bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diminishment of respiratory sinus arrhythmia foreshadows doxorubicin-induced cardiomyopathy.
Authors: Hrushesky W J , Fader D J , Berestka J S , Sommer M , Hayes J , Cope F O 
Published: June 2012

BACKGROUND
The development of a microcomputer-based device permits quick, simple, and noninvasive quantification of the respiratory sinus arrhythmia (RSA) during quiet breathing.

METHODS AND RESULTS
We prospectively and serially measured the radionuclide left ventricular ejection fraction and the RSA amplitude in 34 cancer patients receiving up to nine monthly bolus treatments with doxorubicin hydrochloride (60 mg/m2). Of the eight patients who ultimately developed symptomatic doxorubicin-induced congestive heart failure, seven (87.5%) demonstrated a significant decline in RSA amplitude; five of 26 subjects without clinical symptoms of cardiotoxicity (19.2%) showed a similar RSA amplitude decline. On average, significant RSA amplitude decline occurred 3 months before the last planned doxorubicin dose in patients destined to develop clinical congestive heart failure.

CONCLUSION
Overall, RSA amplitude abnormality proved to be a more specific predictor of clinically significant congestive heart failure than did serial resting radionuclide ejection fractions.
Contrasting effects of digitalis and dobutamine on baroreflex sympathetic control in normal humans.
Authors: Schobel H P , Oren R M , Roach P J , Mark A L , Ferguson D W 
Published: June 2012

BACKGROUND
Digitalis glycosides augment cardiopulmonary baroreceptor mechanisms in animals. This could result from inotropic actions or from direct sensitization of cardiac mechanoreceptors.

METHODS AND RESULTS
To determine if digitalis has similar actions in humans and to evaluate the mechanisms involved, we measured muscle sympathetic nerve activity (MSNA; microneurography) during unloading of cardiopulmonary baroreceptors with incremental lower body negative pressure (LBNP; 0 to -15 mm Hg) and during the cold pressor test in 22 normal subjects (age 22 +/- 1 year, mean +/- SEM). Arterial and central venous pressures, heart rate, and MSNA were measured during LBNP before and after intravenous digitalis (Cedilanid 0.02 ng/kg, n = 8), dobutamine (2.8 +/- 0.5 micrograms/kg/min, n = 8), or placebo (n = 6). Digitalis and dobutamine produced similar increases in baseline mean arterial pressure and decreases in central venous pressure and MSNA. LBNP produced similar decreases in central venous pressure in all groups before and after drug administration. The MSNA responses to LBNP were markedly potentiated by digitalis but not by dobutamine or placebo.

CONCLUSIONS
Digitalis did not alter responses to the cold pressor test. Thus, digitalis selectively potentiated cardiopulmonary baroreflex regulation of sympathetic neural responses in normal humans, whereas dobutamine (another positive inotropic agent) did not produce this effect. We conclude that digitalis augments cardiopulmonary baroreflex control of sympathetic activity, probably by direct baroreceptor sensitization.
Balloon angioplasty for recurrent coarctation of aorta. Immediate and long-term results.
Authors: Hijazi Z M , Fahey J T , Kleinman C S , Hellenbrand W E 
Published: June 2012

BACKGROUND
As angioplasty techniques have been refined and larger low-profile balloons developed, a nonsurgical approach to recoarctation has become available. Several reports have documented both the efficacy and safety of this procedure. However, there are little data available on the long-term follow-up of these patients. This report details the initial results and long-term evaluation of both the relief of obstruction and the presence of hypertension after balloon angioplasty for recurrent coarctation.

METHODS AND RESULTS
Balloon angioplasty for recurrent coarctation of the aorta was performed 29 times in 26 patients at a median age of 4 years and 9 months (range, 4 months to 29 years), with eight patients less than 1 year old. Initial surgical techniques were end-to-end anastomosis in 11 patients, subclavian flap aortoplasty in 11 patients, and patch aortoplasty in four patients. Angioplasty was performed at a median interval of 2 years and 7 months (range, 4 months to 23 years) after surgery. Mean peak systolic pressure difference across the coarctation decreased from 40.0 +/- 16.8 to 10.3 +/- 9.5 mm Hg (p less than 0.05) after the initial angioplasty, and mean diameter of the aortic lumen at the coarctation site increased from 5.8 +/- 3.5 to 9.0 +/- 4.3 mm (p less than 0.05). There was no mortality, and only one patient developed an aneurysm (4%). Three patients underwent repeat angioplasty for a pressure difference of more than 20 mm Hg. Long-term follow-up is available on 24 of 26 patients with a mean follow-up of 42 +/- 24 months (range, 12-88 months). Mean peak systolic pressure difference across the area of coarctation decreased from 40.3 +/- 17.4 before angioplasty to 8.5 +/- 8.3 mm Hg after final angioplasty (p less than 0.05) and 7.5 +/- 7.5 mm Hg at follow-up. Mean peak systolic blood pressure in the upper extremities decreased from 133.1 +/- 14.9 before angioplasty to 111.1 +/- 14.1 mm Hg at long-term follow-up (p less than 0.05).

