bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic pulmonary thromboembolism in dogs treated with tranexamic acid.
Authors: Moser K M , Cantor J P , Olman M , Villespin I , Graif J L , Konopka R , Marsh J J , Pedersen C 
Published: June 2012

BACKGROUND
Many questions remain regarding the pathogenesis, natural history, diagnosis, and treatment of chronic thromboembolic pulmonary hypertension in patients. To answer such questions, we developed an animal model of this disorder. The brisk thrombolytic response of canines to acute embolism has, previously, prevented the establishment of such a model.

METHODS AND RESULTS
The fibrinolytic inhibitor tranexamic acid was given orally to canines before, and for intervals after, pulmonary emboli were released from venous thrombi formed in vivo in femoral veins or the inferior vena cava. Preliminary studies disclosed that embolic residuals from femoral vein thrombi were not sufficient to cause significant, persistent pulmonary hypertension. With repetitive, larger thrombi embolized from the inferior vena cava, however, persistent pulmonary hypertension was achieved in most animals.

CONCLUSIONS
Resolution of emboli in the canine can be inhibited by tranexamic acid. As in humans, a spectrum of embolic residuals is encountered, and the perfusion lung scan consistently underestimates the extent of embolic residuals. Studies of this animal model continue.
No effect of coronary perfusion on regional myocardial function within the autoregulatory range in pigs. Evidence against the Gregg phenomenon.
Authors: Schulz R , Guth B D , Heusch G 
Published: June 2012

BACKGROUND
The hypothesis that increases in coronary perfusion increase ventricular performance independently from providing enhanced oxygen supply ("Gregg phenomenon") remains controversial.

METHODS AND RESULTS
To study the physiological significance of changes in coronary perfusion on global and regional myocardial function in situ, the left anterior descending coronary artery of isoflurane-anesthetized swine was cannulated, and perfusion was varied. In one group of swine (n = 5), coronary arterial pressure was increased in four steps from 88 +/- 11 to 186 +/- 11 mm Hg by increasing the speed of the pump circuit providing coronary blood flow. No changes in left ventricular end-diastolic pressure, peak pressure, or maximum left ventricular dP/dt were observed. Subendocardial blood flow (by radiolabeled microspheres) increased from 0.96 +/- 0.27 to 2.04 +/- 0.73 ml/min/g without any increase in systolic wall thickening (by sonomicrometry) or myocardial oxygen consumption of the anterior myocardium. In a second group of swine (n = 8), coronary arterial pressure was kept constant and coronary blood flow was increased stepwise by intracoronary adenosine infusion. End-diastolic pressure, peak pressure, and maximum left ventricular dP/dt remained unchanged when coronary blood flow increased from 21.7 +/- 9.8 to 93.8 +/- 34.1 ml/min. Subendocardial blood flow increased from 0.89 +/- 0.26 to 3.28 +/- 1.02 ml/min/g, again without any increase in systolic wall thickening (45.6 +/- 8.6 versus 42.6 +/- 9.8%) and myocardial oxygen consumption (5.75 +/- 1.18 versus 5.87 +/- 1.67 ml/min/100 g). In a third group of swine (n = 10), coronary arterial pressure was lowered by intracoronary adenosine infusion during constant coronary inflow. Left ventricular hemodynamics remained unchanged. With a decrease in coronary arterial pressure from 130 +/- 25 to 71 +/- 14 mm Hg, no decreases in subendocardial blood flow and systolic wall thickening were observed. Only when coronary arterial pressure was further reduced to 57 +/- 13 mm Hg did systolic wall thickening fall to 25.7 +/- 9.9% (control, 31.1 +/- 11.1%), associated with a decrease in subendocardial blood flow from 1.17 +/- 0.39 to 0.87 +/- 0.52 ml/min/g.

CONCLUSIONS
Thus, the Gregg phenomenon plays no significant role within or above the autoregulatory pressure-flow range normally seen in anesthetized swine in situ.
On the mechanisms of ventricular tachycardia acceleration during programmed electrical stimulation.
Authors: Brugada J , Brugada P , Boersma L , Mont L , Kirchhof C , Wellens H J , Allessie M A 
Published: June 2012

BACKGROUND
The pathophysiological mechanisms leading to acceleration of ventricular tachycardia (VT) are still unclear.

