bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of Subendocardial Myocardial Perfusion After Percutaneous Transluminal Coronary Angioplasty
Authors: Perchet Hervé , Dupouy Patrick , Duval-Moulin Anne-Marie , Hittinger Luc , Pelle Gabriel , Brun Philippe , Castaigne Alain , Geschwind Herbert , Dubois-Randé Jean-Luc
Published: June 2012

Background
After angioplasty coronary reserve improves but does not normalize in most patients. The purpose of this study was to examine before and after angioplasty coronary reserve and transmural myocardial blood flow distribution using myocardial contrast echocardiography.

Methods and Results
Twelve patients with left anterior descending coronary artery stenosis were investigated before and immediately after angioplasty. A Doppler catheter was placed in the proximal segment. Myocardial contrast echocardiography was performed by imaging the septum in M mode in a parasternal view using a 3.0-mL bolus of sonicated amidotrizoate sodium meglumine through the guiding catheter. The gray level before injection was subtracted from the gray level after injection to maximize contrast time-intensity curves. The area under the curve was used as an indicator of myocardial blood flow, and subendocardial/subepicardial ratios were measured. After baseline measurements were obtained, Doppler and echographic data were recorded after a bolus infusion of papaverine into the left main coronary artery. The same protocol was performed in patients after angioplasty and in five control subjects with normal coronary arteries. Before angioplasty, echocardiographic and Doppler coronary reserve were 2.57±0.48 and 2.54±0.57, respectively. Both increased after angioplasty to 3.65±0.57 and 3.36±0.70, respectively (
P
<.05). Coronary reserve values obtained in patients with these two methods under the different conditions and in control subjects were correlated (
r
=.81;
P
=.0001). Before angioplasty, subendocardial/subepicardial septal ratios decreased from 0.80±0.48 to 0.60±0.27 after papaverine (
P
<.05). However, after angioplasty, these ratios tended to increase, from 0.72±0.27 to 0.92±0.45 after papaverine, but they did not change in control subjects (1.11±0.23 to 0.92±0.11).

Conclusions
These results show that myocardial contrast echocardiography yields flow reserve values that correlate with values obtained using intracoronary Doppler. This technique may be considered as an accurate tool to assess coronary reserve in humans.
Angiotensin II
Authors: Lyons Declan , Webster John , Benjamin Nigel
Published: June 2012

Background
Angiotensin II (Ang II) facilitates adrenergic neurotransmission in normotensive and hypertensive subjects, whereas angiotensin-converting enzyme inhibitors have been shown to depress circulating catecholamine concentrations in some studies. We investigated the effect of local intra-arterial infusion of Ang II into the brachial artery of healthy volunteers during blockade of postsynaptic α-receptors with phentolamine. The response was compared with that seen with Ang II infused during nitroprusside administration at a dose designed to give a dilator response similar to that with phentolamine.

Methods and Results
Ang II (6.25, 25, and 100 pmol/min) was infused alone and then together with sodium nitroprusside (4 μg/min) and phentolamine (40 μg/min) in eight healthy volunteers. Forearm blood flow was measured by strain-gauge plethysmography. The percentage reduction in forearm blood flow produced by Ang II 100 pmol/min in the phentolamine-predilated vascular bed was significantly lower than that seen in the sodium nitroprusside–predilated forearm bed (28.1±2.9% versus 52.9±4.2%;
P
=.006). Comparison of the rate of change of blood flow in response to quadrupling doses of Ang II during blockade of α-receptors with phentolamine and during nitroprusside administration was calculated from the mean slope of the regression line of log-transformed blood flow versus dose of Ang II. The mean slope during nitroprusside administration (−0.16±0.025) was significantly greater than that during blockade with phentolamine (−0.098±0.020) (
P
=.046).

