bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of surgical relief of outflow obstruction on thallium perfusion abnormalities in hypertrophic cardiomyopathy.
Authors: Cannon R O , Dilsizian V , O'Gara P T , Udelson J E , Tucker E , Panza J A , Fananapazir L , McIntosh C L , Wallace R B , Bonow R O 
Published: June 2012

BACKGROUND
To assess the impact of surgical relief of left ventricular outflow obstruction on myocardial perfusion abnormalities in patients with obstructive hypertrophic cardiomyopathy, 20 symptomatic patients who underwent a septal myectomy or mitral valve replacement were studied with assessment of myocardial perfusion during exercise by 201Tl emission computed tomography before and 6 months after surgery.

METHODS AND RESULTS
Before surgery, 15 patients had myocardial perfusion defects during exercise that completely normalized at rest, one patient had both reversible and fixed perfusion defects, two patients had fixed defects only, and two patients had normal exercise and rest thallium scans. After surgical relief of left ventricular outflow obstruction (basal gradient reduced from 62 +/- 40 to 7 +/- 12 mm Hg, p less than 0.001; peak provokable gradient reduced from 131 +/- 27 to 49 +/- 36 mm Hg, p less than 0.001), repeat exercise thallium studies showed complete normalization of perfusion defects in 11 patients, including the two patients with fixed defects alone before surgery, and improvement in the magnitude and distribution of perfusion defects in five additional patients. This was associated with a significant reduction in the number of patients with reversible regional defects (five patients compared with 13 patients before surgery, p = 0.026) and of patients with endocardial hypoperfusion (four patients compared with 12 patients before surgery, p = 0.024). Furthermore, increased lung uptake of thallium was noted in five patients after surgery, compared with 12 patients before surgery (p = 0.055). Only two patients with reversible perfusion defects before surgery had unchanged postoperative studies. However, four patients acquired new fixed defects as a consequence of surgery, and two of these four had the greatest severity and distribution of left ventricular hypertrophy by echocardiography. These four patients experienced a substantially greater decrease in ejection fraction (-26 +/- 15%) after surgery than the remaining patients (-3 +/- 14%, p less than 0.01).

CONCLUSIONS
Surgical relief of left ventricular outflow obstruction results in normalization or improvement of myocardial perfusion in the majority of patients with reversible and fixed perfusion defects by 201Tl scintigraphy. However, surgery may result in myocardial injury and scarring, with consequent decreased left ventricular ejection fraction in some patients.
Isolated presynaptic inotropic beta-adrenergic supersensitivity of the transplanted denervated human heart in vivo.
Authors: von Scheidt W , Böhm M , Schneider B , Reichart B , Erdmann E , Autenrieth G 
Published: June 2012

BACKGROUND
The regulation of contractility of the transplanted heart depends on circulating catecholamines resulting from cardiac denervation. Supersensitivity to circulating catecholamines may result from loss of presynaptic neuronal uptake or upregulation of postsynaptic beta-adrenergic receptors.

METHODS AND RESULTS
Dose-response curves using the beta-adrenergic receptor agonists isoprenaline (no neuronal uptake) and epinephrine (neuronal uptake) were performed in vivo. The inotropic response was measured echocardiographically as the increase of fractional shortening (delta FS) and the increase of the systolic pressure/dimension ratio (delta P/D). The inotropic response to increasing doses of isoprenaline (5-20 ng/kg.min) was identical in 36 heart transplant recipients compared with 13 control subjects: delta FS during 20 ng/kg.min isoprenaline amounted to 18.2 +/- 6.2% versus 17.4 +/- 4.0% (NS) and delta P/D to 2.3 +/- 1.2 mm Hg/mm versus 2.2 +/- 0.5 mm Hg/mm (NS), respectively. A vagally mediated indirect negative inotropic effect in the innervated hearts was excluded by identical inotropic responses to isoprenaline in control subjects without and after atropine pretreatment. The inotropic response to increasing doses of epinephrine (10-40 ng/kg.min) was significantly augmented in 13 heart transplant recipients compared with 11 control subjects: delta FS during 40 ng/kg.min epinephrine amounted to 19.9 +/- 2.6% versus 8.6 +/- 2.0% (p less than 0.001) and delta P/D to 2.3 +/- 0.9 mm Hg/mm versus 0.6 +/- 0.3 mm Hg/mm (p less than 0.001), respectively. Pretreatment with desipramine (blockade of neuronal uptake) in control subjects resulted in a significantly increased inotropic response: delta FS during 40 ng/kg.min epinephrine amounted to 17.6 +/- 3.6% (p less than 0.001 versus untreated controls, NS versus heart transplant recipients) and delta P/D to 1.7 +/- 0.8 mm Hg/mm (p less than 0.001 versus untreated controls, NS versus heart transplant recipients).

