bluuebunny/crossref_metadata_2025 huggingface dataset:
Late Left Ventricular Function After Surgery for Children With Chronic Symptomatic Mitral Regurgitation
Authors: Krishnan Usha S. , Gersony Welton M. , Berman-Rosenzweig Erika , Apfel Howard D.
Published: June 2012

Background
The use of quantitative echocardiography has been emphasized in optimizing timing of surgery in adult patients with mitral regurgitation to avoid irreversible left ventricular dysfunction. In contrast, surgery for infants and children is often delayed until the appearance of severe symptoms because of the patient’s size and anticoagulation requirements and the possible need for early reoperation. The purpose of this study was to determine long-term ventricular function after mitral valve surgery in symptomatic children and to analyze risk factors for adverse outcome.

Methods and Results
Thirty-three patients (0.5 to 19 years old) operated on for mitral regurgitation as a single hemodynamically significant lesion were studied. All but 3 had medically refractory symptoms. One patient died during surgery, and 32 were followed for 0.3 to 17.1 years (mean, 4.5 years). The mean preoperative left ventricular shortening fraction was 0.38±0.09. Successful mitral valvuloplasty or replacement was documented by long-term normalization of end-diastolic dimensions. Early postoperative shortening fraction was significantly reduced (0.28±0.1,
P
<.01), but it improved to 0.40±0.07 (
P
<.01) on late follow-up, at which time only 1 patient had ventricular dysfunction. Preoperative shortening fractions did not correlate well with early or late postoperative values (
r
=.18 and
r
=.31, respectively). Seven of 32 surviving patients had preoperative shortening fractions <0.33 (mean, 0.26±0.05) and 25 >0.33 (mean, 0.39±0.08). Analysis of these subgroups showed no significant differences between the groups in early or late postoperative function. Duration of mitral insufficiency appeared to be associated with the development of atrial arrhythmias.

Conclusions
Late left ventricular function normalizes in children after surgical correction of mitral insufficiency. In contrast to adults, delay of surgery in children with significant mitral regurgitation until the onset of severe symptoms does not increase the risk for long-term ventricular dysfunction, although late atrial arrhythmias are more likely to be encountered.
Relationship Between Repeated Measures of Hemodynamics, Muscle Sympathetic Nerve Activity, and Their Spectral Oscillations
Authors: van de Borne Philippe , Montano Nicola , Zimmerman Bridget , Pagani Massimo , Somers Virend K.
Published: June 2012

Background
We determined the intraclass correlation coefficients (ICC) of repeated measures of the mean levels and variability of RR and muscle sympathetic nerve activity (MSNA) in 7 normal subjects. We examined whether spontaneous fluctuations in RR and MSNA over repeated measurements were mirrored by changes in spectral components of RR and MSNA.

Methods and Results
Twenty-minute recordings of respiration, RR, blood pressure (BP), and MSNA were performed at day 1, 1 week, 1 month, and 3 months and divided into two 10-minute periods for the analysis of short-term reliability. Comparison between these recordings also determined the long-term reliability. Linear regressions examined the relationship between changes in these measurements and changes in spectral components of RR and MSNA. All analyses were carried out blinded to subject and session. Short-term ICC of RR, BP, MSNA and of the variabilities of RR and MSNA (in % of total power) ranged between .98 and .70 and indicated a good short-term reliability. The long-term reliability of RR variability was comparable to MSNA variability (range of ICC, .34 to .52). Spontaneous decreases in RR during the repeated recordings were accompanied by increases in sympathetic drive, as evidenced by increases in the ratio of low-frequency to high-frequency variability (LF/HF ratio) of RR interval (
r
=−.43,
P
<.01) and by increases in MSNA (
r
=−.36,
P
=.01). The changes in the LF/HF ratio of RR were mirrored by parallel changes in the LF/HF ratio of MSNA (
r
=+.30,
P
<.05). Spontaneous decreases in BP were accompanied by increases in the LF/HF ratio of MSNA (
r
=−.52;
P
=.0001).

Conclusions
Heart rate, MSNA, and their variability are stable in the short-term, but less so over the long term. Spontaneous changes in repeated measurements of RR interval and blood pressure over the long term are accompanied by parallel changes in the normalized spectral components of RR and MSNA variability. Thus even over an extended period, there is a synchrony between changes in absolute cardiovascular measures and changes in their spectral components.
Small Heat Shock Proteins and Protection Against Ischemic Injury in Cardiac Myocytes
Authors: Martin Jody L. , Mestril Ruben , Hilal-Dandan Randa , Brunton Laurence L. , Dillmann Wolfgang H.
Published: June 2012

Background
Overexpression of the inducible hsp70 protects against ischemic cardiac damage. However, it is unclear whether the small heat shock proteins hsp27 and αB-crystallin protect against ischemic injury.

Methods and Results
Our aim was to examine whether the overexpression of hsp27 and αB-crystallin in neonatal and adult rat cardiomyocytes would protect against ischemic injury. Recombinant adenovirus expressing hsp27 or αB-crystallin under the control of the cytomegalovirus promoter was used to infect cardiac myocytes at high efficiency as assessed by immunostaining. Overexpression was confirmed by Western blot analysis. Cardiomyocytes were subjected to simulated ischemic stress, and survival was estimated through assessment of lactate dehydrogenase and creatine phosphokinase release. The hsp27 overexpression decreased lactate dehydrogenase release by 45±7.5% in adult cardiomyocytes but had no effect in the neonatal cells. In contrast, αB-crystallin overexpression was associated with a decrease in cytosolic enzyme release in both adult (29±6.6%) and neonatal (32±5.4%) cardiomyocytes. Decreased endogenous hsp25 with an antisense adenovirus produced a 29±9.9% increase in damage with simulated ischemia. Overexpression of the inducible hsp70 in adult cardiomyocytes was associated with a 34±4.6% decrease in lactate dehydrogenase release and is in line with our previous results in neonatal cardiomyocytes.