METHODS AND RESULTS
High-resolution epicardial mapping was used to study the mechanisms of VT acceleration by programmed electrical stimulation (PES) in a model of sustained reentrant VT in Langendorff-perfused rabbit hearts (n = 40). Three different mechanisms responsible for acceleration of VT were identified: 1) induction of double-wave reentry (n = 6), defined as the occurrence of two successive activation waves circulating in the same direction in the same circuit; 2) change to a functionally determined circuit (n = 4), defined as reentry of the impulse around a functional line of block without involvement of a fixed obstacle; and 3) change of the reentrant circuit to reentry within a different, faster anatomic pathway (n = 3). Analysis of 81 episodes of sustained monomorphic VT induced by PES in 74 patients with clinically documented sustained VT in the setting of chronic coronary artery disease showed that in 22 episodes VT was suddenly accelerated by PES (mean cycle length, from 345 +/- 73 to 277 +/- 71 msec, p less than 0.01).

CONCLUSIONS
With the observations made in the experimental model, the following tentative classification of the mechanisms of VT acceleration of the 22 episodes was made: 1) induction of double-wave reentry in two, 2) change to a functionally determined circuit in four, and 3) change to reentry within a faster anatomic circuit in 16. Simple criteria suggest that these mechanisms may apply in the clinical situation.
Circus movement atrial flutter in canine sterile pericarditis model. Activation patterns during entrainment and termination of single-loop reentry in vivo.
Authors: Schoels W , Restivo M , Caref E B , Gough W B , el-Sherif N 
Published: June 2012

BACKGROUND
Recently, we used a custom designed "jacket" electrode with 127 bipolar electrodes in a flexible nylon matrix to map the total atrial epicardial surface in the in situ canine heart. Atrial flutter in dogs with sterile pericarditis was shown to be due to a single wave front circulating around a combined functional/anatomic obstacle, with the arc of functional conduction block contiguous with one or more of the atrial vessels.

METHODS AND RESULTS
In the present study, this model was used to analyze the activation pattern during pacing-induced entrainment and termination of single reentrant loops in a syncytium without anatomically predetermined pathways. Sustained atrial flutter was induced in five dogs with 3-5-day-old sterile pericarditis. Atrial pacing at a cycle length 5-30 msec shorter than the spontaneous cycle length entrained the arrhythmia and could result in a "classical" activation pattern, characterized by an antidromic stimulated wave that collided with the reentrant orthodromic wave front of the previous beat at a constant site. However, two variations of this classical activation pattern were also observed: 1) Pacing at short cycle lengths could lead to localized conduction block in antidromic direction, forcing a change in the pathway of the antidromic wave front. This could prevent the expected shift of the site of collision in antidromic direction. 2) The stimulated orthodromic wave front could also use a pathway different from that of the original reentrant impulse, so that a different circuit was active during the pacing period. Termination of atrial flutter by rapid atrial stimulation was associated with progressive slowing and finally blocking of the paced orthodromic wave front and a progressive shift of the site of collision in antidromic direction. The occurrence of conduction block was determined by the cycle length of stimulation and the number of stimulated beats. A longer train at the critical cycle length or the critical number of beats at a shorter cycle length could reinduce the same reentrant circuit or a different reentrant circuit, respectively, during stimulated cycles following the beat that terminated reentry.

CONCLUSIONS
The epicardial activation sequence during entrainment of reentrant arrhythmias does not necessarily follow a standard activation pattern. Instead, the stimulated orthodromic as well as the antidromic wave front might use a pathway different from that of the original reentrant wave front. The mechanisms of termination, failure of termination, and reinitiation of single-loop reentry are similar to those in the "figure-eight" reentrant circuit.
Response of atrial natriuretic factor to acute and chronic increases of atrial pressures in experimental heart failure in dogs. Role of changes in heart rate, atrial dimension, and cardiac tissue concentration.
Authors: Moe G W , Grima E A , Angus C , Wong N L , Hu D C , Howard R J , Armstrong P W 
Published: June 2012

BACKGROUND
This study evaluated the role of changes in heart rate, atrial pressure, volume, and cardiac tissue atrial natriuretic factor (ANF) concentration in the modulation of plasma ANF concentration in a model of pacing-induced heart failure.