CONCLUSIONS
These findings provide evidence against a postsynaptic inotropic supersensitivity or subsensitivity of the beta-adrenergic receptor-effector system of the transplanted denervated human heart in vivo. However, a marked presynaptic inotropic supersensitivity is present because of denervation-associated loss of neuronal catecholamine uptake.
High-dose aspirin inhibits shear-induced platelet reaction involving thrombin generation.
Authors: Ratnatunga C P , Edmondson S F , Rees G M , Kovacs I B 
Published: June 2012

BACKGROUND
A unifying concept of explaining all pharmacological actions of aspirin by the irreversible blockage of the enzyme cyclooxygenase and therefore the inhibition of prostaglandin biosynthesis has left many unanswered questions.

METHODS AND RESULTS
Two hundred ninety-four patients taking 75 mg/day aspirin were tested 3 months after coronary artery bypass surgery. Platelet thromboxane formation (whole blood aggregation to arachidonate) was completely prevented in 80% of patients. Compared with matched healthy controls (n = 95), a significant platelet hyperreactivity was observed in patients (p less than 0.0001 versus less than 0.002). Ninety patients were advised to increase their daily dose of aspirin from 75 mg to 300 mg. Platelet reactivity retested 1 month after increasing the dose has significantly decreased (p = 0.0008; less than 0.0001), whereas it remained unchanged in those patients (n = 84) who continued with the same dose regimens. In normal subjects, ingestion of a single 600-mg aspirin significantly inhibited shear-induced platelet reaction.

CONCLUSIONS
It is concluded that aspirin does affect the platelet response to shear forces, but this requires higher dosage (greater than 300 mg/day), suggesting a mechanism probably different from that of interference with thromboxane formation.
Effect of alpha-adrenergic blockade with prazosin on large coronary diameter during exercise.
Authors: Baran K W , Bache R J , Dai X Z , Schwartz J S 
Published: June 2012

BACKGROUND
Exercise-induced dilation of coronary resistance vessels is limited by alpha-adrenergic mechanisms. However, the effect of alpha-adrenergic mechanisms on large coronary arteries during exercise is not known.

METHODS AND RESULTS
In the present study, sonomicrometry was used to measure circumflex coronary arterial diameter during treadmill exercise before and after alpha 1-adrenergic blockade with prazosin in eight instrumented dogs. Before infusion of prazosin, exercise caused a fall in coronary vascular resistance (2.1 +/- 0.4 to 1.6 +/- 0.2 units, p less than 0.05) and dilation of the circumflex coronary artery (4.66 +/- 0.37 to 4.79 +/- 0.34 mm, p less than 0.05). Intracoronary infusion of prazosin during exercise caused a further decrease in coronary vascular resistance (1.6 +/- 0.2 to 1.4 +/- 0.2 units, p less than 0.05) and a further increase in circumflex coronary arterial diameter (4.79 +/- 0.34 to 4.83 +/- 0.34 mm, p less than 0.05). Intracoronary infusion of vehicle without prazosin during exercise did not cause a further decrease in coronary vascular resistance or increase in coronary diameter. Prazosin caused no significant increase in heart rate, aortic pressure, or coronary blood flow. Therefore, both small coronary resistance vessels and large epicardial coronary arteries dilated during exercise and dilated further after alpha-adrenergic blockade.

CONCLUSIONS
This finding indicates that alpha 1-adrenergic activity during exercise limits dilation of both large and small coronary arteries.
T wave changes persisting after ventricular pacing in canine heart are altered by 4-aminopyridine but not by lidocaine. Implications with respect to phenomenon of cardiac 'memory'.
Authors: del Balzo U , Rosen M R 
Published: June 2012

BACKGROUND
Cardiac "memory" refers to changes in T wave polarity induced by ventricular pacing that persist long after resumption of normal atrioventricular conduction.

