bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized trial of thrombolysis versus heparin in unstable angina.
Authors: Schreiber T L , Rizik D , White C , Sharma G V , Cowley M , Macina G , Reddy P S , Kantounis L , Timmis G C , Margulis A 
Published: June 2012

BACKGROUND
The clinical usefulness of intravenous thrombolytic therapy in unstable angina is currently unknown, despite the pathogenetic similarity of this entity to acute myocardial infarction, for which thrombolysis has enjoyed great success. To compare the clinical benefit of intravenous urokinase with that of conventional antithrombotic therapy in preventing the progression of unstable angina to new myocardial infarction, intractable angina, or death within the first 96 hours after hospitalization, 149 patients with unstable angina were randomized to one of two intravenous thrombolytic strategies.

METHODS AND RESULTS
Forty-nine patients received 3 million units urokinase i.v. over 90 minutes plus intravenous heparin (group A); 47 patients received unblinded 3 million units urokinase i.v. plus 325 mg aspirin p.o. daily (group B); and 53 patients received placebo thrombolytic infusion plus full-dose heparin (group C). The primary end point of this trial was 96-hour clinical status. There were no significant differences in the baseline characteristics (age, sex, previous myocardial infarction, hypertension prevalence, diabetes, tobacco use, or previous revascularization) among the three groups. Despite an excess of minor untoward reactions for the urokinase groups (chills, 26.5% and 23.4% for groups A and B versus 0% for group C; p < 0.01), there was no significant difference with respect to major bleeds (two, none, and two for groups A, B, and C, respectively; p = NS). At 96 hours after presentation, no significant difference emerged in the incidence of new cardiac events: new myocardial infarctions developed in 10.2% of group A, 6.4% of group B, and 3.8% of group C (p = NS); intractable angina occurred in 6.1% of group A, 10.6% of group B, and 9.4% of group C (p = NS). There were no deaths. All three groups encountered a similar incidence of overall cardiac events: 16.3%, 17.0%, and 13.2% for groups A, B, and C, respectively (p = NS). Although trial enrollment was to extend to 600 patients, interim analysis led to early cessation of enrollment due to a negative trend in respect to outcome after thrombolysis.

CONCLUSIONS
High-dose intravenous urokinase followed by either heparin or aspirin can be safely administered to a broad, unselected group of patients with unstable angina. However, this study suggests that no clinical advantage is conferred by urokinase, with either adjunctive antithrombotic therapy over standard heparin therapy alone, when given relatively late (mean, 8.7 hours) after admission for unstable angina. A possible detrimental effect cannot be excluded.
Dynamic intraventricular obstruction during dobutamine stress echocardiography. A new observation.
Authors: Pellikka P A , Oh J K , Bailey K R , Nichols B A , Monahan K H , Tajik A J 
Published: June 2012

BACKGROUND
The implications of hypotension occurring during dobutamine stress echocardiography have not been elucidated. We observed in some patients that hyperdynamic left ventricular function developed during dobutamine stress echocardiography and hypothesized that intracavitary obstruction was occurring and might account for hypotension in some patients.

METHODS AND RESULTS
Fifty-seven consecutive patients undergoing dobutamine stress echocardiography underwent pulsed-wave and continuous-wave Doppler examination of the left ventricular cavity at rest and at peak dobutamine infusion. The development of an intraventricular gradient with dobutamine stress was defined as a late-peaking left ventricular Doppler velocity profile that exceeded basal velocity by at least 1 m/sec. During dobutamine stress testing, left ventricular outflow velocity or intracavitary velocity increased in all patients. Obstruction occurred in 12 patients (21%, group 1). Group 2 was the remaining 45 patients. Peak velocities in group 1 ranged from 2.0 to 5.0 m/sec (mean, 3.5 m/sec), and the mean increase from velocity at rest was 2.3 m/sec. The mean change in systolic blood pressure was significantly lower in patients in group 1 (-15 versus 4 mm Hg, p = 0.02). When the 18 patients with an ischemic response to stress testing (evidenced by new or worsening wall motion abnormalities) were excluded from analysis, systolic blood pressure response was still significantly different for the two groups (-19 versus 2 mm Hg, p = 0.03).

