bluuebunny/crossref_metadata_2025 huggingface dataset:
Ventricular Tachycardia in Valvular Heart Disease
Authors: Narasimhan Calambur , Jazayeri Mohammad R. , Sra Jasbir , Dhala Anwer , Deshpande Sanjay , Biehl Michael , Akhtar Masood , Blanck Zalmen
Published: June 2012

Background
The clinical characteristics of sustained monomorphic ventricular tachycardia (SMVT), when it develops after valve surgery, have not been described.

Methods and Results
Between 1985 and 1996, 31 patients (30 men and 1 woman) who had undergone valve surgery were found to have inducible SMVT. Nine patients (29%) had sustained VT due to bundle-branch reentry (BBR) (group 1). Four of these patients had normal left ventricular function, and VT with a right bundle-branch morphology was inducible in 4 patients. Group 2 included 20 patients with inducible myocardial (ie, non-BBR) VT. Coronary artery disease was present in 15 group 2 patients (75%) due to atherosclerotic (n=12) and nonatherosclerotic (n=3) causes. Two patients had both inducible sustained BBR and myocardial VT (group 3). Sustained BBR VT occurred significantly earlier after valve surgery (median, 10 days) than the onset of postoperative myocardial VT (median, 72 months;
P
<.005).

Conclusions
Myocardial VT was the most common type of inducible SMVT in patients with valvular heart disease. The majority of these patients had underlying coronary artery disease and significant left ventricular dysfunction. However, in almost one third of the patients, sustained BBR VT was the only type of inducible SMVT. This type of VT was facilitated by the valve procedure occurring within 4 weeks after surgery in most patients. In these patients, left ventricular function was relatively well preserved, and the right bundle-branch block type of BBR was frequently induced. Because a curative therapy can be offered to these patients (ie, bundle-branch ablation), BBR should be seriously considered as the mechanism of VT in patients with valvular heart disease, particularly if the arrhythmia occurs soon after valve surgery.
Cardiovascular Risk Factors in Mexican-American and Non-Hispanic White Children
Authors: Tortolero Susan R. , Goff David C. , Nichaman Milton Z. , Labarthe Darwin R. , Grunbaum Jo Anne , Hanis Craig L.
Published: June 2012

Background
Information concerning differences in cardiovascular disease risk factors between Mexican-American and non-Hispanic white children is limited. We conducted a study to determine if there were ethnic differences in cardiovascular disease risk factors in children and whether such differences were explained by differences in body mass index.

Methods and Results
Fasting glucose, insulin, and blood lipid concentrations, blood pressure, weight, and height were measured in a cross-sectional survey among 403 third-grade children in Corpus Christi, Tex. We found significantly higher fasting insulin and glucose concentrations among Mexican-American than among non-Hispanic white children. Mexican-American boys had slightly lower levels of HDL cholesterol and higher systolic blood pressure than non-Hispanic white boys. Ethnic differences in insulin and glucose were not explained by body mass index.

Conclusions
These results provide preliminary evidence that ethnic differences in insulin, glucose, body mass index, and other risk factors occur as early as age 8 to 10 years. Additional research is warranted on differences in risk factors in Mexican-American and non-Hispanic white children and the potential importance of insulin in influencing the natural history of these characteristics.
In-Hospital Outcome of Elderly Patients With Acute Inferior Myocardial Infarction and Right Ventricular Involvement
Authors: Bueno Héctor , López-Palop Ramón , Bermejo Javier , López-Sendón José L. , Delcán Juan L.
Published: June 2012

Background
There are some specific high-risk subgroups of patients with acute inferior myocardial infarction, such as older patients and those with right ventricular involvement. However, the clinical implications of right ventricular infarction in elderly subjects have not been studied previously.

Methods and Results
To determine the clinical impact of right ventricular involvement in elderly patients with inferior myocardial infarction, we studied the in-hospital outcome of 198 consecutive patients ≥75 years of age with a first acute inferior myocardial infarction according to the presence of ECG or echocardiographic criteria of right ventricular infarction. In patients with right ventricular involvement (41%), in-hospital case fatality rate was 47% (mainly because of nonreversible low cardiac output cardiogenic shock) compared with 10% in patients without right ventricular involvement (
P
<.001). Patients with right ventricular involvement also had a significantly higher incidence of cardiogenic shock (32% versus 5%), which was independent of left ventricular ejection fraction, complete AV block (33% versus 9%), and interventricular septal rupture (9% versus 0%). After adjustment for age, sex, diabetes, shock on admission, left ventricular systolic dysfunction, and complete AV block, right ventricular infarction remained a powerful independent predictor of in-hospital death (adjusted odds ratio, 4.0; 95% confidence interval, 1.3 to 14.2).

Conclusions
Elderly patients with acute inferior myocardial infarction have a substantially increased risk of death during hospitalization when right ventricular involvement is present. The poorer outcome is due mainly to the high incidence of cardiogenic shock and its infrequent reversibility.
Effects of Ramipril on Plasma Fibrinolytic Balance in Patients With Acute Anterior Myocardial Infarction
Authors: Vaughan Douglas E. , Rouleau Jean-Lucien , Ridker Paul M. , Arnold J. Malcolm O. , Menapace Francis J. , Pfeffer Marc A.
Published: June 2012

Background
The long-term administration of ACE inhibitors to selected patients with left ventricular dysfunction appears to reduce the incidence of recurrent myocardial infarction (MI) and unstable angina pectoris. The mechanisms responsible for the reduction in ischemic events are unknown, but likely candidates include effects on the atherosclerotic process, thrombosis, and/or vascular tone.