METHODS AND RESULTS
We studied the occurrence and mechanism of T wave changes in the open-chest anesthetized dog subjected to three discontinuous 20-minute periods of right ventricular pacing. ECG changes were recorded in the standard limb leads during normal conduction (prepacing) and three trains (T1, T2, and T3) of right ventricular pacing at a rate 50% higher than normal (pacing), each followed by a period of normal conduction (postpacing) lasting as long as necessary for T wave changes to return to control values. During each of these phases, heart rate, QRS, corrected QT (QTc) duration, and T wave amplitude were measured. In the first group (control), T wave inversions occurred during normal atrioventricular conduction after a period of right ventricular pacing. These T wave anomalies appeared in the absence of any change in heart rate, QRS, or QTc duration. The magnitude of the T wave amplitude change was significantly greater after each successive pacing period. Furthermore, the changes in T wave morphology persisted for a longer period after each successive pacing train. In a second experimental group, lidocaine, which depresses the sodium window current, was administered to six dogs that were subjected to the same pacing protocol. Lidocaine decreased the QTc interval and prolonged QRS duration but did not alter the magnitude of changes in T wave amplitude and time to recovery described in control animals during the three postpacing intervals. In contrast, in the third group, 4-aminopyridine, a drug that blocks the transient outward current (ito), abolished the changes in T wave morphology that occurred during any postpacing interval.

CONCLUSIONS
These results demonstrate that the manifestation of cardiac memory in the in situ dog heart is not altered by lidocaine but is abolished by 4-aminopyridine. Thus, cardiac memory may be based on a physiological property of the myocardium that is related to specific K+ channels.
Altered myocardial force-frequency relation in human heart failure.
Authors: Mulieri L A , Hasenfuss G , Leavitt B , Allen P D , Alpert N R 
Published: June 2012

BACKGROUND
In congestive heart failure (idiopathic dilated cardiomyopathy), exercise is accompanied by a smaller-than-normal decrease in end-diastolic left ventricular volume, depressed peak rates of left ventricular pressure rise and fall, and depressed heart-rate-dependent potentiation of contractility (bowditch treppe). We studied contractile function of isolated left ventricular myocardium from New York Heart Association class IV-failing and nonfailing hearts at physiological temperature and heart rates in order to identify and quantitate abnormalities in myocardial function that underlie abnormal ventricular function.

METHODS AND RESULTS
The isometric tension-generating ability of isolated left ventricular strips from nonfailing and failing human hearts was investigated at 37 degrees C and contraction frequencies ranging from 12 to 240 per minute (min-1). Strips were dissected using a new method of protection against cutting injury with 2,3-butanedione monoxime (BDM) as a cardioplegic agent. In nonfailing myocardium the twitch tension-frequency relation is bell-shaped developing 25 +/- 2 mN/mm2 at a contraction frequency of 72 min-1 and peaking at 44 +/- 3.7 mN/mm2 at a contraction frequency of 174 +/- 4 min-1. In failing myocardium the peak of the curve occurs at lower frequencies between 6 and 120 min-1 averaging 81 +/- 22 min-1, and it develops 48% (p less than 0.001) and 80% (p less than 0.001) less tension than in nonfailing myocardium at 72 and 174 min-1, respectively. Between 60 and 150 min-1 tension increases by 107% in nonfailing myocardium, but it does not change significantly in failing myocardium. Peak rates of rise and fall of isometric twitch tension vary in parallel with twitch tension as stimulation frequency rises in nonfailing myocardium but not in failing myocardium.