CONCLUSIONS
Dynamic left ventricular obstruction is a new observation; it may develop frequently in patients undergoing dobutamine stress echocardiography. Obstruction rather than ischemia may explain a decrease in blood pressure during dobutamine stress echocardiography.
Serotonin selectively aggravates subendocardial ischemia distal to a coronary artery stenosis during exercise.
Authors: Bache R J , Stark R P , Duncker D J 
Published: June 2012

BACKGROUND
The coronary circulation has been shown to remain responsive to vasodilator and vasoconstrictor stimuli during myocardial ischemia. Because serotonin possesses both vasodilator and vasoconstrictor properties, we examined its effect in the coronary circulation distal to an arterial stenosis that resulted in myocardial hypoperfusion during exercise.

METHODS AND RESULTS
Seven chronically instrumented dogs were studied during treadmill exercise in the presence of a stenosis that reduced distal left circumflex coronary artery perfusion pressure to 42 +/- 1 mm Hg. Myocardial blood flow was assessed with radioactive microspheres during exercise before and during intracoronary infusion of 0.4 and 2.0 micrograms/kg-1.min-1 serotonin. The stenosis was adjusted to maintain distal coronary pressure constant during control exercise and with the two doses of serotonin. In seven dogs, the effect of serotonin (2.0 micrograms/kg-1.min-1) was also studied during exercise with normal arterial inflow. During control exercise, the stenosis decreased mean myocardial blood flow to 45% of flow in the normally perfused region. This decrease was most pronounced in the subendocardium (endocardial/epicardial ratio 0.36 +/- 0.06 versus 1.46 +/- 0.14 in the control region; p < 0.01). With no change in pressure distal to the stenosis, serotonin decreased subendocardial flow from 0.51 +/- 0.09 ml/min-1.g-1 to 0.41 +/- 0.12 (p < 0.05) and then to 0.35 +/- 0.08 ml/min-1.g-1 (p < 0.05) and tended to increase subepicardial flow from 1.47 +/- 0.17 to 1.91 +/- 0.23 and 1.85 +/- 0.21 ml/min-1.g-1 (p = 0.08) during infusions of 0.5 and 2.0 micrograms/kg-1.min-1, respectively, with no change in total arterial inflow. In contrast, in the absence of a stenosis, serotonin (2.0 micrograms/kg-1.min-1) increased subendocardial flow from 2.43 +/- 0.25 to 3.73 +/- 0.25 ml/min-1.g-1 (p < 0.01) and subepicardial flow from 1.88 +/- 0.20 to 5.29 +/- 0.38 ml/min-1.g-1 (p < 0.01).

CONCLUSIONS
During normal arterial inflow, serotonin dilated coronary resistance vessels and increased flow to all myocardial layers. During hypoperfusion, a vasodilator response was still present in the subepicardium, but vasoconstriction was then observed in the subendocardium. Our data suggest that serotonin constricts the intramural penetrating arteries, thereby selectively increasing resistance to subendocardial blood flow.
Persistence of viral genome into late stages of murine myocarditis detected by polymerase chain reaction.
Authors: Wee L , Liu P , Penn L , Butany J W , McLaughlin P R , Sole M J , Liew C C 
Published: June 2012

BACKGROUND
Enteroviruses have been considered as the most common etiologic agents in clinical myocarditis and dilated cardiomyopathy; however, their pathogenetic role remains unknown. Hence, the relation of viral replication and development of cardiomyopathy has been determined in a murine model of myocarditis by evaluating the persistence of viral genome during acute and chronic stages of myocarditis by means of Northern blot hybridization and polymerase chain reaction (PCR).

METHODS AND RESULTS
DBA/2 mice (n = 146) were injected peritoneally with 10 plaque-forming units of encephalomyocarditis (EMC) virus, and the control mice (n = 33) were injected with normal saline. Animals were randomly killed at 4, 7, 10, 14, 21, 28, 35, and 42 days after infection. Histology revealed acute myocardial necrosis with massive inflammatory cell infiltrate peaking on day 14 followed by increasing fibrosis and declining chronic inflammation features compatible with dilated cardiomyopathy between days 21 and 42. Northern blot analysis of control and infected hearts showed detectable viral RNA in the infected hearts initially at day 4, peaking by day 7, diminishing between day 7 and day 14, and absent at day 21 and day 28. However, potential viral remnants present in low quantities and undetectable by Northern blot were further detected by PCR followed by confirmation with an internal oligonucleotide probe after day 14 up to day 42.

