bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of
d,l
-Sotalol and Implantable Defibrillators for Treatment of Sustained Ventricular Tachycardia or Fibrillation in Patients With Coronary Artery Disease
Authors: Bo¨cker Dirk , Haverkamp Wilhelm , Block Michael , Borggrefe Martin , Hammel Dieter , Breithardt Gu¨nter
Published: June 2012

Background
Implantable cardioverter-defibrillators (ICDs) and
d,l-
sotalol are widely used to treat ventricular tachyarrhythmia and ventricular fibrillation (VT/VF). The purpose of this study was to compare the long-term efficacy of
d,l
-sotalol and ICDs in patients with coronary artery disease.

Methods and Results
In a case-control study, 50 patients treated with oral
d,l
-sotalol were matched to 50 patients treated with ICDs. Both groups were matched for sex (82 men), age (58±10 years), ejection fraction (40±12%), extent of coronary artery disease, presenting arrhythmia, and year that treatment began. In all patients in the sotalol group, VT/VF was inducible in the drug-free electrophysiological study. Induction of sustained VT/VF was suppressed by
d,l
-sotalol (438±95 mg/d). In the ICD group, either VT/VF was not inducible (n=5) or inducible sustained VT/VF was refractory to antiarrhythmic drug treatment (n=45). Sotalol treatment led to a marked reduction in arrhythmic events. Whereas 83% of the patients in the sotalol group were free of sudden death and nonfatal VT at 3 years, only 33% of the ICD patients did not receive appropriate ICD therapies (
P
<.005). Actuarial rates for absence of sudden death at 3 years were 85% in the sotalol group and 100% in the ICD group (
P
<.005). Actuarial rates for overall survival at 3 years were 75% in the sotalol group and 85% in the ICD group (
P
=.02).

Conclusions
In this case-control study, ICD therapy was more effective than electrophysiologically guided antiarrhythmic treatment with
d,l
-sotalol in prevention of sudden death and reduction of total mortality in patients with coronary artery disease. Prospective studies are needed to confirm these results.
Different Effects of Estrogen and Progesterone on Experimental Atherosclerosis inFemale Versus Male Rabbits
Authors: Hanke Hartmut , Hanke Sybille , Finking Gerald , Muhic-Lohrer Alexandra , Mu¨ck Alfred O. , Schmahl Friedrich W. , Haasis Rainer , Hombach Vinzenz
Published: June 2012

Background
The aim of the present study was to compare the effect of estrogen and progesterone on the development of experimental atherosclerosis in female versus male rabbits to assess possible sex-specific differences.

Methods and Results
A total of 32 female and 32 male New Zealand White rabbits were ovariectomized or castrated. In addition to a 0.5% cholesterol diet, the rabbits received estradiol alone (1 mg/kg body wt [BW] per week), progesterone alone (25 mg/kg BW per week), or combined estradiol-progesterone in these dosages during 12 weeks. Ovariectomized female and castrated male rabbits served as control groups without hormone treatment. Before excision of the vessels, bromodeoxyuridine labeling was performed to determine the extent of cellular proliferation in the atherosclerotic lesions. The aortic arch was analyzed immunohistologically and morphometrically. An inhibitory effect of estrogen on intimal plaque size was found in female rabbits compared with the ovariectomized control group (0.7±0.5 versus 3.7±2.5 mm
2
,
P
<.002; proliferating cells, 3.1±1.8% versus 8.5±2.6%,
P
<.002). In combination with progesterone, however, estrogen was not able to reduce intimal plaque size or cellular proliferation. In contrast, estradiol in castrated male rabbits was not associated with an inhibitory effect on cellular proliferation or intimal thickening compared with controls (estrogen treatment, 7.6±2.1% proliferating cells and 2.8±1.0 mm
2
neointima; control group, 7.2±2.1% cellular proliferation and 2.9±1.2 mm
2
intimal thickening).

Conclusions
Our data suggest that the atheroprotective effect of estrogen is probably due to a mechanism that is present in female rabbits only.
Transcatheter Coil Occlusion of Surgical Fenestration After Fontan Operation
Authors: Sommer Robert J. , Recto Michael , Golinko Richard J. , Griepp Randall B.
Published: June 2012

Background
Fenestration of the Fontan circulation that results in a residual right-to-left shunt has improved operative survival rates among high-risk patients. Late closure of the fenestration by use of a transcatheter umbrella device has achieved separation of the systemic and pulmonary venous circulations, “completing” the Fontan pathway. Because use of umbrella devices is restricted, many institutions continue to perform only nonfenestrated Fontan procedures.

Methods and Results
Five children 3.5 to 8.3 years old (mean, 5.1 years) underwent cardiac catheterization 0.5 to 24 months (mean, 10 months) after operation for the purpose of occluding a persistently patent Fontan fenestration. Once candidacy was determined, an 8-mm×10-cm Gianturco coil was delivered to straddle the fenestration with established techniques for coil occlusion of patent ductus arteriosus. Complete occlusion occurred in 4 of 5 patients, in 2 of the 4 before they left the catheterization laboratory. One patient had a residual angiographic shunt but had complete closure within 24 hours by echocardiography. In 1 patient who had a residual shunt at 24 hours, the fenestration was completely closed at 1 month after coil placement. One patient had residual shunting at 2 months but saturations have increased 15% to 17% since coil placement. No embolizations (early or late), clinical hemolysis, thromboembolic events, or hemodynamic deterioration occurred among patients during 1- to 14-month follow-up periods.