Methods and Results
The effects of ACE inhibitor therapy with ramipril on plasma fibrinolytic variables were assessed in 120 subjects participating in the Healing and Early Afterload Reduction Therapy (HEART) study, a double-blind, placebo-controlled trial of acute anterior MI patients who were randomly assigned within 24 hours of the onset of symptoms to receive low-dose ramipril (0.625 mg daily), full-dose ramipril (1.25 mg titrated to 10 mg/d), or placebo for 14 days. Plasma levels of plasminogen activator inhibitor-1 (PAI-1) activity and PAI-1 antigen and tissue plasminogen activator (TPA) antigen were measured before randomization and on day 14. Clinical characteristics of the three study groups were similar, as were the prerandomization plasma levels of PAI-1 antigen, PAI-1 activity, and TPA antigen. Compared with the placebo group, PAI-1 antigen levels were 44% lower (
P
=.004) at day 14 in the ramipril-treated patients, and PAI-1 activity levels were 22% lower (
P
=.02). In contrast, plasma TPA levels were not significantly different between the placebo-treated and ramipril-treated groups.

Conclusions
Treatment with ramipril has a significant impact on plasma fibrinolytic variables during the recovery phase after acute MI. The renin-angiotensin system appears to play an important role in the regulation of vascular fibrinolysis, and interruption of this regulatory pathway may contribute to the clinical benefits of ACE inhibitors.
Inhibition of Sarcolemmal Na
+
,K
+
-ATPase Activity Reduces the Infarct Size–Limiting Effect of Preconditioning in Rabbit Hearts
Authors: Nawada Ryuzo , Murakami Tomoyuki , Iwase Tomoyuki , Nagai Kunihiko , Morita Yasuhiro , Kouchi Ichiro , Akao Masaharu , Sasayama Shigetake
Published: June 2012

Background
The inhibition of sarcolemmal Na
+
,K
+
-ATPase activity is closely related to ischemic myocardial cell injury. However, the involvement of this enzyme in preconditioning has not been determined.

Methods and Results
We assessed the effect of ischemia on sarcolemmal Na
+
,K
+
-ATPase activity. Control and preconditioned rabbits were subjected to 0, 10, 20, 30, and 60 minutes of coronary occlusion. Ten to 60 minutes of ischemia reduced Na
+
,K
+
-ATPase activity, whereas preconditioning preserved the activity of this enzyme only during the first 20 minutes of ischemia. To determine whether the preservation of Na
+
,K
+
-ATPase activity in the early phase of ischemia contributed to limiting the infarct size, additional rabbits underwent 30 minutes of occlusion followed by 3 hours of reperfusion with or without pretreatment with digoxin, an inhibitor of Na
+
,K
+
-ATPase. Infarct size in animals pretreated with digoxin in the absence of preconditioning did not differ from that in controls. It was markedly reduced by preconditioning, whereas digoxin reduced the infarct size–limiting effect. Moreover, preconditioning increased sarcolemmal Na
+
-Ca
2+
exchange activity in rabbits subjected to 20 minutes of ischemia, whereas digoxin diminished this increase.

Conclusions
Preconditioning preserves the ischemia-induced reduction in sarcolemmal Na
+
,K
+
-ATPase activity in the early phase of ischemia in rabbit hearts. Inhibition of Na
+
,K
+
-ATPase activity reduces the infarct size–limiting effect of preconditioning with a loss of increased Na
+
-Ca
2+
exchange activity, implying that this preservation is responsible for the cardioprotective effect of preconditioning.
Lactate and P
o
2
Modulate Superoxide Anion Production in Bovine Cardiac Myocytes
Authors: Mohazzab-H. Kamal M. , Kaminski Pawel M. , Wolin Michael S.
Published: June 2012

Background
Lactate increases lucigenin chemiluminescence (CL)–detectable superoxide anion (O
2
•
−
) generation in bovine vascular smooth muscle and endothelium, and a microsomal flavoprotein-containing NADH oxidase whose activity is regulated by P
o
2
and cytosolic NAD(H) redox appears to be the detected source of O
2
•
−
production. Little is known about the importance of this O
2
•
−
-producing system in cardiac myocytes.

Methods and Results
In isolated bovine cardiac myocytes, lactate (10 mmol/L) increased lucigenin-detectable O
2
•
−
levels to ≈1.8 times baseline, whereas pyruvate (10 mmol/L) and mitochondrial probes did not increase the detection of O
2
•
−
. A nonmitochondrial NADH oxidase activity, found in microsomes containing a cytochrome
b
558
, was a major source of O
2
•
−
production in the homogenate of myocytes, because NADH (0.1 mmol/L) increased basal lucigenin CL >100-fold. NADPH oxidases, mitochondria, and xanthine oxidase were minor sources of detectable O
2
•
−
production. However, mitochondria released H
2
O
2
in the presence of 5 mmol/L succinate and 30 μmol/L antimycin, based on its detection as catalase-inhibitable luminol (+horseradish peroxidase)–elicited CL. Diphenyliodonium (DPI), an inhibitor of flavoprotein-containing oxidases, significantly attenuated basal, lactate, and NADH-elicited lucigenin CL. Hypoxia eliminated myocyte lucigenin CL, and posthypoxic reoxygenation caused an 8.6-fold increase in the detection of O
2
•
−
that was potentiated by lactate and inhibited by DPI.

Conclusions
NADH oxidase activity linked to cytosolic NAD(H) redox appears to be a key source of O
2
•
−
production in cardiac myocytes that could contribute to oxidant signaling mechanisms and injury upon exposure to changes in P
o
2
and metabolites produced under hypoxia, such as lactate. These processes could contribute to the previously observed potentiation of injury caused by lactate in cardiac ischemia/reperfusion.
Reduction in Stent and Vascular Graft Thrombosis and Enhancement of Thrombolysis by Recombinant Lys-Plasminogen in Nonhuman Primates
Authors: Sundell I. Birgitta , Marzec Ulla M. , Kelly Andrew B. , Chronos Nicolas A. F. , Petersen Lars C. , Hanson Stephen R. , Hedner Ulla , Harker Laurence A.
Published: June 2012

Background
To enhance thrombolytic responses without increasing hemorrhagic risks, the antithrombotic effects of recombinant Lys-plasminogen (r-LysPgn), a prothrombolytic plasminogen intermediate, were examined in baboon models of thrombus formation and dissolution.