CONCLUSIONS
The quantitative agreement between these results from isolated myocardium and those from catheterization laboratory measurements on intact humans suggest that alterations of myocardial origin, independent of systemic factors, may contribute to the above mentioned abnormalities in left ventricular function seen in dilated cardiomyopathy.
Sympathetic nervous function in human heart as assessed by cardiac spillovers of dihydroxyphenylglycol and norepinephrine.
Authors: Eisenhofer G , Esler M D , Meredith I T , Dart A , Cannon R O , Quyyumi A A , Lambert G , Chin J , Jennings G L , Goldstein D S 
Published: June 2012

BACKGROUND
Measurement of cardiac norepinephrine spillover may indicate the amount of transmitter at neuroeffector sites but does not distinguish neuronal release or reuptake in determining this amount or provide information about other aspects of sympathetic function. This report examines how cardiac spillover of the norepinephrine metabolite dihydroxyphenylglycol (DHPG) provides additional distinct information about cardiac sympathetic function.

METHODS AND RESULTS
Arterial and coronary venous blood samples were taken during cardiac catheterization and intravenous infusion of [3H]norepinephrine in 57 subjects. Subjects were given intravenous yohimbine or underwent mental stress, handgrip exercise, and cycling exercise to activate sympathetic nerves or were given intravenous desipramine to block norepinephrine reuptake. Cardiac DHPG spillover (601 +/- 41 pmol/min) was eightfold greater than norepinephrine spillover (78 +/- 10 pmol/min) at rest and increased during sympathetic activation by 65% of the increase of norepinephrine. This and the desipramine-sensitive cardiac production of [3H]-labeled DHPG from [3H]norepinephrine indicated that 10.5 times more endogenous norepinephrine is recaptured than escapes into plasma; that more than 90% of recaptured norepinephrine is sequestered into storage vesicles; and that under resting conditions, most cardiac spillover of DHPG and turnover of norepinephrine are from metabolism of transmitter leaking from vesicles; the latter process is independent of exocytotic transmitter release with a rate at rest over 100-fold that of norepinephrine spillover and over 10-fold that of norepinephrine reuptake.

CONCLUSIONS
Cardiac spillover of DHPG provides information about processes close to or within sympathetic nerve endings that cannot be provided by measurements of norepinephrine spillover alone. This includes quantitative information about the role of neuronal uptake in terminating the actions of norepinephrine at neuroeffector sites and the importance of vesicular-axoplasmic exchange of norepinephrine as a dynamic process contributing to norepinephrine turnover.
Prevalence of circadian variations and spontaneous variability of cardiac disorders and ECG changes suggestive of myocardial ischemia in systemic arterial hypertension.
Authors: Zehender M , Meinertz T , Hohnloser S , Geibel A , Gerisch U , Olschewski M , Just H 
Published: June 2012

BACKGROUND
Systemic hypertension is a well-known risk factor for coronary artery disease and sudden cardiac death. Recent interest focused on the presence of malignant ventricular arrhythmias (VA) and myocardial ischemia in hypertensive patients and provided a potential link for fatal tachyarrhythmic events.

METHODS AND RESULTS
We studied 150 untreated normokalemic hypertensive patients (56 +/- 9 years; 56 women and 94 men) without manifest coronary artery disease to determine prevalence, severity, and interaction of VA and significant ST segment changes induced by daily activities. One third of the patients were randomized to 4 weeks of placebo and restudied for spontaneous variability of the two parameters. All patients were included in a 3-year follow-up study. VA were observed in 129 of 150 hypertensive patients (86%) and peaked in the early morning and late afternoon. Twenty-two patients (15%) had ventricular pairs, and 20 patients (13%) had nonsustained ventricular tachycardia. Transient ST segment depression observed in 47 patients (33%; mean incidence, 2.7 +/- 0.8 episodes/24 hr) showed a characteristic circadian variation similar to VA and were asymptomatic in 93% of the episodes. At the time of transient ST segment depression, VA increased 4.6 times (p less than 0.01). After 4 weeks of placebo, marked variations in the incidence of VA (VA suppression rate -100%, or increase greater than 400%) were observed in 29% of the patients, and in 60% of all patients repetitive VA were present in only one of the two Holter recordings. Day-and-night variations of VA and transient ST segment changes were highly reproducible during the placebo period. After 3 years of follow-up, eight of 146 patients (5%) had suffered myocardial infarction, and five patients had died from cardiac events (three patients died from sudden cardiac death). Logistic regression analysis revealed left ventricular hypertrophy (relative risk, 6.1; p less than 0.01) and transient ST segment abnormalities during daily activities (relative risk, 4.4; p less than 0.05) to be of independent prognostic significance to predict cardiac events during follow-up instead of repetitive VA (relative risk, 1.3; NS).