Conclusions
The increased expression of hsp27 and αB-crystallin through an adenovirus vector system protects against ischemic injury in adult cardiomyocytes. Likewise, the overexpression of αB-crystallin protects against ischemic damage in neonatal cardiomyocytes. Decreasing the high levels of endogenous hsp25 present in neonatal cardiomyocytes renders them more susceptible to damage caused by simulated ischemia.
Assisted Ventilation During ‘Bystander’ CPR in a Swine Acute Myocardial Infarction Model Does Not Improve Outcome
Authors: Berg Robert A. , Kern Karl B. , Hilwig Ronald W. , Ewy Gordon A.
Published: June 2012

Background
Mouth-to-mouth rescue breathing is a barrier to the performance of bystander cardiopulmonary resuscitation (CPR). We evaluated the need for assisted ventilation during simulated single-rescuer bystander CPR in a swine myocardial infarction model of prehospital cardiac arrest.

Methods and Results
Steel cylinders were placed in the mid left anterior descending coronary arteries of 43 swine. Two minutes after ventricular fibrillation, animals were randomly assigned to 10 minutes of hand–bag-valve ventilation with 17% oxygen and 4% carbon dioxide plus chest compressions (CC+V), chest compressions only (CC), or no CPR (control group). Standard advanced life support was then provided. Animals successfully resuscitated received 1 hour of intensive care support and were observed for 24 hours. Five of 14 CC animals, 3 of 15 CC+V animals, and 1 of 14 controls survived for 24 hours (CC versus controls,
P
=.07). Myocardial oxygen delivery and consumption were greater among surviving animals than nonsurvivors but did not differ between CC and CC+V animals.

Conclusions
In this acute myocardial infarction model of prehospital single-rescuer bystander CPR, assisted ventilation did not improve outcome.
Effect of Altering Filling Pattern on Diastolic Pressure-Volume Curve
Authors: Fraites Thomas J. , Saeki Akio , Kass David A.
Published: June 2012

Background
The early-to-late ventricular filling ratio (E:A) is widely used to index diastolic function. While filling patterns reflect diastolic properties, they can also modulate chamber pressures due to myocardial viscoelasticity. We hypothesized that such feedback can potentially temper effects of delayed relaxation and/or volume loading on diastolic pressures.

Methods and Results
Six isolated blood-perfused canine left ventricles were studied with ejection and filling controlled by an intracavitary volume servo-pump. Diastolic filling was determined by a simulated atrial pressure source that was either constant or varied to yield dual-phase filling at a specified E:A ratio. E:A ratio was randomly set to 3:1, 1:3, or 1:1, and data were recorded at each ratio at three different preloads. With principally early filling (E:A=3:1), diastolic pressure rise from viscosity increased in proportion with the relaxation time constant (
r
=.91,
P
<.0001). However, this dependence was lost as E:A ratio declined (eg,
P
=.63 for E:A 1:3). Furthermore, E:A=3:1 yielded 37% to 50% lower end-diastolic pressures at similar volumes (versus E:A=1:3) as initial viscous forces decayed. Offsetting early and late filling effects led to little net change in mean diastolic pressure independent of E:A ratio or preload.

Conclusions
Diastolic filling pattern itself influences chamber pressures early and late in diastole due to viscoelasticity, with larger net effects on end-diastolic pressure. Since E:A ratio normally falls with delayed relaxation but rises with higher preload or reduced compliance, the present results suggest that changes in filling pattern may modulate direct effects of such factors on elevating diastolic pressure.
Reduction of Restenosis After Angioplasty in an Atheromatous Rabbit Model by Suicide Gene Therapy
Authors: Steg P. Gabriel , Tahlil Ouafae , Aubailly Nathalie , Caillaud Jean-Michel , Dedieu Jean-François , Berthelot Karine , Le Roux Aude , Feldman Laurent , Perricaudet Michel , Denèfle Patrice , Branellec Didier
Published: June 2012

Background
Gene delivery of the thymidine kinase (tk) gene combined with ganciclovir (GCV) limits intimal hyperplasia after abrasion of normal arteries. However, the low efficiency of adenoviral-mediated gene transfer to atherosclerotic arteries has raised concerns about the applicability of this strategy to the prevention of restenosis.

Methods and Results
A replication-defective adenoviral vector expressing tk (Ad-RSVtk) demonstrated selective toxicity toward GCV-treated arterial smooth muscle cells, with oligonucleolytic cleavage suggesting apoptosis. In vivo, after demonstration of tk expression after Ad-RSVtk delivery, the combination of Ad-RSVtk followed by GCV was tested in a rabbit model of angioplasty of atheromatous iliac arteries. Angioplasty (8 atm, 20 minutes) was performed by use of a hydrogel balloon coated with Ad-RSVtk (4×10
9
plaque forming units). GCV was infused (25 mg.kg
−1
IV BID) from days 2 through 7 after angioplasty in 8 of 12 rabbits. Four weeks later, morphometric analysis demonstrated a reduced intima-to-media ratio in the group receiving combination therapy compared with Ad-RSVtk alone (3.0±1.2 versus 5.2±0.5,
P
<.018). GCV per se had no effect on intimal hyperplasia after arterial injury.

Conclusions
In vitro, Ad-RSVtk demonstrates selective toxicity toward GCV-treated arterial smooth muscle cells involving apoptosis. In vivo, GCV conditions reduction of neointimal formation after percutaneous delivery of Ad-RSVtk during angioplasty of atheromatous arteries.
Remodeling of Human Coronary Arteries Undergoing Coronary Angioplasty or Atherectomy
Authors: Kimura Takeshi , Kaburagi Satoshi , Tamura Takashi , Yokoi Hiroyoshi , Nakagawa Yoshihisa , Yokoi Hiroatsu , Hamasaki Naoya , Nosaka Hideyuki , Nobuyoshi Masakiyo , Mintz Gary S. , Popma Jeffery J. , Leon Martin B.
Published: June 2012

Background
Recently, long-term constriction of the vessel has been suggested as an alternative mechanism of restenosis after coronary angioplasty.

