reduced by 40% in the placebo group, 10% in the enalapril group, and 2% in the captopril group. This attenuation was significant only in the placebo group (p less than 0.01). Pairwise comparison of nitrate response between groups was significantly different between the captopril and placebo groups (p less than 0.01) and between the placebo and enalapril groups (p less than 0.05). Plasma renin levels increased equally in the enalapril and captopril groups. Body weight increased only in the placebo group, suggesting prevention of nitrate-induced volume expansion in the ACE inhibitor groups.

CONCLUSIONS
This study demonstrates that ACE inhibitors may prevent nitrate tolerance to long-term nitrate therapy.
Diagnostic implications of spectral and temporal analysis of the entire cardiac cycle in patients with ventricular tachycardia.
Authors: Cain M E , Ambos H D , Markham J , Lindsay B D , Arthur R M 
Published: June 2012

BACKGROUND
Available methods for analysis of signal-averaged electrocardiograms (ECGs) have a low-positive predictive accuracy for identifying patients at risk for ventricular arrhythmias. Identification of the spectral and temporal features in ECGs that distinguish patients prone to ventricular tachycardia (VT) is a prerequisite to implementing refinements in methods that increase the diagnostic power of the signal-averaged ECG.

METHODS AND RESULTS
Fast Fourier transforms and time-domain reconstructions based on inverse fast Fourier transforms were computed over the entire cardiac cycle of signal-averaged ECGs of sinus beats from 40 patients with myocardial infarction and sustained VT, 41 with infarction without VT, and 20 normal controls. Ventricular depolarization and repolarization were analyzed by procedures that obviate limited resolution due to short data segments and window functions. Spectral magnitudes of ECGs from patients in each group were compared, and the phase data were used for time-domain reconstructions to determine the temporal distributions of distinguishing frequency bands during the cardiac cycle. Magnitudes of 1-7-Hz frequencies were increased (from p less than 0.05 to p less than 0.00001), and magnitudes of 13-56-Hz and 70-128-Hz frequencies were decreased (from p less than 0.05 to p less than 0.00001) in the spectra of ECGs from patients with VT compared with patients without VT. Time-domain reconstructions demonstrated that 1-7-Hz frequencies were detectable throughout the QRS complex, ST segment, and T wave in ECGs from each group. The 13-56-Hz and 70-128-Hz frequency bands not only contributed to the terminal QRS and ST segment but were also detectable throughout the QRS complex of ECGs from patients with VT.

CONCLUSIONS
Results define new spectral and temporal features in signal-averaged ECGs from patients with VT that are excluded from analysis by available techniques that limit the bandwidth or restrict interrogation to portions of the cardiac cycle. These findings provide an objective basis for developing new indexes for signal-averaged ECG analysis.
Evidence for superoxide radical-dependent coronary vasospasm after angioplasty in intact dogs.
Authors: Laurindo F R , da Luz P L , Uint L , Rocha T F , Jaeger R G , Lopes E A 
Published: June 2012

BACKGROUND
Active oxygen species can influence vascular tone and platelet activation through a variety of mechanisms. This study assessed the role of the superoxide anion, the hydroxyl radical, and hydrogen peroxide in vasoconstriction and mural thrombosis after coronary artery angioplasty in intact dogs.

METHODS AND RESULTS
Injury was induced by inflation of a balloon catheter 50 +/- 6% above baseline arterial diameter; dogs were followed for 2 hours before death. Epicardial coronary diameters at arteriography and extent of thrombus deposition at serial histological sections were analyzed in controls (n = 20) and in dogs pretreated with superoxide dismutase (SOD, a superoxide radical scavenger, n = 10); other dogs were pretreated with the hydrogen peroxide scavenger catalase (n = 8), the iron chelator deferoxamine (n = 6), or the hydroxyl radical scavenger 1,3-dimethyl-2-thiourea (n = 9). Angioplasty-induced injury was similar among groups. After angioplasty, control dogs exhibited localized and persistent vessel constriction, which was maximal at the initial 5 minutes (28.9 +/- 6.3% diameter decrease versus baseline). Corresponding arterial diameters of SOD-treated dogs were 24-69% larger (95% confidence interval, p less than 0.001) than controls at 5 minutes and, on average, 32% larger than controls thereafter (p less than 0.01). Vasoconstriction was not prevented by the other treatments. The SOD dose used accounted for inhibition of zymosan-stimulated blood cytochrome c reduction versus baseline (7 +/- 3 versus 30 +/- 6 nmol/min/10(6) cells, respectively, p = 0.003); such inhibition occurred in no other group. Prevalence of mural thrombosis was similar among all groups, but large thrombi (greater than 15% of lumen area) were absent in SOD-treated dogs, contrary to control group (p = 0.028); other groups were similar to control. In the absence of injury, SOD alone induced no change in coronary diameter, coronary blood flow, or platelet aggregation.