Conclusions
We conclude that a significant part of the vasoconstrictive action of exogenous Ang II on forearm resistance vessels in humans is sympathetically mediated.
Endovascular Low-Dose Irradiation Inhibits Neointima Formation After Coronary Artery Balloon Injury in Swine
Authors: Waksman Ron , Robinson Keith A. , Crocker Ian R. , Gravanis Michael B. , Cipolla Gustavo D. , King Spencer B.
Published: June 2012

Background
Restenosis after percutaneous transluminal coronary angioplasty remains a major limitation of the long-term success of this procedure. Restenosis is a form of wound healing. Low-dose ionizing radiation has been effective in inhibiting exuberant wound healing responses in a variety of clinical situations.

Methods and Results
Vascular neointimal lesions resembling human restenosis were created in the coronary arteries of normal pigs by overstretch balloon angioplasty injury. To test the effect of low-dose endovascular gamma radiation on lesion formation, a high-activity
192
Ir source was introduced into one of the injured arteries in each animal and left in place for a period sufficient to deliver one of three doses: 350, 700, or 1400 cGy. To test potential benefits of delayed irradiation, 700 cGy was given in another group 2 days after injury. Animals were killed 14 days after balloon injury and the coronary vasculature was pressure-perfusion fixed. To test the late effect and safety of endovascular low-dose irradiation, 700 or 1400 cGy was given in miniswine coronary arteries after injury as well as in noninjured carotid arteries; this group was followed up for 6 months. Tissue sections were measured by computer-assisted planimetry. All arteries treated with radiation demonstrated significantly decreased neointima formation compared with control arteries. The ratio of intimal area–to–medial fracture length (IA/FL) was inversely correlated with the different radiation doses: control, 0.59; 350 cGy, 0.38; 700 cGy, 0.42; and 1400 cGy, 0.17 (
r
=−0.75,
P
<.0001). Delay of 700-cGy irradiation for 2 days after injury significantly decreased neointima formation compared with the same dose given immediately after injury. Analysis of long-term specimens showed reduction of IA/FL in the arteries irradiated with 700 cGy (0.3,
P
=.009) and 1400 cGy (0.31,
P
=.001) compared with control arteries (0.50). There was no excess fibrosis in the media, adventitia, or perivascular space of the coronary arteries or adjacent myocardium in pigs that received radiation compared with control animals.

Conclusions
Low-dose intracoronary irradiation delivered to the site of coronary arterial overstretch balloon injury in pigs inhibited subsequent intimal thickening (hyperplasia). A dose-response relationship was demonstrated, and delay of treatment for 48 hours appeared to augment the inhibitory effect. Six months of follow-up without fibrosis or arteriosclerosis demonstrated the durability of the beneficial effect in the treated group. These data suggest that intracoronary irradiation therapy may aid in preventing clinical restenosis.
Loss of Flow-Dependent Coronary Artery Dilatation in Patients With Hypertension
Authors: Antony Isabelle , Lerebours Guy , Nitenberg Alain
Published: June 2012

Background
Abnormal endothelium-dependent coronary response to acetylcholine has been shown in patients with essential hypertension. We tested the hypothesis that flow-dependent dilatation, which has been shown in normal human coronary arteries, is impaired in hypertensive patients.

Methods and Results
The coronary vasomotor response to maximal increase of blood flow induced by papaverine was studied in 10 control subjects and in 14 hypertensive patients with no other risk factors and angiographically normal coronary arteries. After the injection of papaverine in the midportion of the left anterior descending coronary artery (LAD), the diameter of the proximal LAD (LAD1) was measured by quantitative angiography, whereas that of the proximal circumflex artery (LCx) served as control segment. Estimates of coronary blood flow in the distal LAD (LAD2) were calculated by intracoronary Doppler flow velocity measurements. An increase in LAD2 blood flow of 521±41% (
P
<.001) in control subjects was associated with a 17.0±3.3% dilatation of the LAD1 (
P
<.001) and with no significant change in the diameter of the LCx. In hypertensive patients, despite a comparable increase in LAD2 blood flow of 406±32% (
P
<.001), the LAD1 failed to dilate (−0.4±0.6%, NS). The dilative response to isosorbide dinitrate was similar in control subjects and hypertensive patients (30.0±4.1%,
P
<.001 and 21.9±1.9%,
P
<.001, respectively).