Conclusions
A persistently patent fenestration after Fontan operation may be closed with a Gianturco coil. This universally available alternative to umbrella devices may make the fenestrated Fontan a more appealing option to centers that had not previously considered its use.
Skeletal Muscle and Cardiovascular Adaptations to Exercise Conditioning in Older Coronary Patients
Authors: Ades Philip A. , Waldmann Mary L. , Meyer William L. , Brown Kenneth A. , Poehlman Eric T. , Pendlebury William W. , Leslie Kevin O. , Gray Peter R. , Lew Richard R. , LeWinter Martin M.
Published: June 2012

Background
Older coronary patients suffer from a low functional capacity and high rates of disability. Supervised exercise programs improve aerobic capacity in middle-aged coronary patients by improving both cardiac output and peripheral extraction of oxygen. Physiological adaptations to aerobic conditioning, however, have not been well studied in older coronary patients.

Methods and Results
The effect of a 3-month and a 1-year program of intense aerobic exercise was studied in 60 older coronary patients (mean age, 68±5 years) beginning 8±5 weeks after myocardial infarction or coronary bypass surgery. Outcome measures included peak aerobic capacity, cardiac output, arteriovenous oxygen difference, hyperemic calf blood flow, and skeletal muscle fiber morphometry, oxidative enzyme activity, and capillarity. Training results were compared with a sedentary, age- and diagnosis-matched control group (n=10). Peak aerobic capacity increased in the intervention group at 3 months and at 1 year by 16% and 20%, respectively (both
P
<.01). Peak exercise cardiac output, hyperemic calf blood flow, and vascular conductance were unaffected by the conditioning protocol. At 3 and 12 months, arteriovenous oxygen difference at peak exercise was increased in the exercise group but not in control subjects. Histochemical analysis of skeletal muscle documented a 34% increase in capillary density and a 23% increase in succinate dehydrogenase activity after 3 months of conditioning (both
P
<.02). At 12 months, individual fiber area increased by 29% compared with baseline (
P
<.01).

Conclusions
Older coronary patients successfully improve peak aerobic capacity after 3 and 12 months of supervised aerobic conditioning compared with control subjects. The mechanism of the increase in peak aerobic capacity is associated almost exclusively with peripheral skeletal muscle adaptations, with no discernible improvements in cardiac output or calf blood flow.
Activation and Entrainment Mapping Defines the Tricuspid Annulus as the Anterior Barrier in Typical Atrial Flutter
Authors: Kalman Jonathan M. , Olgin Jeffrey E. , Saxon Leslie A. , Fisher Westby G. , Lee Randall J. , Lesh Michael D.
Published: June 2012

Background
The importance of anatomic barriers in the atrial flutter reentry circuit has been well demonstrated in canine models. It has been shown previously that the crista terminalis and its continuation as the eustachian ridge form a posterior barrier. In this study we tested the hypothesis that the tricuspid annulus forms the continuous anterior barrier to the flutter circuit.

Methods and Results
Thirteen patients with typical atrial flutter were studied. A 20-pole halo catheter was situated around the tricuspid annulus. A mapping catheter was used for activation and entrainment mapping from seven sequential sites around the tricuspid annulus and from three additional sites including the tip of the right atrial appendage, at the fossa ovalis, and in the distal coronary sinus. Sites were considered to be within the circuit when the postpacing interval minus the flutter cycle length and the stimulus time minus the activation time were ≤10 ms; sites were considered to be outside the circuit when these intervals were >10 ms. All seven annular sites were within the circuit; activation occurred sequentially around the annulus and accounted for 100% of the flutter cycle length. The fossa ovalis, the distal coronary sinus, and the right atrial appendage were outside the circuit.

Conclusions
Closely spaced sites around the tricuspid annulus are activated sequentially, and are all within the flutter circuit according to entrainment criteria. This demonstrates that the tricuspid annulus constitutes a continuous anterior barrier constraining the reentrant wave front of human counterclockwise atrial flutter.
Prognostic Significance of Heart Rate Variability in Post–Myocardial Infarction Patients in the Fibrinolytic Era
Authors: Zuanetti Giulio , Neilson James M.M. , Latini Roberto , Santoro Eugenio , Maggioni Aldo P. , Ewing David J.
Published: June 2012

Background
Studies performed before the introduction of fibrinolysis showed that a low heart rate variability (HRV) is associated with higher mortality in post–myocardial infarction (MI) patients. We evaluated whether HRV adds information relevant to risk stratification in patients treated with fibrinolysis as well.

Methods and Results
From 24-hour ECG recordings obtained at discharge in patients treated with recombinant tissue-type plasminogen activator or streptokinase, we measured several time-domain indexes of HRV: standard deviation (SDNN), root-mean-square of successive differences (RMSSD), and number of RR interval increases >50 ms (“NN50+”). The prognostic value of HRV for total and cardiovascular mortality was assessed. Of 567 patients with valid recordings, 52 (9.1%) died during the 1000 days of follow-up, 44 (7.8%) of cardiovascular causes. All indexes of low HRV were able to identify patients (16% to 18% of total population) with a higher total mortality (20.8% to 24.2% versus 6.0% to 6.8%, depending on index used). The independent predictive value of low HRV was confirmed by the adjusted analysis with the following relative risks: NN50+, 3.5 (95% CI, 1.9 to 6.7); SDNN, 3.0 (95% CI, 1.55 to 5.9); and RMSSD, 2.8 (95% CI, 1.5 to 5.3). Advanced age, previous MI, Killip class at entry, and use of digitalis were also independent predictors. Similar data were obtained for cardiovascular mortality.

Conclusions
Time-domain indexes of HRV retain their independent prognostic significance even in post-MI patients of all ages treated with fibrinolysis.
Effects of Dietary
l
-Arginine on Atherosclerosis and Endothelium-Dependent Vasodilatationin the Hypercholesterolemic Rabbit
Authors: Jeremy Richmond W. , McCarron Hugh , Sullivan David
Published: June 2012

Background
Nitric oxide (NO) may protect arteries against atherosclerosis. In the present study, we examined whether di-etary
l
-arginine, the precursor of NO, could chronically preserve endothelium-dependent vasodilatation in vivo and/or limit atherogenesis.