Methods and Results
To understand remodeling of human coronary arteries undergoing coronary angioplasty or atherectomy, serial intravascular ultrasonographic examinations were performed at preintervention and postintervention examinations and at 24 hours, 1 month, and 6 months. Complete serial data were obtained in 61 lesions (balloon angioplasty, 35 lesions; directional atherectomy, 26 lesions). Lumen area improved from 6.81±2.24 mm
2
after intervention to 8.22±2.79 mm
2
at 1 month (
P
=.0001) and decreased to 4.88±2.86 mm
2
at 6 months (
P
=.0001). Vessel area enlarged from 17.32±5.35 mm
2
after intervention to 19.39±5.33 mm
2
at 1 month (
P
=.0001) and decreased to 16.33±5.54 mm
2
at 6 months (
P
=.0001). Plaque+media area increased significantly from postintervention examination to 24 hours (10.51±4.38 versus 10.96±4.49 mm
2
,
P
=.0008) and from 24 hours to 6 months (10.96±4.49 versus 11.45±4.45 mm
2
,
P
=.03). Changes in lumen area in each study interval correlated more closely with changes in vessel area than with changes in plaque+media area. Restenotic lesions compared with nonrestenotic lesions had a greater decrease in the vessel area between 1 month and 6 months (−4.33±2.73 versus −2.49±2.15 mm
2
,
P
=.006) and greater increase in the plaque+media area both within 24 hours (0.84±1.22 versus 0.27±0.38 mm
2
,
P
=.04) and between 24 hours and 6 months (1.19±2.19 versus 0.18±1.46 mm
2
,
P
=.04).

Conclusions
Remodeling after coronary angioplasty or atherectomy was characterized by early adaptive enlargement and late constriction of the vessel.
Comparison of Coronary Luminal Quantification Obtained From Intracoronary Ultrasound and Both Geometric and Videodensitometric Quantitative Angiography Before and After Balloon Angioplasty and Directional Atherectomy
Authors: Ozaki Yukio , Violaris Andonis G. , Kobayashi Tadashi , Keane David , Camenzind Edoardo , Di Mario Carlo , de Feyter Pim , Roelandt Jos R. T. C. , Serruys Patrick W.
Published: June 2012

Background
Debate exists regarding the relationship between angiographic and intracoronary ultrasound (ICUS) measurements of minimal luminal cross-sectional area after coronary intervention. We investigated this and the factors that may influence it by using ICUS and quantitative angiography.

Methods and Results
Patients who underwent successful balloon angioplasty (n=100) or directional atherectomy (n=50) were examined by using ICUS and quantitative angiography (edge-detection [ED] and videodensitometry [VID]) before and after intervention. Luminal damage postintervention was qualitatively graded into three categories based on angiographic results (smooth lumen, haziness, or dissection). Correlation of minimal luminal cross-sectional area measurements by ICUS and ED was .59 before and .47 after balloon angioplasty. Correlation between ICUS and VID was .50 before and .63 after balloon angioplasty. Postintervention, the difference between ICUS and VID was less than the difference between ICUS and ED (
P
<.01). Additionally, the correlation was .74 between ICUS and ED measurements and .78 between ICUS and VID measurements in the smooth lumen group, .46 and .63, respectively, in the presence of haziness, and .26 and .46, respectively, in lesions with dissection. Similar results were obtained after directional atherectomy: the agreement between ICUS and quantitative angiography deteriorated according to the degree of vessel damage, but less so with VID than ED.

Conclusions
Complex morphological changes induced by intervention may contribute to discordance between the two quantitative imaging techniques. In the absence of ICUS, VID may be a complementary technique to ED in lesions with complex morphology after balloon angioplasty and directional atherectomy.
Patients With Valvular Heart Disease Presenting With Sustained Ventricular Tachyarrhythmias or Syncope
Authors: Martínez-Rubio Antoni , Schwammenthal Yvonne , Schwammenthal Ehud , Block Michael , Reinhardt Lutz , Garcia-Alberola Arcadi , Sierra Gilberto , Shenasa Mohammad , Haverkamp Wilhelm , Scheld Hans H. , Breithardt Günter , Borggrefe Martin
Published: June 2012

Background
Programmed ventricular stimulation is commonly used to guide therapy in post–myocardial infarction patients with sustained monomorphic ventricular tachycardia (VT) or ventricular fibrillation (VF). In patients with valvular heart disease presenting with spontaneous VT, VF, or syncope, the usefulness of this technique is still unclear. The aim of the study was to analyze whether programmed ventricular stimulation was helpful in guiding therapy and determining prognosis in 97 patients with valvular heart disease presenting with VT (60%), VF (18%), or syncope (22%).

Methods and Results
Patients were classified as having either predominant ventricular pressure or volume overload or no significant pressure or volume overload. Overall, sustained VT or VF was inducible in 38 (39%) and 19 (20%) patients, respectively. Forty-six (47%) patients were discharged on antiarrhythmic drugs, 29 (30%) received an implantable cardioverter-defibrillator, and 22 (23%) remained without therapy. With serial drug testing, inducibility was completely or partially suppressed in 18 (19%) and 9 (9%) patients, respectively. During a mean follow-up of 51 months (n=97), 17 patients (18%) died (sudden death, n=7; heart failure, n=4; noncardiac causes, n=6). One-, 2- and 3-year event-free survival for sudden death, sustained VT, or VF was 77%, 68%, and 61%, respectively. Only inducibility of VT during baseline study (
P
<.0003) and left ventricular volume overload (
P
<.008) were significant predictors of arrhythmic events. Recurrence of arrhythmic events occurred in 56% and 56% of patients with complete or partial suppression of inducibility during serial drug testing as well as in 10 of 19 (53%) patients without a change in inducibility.