Methods and Results
The dose-response effects of r-LysPgn, alone or in combination with subthreshold dosing of tissue plasminogen activator (TPA), were measured with respect to the accumulation of
111
In-labeled platelets and
125
I-fibrin in thrombus forming on endovascular metallic stents or thrombogenic segments of vascular graft interposed in exteriorized long-term arteriovenous (AV) femoral shunts. Thrombolytic losses have also been determined for preformed, stable,
111
In-platelet– and
125
I-fibrin–labeled graft thrombus and corresponding propagated thrombotic tails, together with changes in blood tests of thrombosis, thrombolysis, and hemostasis. Bolus intravenous r-LysPgn in escalating doses (2, 4, or 8 mg/kg) increased circulating plasminogen levels in a dose-dependent manner, was removed by log-linear clearance with a T
50
of 120 minutes, and reciprocally decreased the accumulating thrombus on metallic stents and segments of vascular graft (
P
<.001 in all cases for 8-mg/kg doses). r-LysPgn also impaired platelet aggregatory responses to physiological agonists in vitro but not ex vivo. Prethrombosis administration of low-dose r-LysPgn (2 mg/kg) greatly enhanced the lysis of radiolabeled nonoccluding thrombus by a subthreshold dose of TPA (0.1 mg/kg) compared with TPA-only controls (
P
=.03).

Conclusions
Elective bolus injections of r-LysPgn before stent deployment decrease the amount of thrombus formed without compromising hemostasis by facilitating endogenous TPA thrombolysis. r-LysPgn may provide effective and safe antithrombotic therapy for interventional vascular procedures.
Role of Preischemic Glycogen Depletion in the Improvement of Postischemic Metabolic and Contractile Recovery of Ischemia-Preconditioned Rat Hearts
Authors: Soares Paulo R. , de Albuquerque Cicero P. , Chacko V. P. , Gerstenblith Gary , Weiss Robert G.
Published: June 2012

Background
Ischemic preconditioning (IPC) attenuates acidosis during prolonged ischemia and improves contractile and metabolic parameters during subsequent reperfusion. Glycogen depletion induced by IPC is proposed as a potential mechanism.

Methods and Results
We studied the influence of manipulations of preischemic glycogen levels (Pre-G, μmol glucose/g wet wt) on contractile and metabolic (via
31
P–nuclear magnetic resonance) parameters during 30 minutes of ischemia and recovery in four groups of isovolumic rat hearts: First, control (Con, n=18, mean Pre-G, 21.5±0.8); second, after two 5-minute IPC periods (IPC, n=12, Pre-G, 11.3±0.7); third, a control group in which Pre-G was depleted by glucose-free, acetate perfusion (Con-LowG, n=9, Pre-G, 7.9±1.2); and fourth, an IPC group in which Pre-G was raised by glucose and lactate perfusion such that Pre-G was similar to Con (IPC-HiG, n=11, Pre-G, 20±1.4). Manipulation of Pre-G significantly altered the pH fall during 30 minutes of ischemia (Con, 5.76±.03, Con-LowG, 6.26±.07; IPC-HiG, 5.91±.02, IPC, 6.05±.09). IPC-HiG hearts had significantly worse metabolic recovery (PCr, 70±7 versus 91±3% initial; IPC-HiG versus IPC,
P
<.05) and contractile recovery (end-diastolic pressure, 52±5 versus 29±5 mm Hg,
P
<.05) than IPC hearts but better recovery than Con (%PCr, 56±6% and end-diastolic pressure, 72±6 mm Hg). An ischemic rise in intracellular magnesium occurred and was atttenuated in preconditioned hearts.

Conclusions
Pre-G levels before ischemia influence but are not the sole determinants of the extent of acidosis during prolonged ischemia and of metabolic and contractile recovery during reperfusion in control and preconditioned hearts.
Evidence of Multifocal Activity of Coronary Disease in Patients With Acute Myocardial Infarction
Authors: Guazzi Maurizio D. , Bussotti Maurizio , Grancini Luca , De Cesare Nicoletta , Guazzi Marco , Pera Isidoro L. , Loaldi Alessandro
Published: June 2012

Background
Destabilization of the fibrous cap facilitates plaque rupture, thrombus formation, and myocardial infarction. Because systemic stimuli, such as lipoproteins, infectious agents, and autoantigens, may incite this reaction, one may wonder whether disruption mechanisms are only local or systemic and infarction is caused by an arbitrary plaque event or by a systemic, acute activity of the coronary disease.

Methods and Results
Early (3 to 5 days) and late (1 month) peri-infarction coronary angiographic data in 23 patients with first infarction were compared with that in 23 similar patients, with angiography performed because of stable angina and repeated after 1 month before angioplasty. Nonculprit lesion changes at the narrowest point defined progression or regression when exceeding 0.27 mm. In patients with recent infarction we found that 16 had progression, 4 had regression, 1 had both, 2 were steady (values in patients with stable angina being 2 [
P
<.001], 1 [NS], 0 [NS], and 20 [
P
<.001]); 27 lesions were infarct related; 17 of the 45 nonculprit lesions progressed and 5 regressed (values in stable angina being 2 [
P
<.001] and 1 [
P
<.05] out of 78); minimal diameter reduction of progressing stenoses averaged 0.39 mm; lumen increase of regressing lesions averaged 0.30 mm; 3 patients developed interim rest angina associated with progression of a nonculprit lesion.