Conclusions
Thus, the flow-mediated coronary dilatation is lost in hypertensive patients, and this may impair normal dilatation observed in response to an increase in myocardial metabolic demand.
Sex, Age, and Disease Affect Echocardiographic Left Ventricular Mass and Systolic Function in the Free-Living Elderly
Authors: Gardin Julius M. , Siscovick David , Anton-Culver Hoda , Lynch James C. , Smith Vivienne Elizabeth , Klopfenstein H. Sidney , Bommer William J. , Fried Linda , O’Leary Daniel , Manolio Teri A.
Published: June 2012

Background
Left ventricular (LV) hypertrophy, as measured by M-mode echocardiography, is an independent predictor of mortality and/or morbidity from coronary heart disease (CHD). LV global and segmental systolic dysfunction also have been associated with myocardial ischemia and cardiovascular morbidity and mortality. Echocardiographic data, especially two-dimensional, have not been available previously from multicenter-based studies of the elderly. This report describes the distribution and relation at baseline of echocardiographic LV mass and global and segmental LV wall motion to age, sex, and clinical disease category in the Cardiovascular Health Study (CHS), a cohort of 5201 men and women (4850 white) 65 years of age and older.

Methods and Results
M-mode LV mass adjusted for body weight increased modestly with age (
P
<.0001), increasing less than one gram per year increase in age for both men and women. After adjustment for weight, LV mass was significantly greater in men than in women and in participants with clinical CHD compared with participants with neither clinical heart disease nor hypertension (both
P
<.001). Across all CHS age subgroups, the difference in weight-adjusted LV mass by sex was greater in magnitude than the difference related to clinical CHD. M-mode measurements of LV mass could not be made in 34% of CHS participants, and this was highly related to age (29% in the 65 to 69 year versus 50% in the 85+ year age group,
P
<.001) and other risk factors. In participants with clinical CHD and with neither clinical heart disease nor hypertension, LV ejection fraction and segmental wall motion abnormalities were more prevalent in men than women (all
P
<.001). Of interest, 0.5% of men and 0.4% of women with neither clinical heart disease nor hypertension had LV segmental wall motion abnormalities, suggesting silent disease, compared with 26% of men and 10% of women in the clinical CHD group (
P
<.0001). Multivariate analyses revealed male sex and presence of clinical CHD (both
P
<.001) to be independent predictors of LV akinesis or dyskinesis.

Conclusions
Significant baseline relations were detected between differences in sex, prevalent disease status, and echocardiographic measurements of LV mass and systolic function in the CHS cohort. Age was weakly associated with LV mass measurements and LV ejection fraction abnormalities. These relations should be considered in evaluating the preclinical and clinical effects of CHD risk factors in the elderly.
Effects of Pulmonary Venous Flow Direction on Mitral Regurgitation Jet Area as Imaged by Color Doppler Flow Mapping
Authors: Mizushige Katsufumi , Shiota Takahiro , Paik Juliana , Griever Gerard , Depp Marianne R. , Passafini Arnaldo , Shandas Robin , DeMaria Anthony N. , Sahn David J.
Published: June 2012

Background
Although the effects of adjacent walls and left atrial pressure on mitral regurgitation (MR) jet area imaged by color Doppler have been examined, few data exist regarding the influence of pulmonary venous (PV) filling flow on regurgitant jets. Therefore, we designed a left atrial model to examine the relation between PV flow direction and MR jet area.