CONCLUSIONS
Viral RNA signals on Northern blot showed a strong correlation with massive myocyte necrosis on day 14, but the viral RNA fragment was consistently detectable into late stages of cardiomyopathy on days 21, 28, 35, and 42 by PCR. This indicated that the mature virions are fully developed early in infection and are capable of persisting in the myocardium after virus-mediated myocytolysis stage. Therefore, PCR is an extremely sensitive method for detecting residual viral genome and viral persistence in the myocardium and may offer insights into the pathogenesis of chronic myocarditis leading to dilated cardiomyopathy.
Changes in pericardial pressure during the perinatal period.
Authors: Grant D A , Kondo C S , Maloney J E , Walker A M , Tyberg J V 
Published: June 2012

BACKGROUND
To determine how the tissues that surround the heart affect diastolic and systolic function during the perinatal period, we studied the pressure-diameter relation of the left ventricle in partially delivered fetal lambs.

METHODS AND RESULTS
We anesthetized (1.5-2.0% halothane, balance O2) and ventilated six pregnant ewes (142-144 days of gestation) and then partially delivered each lamb by cesarean section. Each lamb was instrumented to record left ventricular anteroposterior diameters (endocardial ultrasonic transducers), pericardial pressure (liquid-containing balloon), and left ventricular pressure (transducer-tipped catheter). Left ventricular pressure-diameter relations were recorded under three conditions: initially, with a closed chest and closed pericardium (before ventilation); second, after interruption of the umbilical circulation and 1 hour of ventilation; and finally, when the lungs and the pericardium were retracted from the heart. Pericardial pressure (recorded at a common diameter, i.e., the maximal end-diastolic diameter recorded before ventilation) decreased by 48% after 1 hour of ventilation (p < 0.05). After ventilation, left ventricular anteroposterior diameters were 4-5% greater (p < 0.05) at each end-diastolic pressure compared (12.5, 15.0, 17.5, and 20 mm Hg). Thus, ventilation appeared to increase left ventricular diastolic compliance. Contractility also appeared to increase after ventilation when evaluated using ventricular stroke work as a function of end-diastolic pressure as preload. When we used a more appropriate measure of preload (i.e., transmural end-diastolic pressure), ventilation did not change left ventricular diastolic compliance or contractility. Thus, left ventricular systolic function increased because of an increase in preload.

CONCLUSIONS
The tissues surrounding the fetal heart significantly augment pericardial pressure and limit left ventricular preload. The initiation of ventilation reduces pericardial pressure, increases left ventricular preload, and increases left ventricular systolic function. At birth, a decrease in pericardial pressure and the resulting increase in preload may help increase left ventricular output through the Frank-Starling mechanism.
Increased expression and regional differences of atrial myosin light chain 1 in human ventricles with old myocardial infarction. Analyses using two monoclonal antibodies.
Authors: Nakao K , Yasue H , Fujimoto K , Jougasaki M , Yamamoto H , Hitoshi Y , Takatsu K , Miyamoto E 
Published: June 2012

BACKGROUND
This study was designed to examine the expression of atrial/fetal-type myosin light chain 1 (ALC1) in human ventricles with old myocardial infarction and in control hearts.

METHODS AND RESULTS
The expression of immunoreactive (ir) ALC1 was examined in the subendocardial and subepicardial myocardium of the infarcted and the noninfarcted regions in the left ventricles with old myocardial infarction (n = 12) and of the control left ventricles (n = 8). For the analysis, we prepared two monoclonal antibodies, KA1 and KB1, that were specific for only ALC1 and for both ALC1 and ventricular myosin light chain 1 (VLC1), respectively. The ir-ALC1 expression ratio [ALC1/(ALC1 + VLC1), %] of the subendocardial myocardium, determined densitometrically by Western blotting with KB1, was significantly higher in the infarcted region (11.4 +/- 7.3%) than in the noninfarcted region (4.7 +/- 2.3%, p < 0.001) and the control ventricle (1.0 +/- 1.5%, p < 0.0001). In the infarcted region, the subendocardial myocardium contained a significantly greater percentage of ir-ALC1 than the subepicardial myocardium (5.8 +/- 6.7%, p < 0.005). The ir-ALC1 expression ratio had a significant negative correlation with the value of tissue protein concentration (milligrams protein per gram wet weight). The immunohistochemical study with KA1 revealed that the surviving myocytes included in the infarcted region, especially in the ventricular aneurysm, expressed ir-ALC1 strongly in comparison with those in the noninfarcted or the control ventricles.