Conclusions
A greater proportion of subjects and lesions with progression or regression (in infarction versus stable angina) supports the hypothesis that infarction is a hallmark of systemic coronary disease activity. Changes might vary according to the “maturation” stage of an atheroma, and maximal expression would be at the level of the offending plaque. Shrinkage, thrombolysis, or vascular remodeling would determine the residual plaque morphology.
Can Adenosine 5′-Triphosphate Be Used to Select Treatment in Severe Vasovagal Syndrome?
Authors: Flammang Daniel , Church Timothy , Waynberger Marc , Chassing Annick , Antiel Mark
Published: June 2012

Background
Selection of treatment in vasovagal syndrome should be guided by the mechanism of symptoms. This study determined whether a simple drug test may assess one mechanism.

Methods and Results
To identify patients at risk of severe cardioinhibitory response of vagal origin, we infused 20 mg ATP into 316 patients hospitalized for recurrent syncope (n=195) or presyncope (n=121) of unknown origin and into normal subjects (n=51). We then assessed the ECG and clinical responses to the drug, recommended therapy, and followed up the subjects chronically. A cardiac pause >10 seconds was seen in only 3 normal subjects (6%). Therefore, a pause ≤10 seconds yielded the ≈95th percentile of the normal range. ATP provoked a pause >10 seconds in 130 symptomatic patients (41%) and a pause ≤10 seconds in 186 symptomatic patients (59%). Thus, symptomatic patients with pauses >10 seconds were proposed for pacemaker implantation; all other patients and normal subjects were simply monitored. Among long-pause patients with follow-up, the observed recurrence rate for the 104 with pacemakers was one-third that for the 21 who were only monitored (
P
<.0001). Among followed-up short-pause patients, the rate in the 153 monitored-only patients did not differ from the 20 implanted patients (
P
=.432).

Conclusions
The vagal effect of ATP may identify the subgroup of patients at high risk of severe cardioinhibitory response of vagal origin who likely will benefit from pacemaker therapy. This fast, uncomplicated test should be considered for further use in screening patients with vasovagal syndrome.
Heart Rate Variability in Patients With Atrial Fibrillation Is Related to Vagal Tone
Authors: van den Berg Maarten P. , Haaksma Jaap , Brouwer Jan , Tieleman Robert G. , Mulder G. , Crijns Harry J. G. M.
Published: June 2012

Background
Analysis of heart rate variability (HRV) has thus far not been applied in patients with atrial fibrillation, probably because of the presumed absence of any form of patterning of the ventricular rhythm, particularly vagally mediated respiratory arrhythmia. However, such patterning is theoretically conceivable given the function of the atrioventricular node in atrial fibrillation and its susceptibility to autonomic influences.

Methods and Results
Sixteen patients (mean age, 56±4 years) with long-term atrial fibrillation on fixed doses of digoxin or verapamil were studied; 12 healthy men in sinus rhythm were used as control subjects. HRV (standard deviation of RR intervals [SD], coefficient of variance [CV], the root-mean-square of successive difference [RMSSD], and low-frequency [LF] and high-frequency power [HF]) was analyzed during 500 RR intervals at baseline, after administration of propranolol (0.2 mg/kg IV), and after subsequent administration of methylatropine (0.02 mg/kg IV). HRV at baseline and changes in HRV after methylatropine were then related to vagal tone (vagal cardiac control), quantified as the decrease in mean RR after methylatropine. Baseline HRV was higher in the atrial fibrillation group than in the control group; after propranolol, HRV increased in both groups; after methylatropine, HRV neared zero in the control group, whereas it returned to baseline values in the atrial fibrillation group. SD, RMSSD, LF, and HF at baseline were significantly (
P
<.05) correlated with vagal tone in the control group but also in the atrial fibrillation group (correlation coefficients of .60, .61, .57, and .64, respectively). Even stronger correlations were observed between changes in these parameters after methylatropine and vagal tone, particularly in the atrial fibrillation group (correlation coefficients of .89, .87, .72, and .90, respectively).

Conclusions
This study shows that HRV in patients with atrial fibrillation is related to vagal tone.
Probability of Successful Defibrillation at Multiples of the Defibrillation Energy Requirement in Patients With an Implantable Defibrillator
Authors: Strickberger S. Adam , Daoud Emile G. , Davidson Theresa , Weiss Raul , Bogun Frank , Knight Bradley P. , Bahu Marwan , Goyal Rajiva , Man K. Ching , Morady Fred
Published: June 2012

Background
The probability of successful defibrillation has been determined in normal animals but not in patients undergoing defibrillator implantation. Therefore, the purpose of this prospective study was to determine the probability of successful defibrillation in humans on the basis of a step-down defibrillation energy requirement.

Methods and Results
Fifty-three consecutive patients underwent five separate inductions of ventricular fibrillation after the defibrillation energy requirement was determined with the use of small decrements and a step-down protocol (20, 15, 12, 10, 8, 6, 5, 4, 3, 2, 1, and 0.8 J). The first shock energy for defibrillation was either 1.0, 1.3, 1.5, 1.7, or 2.0 times the defibrillation energy requirement, and the likelihoods of successful defibrillation were 70±27%, 84±12%, 86±25%, 80±29%, and 88±32%, respectively (
P
=.03). The frequencies of uniformly successful defibrillation (5 of 5 defibrillation attempts) were 30%, 27%, 60%, 64%, and 73%, respectively (
P
=.01). Seven patients in whom the defibrillation energy requirement was <4 J had an overall rate of successful defibrillation of 54±20% compared with 86±20% in the remaining 47 patients (
P
=.002). The likelihood of successful defibrillation at twice the defibrillation energy requirement was 98% in the 46 patients with a defibrillation energy requirement of >4 J and 67% in the 7 patients with a defibrillation energy requirement of <4 J (
P
=.17). An absolute safety margin of 7 J was associated with a 96% probability of successful defibrillation.