Methods and Results
The left atrial chamber (7.6 cm in diameter) was built with a PV inflow (1.0 cm in diameter) and mitral valve regurgitant orifice in the same plane. The MR jet was simulated as fixed in volume and velocity (3.5 m/s) and directed with a pulsatile pump into the left atrial model. PV flow with a constant velocity (30 cm/s) was driven by gravity (83 cm H
2
O). With left atrial mean pressure at either 10, 30, or 50 mm Hg, four flow patterns were examined: (1) PV flow away from the mitral valve, MR jet toward the pulmonary vein; (2) PV flow toward the mitral valve, MR jet toward the pulmonary vein; (3) PV flow away from the mitral valve, MR jet away from the pulmonary vein; and (4) PV flow toward the mitral valve, MR jet away from the pulmonary vein. MR color Doppler images were recorded with a 3.5-mHz frequency transducer and at 7-kHz pulse repetition frequency. For each condition, we compared jet area, length, and width of the MR signal. MR jet areas for conditions 3 and 4 were larger at 10 mm Hg than at 30 or 50 mm Hg left atrial pressure. Especially at the lower pressures, PV flow diminished the MR jet area in condition 4 compared with that in condition 3, such that MR jets were smaller in condition 4. In conditions 1 and 2, the jets were imaged at an oblique angle and were smaller than in conditions 3 and 4 (
P
<.001), but they were not significantly different from each other as imaged.

Conclusions
In this model, factors including the direction of PV flow, the direction of MR as relates to the angle of interrogation, and the level of left atrial pressure influenced the size of MR jets. The effect of PV flow direction was diminished by increased left atrial pressure. PV flow directed away from the mitral valve was associated with larger MR jets than when PV flow was directed toward it (condition 4), probably because of jet distortion and flattening.
New Gianturco-Grifka Vascular Occlusion Device
Authors: Grifka Ronald G. , Mullins Charles E. , Gianturco Cesare , Nihill Michael R. , O’Laughlin Martin P. , Slack Michael C. , Clubb Fred J. , Myers Timothy J.
Published: June 2012

Background
Transcatheter closure of cardiovascular defects remains a challenge. Several occlusion devices are available, but each device has limitations. The purpose of this study was to evaluate the new Gianturco-Grifka vascular occlusion device (GGVOD) in a canine model.

Methods and Results
A total of 26 GGVODs were implanted as part of short- and long-term studies. In the short-term study, 1 GGVOD was implanted in each of 11 systemic arteries from 3.2 to 9.0 mm in diameter. All 11 arteries were occluded immediately. In the long-term study, an aortopulmonary shunt was placed in 10 dogs (9, Gore-tex graft; 1, subclavian artery) followed by GGVOD implantation; additionally, a GGVOD was implanted in 5 subclavian arteries. The dogs were boarded for 3 to 6 months, then recatheterized and euthanatized. Immediately after implantation, the 5 subclavian arteries and 9 Gore-tex shunts were occluded completely; the 1 subclavian artery shunt had a small residual leak. At recatheterization, all 10 shunts and 5 subclavian arteries were occluded completely. Necropsy revealed all shunts to be occluded, with the aortic and pulmonic orifices covered with a neointimal layer. The mean fluoroscopic time needed for GGVOD implantation was 9 minutes (range, 3 to 22 minutes).

Conclusions
(1) In a canine model, the GGVOD is effective for transcatheter occlusion of arteries and aortopulmonary shunts from 3 to 9 mm in diameter. Possible indications in children include aortopulmonary collateral vessels, long patent ductus arteriosus, systemic-pulmonary shunts, AV malformations, and arteries supplying tumors. (2) GGVOD implantation requires a short fluoroscopic time.
Significance and Incidence of Concordance of Drug Efficacy Predictions by Holter Monitoring and Electrophysiological Study in the ESVEM Trial
Authors: Reiter Michael J. , Mann David E. , Reiffel James E. , Hahn Elizabeth , Hartz Vernon
Published: June 2012

Background
Selection of antiarrhythmic therapy may be based on either suppression of spontaneous ventricular arrhythmias assessed by Holter monitoring or by suppression of inducible ventricular arrhythmias during electrophysiological study. This study examines the frequency and significance of concordance of these two approaches in the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial.