Conclusions
Although programmed ventricular stimulation seems to predict adverse outcome, serial drug testing is unreliable in guiding therapy. The type of workload imposed on the ventricles influences outcome, being worse in patients with left ventricular volume overload. Therefore, implantation of a cardioverter-defibrillator should be considered early for the management of these patients.
Aprotinin Inhibits Plasmin-Induced Platelet Activation During Cardiopulmonary Bypass
Authors: Shigeta Osamu , Kojima Hiroshi , Jikuya Tomoaki , Terada Yasushi , Atsumi Naotaka , Sakakibara Yuzuru , Nagasawa Toshiro , Mitsui Toshio
Published: June 2012

Background
In the past few years, aprotinin has been used in cardiac surgery with impressive results of reducing blood loss, but several adverse effects of aprotinin also have been reported. One of the most likely mechanisms is the inhibition of plasmin by aprotinin, although this indirect effect has not been reproduced in all experimental studies.

Methods and Results
We evaluated the platelet function and fibrinolytic activity during human cardiac surgery, with or without aprotinin. During cardiopulmonary bypass (CPB) in humans without aprotinin (n=16), decrease of platelet aggregation induced by thrombin, increase of α-granule secretion of platelet and microparticle formation, and increase of plasmin/α
2
-antiplasmin complex (PIC) were observed. In contrast, low-dose aprotinin (1.0×10
6
KIU), which was administered only into the priming fluid of extracorporeal circuits (n=10), maintained platelet aggregation induced by thrombin and reduced α-granule secretion and microparticle formation of platelets during CPB. In vitro, plasmin (0.8 CU/mL) released α-granules of washed platelets, and this activation was completely inhibited by aprotinin (10 KIU/mL).

Conclusions
Aprotinin has indirect effects to inhibit platelet activation, and this may partly explain the reduction of blood loss during cardiac surgery. To prevent the adverse effects, a single and minimal use of aprotinin is important. The results of in vivo and in vitro studies suggest that platelet preservation was demonstrated by the lower concentration of aprotinin (1.0×10
6
KIU per patient or 10 KIU/mL) compared with the concentration that inhibits plasma fibrinolysis.
Effects of Volume Loading and Pressor Agents in Idiopathic Orthostatic Tachycardia
Authors: Jacob Giris , Shannon John R. , Black Bonnie , Biaggioni Italo , Mosqueda-Garcia Rogelio , Robertson Rose Marie , Robertson David
Published: June 2012

Background
Idiopathic orthostatic tachycardia (IOT) is characterized by an increase in heart rate (HR) with standing of ≥30 bpm that is associated with elevated catecholamine levels and orthostatic symptoms. A dynamic orthostatic hypovolemia and α
1
-adrenoreceptor hypersensitivity have been demonstrated in IOT patients. There is evidence of an autonomic neuropathy affecting the lower-extremity blood vessels.

Methods and Results
We studied the effects of placebo, the α
1
-adrenoreceptor agonist midodrine (5 to 10 mg), the α
2
-adrenoreceptor agonist clonidine (0.1 mg), and IV saline (1 L) in 13 patients with IOT. Supine and upright blood pressure (BP) and HR were measured before and at 1 and 2 hours after intervention. Midodrine decreased both supine and upright HR (all HR values are given as bpm) at 2 hours (from 78±2 supine to 108±5 upright before treatment and from 69±2 supine to 95±5 upright after treatment,
P
<.005 for supine and
P
<.01 for upright). Saline decreased both supine and upright HR (from 80±3 supine to 112±5 upright before infusion and from 77±3 supine to 91±3 upright 1 hour after infusion,
P
<.005 for supine and
P
<.001 for upright). Clonidine decreased supine HR (from 78±2 to 74±2,
P
<.03) but did not affect the HR increase with standing. Clonidine very significantly decreased supine systolic BP (from 109±3 at baseline to 99±2 mm Hg at 2 hours,
P
<.001), and midodrine decreased supine systolic BP mildly.

Conclusions
IOT responds best acutely to saline infusion to correct the underlying hypovolemia. Chronically, this can be accomplished with increased salt and water intake in conjunction with fludrocortisone. The response of patients to the α
1
-agonist midodrine supports the hypothesis of partial dysautonomia and indicates that the use of α
1
-agonists to pharmacologically replace lower-extremity postganglionic sympathetics is an appropriate overall goal of therapy. These findings are consistent with our hypothesis that the tachycardia and elevated catecholamine levels associated with IOT are principally due to hypovolemia and loss of adequate lower-extremity vascular tone.
l
-Arginine Treatment Alters the Kinetics of Nitric Oxide and Superoxide Release and Reduces Ischemia/Reperfusion Injury in Skeletal Muscle
Authors: Huk Igor , Nanobashvili Joseph , Neumayer Christoph , Punz Andreas , Mueller Markus , Afkhampour Kaweh , Mittlboeck Martina , Losert Udo , Polterauer Peter , Roth Erich , Patton Stephen , Malinski Tadeusz
Published: June 2012

Background
Constitutive nitric oxide synthase (cNOS) may produce species involved in ischemia/reperfusion (I/R) injury: NO in the presence of sufficient
l
-arginine and superoxide at the diminished local
l
-arginine concentration accompanying I/R.