Conclusions
The probability of successful defibrillation is 70% at the defibrillation energy requirement. The probability plateaus at 88%, at twice the defibrillation energy requirement. A 96% probability of successful defibrillation is achieved at an absolute safety margin of 7 J, and a 98% success rate is achieved at energies that are twice the defibrillation energy requirement if the defibrillation energy requirement is >4 J. If the defibrillation energy requirement is <4 J, larger multiples of the defibrillation energy requirement are needed to achieve a high probability of successful defibrillation.
Regional Alteration of the Transient Outward Current in Human Left Ventricular Septum During Compensated Hypertrophy
Authors: Bailly Patrick , Bénitah Jean-Pierre , Mouchonière Maud , Vassort Guy , Lorente Paco
Published: June 2012

Background
A large calcium-insensitive transient outward current (
I
to
) has been recorded in atria, left ventricular (LV) free wall, and right ventricular septal subendocardium of the human heart. Recent studies suggested a major contribution of this current to the electrical heterogeneity of the heart. However, no data have been reported on the distribution of
I
to
density within the LV septal wall from compensated human LV hypertrophy.

Methods and Results
Microelectrode and patch-clamp techniques were used to record action potentials and
I
to
in myocytes isolated from superficial (<3 mm deep) and deep (3 to 6 mm deep) layers of LV septum from patients with aortic stenosis and compensated LV hypertrophy. Subendocardial specimens were also obtained from undiseased donor hearts. In none of the superficial subendocardial cells from diseased hearts was a macroscopic
I
to
recorded (n=42), whereas in cells from the same location from donor hearts, a typical
I
to
was clearly present, with a peak density of 5.88±0.78 pA/pF at +60 mV (n=4). However, in deep layers from patients with compensated LV hypertrophy, macroscopic
I
to
was present, with a peak density of 10.50±2.58 pA/pF at +60 mV (n=4). The absence of
I
to
in superficial septal cells from hypertrophied hearts was not due to a divalent cation–related shift of the current kinetics. Instead, extracellular Ca
2+
removal induced an
I
to
-like current, possibly carried by K
+
ions, with a peak density of 30.7±2.6 pA/pF at +60 mV (n=29). However, its magnitude, kinetics, and pharmacological characteristics did not allow identification of this current as the usual
I
to
.

Conclusions
Both topography and pathology can be major modulating factors of the regional distribution of
I
to
density in human LV septum. Therefore, they may play a prominent role in determining electrical gradients within this region from which the early depolarization vectors start and the left-to-right activation sequence of the interventricular septum proceeds.
Relations of Left Ventricular Mass to Demographic and Hemodynamic Variables in American Indians
Authors: Devereux Richard B. , Roman Mary J. , de Simone Giovanni , O’Grady Michael J. , Paranicas Mary , Yeh JeunLiang , Fabsitz Richard R. , Howard Barbara V.
Published: June 2012

Background
Previous studies have identified associations of left ventricular (LV) mass with demographic (body habitus and sex) and hemodynamic variables (blood pressure, stroke volume [SV], and myocardial contractility), but the relative strength and independence of these associations remain unknown.

Methods and Results
We examined the relations of echocardiographically determined LV mass to demographic variables, blood pressure, Doppler SV, and measures of contractility (end-systolic stress [ESS]/end-systolic volume index and midwall fractional shortening [MFS] as a percentage of predicted for circumferential end-systolic stress [stress-independent shortening]) in 1935 American Indian participants in the Strong Heart Study phase 2 examination without mitral regurgitation or segmental wall motion abnormalities. Weak positive relations of LV mass with systolic and diastolic pressures (
r
=.22 and
r
=.20) were exceeded by positive relations with height (
r
=.30), weight (
r
=.47), body mass index (
r
=.31), body surface area (
r
=.49), and Doppler SV (
r
=.50) and negative relations with ESS/volume index ratios (
r
=−.33 and −.29) and stress-independent MFS (
r
=−.26, all
P
<.0001). In multivariate analyses that included blood pressure, SV, and a different contractility measure in each model, systolic pressure, stroke volume, and the contractility measure were independent correlates of LV mass (multiple
R
=.60 to .66, all
P
<.0001). When demographic variables were added, LV mass was more strongly predicted by higher SV and lower afterload-independent MFS than by greater systolic pressure, height, and body mass index (each
P
<.00001, multiple
R
=.71).

Conclusions
Additional characterization of volume load and contractile efficiency improves hemodynamic prediction of LV mass (
R
2
=.30 to .44) over the use of systolic blood pressure alone (
R
2
=.05), with a further increase in
R
2
to .51 when demographic variables are also considered. However, nearly half of the ventricular mass variability remains unexplained.
Vitamin C Improves Endothelial Dysfunction of Epicardial Coronary Arteries in Hypertensive Patients
Authors: Solzbach Ulrich , Hornig Burkhard , Jeserich Michael , Just Hanjörg
Published: June 2012

Background
There is evidence for increased formation of free radicals in patients with hypertension, raising the possibility that NO is inactivated by free radicals, which impairs coronary endothelial function. Therefore, we tested the hypothesis that the antioxidant vitamin C could improve abnormal endothelial function of coronary arteries in patients with hypertension.