Methods and Results
Rabbits were randomized according to sex to receive 2% dietary cholesterol, with or without
l
-arginine (2.25% solution), for 7 or 14 weeks. Hindlimb vasodilator responses to acetylcholine and nitroprusside were measured with an electromagnetic flow probe. Atherosclerosis was measured with planimetry of aortic lesions stained with Oil-Red-O. In rabbits administered
l
-arginine, plasma arginine levels increased to 483±30 μmol/L at 3 weeks (mean±SEM,
P
<.0001 versus control animals) but declined to 224±25 μmol/L at 7 weeks (
P
=.02) and to 100±23 μmol/L at 14 weeks (NS versus control animals). At 7 weeks, peak hindlimb conductance in response to acetylcholine in cholesterol-fed males was 249±49% of baseline compared with 332±9% in control animals (
P
=.04), but peak response in arginine-fed rabbits (314±24%) did not differ from that of control animals. At 14 weeks, peak responses to acetylcholine were equally reduced in males fed cholesterol with (266±21%,
P
=.02 versus control) or without (263±13%,
P
=.01 versus control)
l
-arginine. Similar impairment of endothelium-dependent vasodilatation was seen in females at 14 weeks. Vasodilator responses to nitroprusside did not differ from those of control animals in any treatment group. After 14 weeks, atherosclerosis was less in the descending aorta of arginine-fed males (16±4% surface area) than that of males fed cholesterol only (42±8%,
P
=.04), but no treatment benefit was seen in the ascending aorta or in females.

Conclusions
Dietary
l
-arginine supplementation causes an early rise in plasma arginine levels, with limitation of atherosclerosis in the descending aorta and preservation of endothelium-dependent vasodilatation in resistance arteries, but this treatment effect is not sustained. Dietary
l
-arginine may not be of long-term benefit in the prevention of atherosclerosis in humans.
Functional and Structural Alterations With 24-Hour Myocardial Hibernation and Recovery After Reperfusion
Authors: Chen Chunguang , Chen Lianglong , Fallon John T. , Ma Lijie , Li Li , Bow Laurine , Knibbs David , McKay Raymond , Gillam Linda D. , Waters David D.
Published: June 2012

Background
Short-term myocardial hibernation of 3 hours resulting from a moderate resting coronary flow reduction has been reproduced in pigs. This study was designed to determine whether any structural changes accompany short-term hibernation caused by a moderate flow reduction maintained for 24 hours and whether any such structural alterations are reversible after reperfusion.

Methods and Results
A severe left anterior descending coronary artery (LAD) stenosis was created with a reduction of resting flow to ≈60% of baseline and maintained for 24 hours. Regional coronary flow was measured by a flowmeter; wall thickening was determined by echocardiography, and local metabolic changes were measured. Of 17 pigs, 11 completed the study protocol of 24 hours. The LAD flow was reduced from 0.91±0.11 to 0.52±0.13 mL·min
−
1
·g
−
1
, a 43% mean decrease, at 15 minutes after the LAD stenosis and was maintained at 0.56±0.11 mL·min
−
1
·g
−
1
at 24 hours. The reduction of regional coronary flow initially produced acute myocardial ischemia, as evidenced by reduced regional wall thickening (from 37.2±6.9% at baseline to 11.5±6.8%), regional lactate production (−0.34±0.28 μmol·g
−
1
·min
−
1
), and a decrease in regional coronary venous pH (from 7.41±0.035 at baseline to 7.30±0.030). At 24 hours, the reductions in coronary flow and wall thickening were maintained relatively constant and the rate-pressure product was relatively unchanged, but lactate production ceased and regional H
+
concentration normalized, with a tendency toward a further reduction in regional oxygen consumption, from 3.10±0.90 mL·min
−
1
·100 g
−
1
at 15 minutes after stenosis to 2.52±0.95 mL·min
−
1
·100 g
−
1
at 24 hours (
P
=.06), indicating metabolic adaptation of the hypoperfused regions. Of 11 pigs, 6 were free of myocardial infarction; 3 had patchy necrosis involving 4%, 5%, and 6% of the area at risk; and 2 other pigs had a few scattered myocytes with necrosis, detected only by light and electron microscopy. Ultrastructural changes consisted of a partial loss of myofibrils and an increase in mitochondria and glycogen deposition. Regional wall thickening recovered 1 week after reperfusion in most pigs, and the ultrastructural changes reverted to normal.

Conclusions
In this pig model, moderately ischemic myocardium undergoes metabolic and structural adaptations but preserves the capacity to recover both functionally and ultrastructurally after reperfusion.
Mechanism of the Systemic, Left Ventricular, and Coronary Vascular Tolerance to a Binge of Cocaine in Conscious Dogs
Authors: Shannon Richard P. , Lozano Pedro , Cai Qing , Manders W. Thomas , Shen You-tang
Published: June 2012

Background
Prior experimental studies have emphasized the cardiovascular effects of acute, single doses of cocaine. However, cardiovascular complications are most often reported in chronic users, who have been exposed to repetitive doses of cocaine. It remains unclear whether there is tolerance or sensitization to the systemic, left ventricular, and coronary hemodynamic effects of a binge of cocaine.