CONCLUSIONS
Balloon angioplasty should be considered the treatment of choice for relief of recurrent aortic coarctation.
Dobutamine increases cardiac output of the total artificial heart. Implications for vascular contribution of inotropic agents to augmented ventricular function.
Authors: Binkley P F , Murray K D , Watson K M , Myerowitz P D , Leier C V 
Published: June 2012

BACKGROUND
The synthetic catecholamine dobutamine increases stroke volume in normal subjects and in patients with congestive heart failure. In addition to its direct influence on myocardial contractility, dobutamine may significantly modulate vascular tone because of its alpha- and beta-adrenergic agonist activity.

METHODS AND RESULTS
To test the hypothesis that such vasoactive properties significantly contribute to the improved ventricular performance noted with this agent, hemodynamic parameters were measured during stepped ascension infusion of dobutamine in a model that is insensitive to positive inotropic stimulation. Administration of dobutamine in nine calves that underwent replacement of the native right and left ventricles with pneumatically driven total artificial hearts resulted in a significant (p = 0.0001) increase in cardiac output from 7.0 +/- 1.8 to 8.2 +/- 1.8 l/min and a significant (p = 0.0001) decrease in total peripheral vascular resistance from 1,224 +/- 559 to 745 +/- 317 dyne.sec/cm5. A less marked influence was noted on the pulmonary vasculature, with pulmonary vascular resistance exhibiting a significant (p less than 0.05) decrease from its baseline value only at the peak infusion. Consistent with an increase in venous return, both left and right atrial pressures increased significantly (p less than 0.005) with dobutamine administration.

CONCLUSIONS
These data demonstrate that the vasoactive properties of dobutamine significantly contribute to improved ventricular performance independent of direct myocardial stimulation. This effect appears to result in part from a direct modulation of myocardial stimulation. This effect appears to result in part from a direct modulation of arterial and venous tones rather than from a reflex response to primary changes in contractility.
Interferon-gamma inhibits arterial stenosis after injury.
Authors: Hansson G K , Holm J 
Published: June 2012

BACKGROUND
Arterial injury initiates a proliferative response among the smooth muscle cells of the artery. This leads to the formation of a thickened intima that may reduce the diameter of the arterial lumen. Such intimal lesions often develop after vascular surgery and angioplastic procedures. Previous cell culture studies have shown that the lymphokine, interferon-gamma (gIFN), inhibits smooth muscle cell proliferation.

METHODS AND RESULTS
We therefore tested whether administration of exogenous gIFN could inhibit the development of intimal lesions. Rat carotid arteries were denuded with a balloon catheter, resulting in the formation of a standardized intimal lesion. The animals were then treated with recombinant rat gIFN at 200,000 units (approximately 400,000 units or 100 micrograms/kg body wt) administered parenterally once daily for 7 days. Autoradiographic analysis of 3H-thymidine incorporation revealed that gIFN reduced the early smooth muscle replication by approximately 75%. gIFN treatment for 1 week resulted in a 50% reduction of intimal cross-section area at 2 weeks after injury when compared to control rats injected with buffer alone. The difference in lesion development persisted in rats analyzed 10 weeks after injury, suggesting that proliferative events during the first week determine the long-term development of the intima. Inhibition of lesion development was accompanied by expression of the class II histocompatibility (Ia) gene, RT1B, suggesting that both were directly related to the administration of gIFN.

CONCLUSIONS
These results show that gIFN is a potent inhibitor of the formation of arterial proliferative lesions in vivo. It is possible that gIFN could be useful in preventing arterial stenosis after surgery and angioplasty in man.
Loss of flow-mediated endothelium-dependent dilation occurs early in the development of atherosclerosis.
Authors: McLenachan J M , Williams J K , Fish R D , Ganz P , Selwyn A P 
Published: June 2012

BACKGROUND
Healthy arteries exhibit endothelium-dependent dilation in response to both local acetylcholine and increased blood flow. In humans, clinically overt coronary artery disease is characterized by loss of dilation to both acetylcholine and blood flow. The temporal relation, however, between functional abnormalities of the endothelium and the development of atherosclerosis has not been established.