METHODS AND RESULTS
The effects of acute right ventricular pacing (250 beats/min), acute volume expansion (35 ml/min), and volume expansion after 1 week of right ventricular pacing on plasma ANF concentration were compared in eight dogs (group 1). As shown during right ventricular pacing previously, volume expansion produced significant increases in cardiac filling pressures and left atrial volume. Right ventricular pacing and volume expansion produced similar increments in plasma ANF concentration: from 32 +/- 12 to 168 +/- 153 pg/ml (p less than 0.05) and from 32 +/- 9 to 137 +/- 113 pg/ml (p less than 0.05), respectively. When pacing was initiated after volume expansion, plasma ANF concentration increased further to 462 +/- 295 pg/ml (p less than 0.05) despite little change in filling pressures and left atrial volume. With repeated volume expansion after 1 week of pacing, there were no significant further increases in left atrial volume and plasma ANF concentrations (from 332 +/- 121 to 407 +/- 113 pg/ml) despite significant increases in filling pressures. Atrial and ventricular tissue samples were also obtained from 21 dogs paced to severe heart failure (group 2) and from 14 normal dogs (controls). In all groups, atrial ANF was higher than ventricular ANF concentration. At 1 week (group 1), left atrial appendage ANF concentration (6.2 +/- 2.5 versus 16.1 +/- 10.3 ng/mg) was reduced, whereas left ventricular free wall ANF concentration (0.62 +/- 0.31 versus 0.24 +/- 0.16 pg/mg) was increased compared with that of controls (both p less than 0.001). At severe heart failure (group 2), atrial ANF remained low, whereas ventricular ANF concentration was similar to that of the controls.

CONCLUSIONS
These data indicate that in pacing-induced heart failure, changes in heart rate, atrial pressure, and volume all contribute to the increased plasma ANF concentration. However, by 1 week (early heart failure), ANF release is attenuated, perhaps because of the inability of the atria to be stretched further and because of reduced atrial ANF concentration. In addition, the ventricle may be an additional source of ANF.
Hemodynamic and electrophysiological actions of cocaine. Effects of sodium bicarbonate as an antidote in dogs.
Authors: Beckman K J , Parker R B , Hariman R J , Gallastegui J L , Javaid J I , Bauman J L 
Published: June 2012

BACKGROUND
Cocaine abuse has been implicated as a cause of death due to sudden cardiac arrest.

METHODS AND RESULTS
We examined the hemodynamic and electrophysiological effects of cocaine administered as a series of 5-mg/kg i.v. boluses coupled with a continuous infusion in anesthetized dogs. Sodium bicarbonate (50 meq i.v.) was administered as a potential antidote in 11 of 15 dogs, and intravenous 5% dextrose was given in the remaining four. In a dose-dependent fashion, cocaine significantly decreased blood pressure, coronary blood flow, and cardiac output; increased PR, QRS, QT, and QTc intervals and sinus cycle length; and increased ventricular effective refractory period and dispersion of ventricular refractoriness. No afterdepolarizations were noted in the monophasic action potential recording. Nonsustained monomorphic ventricular tachycardia occurred spontaneously in two dogs, and sustained ventricular tachycardia could be induced by programmed stimulation at the end of the dosing protocol in five of 11 animals. Sodium bicarbonate promptly decreased cocaine-induced QRS prolongation to nearly that measured at baseline but had no effect on the other electrocardiographic or hemodynamic variables. In one dog, sodium bicarbonate administration was associated with reversion of ventricular tachycardia to sinus rhythm.

CONCLUSIONS
We conclude that high-dose cocaine possesses negative inotropic and potent type I electrophysiological effects. Sodium bicarbonate selectively reversed cocaine-induced QRS prolongation and may be a useful treatment of ventricular arrhythmias associated with slowed ventricular conduction in the setting of cocaine overdose.
Kinetics of use-dependent ventricular conduction slowing by antiarrhythmic drugs in humans.
Authors: Ranger S , Talajic M , Lemery R , Roy D , Villemaire C , Nattel S 
Published: June 2012

BACKGROUND
Rate-dependent conduction slowing by class I antiarrhythmic agents has clinically important consequences. Class I drugs are known to produce use-dependent sodium channel blockade. If rate-dependent conduction slowing by class I agents is due to sodium channel blocking actions, the kinetics of conduction slowing should be similar to those of depression of sodium current indexes in vitro. The purpose of the present investigation was to study the onset time course of ventricular conduction slowing caused by a variety of class I agents in humans.