Methods and Results
We studied 11 conscious, chronically instrumented dogs to determine the systemic pressor, inotropic, chronotropic, and coronary vascular resistance responses to cocaine (1 mg/kg IV) administered every 25 minutes for five doses. There was progressive tolerance to the systemic pressor (mean arterial pressure: first dose, +42±4% from 97±2 mm Hg; fifth dose, +8±3% from 116±7 mm Hg;
P
<.01) and heart rate (first dose, +45±8% from 93±5 bpm; fifth dose, +8±2% from 109±9 bpm;
P
<.01) responses and abolition of the positive inotropic (left ventricular dP/dt: first dose, +19±4% from 2824±75 mm Hg/s; fifth dose, −3±5% from 2531±436 mm Hg/s;
P
<.01) and coronary vasoconstrictor (coronary vascular resistance: first dose, +38±9% from 1.9 mm Hg·mL
−1
·min
−1
; fifth dose, −7±2% from 2.6±0.2 mm Hg·mL
−1
·min
−1
;
P
<.01) responses to a binge of cocaine despite progressive increases in peak plasma cocaine concentrations. In contrast, both the plasma norepinephrine and epinephrine responses were attenuated with repetitive exposure to cocaine, whereas myocardial α- and β-adrenergic responsiveness was maintained.

Conclusions
Repetitive cocaine administration is associated with the development of early and progressive tolerance to systemic, left ventricular, and coronary vascular effects of cocaine. The mechanism of the tolerance involves neither impaired myocardial nor coronary vascular responsiveness to adrenergic stimulation but, rather, attenuated catecholamine responses to repetitive cocaine administration.
Suppression of Plasminogen Activator Inhibitor-1 Release From Human Cerebral Endothelium by Plasminogen Activators
Authors: Shatos Marie A. , Doherty Jacqueline M. , Penar Paul L. , Sobel Burton E.
Published: June 2012

Background
Intracranial bleeding is the most catastrophic potential complication of treatment with thrombolytic agents. To identify potential factors that may contribute to this problem, we characterized elaboration by human brain endothelial cells of plasminogen activator inhibitor-1 (PAI-1) and measured PAI-1 mRNA levels.

Methods and Results
When human cerebral microvascular endothelial cells (HCMEC), pial arterial endothelial cells, and middle meningeal arterial endothelial cells were exposed to 10 to 1000 ng/mL recombinant tissue-type plasminogen activator (RTPA), urokinase-type plasminogen activator (UPA), or streptokinase/plasminogen (37 U streptokinase plus 2 μmol/L plasminogen) for 24 hours, they exhibited concentration-dependent decreases in elaboration of PAI-1 of 65±3%, 48±3%, and 59±8%. UPA and streptokinase/plasminogen elicited decreases of 33±8% and 35±4%, respectively, that were specific with respect to the protease agonists as to total protein synthesis and cell type; ie, neither human umbilical vein endothelial cells nor cerebral pericytes exhibited inhibition of PAI-1 elaboration. No decrease in HCMEC PAI-1 elaboration was induced by coagulation factor Xa (10 nmol/L). A 2.7±0.5-fold increase was induced by α-thrombin (10 nmol/L). PAI-1 secretion from HCMEC decreased within 4 hours of exposure to 100 ng/mL RTPA. In HCMEC exposed to RTPA for 8 hours, PAI-1 mRNA decreased from 176±20 to 43±2.2 pg/μg RNA.

Conclusions
These results indicate that brain endothelial cells exposed to RTPA exhibit paradoxically diminished elaboration of PAI-1. This property may render brain vasculature vulnerable to attack by serine proteases, thereby predisposing to injury and initiating an underlying subsequent intracerebral hemorrhage in patients given plasminogen activators for treatment of coronary thrombosis.
Remote Noninfarcted Region Dysfunction Soon After First Anterior Myocardial Infarction
Authors: Kramer Christopher M. , Rogers Walter J. , Theobald Therese M. , Power Thomas P. , Petruolo Susan , Reichek Nathaniel
Published: June 2012

Background
Previous studies have demonstrated hyperkinetic endocardial motion of noninfarcted myocardium early after myocardial infarction (MI). We wished to substantiate the findings of increased function of remote noninfarcted regions using magnetic resonance (MR) myocardial tagging in patients soon after anterior MI.

Methods and Results
Twenty-eight patients (25 male; mean age, 52 years) were studied on day 5±2 after first anterior MI. All had single-vessel left anterior descending coronary artery (LAD) disease and had received reperfusion therapy but had evidence of regional left ventricular (LV) dysfunction and an ejection fraction (EF) ≤50%. Breath-hold, segmented k-space, gradient-echo MR tagging was performed with short-axis imaging spanning the LV. Percent circumferential shortening (%S) on a topographic basis, LV mass, and EF were measured. Regional %S was compared with that in 10 normal subjects (7 male; mean age, 43 years). We found reduced intramyocardial %S throughout the LV in the patient group. Percent shortening was lower in patients compared with control subjects at all sites along the long axis of the ventricle (9±5% versus 23±3% at the apex,
P
<.0001; 11±5% versus 21±3% at the midventricle,
P
<.0001; 14±3% versus 17±5% at the base,
P
<.02). The basal lateral and midinferior regions, remote from LAD territory, demonstrated reduced %S and a strong trend toward reduced %S, respectively.

Conclusions
Patients on day 5 after first anterior MI with single-vessel disease demonstrate reduced intramyocardial circumferential shortening throughout the LV, including remote noninfarcted regions. Potential mechanisms include altered coronary vasodilatory properties, changes in regional mechanical load, or mechanical tethering to infarcted regions.
Control Mechanisms for Physiological Hypertrophy of Pregnancy
Authors: Mone Suzanne M. , Sanders Stephen P. , Colan Steven D.
Published: June 2012

Background
Pregnancy represents an excellent model of acute physiological hypertrophy and atrophy secondary to a transient hemodynamic load. This investigation examined the effects of pregnancy on ventricular mechanics using load-independent indexes of contractility to test the hypothesis that the cardiac trophic response functions as a servomechanism with wall stress as the feedback variable.