METHODS AND RESULTS
We examined endothelial vasodilator function in vivo at an early stage of the development of atherosclerosis. Two groups of seven Macaca fascicularis monkeys were studied; one group was fed a high cholesterol diet (0.73-1.0 mg cholesterol per calorie) for 11 months. Cholesterol feeding was associated with increased plasma cholesterol levels and with intimal thickening of the iliac arteries but with no reduction in luminal diameter. Endothelium-dependent vasomotor responses of the iliac arteries were then examined in vivo by quantitative contrast angiography. Acetylcholine produced significant dilation in the controls but paradoxical constriction in the group with early atherosclerosis (+9.0 +/- 3.2% versus -5.3 +/- 5.4%, p less than 0.05). In response to a twofold increase in blood flow achieved by administering adenosine distal to the arterial segment under examination, the controls again dilated, whereas the atherosclerotic group failed to dilate (+ 11.6 +/- 2.1% versus + 0.5 +/- 2.4%, p less than 0.05). Both groups, however, were able to dilate, and dilated equally, to the nonendothelium-dependent agent nitroglycerin (+ 13.7 +/- 4.8% versus + 19.1 +/- 4.3%, NS).

CONCLUSIONS
Endothelium-dependent vasodilation in response to both acetylcholine and increased blood flow may be lost early in the course of developing atherosclerosis before the appearance of stenosing and occlusive disease.
Neuronal reuptake of norepinephrine and production of dihydroxyphenylglycol by cardiac sympathetic nerves in the anesthetized dog.
Authors: Eisenhofer G , Smolich J J , Cox H S , Esler M D 
Published: June 2012

BACKGROUND
Reuptake of norepinephrine by cardiac sympathetic nerves before and during two levels of electrical stimulation of the left ansa subclavia was estimated in anesthetized dogs from the cardiac production of dihydroxyphenylglycol (DHPG), the intraneuronal metabolite of norepinephrine.

METHODS AND RESULTS
The method depended on the effects of neuronal uptake blockade with desipramine on the cardiac production of [3H]DHPG from intravenously infused [3H]norepinephrine. The ratio of the desipramine-induced decrease in the cardiac extraction of [3H]norepinephrine to the production of [3H]DHPG was used to transform the cardiac production of DHPG from recaptured norepinephrine into a rate for norepinephrine reuptake. Cardiac spillover of norepinephrine into plasma increased from 49 +/- 12 to 205 +/- 40 and 451 +/- 118 pmol/min during sympathetic activation. Cardiac DHPG production increased from 108 +/- 18 to 166 +/- 34 and 240 +/- 47 pmol/min. Desipramine decreased resting cardiac DHPG production by 20% and completely blocked the stimulation-induced increase. Thus, most (80%) cardiac DHPG produced at rest was derived from norepinephrine leaking from storage vesicles. This amount remained constant, and that derived from recaptured norepinephrine increased during sympathetic activation. The cardiac extraction of [3H]norepinephrine (126,000 dpm/min) and production of [3H]DHPG (3,790 dpm/min) were decreased by 55-57% after desipramine. Thus, only 3% of the norepinephrine recaptured by cardiac sympathetic nerves appeared in plasma as DHPG. The remainder was sequestered into storage vesicles (more than 94%) or ultimately formed metabolites other than DHPG (less than 3%). Reuptake of norepinephrine by cardiac sympathetic nerves was 1,188 +/- 476 pmol/min and increased in parallel with cardiac norepinephrine spillover to 4,182 +/- 1,982 and 6,594 +/- 2,241 pmol/min during sympathetic stimulation.

CONCLUSIONS
Of the norepinephrine released by cardiac sympathetic nerves, 16-fold more was recaptured than entered plasma. Combined estimation of norepinephrine reuptake and spillover offers an approach to assess the efficiency of neuronal reuptake in disorders of cardiac function.
Atrial contribution to ventricular filling in mitral stenosis.
Authors: Meisner J S , Keren G , Pajaro O E , Mani A , Strom J A , Frater R W , Laniado S , Yellin E L 
Published: June 2012

BACKGROUND
The importance of the contribution of atrial systole to ventricular filling in mitral stenosis is controversial. The cause of reduced cardiac output following the onset of atrial fibrillation may be due to an increased heart rate, a loss of booster pump function, or both.