Methods and Results
In 22 hypertensive patients without relevant coronary artery stenoses, endothelium-dependent vascular responses of the left anterior descending coronary artery (LAD) to acetylcholine (0.01, 0.1, and 1.0 μmol/L) were determined before and immediately after intravenous infusion of 3 g vitamin C (17 patients) or placebo (5 patients). In a subgroup of 10 patients, papaverine-induced flow-dependent vasodilation (FDD) was measured before and after vitamin C (5 patients) or placebo (5 patients) infusion. Segmental responses of the coronary artery luminal area were analyzed with quantitative coronary angiography. Before vitamin C infusion, the mean changes of LAD luminal areas at increasing doses of acetylcholine were −6.1±2.2%, −15.2±4.9%, and −33.9±8.1% (negative numbers symbolize vasoconstriction) and during FDD, 5.4±1.0%. The vasoconstrictor response during acetylcholine was reduced and FDD was augmented by vitamin C. After vitamin C infusion, LAD luminal areas changed by −3.2±2.3%, −5.8±3.6%, and −10.2±5.6% (
P
<.05, acetylcholine) and 17.8±2.8% (
P
<.05, FDD). Doppler flow velocity (during baseline, acetylcholine, and FDD) was not significantly affected by vitamin C.

Conclusions
Vitamin C improves the endothelium-dependent vasomotor capacity of coronary arteries in patients with hypertension and patent coronary arteries. These findings suggest that increased oxidative stress contributes to endothelial dysfunction in hypertensive patients.
Inhibition of Nitric Oxide Synthesis Increases Adenosine Production via an Extracellular Pathway Through Activation of Protein Kinase C
Authors: Minamino Tetsuo , Kitakaze Masafumi , Node Koichi , Funaya Hiroharu , Hori Masatsugu
Published: June 2012

Background
NO is known to deactivate protein kinase C (PKC). Because we have reported that the activation of PKC activates ecto-5′-nucleotidase, we examined whether the inhibition of NO synthesis increases ecto-5′-nucleotidase activity through the activation of PKC.

Methods and Results
The left anterior descending coronary artery (LAD) was cannulated and perfused with blood through a bypass tube from the left carotid artery in 65 open-chest dogs. The intracoronary administration of
N

G

-nitro-
l
-arginine methyl ester (L-NAME, 10 μg · kg
−1
· min
−1
), an NO synthase inhibitor, for 30 minutes increased (
P
<.05) adenosine levels in coronary venous blood (123±10 versus 21±3 pmol/mL) and ecto-5′-nucleotidase activity (64±6 versus 41±4 nmol · mg
−1
· min
−1
) in the LAD-perfused myocardium. The intracoronary administration of α,β-methyleneadenosine 5′-diphosphate, an inhibitor of ecto-5′-nucleotidase, or GF109203X or calphostin C, both of which are PKC inhibitors, attenuated the L-NAME–induced increases in adenosine levels and ecto-5′-nucleotidase activity. Treatment of cultured human coronary arterial endothelial cells (HCAECs) with L-NAME for 30 minutes increased ecto-5′-nucleotidase activity, which was inhibited by either GF109203X or calphostin C. NO releasers decreased both ecto-5′-nucleotidase and PKC activities in HCAECs. Treatment of HCAECs with zaprinast, a selective inhibitor of cGMP-specific phosphodiesterase, with or without atrial natriuretic peptide, increased intracellular cGMP concentrations but did not change ecto-5′-nucleotidase activity.

Conclusions
These results indicate that the inhibition of NO synthesis increases both adenosine production and ecto-5′-nucleotidase activity through the activation of PKC and that NO modulates ecto-5′-nucleotidase via cGMP-independent mechanisms.
Two- and Three-Dimensional Transesophageal Echocardiography in Patient Selection and Assessment of Atrial Septal Defect Closure by the New DAS–Angel Wings Device
Authors: Magni Giuseppina , Hijazi Ziyad M. , Pandian Natesa G. , Delabays Alain , Sugeng Lissa , Laskari Cleo , Marx Gerald R.
Published: June 2012

Background
Transcatheter closure of atrial septal defects (ASDs) has been feasible and successful. Two-dimensional echocardiography (2DE) was applied to patients before selection and during device deployment. Three-dimensional echocardiography (3DE) can provide unique anatomic perspectives that might aid in improving device closure of ASDs.

Methods and Results
Twenty-two consecutive patients were enrolled in an initial protocol for ASD device closure by the new DAS–Angel Wings occluder device. On the basis of transesophageal (TEE) 2DE and 3DE, 13 patients were considered eligible for device closure (9 secundum ASDs and 4 with patent foramen ovale associated with a cerebral vascular accident). Maximal ASD diameter and surrounding rim tissues were compared by TEE 2DE and 3DE and with balloon sizing measurements at catheterization. ASD size measured by TEE 2DE and 3DE correlated well (
y
=1.0
x
+0.049,
r
=.95), with good limits of agreement. However, balloon-stretched diameter measurements were systematically larger than echocardiographic measurements. Rim tissue measurements correlated well; however, TEE 3DE could demonstrate the entire shape and perimeter of the defect. Two-dimensional imaging provided reliable information during device deployment and for closure of small ASDs. However, 3DE was superior for imaging the device, especially when abnormally placed.

Conclusions
Three-dimensional imaging provides unique images and projections that were essential for understanding the spatial relationship of the device to the atrial septum. Three-dimensional echocardiography significantly enhanced our understanding of two-dimensional images and provided an imaging conceptualization that should aid in future development of device closures.
Plasminogen Activator Inhibitor-1 in Neointima of Vein Grafts
Authors: Kauhanen Petteri , Sirén Vappu , Carpén Olli , Vaheri Antti , Lepäntalo Mauri , Lassila Riitta
Published: June 2012

Background
Intimal smooth muscle cell proliferation is an underlying pathogenetic mechanism for neointimal hyperplasia and consequent vein graft failure. This study characterizes the expression of tissue-type plasminogen activator (TPA), urokinase-type plasminogen activator (UPA), and plasminogen activator inhibitor-1 (PAI-1) in hyperplastic vein grafts and normal venous tissue.