Methods and Results
Twenty-four-hour Holter monitoring was performed in patients randomized to the electrophysiology limb of the ESVEM study at the time of the first drug trial and at the time of an effective drug trial. Holter monitors were available in 65% (146/226) of patients at the time of the first drug trial and in 93% (100/108) of patients at the time of an electrophysiology study predicting drug efficacy. There were no clinical differences between patients who had and those who did not have a Holter monitor. At the time of the first drug trial, concordance of Holter and electrophysiological predictions of drug efficacy was observed in 46% of patients (both techniques predicted efficacy in 23%; neither predicted efficacy in 23%). Discordant results were observed in 54% (Holter suppression without electrophysiological suppression in 44%; electrophysiological suppression without Holter suppression in 10%). At the time of an electrophysiology study predicting drug efficacy, 68 of the 100 patients without inducible ventricular tachyarrhythmias also had suppression of spontaneous ventricular arrhythmias on the Holter recorded at the time of the electrophysiological study. Neither arrhythmia recurrence nor mortality was significantly different in patients with suppression of both inducible and spontaneous ventricular arrhythmias compared with those with only suppression of inducible arrhythmias. Comparison of patients with suppression of both inducible and spontaneous ventricular arrhythmias with the 188 patients in the Holter limb, in whom efficacy was predicted by Holter monitoring only, revealed no difference in outcome.

Conclusions
In this population, (1) there is frequent discordance in prediction of drug efficacy and inefficacy between electrophysiological study and Holter monitoring; (2) a requirement to fulfill both Holter and electrophysiological efficacy criteria reduces the number of patients with an efficacy prediction; and (3) suppression of both spontaneous ventricular ectopy and inducible ventricular tachyarrhythmias does not identify a group with better outcome.
Body Surface Potential Distributions During Idiopathic Ventricular Tachycardia
Authors: Klug Didier , Ferracci Ange , Molin Franck , Dubuc Marc , Savard Pierre , Kus Teresa , Hélie François , Cardinal René , Nadeau Réginald
Published: June 2012

Background
The purpose of this report is to describe the body surface potential maps (BSPMs) during idiopathic ventricular tachycardia (VT) and to determine what differences exist between different idiopathic VT morphologies.

Methods and Results
We performed BSPMs during VT on 12 consecutive patients (3 women and 9 men; mean age, 42±13 years) presenting symptomatic idiopathic VT referred to our institution for electrophysiological study. Basal ECG, chest radiograph, and echocardiogram were normal in all patients. Clinical tachycardia showed left bundle branch block pattern (LBBB) in 9 patients, with sustained VT in 5 and nonsustained VT in 4, and right bundle branch block pattern (RBBB) in 3 with sustained VT. We found a unique pattern of BSPMs in each of the 9 patients during idiopathic LBBB VT configuration, whether sustained or nonsustained VT. This pattern appeared at the onset of the QRS and remained stable during the whole QRS complex. The area of minimal potential located in the upper anterior part of the torso was compatible with an origin of VT in the right ventricular outflow tract, as confirmed in 5 patients by successful radiofrequency ablation. We found an evolving pattern with two phases in each of the three RBBB VTs. The electrical axis during the initial part of the QRS could correspond to an endocardial-epicardial vector. The second phase, with a high voltage and area of minimal potential located in the inferior and anterior part of the torso, was compatible with a left ventricular apical origin that was confirmed by epicardial and endocardial mapping during cryosurgery in 1 patient. For all the VTs, the QRS isoarea maps showed the same pattern as the second phase of the QRS.