METHODS AND RESULTS
We studied the atrial contribution to filling under a variety of conditions by combining noninvasive studies of patients with computer modeling. Thirty patients in sinus rhythm with mild-to-severe stenosis were studied with two-dimensional and Doppler echocardiography for measurement of mitral flow velocity and mitral valve area (MVA). The mean +/- SD atrial contribution to left ventricular filling volume was 18 +/- 10% and varied inversely with mitral resistance. Patients with mild mitral stenosis (MVA, 1.8 +/- 0.7 cm2) and severe mitral stenosis (MVA, 0.9 +/- 0.2 cm2) had atrial contributions of 29 +/- 4% and 9 +/- 5%, respectively. The pathophysiological mechanisms responsible for these trends were further investigated by the computer model. In modeled severe mitral stenosis, increasing heart rate from 75 to 150 beats/min caused an increase of 5.2 mm Hg in mean left atrial pressure, whereas loss of atrial contraction at a heart rate of 150 beats/min caused only a 1.3 mm Hg increase.

CONCLUSIONS
The atrial booster pump contributes less to ventricular filling in mitral stenosis than in the normal heart, and the loss of atrial pump function is less important than the effect of increasing heart rate as the cause of decompensation during atrial fibrillation.
Polymorphous ventricular tachycardia associated with acute myocardial infarction.
Authors: Wolfe C L , Nibley C , Bhandari A , Chatterjee K , Scheinman M 
Published: June 2012

BACKGROUND
During a 2.9-year period, 11 patients developed polymorphous ventricular tachycardia 1-13 days after acute anterior (seven patients) or inferior (four patients) myocardial infarction. None of the 11 patients had sinus bradycardia (mean heart rate, 90 +/- 23 beats/min), but three had a sinus pause immediately before the onset of polymorphous ventricular tachycardia. In all 11 patients, the QT interval and corrected QT interval (QTc) were normal or minimally prolonged (QT, 385 +/- 34 msec; QTc, 442 +/- 40 msec). None had significant hypokalemia (mean serum potassium concentration, 4.3 +/- 0.5 meq/l) or a grossly abnormal serum magnesium or calcium concentration (2.1 +/- 0.4 and 8.9 +/- 0.7 mg/dl, respectively).

METHODS AND RESULTS
Immediately before the onset of polymorphous ventricular tachycardia, symptoms and/or electrocardiographic changes consistent with recurrent myocardial ischemia occurred in nine of 11 patients. One patient died before drug therapy could be initiated. Lidocaine was used in 10 patients and proved to be effective in only one. Intravenous procainamide was used in six patients: one improved, and five had recurrence of polymorphous ventricular tachycardia. Bretylium was used in five patients and was ineffective in all cases. Overdrive pacing was used in four patients and failed to suppress recurrent arrhythmias in all cases. Four patients with persistent polymorphous ventricular tachycardia unresponsive to lidocaine, procainamide, or bretylium responded to intravenous amiodarone. One patient with polymorphous ventricular tachycardia that was consistently preceded by ST segment elevation responded to intravenous nitroglycerin. Two patients with persistent polymorphous ventricular tachycardia and obvious recurrent ischemia unresponsive to pharmacological intervention responded to emergency coronary revascularization. A third patient who experienced recurrent angina and polymorphous tachycardia was initially stabilized with pharmacological therapy but subsequently underwent elective revascularization and has remained stable without antiarrhythmic therapy.

CONCLUSIONS
Post-myocardial infarction polymorphous ventricular tachycardia is not consistently related to an abnormally long QT interval, sinus bradycardia, preceding sinus pauses, or electrolyte abnormalities. This arrhythmia has a variable response to class I antiarrhythmics but may be suppressed by intravenous amiodarone therapy. It is often associated with signs or symptoms of recurrent myocardial ischemia. Furthermore, coronary revascularization appears to be effective in preventing the recurrence of polymorphous ventricular tachycardia when associated with recurrent postinfarction angina.
Effects of myocardial alpha 1-adrenergic receptor stimulation and blockade on contractility in humans.
Authors: Landzberg J S , Parker J D , Gauthier D F , Colucci W S 
Published: June 2012

BACKGROUND
Although alpha-adrenergic receptors are present in both normal and failing human left ventricular myocardium and mediate a positive inotropic effect in several other species, it is not known whether stimulation of myocardial alpha-adrenergic receptors exerts a positive inotropic effect or contributes to basal contractile state in vivo in humans.