Methods and Results
Serial studies were performed in 33 women at six time periods during and shortly after normal gestation. Changes in ventricular dimension, wall thickness, and left ventricular mass were parallel to changes in body size. Fractional shortening and velocity of shortening progressively diminished during pregnancy, with a nadir at the first postpartum examination, despite a progressive fall in afterload. Cardiac index rose rapidly in early gestation and remained elevated throughout pregnancy. Peak wall stress was elevated in early gestation coincident with the rapid rise in cardiac index due to elevated volume before compensatory rise in mass. With compensatory hypertrophy, peak wall stress normalized by midgestation. The change in left ventricular mass was closely related to peak wall stress but correlated poorly with mean, total, and end-systolic wall stress.

Conclusions
Normal pregnancy is associated with a reversible fall in contractility. Systolic function is preserved throughout most of pregnancy by a fall in afterload but decreases near term and early postpartum because of decreased contractility and diminished preload. Left ventricular hypertrophy and atrophy are temporally related to changes in hemodynamic load. The response is consistent with a tightly coupled servomechanism transduced by peak wall stress with a 1- to 4-week compensatory response time.
Transcutaneous Ultrasound Augments Lysis of Arterial Thrombi In Vivo
Authors: Luo Huai , Nishioka Toshihiko , Fishbein Michael C. , Cercek Bojan , Forrester James S. , Kim Chong-Jin , Berglund Hans , Siegel Robert J.
Published: June 2012

Background
External ultrasound has a synergistic effect on thrombus disruption with thrombolytic agents in vitro. We hypothesized that transcutaneous ultrasound could augment thrombolysis in vivo.

Method and Results
Thrombus formation was induced electrically in 48 pairs of iliofemoral arteries of 24 rabbits; arterial occlusions were documented angiographically. In 17 of 24 rabbits, 25 000 units/kg streptokinase was then administered intravenously. The pairs of iliofemoral arteries were randomized to receive ultrasound treatment or no ultrasound treatment. Low-frequency (26 kHz) ultrasound (continuous wave, 18 W/cm
2
) was applied transcutaneously over the area of occlusion. In 7 of 24 rabbits, 14 thrombotically occluded iliofemoral arteries were exposed to ultrasound alone without streptokinase. The results were evaluated through the use of angiography (TIMI grade flow) and histopathology. After 30±10 minutes of activated sonication combined with intravenous streptokinase, 10 of 17 iliofemoral arteries (59%) treated with transcutaneous ultrasound were widely patent angiographically, with TIMI grade 3 flow. Histologically, the patent arteries had only minimal focal mural thrombus. The angiographic patency rate was significantly lower in the control groups: 1 of 17 arteries (6%) treated with streptokinase alone (
P
=.0012) and 1 of 14 arteries (7%) treated with ultrasound alone (
P
=.0036).

Conclusions
In vivo transcutaneous ultrasound significantly augments lysis of thrombi with streptokinase in rabbit iliofemoral arteries.
Assessment of Myocardial Viability With
99m
Tc Sestamibi in Patients Undergoing Cardiac Transplantation
Authors: Medrano Rafael , Lowry Richard W. , Young James B. , Weilbaecher Donald G. , Michael Lloyd H. , Afridi Imran , He Zuo-Xiang , Mahmarian John J. , Verani Mario S.
Published: June 2012

Background
99m
Tc sestamibi and
201
Tl are tracers that allow equivalent detection of myocardial infarction. However, because sestamibi does not undergo as much time-dependent redistribution as does
201
Tl, it has been considered suboptimal for the detection of myocardial viability.

Methods and Results
Fifteen consecutive patients with ischemic cardiomyopathy who underwent orthotopic cardiac transplantation received an intravenous injection of
99m
Tc sestamibi at 1 to 6 hours before transplantation. Rotational tomography of the excised, intact, native hearts was performed to quantify the extent of myocardial hypoperfusion. The hearts were then sliced and reimaged on a gamma camera, followed by pathological quantification of the extent and severity of scarred and normal myocardium. Samples of normally and abnormally perfused myocardium underwent gamma well counting to determine tissue radioactivity and were examined under light microscopy for delineation of myocardial structure after trichrome staining. The mean extent of scintigraphic scar quantified through the use of rotational tomography was 45±14% of the left ventricle and correlated closely with pathological scar size (
r
=.89), despite a slight overestimation. Scintigraphic scar size determined with planar imaging of the individual myocardial slices also correlated closely with pathological scar size (
r
=.88). A good correlation existed between tissue
99m
Tc sestamibi activity determined through well counting and histological evidence of myocardial viability (
r
=.89). Most hypokinetic and 40% of akinetic/dyskinetic myocardial segments contained scintigraphically and histologically normal myocardium.

Conclusions
99m
Tc sestamibi scintigraphy can be used to accurately quantify the extent of myocardial scarring. Furthermore, the relative sestamibi activity in perfusion defects, measured several hours after administration, is a good indicator of myocardial viability determined with microscopy.
Genetically Defined Therapy of Inherited Long-QT Syndrome
Authors: Compton Steve J. , Lux Robert L. , Ramsey Matthew R. , Strelich Katie R. , Sanguinetti Michael C. , Green Larry S. , Keating Mark T. , Mason Jay W.
Published: June 2012

Background
Many members of families with inherited long-QT (LQT) syndrome have mutations in
HERG
, a gene encoding a cardiac potassium channel that is modulated by extracellular potassium. We hypothesized that an increase in serum potassium would normalize repolarization in these patients.