Methods and Results
During hindlimb I/R (2.5 hours/2 hours), in vivo NO was continuously monitored (porphyrinic sensor), and
l
-arginine (chromatography), superoxide (chemiluminescence), and I/R injury were measured intermittently. Normal rabbits were compared with those infused with
l
-arginine 4 mg·kg
−1
·min
−1
for 1 hour. In both groups, ≈6 minutes into ischemia, a rapid increase of NO from its basal level of 50±17 to 115±7 nmol/L,
P
<.005 (microvessels), was observed. In animals not treated with
l
-arginine, NO dropped below basal to undetectable levels (<1 nmol/L) during reperfusion. In animals treated with
l
-arginine, the decrease of NO was slower, such that substantial amounts accumulated during reperfusion (25 nmol/L). Decreased NO during I/R was accompanied by increased superoxide, which during reperfusion reached 50 nmol/L without or 23 nmol/L with
l
-arginine treatment. Calcium-dependent cNOS was a major source of superoxide release (inhibited 70% by L-NMMA and 25% by L-NAME) during I/R.

Conclusions
l
-Arginine treatment decreased superoxide generation by cNOS while increasing NO accumulation, leading to protection from constriction (microvessel area, 17.77±0.95 versus 11.66±2.21 μm
2
untreated,
P
<.0005) and reduction of edema after reperfusion (interfiber area, 16.56±2.13% versus 27.68±7.70% untreated,
P
<.005).
Comparative Effects of Enalapril and Verapamil on Myocardial Blood Flow in Systemic Hypertension
Authors: Parodi Oberdan , Neglia Danilo , Palombo Carlo , Sambuceti Gianmario , Giorgetti Assuero , Marabotti Claudio , Gallopin Michela , Simonetti Ignazio , L’Abbate Antonio
Published: June 2012

Background
The comparative effects of calcium channel blockers and ACE inhibitors on myocardial blood flow (MBF) in hypertensive patients after long-term treatment are still unknown.

Methods and Results
Twenty hypertensive subjects with normal coronary arteries were randomly assigned to verapamil 240 to 480 mg/d or enalapril 10 to 40 mg/d. MBF was quantified at rest, during pacing tachycardia, and after dipyridamole by positron emission tomography and
13
N-ammonia before and 6 months after treatment after 1 week of pharmacological washout. In both groups, blood pressure and heart rate during flow measurements were not different before and after therapy. Before treatment, mean MBF at rest, during pacing tachycardia, and after dipyridamole infusion was similar in the two groups; however, pacing and dipyridamole flows were significantly lower than those obtained in a control group of normotensive subjects. After treatment, in the enalapril-treated patients, MBF did not change in the three study conditions. In the verapamil-treated patients, MBF did not change at rest and significantly increased during pacing and after dipyridamole. The inhomogeneity of regional MBF distribution, evaluated from the coefficient of variation, decreased at rest after both treatments and, in the enalapril group, also during pacing. No relation was found between changes in MBF and changes in left ventricular mass.

Conclusions
In arterial hypertension, MBF during pacing tachycardia and after dipyridamole is impaired. Successful therapy with verapamil increases MBF response to these stimuli, independent of changes in perfusion pressure and left ventricular mass. These results suggest that verapamil directly improves coronary microcirculatory function in hypertension. Enalapril does not significantly change MBF but reduces the inhomogeneity of regional flow distribution.
Overexpression of Transforming Growth Factor-β1 and Insulin-Like Growth Factor-I in Patients With Idiopathic Hypertrophic Cardiomyopathy
Authors: Li Ren-Ke , Li Guangming , Mickle Donald A. G. , Weisel Richard D. , Merante Frank , Luss Hartmut , Rao Vivek , Christakis George T. , Williams William G.
Published: June 2012

Background
Idiopathic hypertrophic cardiomyopathy (HCM) is characterized by regional myocardial hypertrophy. To investigate involvement of growth factors on myocardial hypertrophy in HCM patients, we evaluated gene expression and cellular localization of transforming growth factor-β1 (TGF-β1), insulin-like growth factors (IGF-I and IGF-II), and platelet-derived growth factor-B (PDGF-B) in ventricular biopsies obtained from patients with HCM (n=8), aortic stenosis (AS) (n=8), or stable angina (SA) (n=8) and from explanted hearts with ischemic cardiomyopathy (TM) (n=7).

Methods and Results
Levels of TGF-β1, IGF-I, IGF-II, and PDGF-B transcripts were quantified with the use of multiplex RT-PCR. Glyceraldehyde 3-phosphate dehydrogenase was used as an internal standard. Antibodies against TGF-β and IGF-I were used to localize their peptides within the myocardium. Antisense and sense (control) cRNA probes of TGF-β1 and IGF-I, labeled with digoxigenin, were used to localize the growth factor transcripts by in situ hybridization. mRNA levels (densitometric ratio of growth factor/glyceraldehyde-3-phosphate dehydrogenase) of TGF-β1 and IGF-I in HCM (0.75±0.05 and 0.85±0.15, respectively; mean±1 SEM) were significantly (
P
<.01 for all groups) elevated in comparison with non-HCM myocardium (AS: 0.38±0.07, 0.29±0.06; SA: 0.32±0.04, 0.18±0.05; TM: 0.25±0.03, 0.15±0.03). mRNA levels of TGF-β1 and IGF-I in the hypertrophic AS myocardium were greater (
P
=.02,
P
=.05) than those in the explanted myocardium (TM). Immunohistochemical and in situ hybridization studies showed increased expression of TGF-β1 and IGF-I in the HCM cardiomyocytes.