CONCLUSIONS
These data provide evidence implicating the superoxide radical in the genesis of vasoconstriction after coronary angioplasty in vivo. Such effects seem to be independent of its conversion to hydroxyl radicals and availability of hydrogen peroxide or catalytic iron complexes.
Doppler and echocardiographic characteristics of patients having an Austin Flint murmur.
Authors: Rahko P S 
Published: June 2012

BACKGROUND
The purpose of this study was to investigate the genesis of the Austin Flint murmur using Doppler and echocardiographic imaging.

METHODS AND RESULTS
A total of 51 patients having significant aortic insufficiency and an anatomically normal mitral valve were evaluated. They were divided into two groups; 30 patients had an audible Austin Flint murmur (AFM+) and 21 did not (AFM-). All patients had a complete M-mode, two-dimensional, and Doppler echocardiographic examination to characterize left ventricular size and function, motion of the mitral valve, transmitral flow velocities, direction of the aortic insufficiency jet, and severity of aortic insufficiency. There was no significant difference in severity of aortic insufficiency between groups. There was, however, a significant difference in direction of the insufficiency jet. In the AFM+ group compared with the AFM- group, for the parasternal long-axis view 24 (80%) versus eight (38%) had their insufficiency jet directed at the mitral valve, for the apical five-chamber view the values were 25 (83%) versus five (24%), and for the apical long-axis view the values were 27 (90%) versus five (24%); for all comparisons p less than 0.01. There was also a greater frequency of localized anterior mitral leaflet distortion by two-dimensional echocardiography (AFM+:23 [77%] versus AFM-:five [24%]; p less than 0.001) and a greater frequency of Doppler striations overlying the aortic insufficiency jet (AFM+:25 [83%] versus AFM-:seven [33%]; p less than 0.001). Regarding transmitral flow velocities, there was no significant difference in filling patterns or absolute velocities during early or late diastole between groups. There was no gradient by Doppler analysis or by hemodynamics (n = 26) across the mitral valve in either group. There also was no difference in the frequency of preclosure of the mitral valve (AFM+:two versus AFM-:three). Systolic function was similar in both groups, but the left ventricular end-diastolic dimension was significantly greater in the AFM+ group (6.8 +/- 0.8 cm) than in the AFM- group (6.2 +/- 0.7 cm, p = 0.008).

CONCLUSIONS
The results of this study suggest that the primary factor responsible for the Austin Flint murmur is the presence of an aortic insufficiency jet directed at the anterior mitral leaflet. This, combined with the biphasic pattern of transmitral flow, distorts the shape of the anterior mitral leaflet as it opens and closes during diastole, making it shudder. The leaflet's shuddering sets up vibrations and shock waves that distort the aortic insufficiency jet, causing the observed Doppler striations and probably the sound of the murmur. There is no evidence from this study to support prior theories that have proposed functional mitral stenosis or diastolic mitral regurgitation as the source of the murmur.
Assessment of aortic regurgitation by the acceleration flow signal void proximal to the leaking orifice in cinemagnetic resonance imaging.
Authors: Yoshida K , Yoshikawa J , Hozumi T , Akasaka T , Yamaura Y , Minagoe S , Nakajima H , Miyamoto T 
Published: June 2012

BACKGROUND
The proximal acceleration flow region is a laminar flow field that is located immediately upstream from the leaking orifice. The purpose of this study was to evaluate whether cinemagnetic resonance imaging can provide information regarding the proximal acceleration flow region in patients with aortic regurgitation and to analyze the relation between the area of the proximal acceleration flow delineated by cinemagnetic resonance imaging and the severity of aortic regurgitation delineated by angiography.