CONCLUSIONS
These results demonstrate increased expression of ALC1 and the regional differences in the failing left ventricles with old myocardial infarction. We conclude that the reexpression of ALC1 in infarcted ventricles occurs as one of the regional responses to increased load and may be a useful biochemical marker for the appearance of fetal-type myocytes.
Epinephrine augments von Willebrand factor-dependent shear-induced platelet aggregation.
Authors: Goto S , Ikeda Y , Murata M , Handa M , Takahashi E , Yoshioka A , Fujimura Y , Fukuyama M , Handa S , Ogawa S 
Published: June 2012

BACKGROUND
Shear-induced platelet aggregation (SIPA) is an important mechanism in thrombogenesis. von Willebrand factor (vWF) binding to platelet glycoprotein Ib (GP Ib) has been found to be crucial for platelet aggregation under the high shear force probably generated in stenosed coronary artery. The physiological significance of vWF-dependent SIPA has not been clarified.

METHODS AND RESULTS
Blood samples were collected from 23 normal volunteers. SIPA was continuously monitored using a modified cone-plate viscometer adapted for measuring the transmitted light intensity of the material. The effects of low concentrations of epinephrine, ADP, and collagen on SIPA under both low shear (12 dyne/cm2) and high shear (108 dyne/cm2) force were investigated. All agonists tested enhanced SIPA under low shear force, whereas only epinephrine augmented SIPA under high shear force. The maximum extents of SIPA under high shear force in the absence and presence of epinephrine (10 ng/ml) were 37.9 +/- 11.5% and 59.7 +/- 13.9%, respectively. The antagonist of the alpha 2-adrenergic receptor yohimbine (1 microgram/ml) antagonized the effects of epinephrine. The monoclonal antibody NMC-4 against vWF, which was shown to inhibit its binding to GP Ib, completely abolished SIPA under high shear force, even in the presence of epinephrine. However, this antibody only partially inhibited SIPA under low shear force.

CONCLUSIONS
Our findings suggest that epinephrine is the agonist that enhances SIPA mediated by vWF through its specific receptor. This may be clinically important because occlusion of the coronary artery often occurs in stenosed atherosclerotic vessels under sympathetic stimulation.
Contribution of myocardium responsible for ventricular tachycardia to abnormalities detected by analysis of signal-averaged ECGs.
Authors: Hood M A , Pogwizd S M , Peirick J , Cain M E 
Published: June 2012

BACKGROUND
Current methods of signal-averaged ECG analysis interrogate the terminal 40 msec of the QRS complex and/or the ST segment and have a low positive-predictive accuracy for detecting vulnerability to sustained ventricular tachycardia (VT). The extent to which abnormalities detected during these ECG intervals are generated by myocardial tissue responsible for VT has not been well defined. The purpose of this study was to determine when, during sinus rhythm, myocardium responsible for VT is activated.

METHODS AND RESULTS
Three-dimensional ventricular activation maps were analyzed during sinus rhythm and during 10 VTs in eight patients with healed myocardial infarctions undergoing arrhythmia surgery for sustained monomorphic VT. The mechanism of VT was focal in five instances and macroreentrant in five. During sinus beats, myocardium responsible for all focal VTs activated 43 +/- 38 msec before the onset of the terminal 40-msec interval of the QRS complex. During sinus rhythm, activation of the myocardium critical to macroreentrant VT began 72 +/- 13 msec before the onset of the terminal QRS interval and in only three instances extended 2-25 msec into the terminal 40 msec of the QRS complex. Electrograms recorded during the ST segment represented late activation of epicardial sites overlying zones of infarction that were temporally and spatially remote from tissue critical to VT.

CONCLUSIONS
Current methods of signal-averaged ECG analysis limiting interrogation to the terminal QRS/ST segment exclude detection of > 95% of the signals generated by myocardium responsible for sustained VT. These results establish a pathophysiological basis for expanding signal-averaged ECG analysis to include more of the cardiac cycle.
Control of sympathetic nerve activity by vagal mechanoreflexes is blunted in heart failure.
Authors: Dibner-Dunlap M E , Thames M D 
Published: June 2012

BACKGROUND
Previous studies have documented abnormalities of arterial baroreflexes in animals and patients with congestive heart failure. This study determined whether cardiopulmonary reflex control of sympathetic nerve activity was abnormal in a canine model of low-output heart failure induced by rapid ventricular pacing.