Conclusions
Gene expression of TGF-β1 and IGF-I was enhanced in idiopathic hypertrophic cardiomyopathy and may be associated with its development.
Association Between Thrombolytic Treatment and the Prognosis of Hemodynamically Stable Patients With Major Pulmonary Embolism
Authors: Konstantinides Stavros , Geibel Annette , Olschewski Manfred , Heinrich Fritz , Grosser Klaus , Rauber Klaus , Iversen Stein , Redecker Matthias , Kienast Joachim , Just Hanjörg , Kasper Wolfgang
Published: June 2012

Background
Thrombolytic treatment has been shown to accelerate resolution of major pulmonary embolism and lead to a rapid improvement of right-side hemodynamics. However, the association between these favorable effects and the clinical outcome of patients who have no severe hemodynamic compromise at presentation remains unknown.

Methods and Results
The present multicenter registry included 719 consecutive patients with major pulmonary embolism according to clinical, echocardiographic, scintigraphic, and cardiac catheterization criteria. Symptom onset was acute (<48 hours) in 63% of patients. All patients were hemodynamically stable (ie, without evidence of cardiogenic shock) at presentation. Primary thrombolytic treatment (within 24 hours of diagnosis) was given to 169 patients (23.5%), whereas the remaining 550 patients were initially treated with heparin alone. Overall 30-day mortality was significantly lower in the patients who received thrombolytic agents (4.7 versus 11.1%,
P
=.016). Clinical factors associated with a higher death rate were syncope (
P
=.012), arterial hypotension (
P
=.021), history of congestive heart failure (
P
=.013), and chronic pulmonary disease (
P
=.032). However, only primary thrombolysis was found by multivariate analysis to be an independent predictor of survival (odds ratio for in-hospital death, 0.46; 95% confidence interval, 0.21 to 1.00). Patients who underwent early thrombolytic treatment had a reduced rate of recurrent pulmonary embolism (7.7 versus 18.7%,
P
<.001) but also a higher frequency of major bleeding episodes (21.9% versus 7.8%,
P
<.001). Cerebral bleeding occurred in 2 patients in each treatment group, and 1 patient in each group died of a bleeding complication.

Conclusions
The results of our study suggest that thrombolysis may favorably affect the clinical outcome of hemodynamically stable patients with major pulmonary embolism.
Value of QT Dispersion in the Interpretation of Exercise Stress Test in Women
Authors: Stoletniy Liset N. , Pai Ramdas G.
Published: June 2012

Background
Exercise testing in women is associated with a high incidence of false-positive ECG changes and should be combined with an imaging study. The QT dispersion (QTD), recorded as the difference between maximum and minimum QT intervals on a 12-lead ECG, is sensitive to myocardial ischemia and may improve the accuracy of exercise testing in women.

Methods and Results
Exercise ECGs were analyzed in 64 women who had undergone exercise ECG and coronary angiography for clinical indications: 20 patients with normal exercise stress test and nonsignificant (≤50% diameter narrowing of a major epicardial coronary artery) coronary artery disease (CAD) on angiography (true-negative; TN group), 20 patients with positive exercise stress tests (≥1 mm ST-segment depression or reversible perfusion defects) and significant CAD (true-positive; TP group), and 24 patients with positive exercise stress tests but no significant CAD (false-positive; FP group). The exercise QTD was 45±15 ms in TN, 80±23 ms in TP (
P
<.0001 versus TP), and 41±14 ms in FP (
P
=NS versus TN and <.0001 versus TP) groups. A stress QTD of >60 ms had a sensitivity of 70% and specificity of 95% for the diagnosis of significant CAD compared with 55% (
P
<.05) and 63% (
P
<.01), respectively, for ≥1 mm ST-segment depression during stress. When QTD of >60 ms was added to ST-segment depression as a condition for positive test, the specificity increased to 100%.

Conclusions
Exercise QTD is an easily measurable ECG variable that significantly increases the accuracy of exercise testing in women.
Ischemic Preconditioning
Authors: Sandhu Reena , Diaz Roberto J. , Mao Guo D. , Wilson Gregory J.
Published: June 2012

Background
We compared ischemic preconditioning (IP) induced with a single cycle of transient ischemia and reperfusion with that induced by multiple cycles in terms of (1) efficacy of protection against myocardial necrosis and (2) susceptibility to pharmacological blockade by inhibition of protein kinase C (PKC) or elevation of cAMP.

Methods and Results
All rabbits were subjected to 30 minutes of regional ischemia and 90 minutes of reperfusion in vivo. IP was induced with either one or three cycles of 5-minute transient ischemia and 10-minute reperfusion given before the 30-minute ischemia. Drug-treated hearts received a bolus dose of one of the following just before the 30-minute ischemia: (1) the PKC inhibitor chelerythrine (3.8 mg/kg), (2) the PKC inhibitor polymyxin B (10 mg/kg), or (3) the cAMP-increasing agent NKH477 (45 μg/kg). IP induced with either one or three cycles of transient ischemia and reperfusion significantly protected the heart against infarction, although the extent of protection was significantly greater with three-cycle IP. Chelerythrine, polymyxin B, or NKH477 alone did not alter infarct size in control hearts, nor did they increase infarct size in hearts preconditioned with three-cycle IP. In contrast, when IP was induced with only a single cycle, all three of these drugs significantly increased infarct size above that of the untreated one-cycle IP group. However, infarct size in all three of these drug-treated one-cycle IP groups was still significantly lower than that in the corresponding drug-treated controls, indicating a partial block of IP.

Conclusions
Three-cycle IP provided more effective protection against myocardial necrosis than one-cycle IP and was less susceptible to blockade by inhibitors of PKC or an agent that increases cAMP levels. However, single-cycle IP was only partially blocked by either inhibition of PKC or stimulation of cAMP production. Neither activation of the PKC pathway nor reduced formation of cAMP alone fully accounted for the necrosis protection by IP even when induced with only a single cycle of transient ischemia.
Association Between Cigarette Smoking and Lipid Peroxidation in a Controlled Feeding Study
Authors: Miller Edgar R. , Appel Lawrence J. , Jiang Long , Risby Terence H.
Published: June 2012

Background
Cigarette smoke may promote atherogenesis by producing oxygen-derived free radicals that damage lipids. However, evidence in support of this hypothesis is inconsistent because most studies did not control for aspects of diet (antioxidants and lipid substrate) that may confound the association between smoking and measures of lipid peroxidation.