METHODS AND RESULTS
Thirty-eight consecutive patients who underwent aortography were examined by cinemagnetic resonance imaging. The region of proximal flow acceleration was identified as a semicircular-shaped signal void in the aorta during diastole. Cinemagnetic resonance imaging detected the proximal acceleration flow region in 26 of the 30 patients who were proved to have this lesion (sensitivity, 87%). In eight patients without aortic regurgitation according to aortography, no proximal acceleration flow region was detected (specificity, 100%). The area of the acceleration flow signal void from the long-axis view was well correlated with angiographic degree of aortic regurgitation.

CONCLUSIONS
Cinemagnetic resonance imaging is useful in detecting the proximal acceleration flow region and permits noninvasive assessment of the severity of aortic regurgitation.
Relation of arteriographically defined coronary artery disease to serum lipoprotein particles mapped with monoclonal antibodies.
Authors: Fiévet C , Nuttens M C , Ducimetière P , Fruchart J C , Bertrand M , Salomez J L 
Published: June 2012

BACKGROUND
This study was designed to investigate the relation of a molecular analysis of apolipoprotein B (apoB)-containing atherogenic lipoprotein particles to coronary artery disease (CAD) in middle-aged men.

METHODS AND RESULTS
Two groups of men were studied. The first consisted of 97 patients with angiographically documented CAD (greater than 50% stenosis of at least one coronary artery). The second group consisted of 145 subjects without symptomatic CAD, who served as controls. In both groups, measurements were obtained for total cholesterol level, triglyceride level, cholesterol contents in apoB- and nonapoB-containing particles (LpB, LpnonB), total apoB and apolipoprotein AI (apoAI levels), lipoprotein particles recognized by monoclonal antibodies anti-apoB (LpBL3, LpBL5, LpBL7) and anti-apoAI (LpAI-2GII). Taking into account age, body mass index, hypertension, diabetes, smoking habits, and drug consumption, the analysis showed that the mean levels of cholesterol were identical in both groups but differed when cholesterol content in LpB and LpnonB subfractions were assessed, thus reflecting an increase in the low density fraction and a decrease in the high density fraction, respectively. This was confirmed by an increase in total apoB and a decrease in total apoAI. Measurements of LpBL3, LpBL5, LpBL7, and LpAI-2GII particles also discriminated between the two groups. After adjustment for cholesterol content in LpnonB particles, a difference in total apoB was no longer significant between groups, whereas LpBL3, LpBL5, and LpBL7 levels remained significantly higher in CAD patients.

CONCLUSIONS
The measurement of separate concentrations of apoB in different particles may permit a more-accurate assessment of CAD risk than measurements of total apoB levels.
Effects of drive train stimulus intensity on ventricular refractoriness in humans.
Authors: Langberg J J , Calkins H , Sousa J , el-Atassi R , Morady F 
Published: June 2012

BACKGROUND
The strength-interval relation between the intensity of premature stimulus and the ventricular effective refractory period (VERP) has been well characterized. The effects of variation in the intensity of the basic drive train stimuli (S1) on VERP are not as well defined. This relation was studied in 44 patients undergoing clinically indicated electrophysiological study.

METHODS AND RESULTS
The outputs of two stimulus isolation units were connected in parallel, allowing the intensity of S1 to be varied independently of intensity of the extrastimulus (S2). To prevent confounding effects from cycle length change, continuous overdrive pacing was performed for 3 minutes before each measurement of VERP. The effect of S1 intensity on VERP was assessed in 24 patients with S2 intensity kept constant at twice threshold. VERP shortened from 232 +/- 19 msec at an S1 intensity of 1.5 times threshold to 219 +/- 20 msec at 5 mA and 211 +/- 19 msec at 10 mA (p less than 0.0001 for baseline versus 5 mA and for 5 mA versus 10 mA). Autonomic blockade with atropine and propranolol blunted but did not completely eliminate this effect. To assess whether the effect of S1 intensity on VERP was independent of S2 intensity, S2 strength-interval curves were generated in 10 patients at low (1.5 times threshold) and high (10 mA) S1 intensities. All portions of the strength-interval curve were shifted to the left by an increase in S1 intensity. The time course of change in VERP after an abrupt increase in S1 intensity was assessed in an additional 10 patients. VERP changed slowly, requiring 18 +/- 28 seconds to shorten by 2 msec and 64 +/- 46 seconds to decrease by 10 msec after a change in S1 intensity from 1.5 times threshold to 10 mA. In a final group of 10 patients, VERP was measured using an eight-beat drive train and a 4-second intertrain interval. With this more conventional protocol, VERP shortened by 14 +/- 8 msec with an increase in S1 intensity from 1.5 times threshold to 10 mA.