METHODS AND RESULTS
We studied 15 patients with angiographically normal coronary arteries (seven with normal left ventricular function and eight with left ventricular failure). To avoid the confounding effects of changes in ventricular loading conditions and systemic reflex mechanisms, the alpha-adrenergic receptor-selective antagonist phentolamine and agonist phenylephrine were infused directly into the left main coronary artery, and the change in contractile state was assessed by measuring left ventricular peak (+)dP/dt. Phentolamine alone had no effect on left ventricular contractility. Phenylephrine exerted a concentration-related positive inotropic effect in patients with normal as well as those with failing ventricles. The alpha-adrenergic effect of phenylephrine, defined as the component blocked by phentolamine, was significantly less in patients with ventricular failure (108 +/- 28 mm Hg/sec) than in normal subjects (248 +/- 54 mm Hg/sec; p less than 0.03).

CONCLUSIONS
Myocardial alpha-adrenergic receptors do not contribute to the maintenance of basal left ventricular contractile state in humans. However, stimulation of myocardial alpha-adrenergic receptors exerts a positive inotropic effect, the magnitude of which may be attenuated in patients with heart failure.
Relative risk analysis of angiographic predictors of restenosis within the coronary Wallstent.
Authors: Strauss B H , Serruys P W , de Scheerder I K , Tijssen J G , Bertrand M E , Puel J , Meier B , Kaufmann U , Stauffer J C , Rickards A F 
Published: June 2012

BACKGROUND
Late angiographic narrowing has been observed following coronary implantation of the Wallstent. To identify the angiographic variables that predict restenosis within the stented segment, a retrospective study of data from the European Wallstent core laboratory was performed.

METHODS AND RESULTS
Follow-up angiograms (excluding patients with in-hospital occlusions) were analyzed for 214 lesions in 176 patients (78% restudy rate). The incidence of restenosis within the stented segment was 35% by lesion and 35% by patient for criterion 1 (greater than or equal to 0.72 mm loss in minimal luminal diameter) and 24% by lesion and 24% by patient for criterion 2 (diameter stenosis greater than or equal to 50% at follow-up). The association between 16 variables and restenosis was determined by a relative risk ratio assessment. Variables with significant risk ratios for restenosis with criterion 1 were use of multiple stents/lesion (relative risk, 1.56; 95% confidence interval [CI], 1.08-2.25) and oversized (unconstrained stent diameter exceeding reference diameter greater than 0.7 mm) stents (relative risk, 1.64; 95% CI, 1.10-2.45), and for criterion 2, oversizing by more than 0.70 mm (relative risk, 1.93; 95% CI, 1.13-3.31), bypass grafts (relative risk, 1.62; 95% CI, 0.98-2.66), use of multiple stents/lesion (relative risk, 1.61; 95% CI, 0.97-2.67) and residual diameter stenosis more than 20% post stenting (relative risk, 1.51; 95% CI, 0.91-2.50).

CONCLUSIONS
It is concluded that several angiographic variables are significantly associated with late angiographic narrowing after stenting in the coronary arteries. We suggest that stent operators avoid excessive oversizing in the selection of stent diameter and the use of multiple stents per lesion to lessen the risk of late restenosis.
Modulation of drug effects by regional sympathetic denervation and supersensitivity.
Authors: Stanton M S , Zipes D P 
Published: June 2012

BACKGROUND
Regional sympathetic denervation, such as that produced by a myocardial infarction, causes electrophysiological heterogeneity in the ventricles. The purpose of this study was to test the hypothesis that such denervation could cause drugs to exert heterogeneous myocardial effects.

METHODS AND RESULTS
Sympathetic stimulation increases the amplitude of cesium chloride-induced early afterdepolarizations (EADs). The amplitude of these induced EADs was used to determine whether drug responses were different in innervated versus denervated areas of the heart. A canine model of sympathetic denervation was created at the cardiac apex by either transmural myocardial infarction (n = 19) or phenol application (n = 11). Cesium chloride (84 mg/kg) was infused while monophasic action potential recordings were simultaneously obtained from the base and apex of the left ventricle using an epicardial contact electrode. We found that control (innervated) dogs (n = 17) showed no difference in the EAD amplitude recorded from the apex compared with the base. In dogs with apical sympathetic denervation, the EAD amplitude was greater at the innervated base during ansae subclaviae stimulation than at the denervated apex (25.8 +/- 6.6% at base versus 18.8 +/- 6.7% at apex, p less than 0.001). However, during norepinephrine infusion, the EADs recorded from the denervated apex were greater than those recorded from the innervated base (23.3 +/- 7.6% at apex versus 20.6 +/- 6.0% at base, p less than 0.02) due to denervation supersensitivity.

CONCLUSIONS
These data show that regional myocardial denervation creates autonomic and electrophysiological heterogeneity and the substrate for heterogeneous drug actions. This drug-induced electrophysiological heterogeneity may be another mechanism for proarrhythmia.