Methods and Results
We studied seven subjects with chromosome 7–linked LQT syndrome and five normal control subjects. Repolarization was measured by ECG and body surface potential mapping during sinus rhythm, exercise, and atrial pacing, before and after serum potassium increase. Potassium administration improved repolarization in the LQT syndrome. At baseline, LQT subjects differed from control subjects: resting corrected QT interval (QT
c
, 627±90 versus 425±25 ms,
P
=.0007), QT
c
dispersion (133±62 versus 36±9 ms,
P
=.009), QT/RR slope (0.35±0.08 versus 0.24±0.07,
P
=.04), and global root-mean-square QT interval (RMS-QT
c
; 525±68 versus 393±22,
P
=.002). All LQT subjects had biphasic or notched T waves. After administration of potassium, the LQT group had a 24% reduction in resting QT
c
interval (from 617±92 to 469±23 ms,
P
=.004) compared with a 4% reduction among control subjects (from 425±25 to 410±45 ms,
P
>.05). The reduction was significantly greater in LQT subjects (
P
=.018). QT dispersion became normal in LQT subjects and did not change in control subjects. The slope of the relation between QT interval and cycle length (QT/RR slope) decreased toward normal. T-wave morphology improved in six of seven LQT subjects. The LQT group had a greater reduction in RMS-QT
c
than control subjects (
P
=.04).

Conclusions
An increase in serum potassium corrects abnormalities of repolarization duration, T-wave morphology, QT/RR slope, and QT dispersion in patients with chromosome 7–linked LQT.
Role of the Pulmonary Circulation in the Distribution of Human Fetal Cardiac Output During the Second Half of Pregnancy
Authors: Rasanen Juha , Wood Dennis C. , Weiner Stuart , Ludomirski Abraham , Huhta James C.
Published: June 2012

Background
By using Doppler echocardiography, we determined the normal distribution of human fetal combined cardiac output (CCO) from the left and right ventricles. We also established weight-indexed pulmonary and systemic vascular resistances (R
Pi
and R
Si
, respectively) and changes during the second half of pregnancy.

Methods and Results
Blood flows at the aortic and pulmonary valve annuli (LVCO and RVCO, respectively), right and left pulmonary arteries (Q
P
), and ductus arteriosus (Q
DA
) were calculated in 63 normal fetuses. Foramen ovale blood flow (Q
FO
=LVCO−Q
P
) was estimated. From 20 to 30 weeks of gestation, the proportion of Q
P
of the CCO increased (from 13% to 25%,
P
<.001), while the proportion of Q
FO
decreased (from 34% to 18%,
P
<.001). After 30 weeks, the proportions of Q
P
and Q
FO
were unchanged. At 38 weeks, the proportion of RVCO (60%) was higher (
P
<.05) than that of LVCO (40%). The proportion of Q
DA
did not change significantly. The correlation between RVCO calculated from blood flow through the pulmonary valve and from Q
DA
and Q
P
was good (
r
=.97,
P
<.0001). R
Pi
(
P
<.001) decreased from 20 to 30 weeks of gestation. From 30 to 38 weeks, R
Pi
increased (
P
<.0001). R
Si
increased (
P
<.001) from 20 to 38 weeks. The ratio of R
Pi
to R
Si
decreased (
P
<.01) from 20 to 30 weeks and later remained unchanged.

Conclusions
The human fetal pulmonary circulation has an important role in the distribution of cardiac output.
Long-term Use of Nicotine Gum Is Associated With Hyperinsulinemia and Insulin Resistance
Authors: Eliasson Bjo¨rn , Taskinen Marja-Riitta , Smith Ulf
Published: June 2012

Background
Insulin sensitivity and cardiovascular risk profile were examined in 20 healthy, nonobese, middle-aged men who were long-term users of nicotine-containing chewing gum and in 20 matched control subjects who did not use nicotine.

Methods and Results
Long-term use of nicotine-containing chewing gum was associated with insulin resistance and hyperinsulinemia. The degree of insulin sensitivity correlated negatively to the extent of nicotine use measured as plasma cotinine levels.

Conclusions
These findings suggest that nicotine is the major constituent in cigarette smoke that leads to insulin resistance, metabolic abnormalities associated with the insulin resistance syndrome, and increased cardiovascular morbidity. Thus, the use of nicotine replacement therapy during smoking cessation should be transient and limited.
Platelet Membrane Receptor Glycoprotein IIb/IIIa Antagonism in Unstable Angina
Authors: The´roux Pierre , Kouz Simon , Roy Louis , Knudtson Merril L. , Diodati Jean G. , Marquis Jean-Franc¸ois , Nasmith James , Fung Anthony Y. , Boudreault Jean-Rock , Delage Franc¸ois , Dupuis Robert , Kells Catherine , Bokslag Marianne , Steiner Beat , Rapold Hans J.
Published: June 2012

Background
Ligand binding to the platelet membrane receptor glycoprotein (GP) IIb/IIIa, the final and obligatory step to platelet aggregation, can now be inhibited by pharmacological agents. This study was designed to evaluate the potential of lamifiban, a novel nonpeptide antagonist of GP IIb/IIIa, for the management of unstable angina.

Methods and Results
In a prospective, dose-ranging, double-blind study, 365 patients with unstable angina were randomized to an infusion of 1, 2, 4, or 5 μg/min of lamifiban or of placebo. Treatment was administered for 72 to 120 hours. Outcome events were measured during the infusion period and after 1 month. Concomitant aspirin was administered to all patients and heparin to 28% of patients. Lamifiban, all doses combined, reduced the risk of death, nonfatal myocardial infarction, or the need for an urgent revascularization during the infusion period from 8.1% to 3.3% (
P
=.04). The rates were 2.5%, 4.9%, 3.3%, and 2.4% with increasing doses. At 1 month, death or nonfatal infarction occurred in 8.1% of patients with placebo and in 2.5% of patients with the two high doses (
P
=.03). The highest dose of lamifiban additionally prevented the need for an urgent intervention. Lamifiban dose-dependently inhibited platelet aggregation. Bleeding times were significantly prolonged with platelet inhibition of >80%. Major (but neither life-threatening nor intracranial) bleedings occurred in 0.8% of patients with placebo and 2.9% with lamifiban.