Methods and Results
Failing graft and control vein specimens from 14 donors were homogenized, and TPA and PAI-1 were quantified with ELISA. The amount of PAI-1 was seven times higher (4.2±2.1 versus 0.6±0.6 ng/mg protein,
P
<.005), but the TPA antigen content was markedly lower (3.1±2.1 versus 8.1±3.7 ng/mg protein,
P
<.005) in the stenosed grafts compared with the control veins. Strong immunohistochemical PAI-1 reactivity and in situ hybridization signals for PAI-1 and UPA mRNA were associated with the smooth muscle cells of the thickened intima of the grafts. Functional assays of the graft specimens showed an increased UPA/TPA ratio and a decreased total fibrinolytic activity in comparison with normal veins.

Conclusions
Upregulation of PAI-1 mRNA expression and markedly increased amounts of PAI-1 antigen were detected in the vein grafts after the development of neointima. Furthermore, augmented UPA activity was found in the graft wall, but TPA was clearly depleted. Altogether, our findings imply decreased fibrinolytic potential in the stenosed graft, which may contribute to the graft occlusion.
Predictors of Arrhythmic Death and Cardiac Arrest in the ESVEM Trial
Authors: Caruso Anthony C. , Marcus Frank I. , Hahn Elizabeth A. , Hartz Vernon L. , Mason Jay W.
Published: June 2012

Background
The purpose of this study was to determine if the presenting ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation/cardiac arrest) predicted the type of arrhythmia recurrence in patients treated with antiarrhythmic drugs.

Methods and Results
In the previously reported Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial, there were 486 patients who were randomized to antiarrhythmic drug testing guided by electrophysiological study or by ambulatory ECG monitoring. Use of a defibrillator (implantable cardioverter-defibrillator, ICD) without stored electrograms among 81 patients precluded determination of the type of arrhythmia recurrence; thus these patients were censored at the time of ICD implantation. Of the 486 patients, 381 presented with ventricular tachycardia and 105 with cardiac arrest. Over a 6-year follow-up period, 285 of the 486 patients had an arrhythmia recurrence; of these, 97 had an arrhythmic death or cardiac arrest as a first recurrence. In the current analysis, all 129 arrhythmic deaths/cardiac arrests that occurred any time during follow-up were evaluated as end points.

Conclusions
Although univariate analysis suggested that there was an association between the presenting arrhythmia and outcome, multivariate analysis failed to substantiate the predictive value of the presenting arrhythmia. Left ventricular ejection fraction was the single most important predictor of arrhythmic death or cardiac arrest. This information may be an important factor in deciding whether to advise ICD therapy.
β
2
-Adrenergic Receptor Antagonists Protect Against Ventricular Fibrillation
Authors: Billman George E. , Castillo Lourdes C. , Hensley James , Hohl Charlene M. , Altschuld Ruth A.
Published: June 2012

Background
The ventricular myocardium contains functional β
2
-adrenergic receptors that when activated increase intracellular Ca
2+
transients. Because elevated Ca
2+
has been implicated in the induction of ventricular fibrillation (VF), it is possible that the activation of these receptors may also provoke malignant arrhythmias.

Methods and Results
To test this hypothesis, a 2-minute occlusion of the left circumflex coronary artery was made during the last minute of exercise in 28 dogs with healed anterior myocardial infarctions: 17 had VF (susceptible) and 11 did not (resistant). On a subsequent day, this test was repeated after administration of the β
2
-adrenergic receptor antagonist ICI 118,551 (0.2 mg/kg). This drug did not alter the hemodynamic response to the coronary occlusion, yet it prevented VF in 10 of 11 animals tested (
P
<.001). However, heart rate was reduced in 6 animals. Therefore, the ICI 118,551 exercise-plus-ischemia test was repeated with heart rate held constant by ventricular pacing (n=3). ICI 118,551 still prevented VF when heart rate was maintained. Next, the effects of increasing doses of the β
2
-adrenergic receptor agonist zinterol on Ca
2+
transient amplitudes were examined in ventricular myocytes. Zinterol elicited significantly greater increases in Ca
2+
transient amplitudes at all doses tested (10
−9
to 10
−6
mol/L) in myocytes prepared from susceptible versus resistant animals. The cardiomyocyte response to isoproterenol (10
−7
mol/L) in the presence or absence of the selective β
1
- (CGP-20712A, 300 nmol/L) or β
2
- (ICI 118,551, 100 nmol/L) adrenergic receptor antagonist was also examined. Isoproterenol elicited larger Ca
2+
transient increases in the susceptible myocytes, which were eliminated by ICI but not by CGP.

Conclusions
When considered together, these data demonstrate that canine myocytes contain functional β
2
-adrenergic receptors that are activated to a greater extent in the susceptible animals. The resulting cytosolic Ca
2+
transient increases may lead to afterpotentials that ultimately trigger VF in these animals.
Chronic Hypoxia Modulates the Interleukin-1β–Stimulated Inducible Nitric Oxide Synthase Pathway in Cardiac Myocytes
Authors: Kacimi Rachid , Long Carlin S. , Karliner Joel S.
Published: June 2012

Background
We wished to determine whether the cytokine-inducible nitric oxide synthase (iNOS) pathway is modulated by chronic hypoxia in vitro.