Conclusions
Two different BSPM patterns were found. All LBBB VTs had the same stable pattern corresponding to an infundibular origin. All RBBB VTs had an evolving pattern that stabilized in the second part of the QRS complex corresponding to an apical origin.
Altered Tissue Degradation and Distribution of Atrial Natriuretic Peptide in Patients With Idiopathic Dilated Cardiomyopathy and Its Relationship With Clinical Severity of the Disease and Sodium Handling
Authors: Iervasi Giorgio , Clerico Aldo , Berti Sergio , Pilo Alessandro , Biagini Andrea , Bianchi Romano , Donato Luigi
Published: June 2012

Background
Atrial natriuretic peptide (ANP) has been suggested to play an important role in heart failure, preserving cardiorenal homeostasis through maintenance of the sodium balance and inhibition of the detrimental effects of the neurohormonal vasoconstrictor system. The current study was designed to investigate whether there is a disturbed renewal and distribution of ANP in patients with idiopathic dilated cardiomyopathy (IDC) with differing clinical severity of disease.

Methods and Results
We used a tracer method to perform a cross-sectional study of 15 IDC patients with differing clinical severity (New York Heart Association functional class I to III), prospectively divided into two groups according to their functional class (group 1, classes I and II; group 2, classes II-III and III). Eleven normotensive, nonobese male volunteers also were studied as a control group. Main ANP kinetic parameters were derived from the disappearance curve of the labeled hormone after the bolus injection of [
125
I]-labeled ANP. A high-performance liquid chromatography technique was used to separate the radiolabeled hormone in each plasma sample. Patients in group 1 showed higher ANP metabolic clearance rate (MCR) (2731.9±726.2 mL · min
−1
· m
−2
) than patients of group 2 (1718.4±621.2 mL · min
−1
· m
−2
) and control subjects (1873.1±551.2 mL · min
−1
· m
−2
). ANP disposal (MCR) positively correlated with biological hormonal effect (urinary sodium excretion) both in control subjects and in patients. In IDC patients of both groups, however, MCR values were always higher (approximately doubled) than the values found in control subjects at the corresponding sodium excretion. This finding indicates that a reduced ANP biological activity is associated with hormone degradation in patients. Moreover, patients of group 2 showed significantly higher ANP production rates (395.6±183.8 ng · min
−1
· m
−2
) than group 1 (166.0±139.0 ng · min
−1
· m
−2
) and control subjects (130.7±105.4 ng · min
−1
· m
−2
) despite a marked reduction in sodium excretion. Patients with IDC showed a progressive reduction in the total distribution volume (group 1, 19.8±5.8 L/m
2
; group 2, 12.7±6.9 L/m
2
; control subjects, 27.0±11.6 L/m
2
) of the hormone; this probably was due to a reduction in exchanges of ANP with peripheral tissues.

Conclusions
Our study demonstrates a markedly altered degradation and distribution of ANP in patients with IDC, even in those at the early stage of clinical disease (classes I and II, group 1) who have ANP plasma levels in the normal range.
Comparison of Effects of High-Dose and Low-Dose Aspirin on Restenosis After Femoropopliteal Percutaneous Transluminal Angioplasty
Authors: Minar E. , Ahmadi A. , Koppensteiner R. , Maca Th. , Stümpflen A. , Ugurluoglu A. , Ehringer H.
Published: June 2012

Background
Long-term treatment with aspirin is recommended in patients with large-vessel peripheral arterial disease since these patients have a high risk of death from cardiovascular causes. Recent studies have demonstrated the prophylactic effect of low-dose aspirin in reducing the risk of cardiovascular events. Since aspirin is also recommended for prevention of late recurrence after peripheral angioplasty, the present study was undertaken to compare the effects of high-dose (1000 mg/d) and low-dose (100 mg/d) aspirin on long-term patency after femoropopliteal angioplasty.