METHODS AND RESULTS
Twenty-seven patients undergoing electrophysiological evaluation for antiarrhythmic therapy were studied. Changes in QRS duration at initiation of ventricular pacing at cycle lengths of 400 and 500 msec were used to evaluate the kinetics of drug action. Mean time constants for each drug were similar to values for Vmax depression reported in vitro studies: flecainide, 24.9 +/- 11.6 beats in eight patients (versus 34.5 beats reported for Vmax block); propafenone, 17.8 +/- 6.9 beats in five patients (versus 8.4-20.8 beats); quinidine, 7.0 +/- 2.4 beats in six patients (versus 5.6-6.2 beats); and amiodarone, 3.6 +/- 2.0 beats for eight patients (versus 3.0 beats). Time constants were significantly different among the various drugs tested (p = 0.0002 at a cycle length of 400 msec; p = 0.002 at 500 msec), and there was a strong correlation (r = 0.89, p less than 0.0001) between values obtained at a cycle length of 400 msec and those at a cycle length of 500 msec. No rate-dependent changes in QRS duration were seen at onset of ventricular pacing among eight age- and disease-matched control patients not taking class I antiarrhythmic drugs, including three patients subsequently showing such changes during type I antiarrhythmic drug therapy.

CONCLUSIONS
We conclude that class I agents produce use-dependent QRS prolongation in humans with characteristic kinetics for each agent that are similar to the kinetics of Vmax depression in vitro. These results suggest that rate-dependent ventricular conduction slowing by antiarrhythmic drugs in humans is due to use-dependent sodium channel blockade.
Left ventricular diastolic collapse. An echocardiographic sign of regional cardiac tamponade.
Authors: Chuttani K , Pandian N G , Mohanty P K , Rosenfield K , Schwartz S L , Udelson J E , Simonetti J , Kusay B S , Caldeira M E 
Published: June 2012

BACKGROUND
Cardiac tamponade after cardiac surgical procedures is often associated with hemodynamically significant localized pericardial effusions. The localized collection of pericardial effusion in the postoperative period and the atypical presentation of cardiac tamponade limit the use of conventional clinical and echocardiographic signs usually seen with a circumferential pericardial effusion. Observation of left ventricular diastolic collapse in the echocardiogram of a patient with postoperative regional cardiac tamponade prompted us to explore the frequency of this sign in regional cardiac tamponade.

METHODS AND RESULTS
We retrospectively analyzed the echocardiograms of 18 patients with postoperative cardiac tamponade for the following echocardiographic findings: right atrial collapse, right ventricular diastolic collapse, left atrial collapse, and left ventricular diastolic collapse. Three of the 18 patients had circumferential pericardial effusion, and 15 had loculated pericardial effusion; in 10, the effusion was predominantly posterior, and in the other five, it extended laterally or inferiorly. The conventional echocardiographic signs of cardiac tamponade such as right atrial collapse, right ventricular diastolic collapse, and left atrial collapse were present in only 3, 1, and 3 of these 15 patients, respectively, but all exhibited left ventricular diastolic collapse. Increasing pressure within the compartment of a loculated pericardial effusion reaching the limit of pericardial distensibility and consequent transient reversal of transmural left ventricular pressure during diastole are most likely the basis for diastolic collapse of the thick-walled ventricle in a setting of regional cardiac tamponade.

CONCLUSIONS
We conclude that left ventricular diastolic collapse is a frequent sign of regional cardiac tamponade and could be a useful marker of tamponade in postoperative patients.
Abnormal automatic rhythms in ischemic Purkinje fibers are modulated by a specific alpha 1-adrenergic receptor subtype.
Authors: Anyukhovsky E P , Rosen M R 
Published: June 2012

BACKGROUND
Recent advances in adrenergic pharmacology have made possible the identification of alpha 1-adrenergic receptor subtypes using the specific blockers chloroethylclonidine and WB 4101.

METHODS AND RESULTS
In the present study, we used these two blockers to determine the mechanisms responsible for automatic rhythms occurring during simulated ischemia and reperfusion of isolated canine Purkinje fibers. Experiments were done in the presence of propranolol to minimize beta-adrenergic contributions to the rhythms studied. In the control situation, all fibers showed membrane potentials greater than -90 mV and normal automatic rhythms. During simulated ischemia, membrane potential depolarized to the -60 mV range. Abnormal automaticity was seen in 20% of fibers not treated with phenylephrine and in 50% of those superfused with 1 x 10(-7) M phenylephrine. The incidence of abnormal automaticity was reduced to 0% by WB 4101 (which blocks phosphoinositide metabolic effects of alpha 1-adrenergic stimulation in the heart) and was increased to 90% by chloroethylclonidine (which blocks Na-K pump-stimulating effects of alpha-agonists). Moreover, the ischemic fibers were significantly more hyperpolarized during superfusion with WB 4101 than with chloroethylclonidine. Triggered activity induced by delayed or early after depolarizations was not seen in any experiment.