Methods and Results
We investigated the effects of the proinflammatory cytokine interleukin (IL)-1β on expression of iNOS mRNA, iNOS protein, and NO production in cultured neonatal rat cardiomyocytes subjected to 1% O
2
for 48 hours. Among several cytokines tested, IL-1β was the most effective in stimulating NO production, which was maximum at 48 hours. In parallel, IL-1β induced expression of both iNOS mRNA and protein. Hypoxia alone had no effect on NO production, iNOS gene expression, or protein induction. However, chronic hypoxia decreased IL-1β–stimulated NO production, mRNA expression, and protein level in cardiac myocytes. Radioligand binding and electrophoretic mobility shift assays showed that during chronic hypoxia, IL-1 receptor density and activity of the transcription factor NF-κB induced by IL-1β were decreased, which may account at least in part for the decrease in iNOS expression.

Conclusions
These data indicate that IL-1β induces iNOS gene expression, de novo synthesis of iNOS protein, and NO generation in neonatal rat cardiomyocytes and that chronic hypoxia appears to be a potent negative regulator of iNOS expression in these cells.
Raloxifene Inhibits Aortic Accumulation of Cholesterol in Ovariectomized, Cholesterol-Fed Rabbits
Authors: Bjarnason Nina Hannover , Haarbo Jens , Byrjalsen Inger , Kauffman Raymond F. , Christiansen Claus
Published: June 2012

Background
The beneficial effect of long-term hormone replacement therapy in terms of a decreased risk of cardiovascular disease is now generally accepted. Raloxifene, a selective estrogen receptor modulator, has demonstrated hypolipidemic properties while leaving the endometrium unstimulated.

Methods and Results
For our study of the effects of raloxifene on atherosclerosis, 75 rabbits were ovariectomized and treated with either raloxifene, 17β-estradiol, or placebo; 25 rabbits were sham operated and treated with placebo. After 45 weeks, the raloxifene group had two thirds of the aortic atherosclerosis, as evaluated by the cholesterol content of the proximal inner part of the aorta, found in the placebo group (placebo, 577±55.1 nmol/mg protein; raloxifene, 397±53.6 nmol/mg protein;
P
<.05); the estrogen group had one third of the aortic atherosclerosis in the placebo group (estrogen, 177±32.1 nmol/mg protein;
P
<.001). The sham-operated group (473±59.6 nmol/mg protein) was not significantly different from placebo. These effects were only partly explained by the changes in serum lipids and lipoproteins, and treatment with both estrogen and raloxifene independently predicted the response in aorta cholesterol. Because plasma levels of total raloxifene were low relative to clinical values in postmenopausal women, dose-response data for raloxifene are required.

Conclusions
Our findings indicate that raloxifene hydrochloride has a potentially important antiatherogenic effect, analogous to that observed with estrogen in this model.
Guidance of Radiofrequency Endocardial Ablation With Real-time Three-dimensional Magnetic Navigation System
Authors: Shpun Shlomo , Gepstein Lior , Hayam Gal , Ben-Haim Shlomo A.
Published: June 2012

Background
Ablation therapy for certain arrhythmias requires the formation of complex lesions based on electrical and anatomic mapping. We tested the accuracy and reproducibility of a nonfluoroscopic mapping and navigation (NFM) system to guide delivery of radiofrequency (RF) energy in the right atrium (RA) of swine.

Methods and Results
The NFM system uses an ultralow magnetic field to measure the real-time three-dimensional (3D) location of the tip of the locatable catheter. While in stable contact with the endocardium, between 30 and 40 consecutive tip locations were sampled and used for the 3D reconstruction of the RA geometry. The location of the catheter tip was presented in real time, superimposed over the RA geometry. We selected a point on the 3D reconstruction and delivered RF energy to that site via the tip of the locatable catheter. The catheter was then completely withdrawn and renavigated twice to the same point, at which RF energy was delivered again. At autopsy, the distance between the centers of the three ablation points (mean±SEM) was 2.3±0.5 mm (n=27). Similarly, we used the NFM system to guide the generation of linear lesions. The measured length of the linear lesions on the NFM 3D view was close to the actual lesion length measured at autopsy (correlation coefficient, .96;
P
=.002; n=6). Furthermore, the location, shape, and continuity of the linear lesions corresponded to the autopsy findings.

Conclusions
We conclude that the NFM system can guide the application of RF energy without the use of fluoroscopy in a highly accurate and reproducible manner.
Importance of Location and Timing of Electrical Stimuli in Terminating Sustained Functional Reentry in Isolated Swine Ventricular Tissues
Authors: Kamjoo Kamyar , Uchida Takumi , Ikeda Takanori , Fishbein Michael C. , Garfinkel Alan , Weiss James N. , Karagueuzian Hrayr S. , Chen Peng-Sheng
Published: June 2012

Background
In excitable chemical media, a spiral wave is formed by reentrant excitation around a core and normal propagation away from the core. Whether or not this applies to cardiac muscle is unknown.

Methods and Results
In six isolated swine ventricular slices, we induced sustained episodes of functional reentry with a stationary core. A train of stimuli applied away from the core (7- to 8-mm distance) and near the core (within 1.6 mm) terminated 5 of 24 and 14 of 17 episodes of reentry, respectively (
P
<.001). When the stimulus was applied away from the core, successful terminations occurred when the line connecting the stimulus and the core was along the myocardial fiber orientation and when the coupling interval was 54±11% of the reentrant cycle length. Stimulation near the core terminated reentry primarily by propagation of the stimulus-induced wave fronts that closed up the excitable gap. However, in two episodes, the application of a stimulus near the core changed the electrogram morphology in only four bipolar pairs. This was sufficient to cause abrupt termination of reentry.

Conclusions
(1) A thin layer of activation near the core is responsible for the maintenance of functional reentry. (2) Access to the tissue near the core is essential for the termination of functional reentry by a point stimulus. (3) To terminate reentry with a stimulus away from the core, the stimulus must occur at certain critical coupling intervals, and the line connecting the stimulus and the core must be roughly parallel to the fiber orientation.