CONCLUSIONS
VA associated with a high spontaneous variability and predominantly asymptomatic transient ST segment changes are common in hypertensives; the interaction of both risk factors may provide an important link for fatal VA. Antiarrhythmic therapy is not to be recommended in the majority of patients. Presence of left ventricular hypertrophy and transient ST segment changes were the most powerful predictors of cardiac events during the follow-up.
Baseline fibrinolytic state and the risk of future venous thrombosis. A prospective study of endogenous tissue-type plasminogen activator and plasminogen activator inhibitor.
Authors: Ridker P M , Vaughan D E , Stampfer M J , Manson J E , Shen C , Newcomer L M , Goldhaber S Z , Hennekens C H 
Published: June 2012

BACKGROUND
Although isolated abnormalities of plasminogen activation and inhibition have been reported among selected patients with venous thrombosis, it is unclear whether these deficiencies of fibrinolysis are important risk factors for thromboembolic disease.

METHODS AND RESULTS
To evaluate whether baseline levels of endogenous tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) predict the future occurrence of venous thrombosis, levels of these proteins were measured in prospectively collected plasma samples from 55 participants in the Physicians' Health Study who later developed deep venous thrombosis or pulmonary embolism and from an equal number of age- and smoking-matched control subjects who remained free of vascular disease during a mean follow-up period of 60.2 months. Overall, there were no statistically significant differences between case patients and control subjects in baseline levels of PAI-1 (50.5 versus 59.5 ng/ml, p = 0.26), t-PA (13.4 versus 13.3 ng/ml, p = 0.94), or PAI-1:t-PA ratio (6.84 versus 6.58, p = 0.82). No evidence of a threshold effect or trend was seen when these data were analyzed by increasing quartiles of PAI-1 (p = 0.73), t-PA (p = 0.62), or PAI-1:t-PA ratio (p = 0.93). These results were unchanged after multivariate analysis that simultaneously controlled for other baseline cardiovascular risk factors.

CONCLUSIONS
In contrast to previous uncontrolled case series and smaller retrospective studies, these prospective data provide strong evidence that baseline fibrinolytic state, as measured by t-PA and PAI-1, does not predict the occurrence of future venous thrombosis.
Echo-wave termination of ventricular tachycardia. A common mechanism of termination of reentrant arrhythmias by various pharmacological interventions.
Authors: Brugada J , Boersma L , Abdollah H , Kirchhof C , Allessie M 
Published: June 2012

BACKGROUND
Based on epicardial mapping, different mechanisms of termination of reentrant ventricular tachycardia by various pharmacological interventions are described.

METHODS AND RESULTS
In 40 Langendorff-perfused rabbit hearts, rings of anisotropic left ventricular epicardium were made by a cryoprocedure. Sustained monomorphic ventricular tachycardia based on continuous circus movement of the impulse around the ring was induced by programmed stimulation. Increasing doses of heptanol (n = 10), potassium (n = 10), tetrodotoxin (n = 6), RP62719 (a new class III drug) (n = 4), flecainide (n = 5), and propafenone (n = 5) were administered to terminate ventricular tachycardia. Epicardial mapping (248 points) was used to study the mechanism of termination of ventricular tachycardia. In 28 of 40 hearts, ventricular tachycardia terminated because the drugs produced complete conduction block of the impulse in a segment of the reentrant pathway. In the remaining 12 hearts (heptanol, n = 2; potassium, n = 3; tetrodotoxin, n = 2; RP62719, n = 2; flecainide, n = 1; and propafenone, n = 2), termination of ventricular tachycardia occurred by collision of the circulating impulse with a spontaneous antidromic wave front reflected within the circuit. This phenomenon occurred when the circulating impulse encountered an arc of functional conduction block that did not extend along the whole width of the ring. As a result, the impulse dissociated into a continuing orthodromic circulating wave and a returning antidromic echo-wave caused by microreentry within the ring.

CONCLUSIONS
Independent of their mechanisms of action, sodium channel blockers, electrical uncouplers, and class III drugs terminate reentrant ventricular tachycardia either by complete conduction block or by collision of the impulse with an echo-wave.