Conclusions
The nonpeptide GP IIb/IIIa antagonist lamifiban protected patients with unstable angina from severe ischemic events during a 3- to 5-day infusion and reduced the incidence of death and infarction at 1 month, suggesting considerable promise for this new therapeutic approach.
Cohort Study of Cytomegalovirus Infection as a Risk Factor for Carotid Intimal-Medial Thickening, a Measure of Subclinical Atherosclerosis
Authors: Nieto F. Javier , Adam Erwin , Sorlie Paul , Farzadegan Homayoon , Melnick Joseph L. , Comstock George W. , Szklo Moyses
Published: June 2012

Background
Animal studies as well as clinical and cross-sectional epidemiological studies in humans have suggested a possible role of cytomegalovirus (CMV) and other herpesvirus infections in the development of cardiovascular disease.

Methods and Results
The present report is based on a case-control study nested within a historical cohort. The case group comprised 150 individuals with elevated carotid intimal-medial thickness (IMT) measured by B-mode ultrasound at the first two examinations of the Atherosclerosis Risk in Communities (ARIC) Study (1987 through 1992). The control group comprised 150 age- and sex-matched individuals with low IMT. Antibody titers for CMV and herpesvirus 1 and 2 were determined in sera obtained in 1974 as part of a community-wide survey conducted in Washington County, Maryland. Case subjects had higher mean CMV antibody titers in 1974 sera than control subjects, although the difference was not statistically significant when adjusted for other cardiovascular risk factors. There was evidence of a graded relation between the odds of intimal-medial thickening and the levels of CMV antibodies that remained significant after adjustment for the main cardiovascular risk factors (
P
=.013). The adjusted odds ratio for a high CMV antibody titer (a positive/negative value ≥20) compared with a positive/negative value <4 was 5.3 (95% confidence interval, 1.5 to 18.0).

Conclusions
The results from this first population-based cohort study of CMV infection and carotid IMT are compatible with the hypothesis of a causal role of CMV in atherosclerosis.
Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Basso Cristina , Thiene Gaetano , Corrado Domenico , Angelini Annalisa , Nava Andrea , Valente Marialuisa
Published: June 2012

Background
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a frequent cause of sudden death in young individuals and athletes. Although familial occurrence has been documented and a gene defect was recently localized on chromosome 14q23-q24 the etiopathogenesis of the disease is still obscure.

Methods and Results
A pathological study was conducted in 30 hearts with ARVC (age range, 15 to 65 years; mean, 28 years). In the 27 autopsy cases, the mode of death was sudden in 24 and congestive heart failure in 3. ECG, available in 19 cases, showed inverted T waves in the right precordial leads in 15 cases (79%) and ventricular arrhythmias in 15 (79%). Right ventricular aneurysms were present in 15 hearts (50%) and located in the inferior wall in 12. Left ventricle and ventricular septum were involved in 14 (47%) and 6 (20%) cases, respectively. Scattered foci of lymphocytes with myocardial death were observed in 20 cases (67%). Electron microscopy studies, although confirming the myocardial death and lymphocyte infiltrates, did not show any specific ultrastructural substrate. Two pathological patterns, fatty (40%) and fibrofatty (60%), were identified. The fibrofatty pattern was associated with a thinner right ventricular wall (
P
<.0001) and a higher occurrence of focal myocarditis (
P
<.001). In sections of right ventricular free wall with maximal fatty infiltration, the mean percentage area of fatty tissue was 35.9±11.1% in control versus 80.4±9.6% in the ARVC, fatty variety (
P
<.00001). Involvement of the left ventricle and/or ventricular septum, right ventricular aneurysms, and inflammation were found almost exclusively in the fibrofatty variety.

Conclusions
In the fibrofatty variety of ARVC, the myocardial atrophy appears to be the consequence of acquired injury (myocyte death) and repair (fibrofatty replacement), mediated by patchy myocarditis. Whether the inflammation is a primary event or a reaction to spontaneous cell death remains unclear.
Alternation in the Coronary Blood Flow Velocity Pattern in Patients With No Reflow and Reperfused Acute Myocardial Infarction
Authors: Iwakura Katsuomi , Ito Hiroshi , Takiuchi Shin , Taniyama Yoshiaki , Nakatsuchi Yoshiaki , Negoro Shinji , Higashino Yorihiko , Okamura Atsunori , Masuyama Tohru , Hori Masatsugu , Fujii Kenshi , Minamino Takazo
Published: June 2012

Background
Experimental and clinical evidence indicates that myocardial ischemia often damages the coronary microvasculature (“no-reflow” phenomenon). In this study, we examined the effect of this phenomenon on the coronary blood flow velocity pattern in patients with reperfused acute myocardial infarction.

Methods and Results
We measured coronary blood flow velocity after coronary angioplasty in 42 patients with acute myocardial infarction using a Doppler guidewire. Myocardial contrast echocardiography (MCE) was also performed before and after angioplasty. Thirty-one patients showed good contrast reperfusion (MCE reflow), whereas the other 11 showed no reflow (MCE no reflow). Peak velocity and duration of systolic coronary flow were significantly less in patients with MCE no reflow than in those with MCE reflow (8±4 versus 17±10 cm/s and 207±79 versus 289±55 ms, respectively;
P
<.01). Early systolic retrograde flow was frequently observed in patients with MCE no reflow, whereas it was observed in only 1 patient among those with MCE reflow (95% versus 3%;
P
<.001). Although peak diastolic flow velocity was similar between the two subsets, diastolic deceleration rate was significantly higher in patients with MCE no reflow than in those with MCE reflow (107±76 versus 56±31 cm/s
2
;
P
<.01).