METHODS AND RESULTS
We stimulated mechanoreceptors throughout the cardiopulmonary region by volume expansion and left atrial mechanoreceptors selectively by inflating small balloons at the junctions of the pulmonary veins and left atrium. Responses of renal sympathetic nerve activity and left atrial and systemic arterial pressures were recorded. In the control group, 15% volume expansion raised left atrial pressure 3.5 +/- 0.8 mm Hg and resulted in a 70 +/- 8% reduction in renal nerve activity. In the heart failure group, 15% volume expansion resulted in a 6.8 +/- 3.0 mm Hg rise in left atrial pressure with only a 16 +/- 20% reduction in renal nerve activity (p < 0.01). When volume expansion was performed after pretreatment with hemorrhage to lower left atrial pressure to the normal range in the heart failure group, the markedly attenuated response in the heart failure group persisted. After vagotomy, volume expansion elicited no change in renal nerve activity. Inflation of the atrial balloons caused a 28 +/- 9% reduction in renal sympathetic nerve activity and a 13 +/- 4 mm Hg decrease in arterial pressure in the control group. Renal nerve activity (-5 +/- 3%) and mean arterial pressure (-1 +/- 1 mm Hg) did not change with balloon inflation in the heart failure group.

CONCLUSIONS
We conclude that dogs with low-output heart failure exhibit marked attenuation of cardiopulmonary mechanoreflex control of sympathetic nerve activity. This attenuated response is mediated via cardiac vagal afferent fibers and is due to either abnormalities in cardiopulmonary baroreceptors or abnormalities in the central nervous system.
Effects of calcium and EMD-53998 on oxygen consumption in isolated canine hearts.
Authors: de Tombe P P , Burkhoff D , Hunter W C 
Published: June 2012

BACKGROUND
Most positive inotropic agents increase cardiac contractility by increasing the amount of Ca2+ cycled with each beat. The additional amount of oxygen that is consumed by the heart to cycle this additional Ca2+ is believed to reduce myocardial efficiency. On the other hand, it has been suggested that the agent EMD-53998 increases the Ca2+ sensitivity of the contractile proteins without affecting the intracellular Ca2+ transient in cardiac muscle. Therefore, application of this agent may increase cardiac contractility without decreasing myocardial efficiency. The purpose of the present study was to test this hypothesis.

METHODS AND RESULTS
We measured myocardial oxygen consumption (MVO2) in six isolated, isovolumically beating blood-perfused canine hearts. The hearts were paced at 120 beats per minute. Contractility was varied in each heart by infusion of either CaCl2 or EMD-53998. With infusion of either agent, MVO2 was a linearly proportional function of contractility. No significant difference between CaCl2 and EMD-53998 could be detected in the interrelation between contractility and MVO2.

CONCLUSIONS
We conclude that the "calcium-sensitizing agent" EMD-53998 is a potent positive inotropic agent in the isolated, blood-perfused canine heart. However, EMD-53998 does not provide an energetic advantage over currently used positive inotropic agents.
Effects of vagal stimulation on cesium-induced early afterdepolarizations and ventricular arrhythmias in rabbits.
Authors: Takahashi N , Ito M , Ishida S , Fujino T , Saikawa T , Arita M 
Published: June 2012

BACKGROUND
Previous evidence has shown that increased sympathetic tone enhances the cesium chloride (Cs)-induced early afterdepolarizations (EADs) and ventricular tachycardias (VTs).

METHODS AND RESULTS
We assessed the effects of vagal stimulation on Cs-induced EADs and ventricular arrhythmias in the rabbit heart. Monophasic action potentials (MAPs) of the left ventricular endocardium were recorded simultaneously with surface ECG. Two protocols were used: 1) While in their intrinsic sinus rhythm, 11 rabbits were given three intravenous Cs injections (1 mM/kg) 20 minutes apart, and the effects of vagal stimulation on the ventricular arrhythmias thus induced were examined. 2) Under constant atrial pacing (cycle length, 250 msec), EAD amplitude was measured after Cs injection (1 mM/kg) without (five rabbits, control group) or with (four rabbits, vagal stimulation group) vagal stimulation. We observed the following. 1) Cs produced EADs and VTs of polymorphic (PVT) and monomorphic (MVT) types. During PVT, the take-off potential of repetitive premature action potentials in MAP recordings was about the same as the peak level of EADs, and during MVT, the take-off potential was the level of full repolarization. Vagal stimulation suppressed PVT but not MVT. Vagal stimulation after spontaneous termination of MVT restarted MVT of the same morphology at a rate much slower than the preceding sinus rate. 2) EAD amplitude was significantly smaller in the vagal stimulation group than in the control group.

CONCLUSIONS
The results suggest that PVT originated from triggering by EADs, whereas MVT was of different origin, and that vagal stimulation suppressed PVT by decreasing the amplitude of EADs.