CONCLUSIONS
Increasing S1 intensity results in clinically significant, progressive shortening of VERP in man. This effect is independent of S2 intensity. The prolonged time course of the change in VERP after an increase in S1 intensity and the attenuation of this effect by autonomic blockade are consistent with stimulation of sympathetic nerve terminals and catecholamine release as a result of intense stimulation.
Protein C activation following coronary artery occlusion in the in situ porcine heart.
Authors: Snow T R , Deal M T , Dickey D T , Esmon C T 
Published: June 2012

BACKGROUND
Activated protein C, the body's natural anticoagulant, may play a role in protecting the heart during and following an occlusion of the left anterior descending coronary artery (LAD) in the porcine heart.

METHODS AND RESULTS
Infusion of 1 unit thrombin over 30 seconds into the LAD of juvenile pigs produced a prolongation of the Xa clotting time (153 +/- 14%) in blood drawn from the anterior interventricular vein (AIV). The action of the anticoagulant was blocked by a polyclonal immunoglobulin G antibody directed against porcine activated protein C. A brief (30 seconds) occlusion of the LAD induced a similar prolongation of the Xa clotting time (138 +/- 11%), which was also blocked by the polyclonal antibody. To determine whether activated protein C helps sustain the heart during and following a 2-minute occlusion, three groups of pigs were studied: 11 controls, six receiving activated porcine protein C, and nine receiving a monoclonal antibody (HPC4) that blocks protein C activation. Relative to the controls, HPC4-treated animals recovered function, as measured by the maximum time derivative of left ventricular pressure and segmental shortening, more slowly and were not able to sustain this recovery. Animals receiving activated protein C recovered more quickly and sustained this recovery.

CONCLUSIONS
These data indicate that an ischemic insult induces rapid activation of protein C in the coronary microcirulation and that blocking this activation impairs recovery.
Disparate effects of substance P on systemic and coronary beds in conscious dogs.
Authors: Nakamura Y , Parent R , Lavallée M 
Published: June 2012

BACKGROUND
Previous studies in anesthetized animals indicated that substance P is a coronary and peripheral vasodilator. However, coronary vasodilation was only transient perhaps because of tachyphylaxis. In the present study, the steady-state effects of intravenous substance P on systemic and coronary beds were investigated in conscious, instrumented dogs.

METHODS AND RESULTS
With intact autonomic reflexes, 5 ng/kg/min i.v. substance P resulted in increases (p less than 0.01) in cardiac output by 22 +/- 5%, in decreases (p less than 0.01) in mean arterial pressure by 9 +/- 2%, and in total peripheral resistance by 23 +/- 4% 7-9 minutes after the beginning of substance P infusion. Heart rate increased (p less than 0.01) by 35 +/- 7% and left ventricular dP/dt (p less than 0.05) by 13 +/- 4%. In this situation, coronary blood flow decreased (p less than 0.01) by 19 +/- 4% and coronary vascular resistance increased (p less than 0.05) by 13 +/- 5%. Myocardial oxygen delivery was reduced (p less than 0.05) by 13 +/- 5% and the arteriovenous oxygen difference widened (p less than 0.01). After ganglionic blockade, increases in cardiac output, heart rate, and left ventricular dP/dt with substance P administration were abolished, but total peripheral resistance and mean arterial pressure decreased (p less than 0.01) by 12 +/- 3% respectively. Under these conditions, coronary blood flow decreased (p less than 0.01) by 37 +/- 5% and coronary vascular resistance increased (p less than 0.01) by 47 +/- 8%, which were more (p less than 0.01) than control responses. In this situation, myocardial oxygen delivery was reduced (p less than 0.01) by 37 +/- 4% and the arteriovenous oxygen difference widened (p less than 0.01). Intracoronary infusion of substance P (0.4 ng/kg/min) resulted in significant and sustained decreases in coronary blood flow, which were similar before and after ganglionic blockade.

CONCLUSIONS
Thus, in conscious dogs, systemic vasodilation is the prevailing effect of substance P, but paradoxically, this peptide simultaneously elicits coronary vasoconstriction.