CONCLUSIONS
Automatic arrhythmias induced by alpha 1-adrenergic stimulation during simulated ischemia may be attributed to a specific alpha 1-adrenergic receptor subtype that is blocked by WB 4101. These results have important implications with respect to the induction of arrhythmias in the setting of ischemia and the means for their prevention or treatment.
Effect of calcification on in vivo mechanical response of rabbit arteries to balloon dilation.
Authors: Demer L L 
Published: June 2012

BACKGROUND
Atherosclerosis has been associated with loss of artery wall distensibility in human cadavers and in experimental animal models, giving it the lay term "hardening of the arteries."

METHODS AND RESULTS
To assess the effect of calcification on arterial distensibility, balloon pressure and volume were recorded during dilation of calcified aortas in Watanabe heritable hyperlipidemic (WHHL) rabbits in vivo. Calcification was induced by dietary supplements of cholesterol, vitamin D2, and calcium. Balloon pressure, volume, and time signals were acquired at high frequency with controls for temperature and balloon inflation rate. Resistance to balloon dilation was minimal in control rabbit aortas (delta Vmax = 5.0 +/- 3.5 microliters) and in excised nonatherosclerotic human coronary arteries, and it was small in aortas from cholesterol-fed rabbits (12.3 +/- 8 microliters), even when lipid levels were markedly elevated by a high cholesterol diet (611 +/- 347 mg/dl). With dietary cholesterol, vitamin D2, and calcium supplements, WHHL rabbits developed mild hypercalcemia (15 +/- 1.9 mg/dl), hypercholesterolemia (1,100 +/- 633 mg/dl), moderate-to-marked aortic calcification, and high resistance to balloon dilation (38 +/- 27) comparable to that seen in angioplasty patients.

CONCLUSIONS
It is concluded that experimentally induced calcification decreases the distensibility of the rabbit aorta in vivo and that it yields to balloon dilation by plastic deformation closely resembling that seen in balloon angioplasty of human coronary arteries. These findings suggest that calcification contributes to arterial "hardening" associated with atherosclerosis.
Fetal cardiovascular morphology of truncus arteriosus with or without truncal valve insufficiency in the rat.
Authors: Momma K , Ando M , Takao A , Miyagawa-Tomita S 
Published: June 2012

BACKGROUND
Recent advances in fetal echocardiography have necessitated further study on fetal in situ cardiovascular morphology of truncus arteriosus and the effects of truncal valve insufficiency.

METHODS AND RESULTS
We studied 55 fetal rats with truncus arteriosus among 300 fetuses from 40 virgin females treated with 200 mg fertilysin on the 10th day of pregnancy. After rapid whole-body freezing on the 21st day, the fetuses were studied by means of serial cross-sectional photographs of the frozen thorax. Thirty-five fetuses with a normal heart treated with fertilysin served as controls. Truncus arteriosus was characterized by a large ventricular septal defect, a solitary artery (truncus arteriosus) overriding the ventricular septum, the right and left pulmonary arteries originating from the truncus arteriosus with or without a common trunk (main pulmonary artery), and absent ductus arteriosus. Fetuses with truncal valve insufficiency had thick truncal valves, a large truncus arteriosus, and large ventricles. The subgroup of 12 fetuses with a large truncus (truncal diameter greater than 160% of the ascending aorta diameter in the controls) showed significantly greater values for right ventricular volume (200% of control) and mass (120% of control), left ventricular volume (170% of control) and mass (110% of control), right (120% of control) and left (110% of control) atrial volume, and pericardial fluid (140% of control) than the controls. These changes were less prominent and ventricular volumes were not increased in the remaining subgroup with a truncal diameter of 160% or less of aorta diameter in the controls.

CONCLUSIONS
In fetal truncus arteriosus, truncal valve insufficiency was associated with increased ventricular volume load and incomplete cardiac compensation in rats.