Methods and Results
Two hundred sixteen patients treated successfully by percutaneous transluminal angioplasty for femoropopliteal lesions were randomly allocated to therapy with either 1000 or 100 mg aspirin daily. The follow-up was 24 months. The long-term results were analyzed using the Kaplan-Meier method, and differences between curves of cumulative patency were determined with the Wilcoxon and log-rank statistics. Complete follow-up information (patency after 24 months, restenosis, and death) was obtained in 207 patients. During the 2-year follow-up period, 72 patients—36 in the high-dose and 36 in the low-dose aspirin group, respectively—developed angiographically verified reobstruction within the recanalized segment. By intention-to-treat analysis, the cumulative patency rates at 24 months were 62.5% in the high-dose and 62.6% in the low-dose aspirin group (Wilcoxon,
P
=.97; log-rank,
P
=.97). The cumulative survival at 24 months of follow-up was 86.6% in the high-dose and 87.7% in the low-dose aspirin group. The number of patients discontinuing therapy was 30 in the high-dose and 11 in the low-dose aspirin group (
P
<.01). Fewer patients receiving 100 mg of aspirin discontinued therapy because of gastrointestinal symptoms (4 versus 20).

Conclusions
The data indicate that 100 mg aspirin is no less effective in the prevention of restenosis after femoropopliteal PTA than a 1000-mg dose and has fewer side effects.
Angiographic Stenosis Progression and Coronary Events in Patients With ‘Stabilized’ Unstable Angina
Authors: Chen Lijia , Chester Michael R. , Redwood Simon , Huang Jian , Leatham Edward , Kaski Juan Carlos
Published: June 2012

Background
Recent studies suggest that angiographically complex coronary stenoses are associated with an adverse short-term outcome. It is not known, however, if this applies to unstable angina patients who stabilize on medical therapy.

Methods and Results
We prospectively studied 85 consecutive patients with unstable angina who stabilized on medical therapy but were found to require angioplasty for treatment of obstructive coronary disease. Angiography was carried out at admission, and patients were restudied 8±4 months (mean±SD) after the first angiogram. Ischemia-related stenoses were identified and classified as “complex” (irregular borders, overhanging edges, or thrombus) or “smooth” (absence of complex features). Stenosis progression (≥20% diameter reduction or new total occlusion) was assessed by automated edge detection. At initial angiography, there were 198 stenoses (≥50%, 102), of which 85 (54 complex and 31 smooth) were ischemia related. At restudy, 21 ischemia-related stenoses and 8 non–ischemia-related stenoses progressed (25% versus 7%,
P
=.001). Seventeen of the 21 ischemia-related stenoses that progressed developed into total occlusion compared with 3 of the 8 non–ischemia-related stenoses (
P
=.02). Changes in average stenosis severity and in absolute stenosis diameter were significantly larger in ischemia-related stenoses than in non–ischemia-related stenoses (
P
=.03). Eighteen (34%) complex stenoses progressed, compared with 3 (10%) smooth lesions (
P
=.02). During follow-up, 1 patient died (myocardial infarction) and 25 patients had nonfatal coronary events that were associated with progression of ischemia-related stenoses in 14 (56%).

Conclusions
In unstable angina patients who stabilize medically, subsequent short-term stenosis progression and coronary events are common. The unstable coronary lesion (particularly complex stenoses) is often not stabilized and will continue to progress over the ensuing months.
Impaired Endothelium-Dependent Vasodilation of Coronary Resistance Vessels Is Associated With Exercise-Induced Myocardial Ischemia
Authors: Zeiher Andreas M. , Krause Thomas , Schächinger Volker , Minners Jan , Moser Ernst
Published: June 2012

Background
The release of endothelium-derived relaxing factors has been shown experimentally to be of pivotal importance for the maintenance of coronary blood flow during increased demand. In humans with coronary atherosclerosis, endothelial vasodilator dysfunction is not confined only to epicardial conductance vessels but may also extend into the coronary microcirculation. We therefore tested the hypothesis that endothelial vasodilator dysfunction of the coronary resistance vasculature is associated with myocardial ischemia during exercise in patients without hemodynamically significant epicardial artery stenoses.