Methods and Results
The relationships between cigarette smoking and two measures of lipid peroxidation, breath ethane (an in vivo assay) and thiobarbituric acid–reactive substances (TBARS, an in vitro assay), were examined in 123 adults (11% of whom were smokers) participating in a controlled feeding study. After 3 weeks of controlled feeding on a common diet (36% total fat, 14% saturated fats, 6% polyunsaturated fats, and 12% monounsaturated fats), breath and fasting serum samples were collected for measurement of ethane and TBARS, respectively. Baseline characteristics of smokers and nonsmokers were similar, including several indices related to diet and nutritional status (albumin, cholesterol, body mass index, and oxygen radical–absorbing capacity). Cigarette smokers had significantly higher breath ethane (8.88 versus 1.71 pmol/L;
P
<.0001) and TBARS (24.0 versus 20.7 μmol/mL;
P
=.008) than nonsmokers. The interval between breath collection and the time the last cigarette was smoked was significantly and inversely correlated with breath ethane. Neither measure of lipid peroxidation was associated with measures of serum cholesterol or albumin, body mass index, or serum oxygen radical–absorbing capacity.

Conclusions
Cigarette smokers have higher rates of in vivo and in vitro lipid peroxidation. These results support the hypothesis that the atherogenic effects of smoking are mediated in part by free radical damage to lipids.
Incidence, Clinical Characteristics, and Prognostic Significance of Right Bundle-Branch Block in Acute Myocardial Infarction
Authors: Melgarejo-Moreno Antonio , Galcerá-Tomás Jose , García-Alberola Arcadio , Valdés-Chavarri Mariano , Castillo-Soria Francisco J. , Mira-Sánchez Enrique , Gil-Sánchez Javier , Allegue-Gallego Jose
Published: June 2012

Background
Whereas the significance of right bundle-branch block (RBBB) in acute myocardial infarction was extensively studied in the prethrombolytic era, a possible change in the overall incidence and meaning of RBBB as a consequence of thrombolytic therapy is not well known.

Methods and Results
A multicenter, prospective study of 1238 patients consecutively diagnosed with acute myocardial infarction and admitted to three coronary care units was conducted. ECGs during the acute phase and clinical events until discharge and 1-year follow-up were monitored. In the 135 (10.9%) patients in whom RBBB was found, there were 51 (37.8%) new cases, 46 (34.1%) old cases, and 38 (28.1%) cases with an indeterminate time of origin. New RBBB was permanent in 26 and transient in 25 patients. RBBB was isolated in 76 (56%) and bifascicular in the remaining 59 (44%) patients. The following complications were more frequently associated with RBBB than non-RBBB patients: heart failure, 24% versus 46% (
P
<.001); use of pacemaker because of atrioventricular block, 3.6% versus 11% (
P
<.001); and 1-year mortality, 17.6% versus 40.7% (
P
<.001). Early mortality was significantly higher for new RBBB (43.1%,
P
<.001) than for old (15.5%) and indeterminate (15.3%) RBBB. These figures for 1-year mortality were 58.8% (
P
<.001), 35.5 (
P
<.01), and 23% (NS), respectively. Permanent and transient RBBB had different mortality rates: early mortality, 76% versus 8%, and 1-year mortality, 84% versus 32% (
P
<.001 for both). For isolated RBBB versus bifascicular block, early mortality was 14.4% versus 40.6%, and 1-year mortality was 30.2% versus 54.2% (
P
<.05 for both). Multivariate analysis showed an independent prognostic value of RBBB for early and 1-year mortality.

Conclusions
The overall meaning of RBBB in acute myocardial infarction has not changed in the thrombolytic era, although a higher rate of new and transient RBBB and a lower rate of bifascicular block may represent a beneficial effect of thrombolytic therapy.
Adenosine-Sensitive Ventricular Tachycardia
Authors: Markowitz Steven M. , Litvak Bonnie L. , Ramirez de Arellano Elizabeth A. , Markisz John A. , Stein Kenneth M. , Lerman Bruce B.
Published: June 2012

Background
Adenosine-sensitive ventricular tachycardia (VT) is thought to be due to cAMP-mediated triggered activity. It typically originates from the RVOT and occurs in patients with apparently normal hearts. Using magnetic resonance imaging (MRI), we tested the hypothesis that adenosine-sensitive VT occurs in patients without structural heart disease.

Methods and Results
Fourteen patients (9 women; age, 47±19 years) presented with sustained VT (n=3), repetitive monomorphic VT (n=7), or both (n=4). VT terminated with adenosine in each patient and was sensitive to vagal maneuvers in 9 of 11 and verapamil in 10 of 12. VT originated from the right ventricular outflow tract in 10 patients, the right ventricular apex in 1, and the left ventricular septum in 3. Conventional studies included normal signal-averaged ECGs in 9 of 9, normal right ventricular echocardiography in 10 of 10, and normal left ventriculography and coronary angiography in 6 of 7. In contrast, MRI scans were abnormal in 10 of 14 patients. These abnormalities included focal thinning (6), fatty infiltration (4), and wall motion abnormalities (4) of the right ventricle. The most common site of MRI abnormalities was the right ventricular free wall, but there was a poor correlation between the site of MRI abnormalities and the origin of VT. Among 18 control patients without clinical heart disease, thinning of the right ventricular wall was noted in only 1 patient (patients versus control subjects,
P
=.0001).