Conclusions
The coronary flow velocity pattern in patients with the no-reflow phenomenon was characterized by the appearance of systolic retrograde flow, diminished systolic antegrade flow, and rapid deceleration of diastolic flow. Thus, the Doppler guidewire allows us to assess the presence of microvascular dysfunction in AMI.
Birth Weight and Adult Hypertension and Obesity in Women
Authors: Curhan Gary C. , Chertow Glenn M. , Willett Walter C. , Spiegelman Donna , Colditz Graham A. , Manson JoAnn E. , Speizer Frank E. , Stampfer Meir J.
Published: June 2012

Background
Low birth weight has been associated with an increased risk of hypertension, and high birth weight has been associated with increased adult body mass index. Published studies on adults have included only a small number of women.

Methods and Results
We studied 71 100 women in the Nurses' Health Study I (NHS I) who were 30 to 55 years of age in 1976 and 92 940 women in the Nurses' Health Study II (NHS II) who were 25 to 42 years of age in 1989. Information on birth weight, blood pressure, physician-diagnosed hypertension, and other relevant variables was collected by biennial mailed questionnaire. Ninety-five percent of the women were white. Compared with women in the middle category of birth weight (NHS I, 7.1 to 8.5 lb; NHS II, 7.0 to 8.4 lb), the age-adjusted odds ratio of hypertension in NHS I women with birth weights <5.0 lb was 1.39 (95% CI, 1.29 to 1.50); in NHS II, for birth weights <5.5 lb, the age-adjusted odds ratio was 1.43 (95% CI, 1.31 to 1.56). There was no material change in the estimates after adjustment for other risk factors. In addition, compared with women in NHS I who weighed 7.1 to 8.5 lb at birth, those who weighed >10 lb had an age-adjusted odds ratio of 1.62 (95% CI, 1.38 to 1.90) of being in the highest (>29.2 kg/m
2
) versus the lowest (<21.9 kg/m
2
) quintile of body mass index in midlife. Similar results were seen in the NHS II cohort.

Conclusions
Early life exposures affecting birth weight may be important in the development of hypertension and obesity in adults.
Long-term Consequences of Kawasaki Disease
Authors: Kato Hirohisa , Sugimura Tetsu , Akagi Teiji , Sato Noboru , Hashino Kanoko , Maeno Yasuki , Kazue Takeyo , Eto Genzyu , Yamakawa Rumi
Published: June 2012

Background
The long-term consequences of the cardiovascular sequelae in Kawasaki disease remain uncertain.

Methods and Results
We identified 594 consecutive children with acute Kawasaki disease between 1973 and 1983, and this cohort was followed up for 10 to 21 years (mean, 13.6 years). In all patients, we evaluated coronary lesions by coronary angiography just after the acute stage. One hundred and forty-six patients (24.6%) were diagnosed as having coronary aneurysms. A second angiogram was performed 1 to 2 years later in all 146 patients who previously had coronary aneurysms, which demonstrated that 72 (49.3%) of these 146 had regression in the coronary aneurysm. A third angiogram was performed for 62 patients, a fourth for 29, and a fifth for 17. By 10 to 21 years after the onset of the illness, stenosis in the coronary aneurysm had developed in 28 patients. Myocardial infarction occurred in 11 patients, 5 of whom died. In the 26 patients with giant coronary aneurysms, stenotic lesions developed in 12, and no regression occurred. The 448 patients with normal findings at the first angiogram subsequently never developed any abnormal cardiac findings. Systemic artery aneurysms developed in 13 patients (2.2%), and valvular heart disease appeared in 7 (1.2%).

Conclusions
The incidence of coronary aneurysm in acute Kawasaki disease was 25%, 55% of which showed regression. During follow-up, ischemic heart disease developed in 4.7% and myocardial infarction in 1.9%. Death occurred in 0.8%.
Expression of bcl-2 Protein, an Inhibitor of Apoptosis, and Bax, an Accelerator of Apoptosis, in Ventricular Myocytes of Human Hearts With Myocardial Infarction
Authors: Misao Jun , Hayakawa Yukihiro , Ohno Michiya , Kato Satoshi , Fujiwara Takako , Fujiwara Hisayoshi
Published: June 2012

Background
In general, myocyte death in myocardial infarctions (MIs) is attributed to necrosis, but recently the involvement of apoptosis has been suggested. The ratio of bcl-2 protein, an inhibitor of apoptosis, to Bax protein, an inducer of apoptosis, determines survival or death after an apoptotic stimulus. We speculated that bcl-2 or Bax expression is induced by ischemia and that it may be related to myocyte death in human hearts.

Methods and Results
We studied immunohistochemically 37 autopsied human hearts (acute MI, n=15; old MI, n=12; normal hearts as a control, n=10) with the use of bcl-2 and Bax antibodies. There were no myocytes with positive bcl-2 immunoreactivity in the controls or hearts with old MI. However, myocytes with positive bcl-2 immunoreactivity were seen in 9 of 15 hearts (60%) with acute MI, in that it was localized only in salvaged areas surrounding the infarcted tissues. Myocytes with slightly positive Bax immunoreactivity were observed in the control hearts. In the salvaged myocytes surrounding the infarcted tissues, Bax was overexpressed in 2 of 15 hearts (13%) with acute MI but in 10 of 12 hearts (83%) with old MI.

Conclusions
bcl-2 protein is induced in salvaged myocytes at the acute stage of infarction, but Bax protein is overexpressed at the old stage. The expression of bcl-2 and the overexpression of Bax may play an important pathophysiological role in the protection or acceleration of the apoptosis of human myocytes after ischemia and/or reperfusion.