Conclusions
Patients with idiopathic adenosine-sensitive VT comprise a heterogeneous group as assessed by MRI, with 70% demonstrating mild structural abnormalities. However, it is unlikely that these findings are causally related to tachycardia, and the functional significance of these anatomic abnormalities is uncertain.
Effect of High-Altitude Exposure in the Elderly
Authors: Levine Benjamin D. , Zuckerman Julie H. , deFilippi Christopher R.
Published: June 2012

Background
More than 5 million people/year over age 60 visit high altitude, which may exacerbate underlying cardiac or pulmonary disease. We hypothesized that the elderly would exhibit an impaired functional capacity at altitude, with increased myocardial ischemia compared with sea level (SL).

Methods and Results
Twenty veterans (68±3 years) were studied at (1) SL, (2) acute simulated altitude to 2500 m, and (3) after 5 days of acclimatization to 2500 m. With acute altitude, Pa
o
2
and oxyhemoglobin saturation decreased and pulmonary artery pressure increased 43%, associated with sympathetic activation. V̇
o
2peak
decreased 12% acutely but normalized after acclimatization. The best predictor of V̇
o
2peak
with acute altitude was V̇
o
2peak
at SL (
r
=.94). The double product that induced 1-mm ST depression during exercise with acute altitude was 5% less than SL but normalized after acclimatization. One patient with severe coronary disease sustained a myocardial infarction after an exercise test.

Conclusions
Moderate altitude exposure in the elderly is associated with hypoxemia, sympathetic activation, and pulmonary hypertension resulting in a reduced exercise capacity that is predictable based on exercise performance at SL. Patients with coronary artery disease who are well compensated at SL do well at moderate altitude, although acutely ischemia may be provoked at modestly lower myocardial and systemic work rates. The elderly acclimatize well with normalization of SL performance after 5 days. A prudent policy would be for elderly individuals, particularly those with coronary artery disease, to limit their activity during the first few days at altitude to allow this acclimatization process to occur.
Passive Cigarette Smoking and Reduced HDL Cholesterol Levels in Children With High-Risk Lipid Profiles
Authors: Neufeld Ellis J. , Mietus-Snyder Michele , Beiser Alexa S. , Baker Annette L. , Newburger Jane W.
Published: June 2012

Background
HDL cholesterol levels are known to be lower in smokers than in nonsmokers. Previous studies have demonstrated an association of decreased HDL cholesterol with passive smoking in children but have not adjusted for potential confounding factors.

Methods and Results
In a cross-sectional, pilot-scale study, we examined the relationship of HDL cholesterol levels to passive smoking in children and adolescents referred to a tertiary hyperlipidemia clinic. Eligibility criteria included (1) first visit to a lipid clinic, (2) LDL cholesterol >95th percentile for age or HDL cholesterol <5th percentile, (3) age between 2 and 18 years, and (4) absence of secondary causes of hyperlipidemia. Sociodemographic information, diet record, medical history, and fasting lipid profiles were obtained. Of 109 eligible patients, 103 (94%) were studied. Twenty-seven percent came from households with cigarette smokers. HDL cholesterol levels were 38.7±1.2 mg/dL (mean±SEM) in passive smokers versus 43.6±1.2 mg/dL in children without smoke exposure (
P
=.005). Smoking exposure was not significantly associated with other lipid values. The effect of smoking on HDL cholesterol was minimally affected by potential confounders. In multivariate regression adjusting for body mass index, age, sex, exercise, and dietary fat intake, passive smoking remained a significant risk factor for decreased HDL cholesterol (
P
=.012).

Conclusions
Mean HDL cholesterol levels are lower in dyslipidemic children from households with smokers than in those without household smoke exposure. Passive smoking may worsen the risk profile for later atherosclerosis among high-risk young persons.
Association of the Platelet Pl
A
Polymorphism of Glycoprotein IIb/IIIa and the Fibrinogen Bβ 448 Polymorphism With Myocardial Infarction and Extent of Coronary Artery Disease
Authors: Carter Angela M. , Ossei-Gerning Nicholas , Wilson Ian J. , Grant Peter J.
Published: June 2012

Background
Platelets and fibrinogen play an integral role in the development of thrombosis and are implicated in the process of atherosclerosis. The fibrinogen Bβ 448 polymorphism and the Pl
A
polymorphism of platelet glycoprotein IIIa are reported to be independently associated with coronary artery disease. The aim of this study was to determine the association of the fibrinogen Bβ 448 and the platelet glycoprotein IIIa Pl
A
polymorphisms in relation to extent of coronary atheroma as characterized by angiography and a past history of myocardial infarction (MI) as assessed by World Health Organization criteria.

Methods and Results
Caucasian patients (n=405) admitted for routine angiography for investigation of chest pain or suspected coronary artery disease were recruited. Caucasian control subjects (n=216) were recruited from local Family Health Services Authority general practice registers. Fibrinogen levels were higher (
P
=.04) in male patients (3.24 g/L; CI, 3.14 to 3.35) than male control subjects (3.06 g/L; CI, 2.91 to 3.21). There was a trend toward a difference (
P
=.06) in fibrinogen genotype distributions between female patients (1/1=93, 1/2=31, and 2/2=1) and female control subjects (1/1=67, 1/2=34, and 2/2=5). In logistic regression models the Pl
A2
genotype was associated with MI (odds ratio, 1.66; CI, 1.15 to 2.39;
P
=.007) and stenosis of more than one vessel (odds ratio, 1.5; CI, 1.01 to 2.26;
P
=.04). In men suffering an MI before the age of 47 years there was a 50% incidence of the Pl
A2
allele (
P
=.05), and in these subjects there was evidence of an interaction with cholesterol (
P
=.04).

Conclusions
We found evidence of an association of the Pl
A2
polymorphism in MI and multiple-vessel stenosis. The association with MI was strongest in young men, in whom there was also evidence of an interaction with cholesterol.