Methods and Results
Coronary vasodilator function was assessed by subselective infusion of the endothelium-dependent dilator acetylcholine (0.036 to 3.6 μg/mL) and the endothelium-independent dilator papaverine (7 mg). Coronary blood flow responses were evaluated by intracoronary Doppler flow velocity recordings and quantitative angiography. Exercise-induced myocardial perfusion was determined by
201
Tl single photon emission computed tomographic imaging. Thirteen patients had exercise-induced myocardial perfusion defects suggestive of myocardial ischemia, whereas 14 patients had normal thallium imaging during exercise. In patients with exercise-induced thallium perfusion defects, coronary blood flow responses to acetylcholine were significantly (
P
<.005) blunted compared with patients with normal thallium imaging during exercise. In contrast, coronary blood flow reserve to the endothelium-independent smooth muscle relaxant papaverine was similar in the two groups. Patients with exercise-induced thallium perfusion defects exhibited a significantly (
P
<.005) reduced (23.9±9.0% [mean±SD]) endothelium-mediated coronary vasodilator capacity compared with patients with normal thallium testing (56.2±27.8%). Epicardial artery vasoreactivity to acetylcholine did not differ between the two groups.

Conclusions
Impaired endothelium-dependent vasodilation of the coronary microcirculation is associated with exercise-induced myocardial ischemia in patients without hemodynamically significant epicardial artery lesions. Endothelial vasodilator dysfunction extending into the coronary microcirculation may thus contribute to the ischemic manifestations of coronary artery disease during times of increased myocardial demand.
Left Ventricular Contractility Predicts How the End-Diastolic Pressure-Volume Relation Shifts During Pacing-Induced Ischemia in Dogs
Authors: Takano Hiroshi , Glantz Stanton A.
Published: June 2012

Background
Two types of ischemia, pacing-induced and coronary occlusion–induced, have different effects on left ventricular diastolic properties. During pacing-induced ischemia, the diastolic pressure-volume relation is said to shift upward, whereas during coronary occlusion, it is said to shift rightward or downward. However, recent studies have shown that the relation can shift in any direction during both types of ischemia. The purpose of this study was to identify determinants of the shift of the end-diastolic pressure-volume relation (EDPVR) during pacing-induced ischemia.

Methods and Results
We retrospectively analyzed 46 pacing-induced ischemia experiments performed in 15 open-pericardium anesthetized dogs. Pacing ischemia was induced by constricting left anterior descending and left circumflex coronary arteries and pacing the left atrium at 150 to 180 beats per minute for 3 minutes. Left ventricular volume was measured with a conductance catheter. Hemodynamics were recorded during baseline, coronary stenosis, rapid pacing, and pacing-induced ischemia (immediately after rapid pacing). For each condition, hemodynamics were recorded in steady state and then during a brief inferior vena caval occlusion (except for during rapid pacing) to obtain left ventricular end-diastolic and end-systolic pressure-volume relations. The shift of the EDPVR from coronary stenosis to pacing-induced ischemia was assessed by an upward shift index (end-diastolic pressure during pacing-induced ischemia minus the pressure during coronary stenosis at the largest end-diastolic volume common to both conditions, S
I-S
) and a rightward shift index (the largest end-diastolic volume during pacing-induced ischemia minus the largest volume during coronary stenosis, ΔEDV
I-S
). The index of left ventricular contractility, the end-systolic elastance (E
es
), or the slope of the dP/dt
max
–end-diastolic volume relation (dE/dt
max
) during pacing-induced ischemia was the strongest determinant of the magnitude of S
I-S
and ΔEDV
I-S
and thus of the shift of the EDPVR. As E
es
or dE/dt
max
decreased, S
I-S
decreased and ΔEDV
I-S
increased.

Conclusions
Our results suggest that left ventricular contractility is the best determinant of the shift of the EDPVR during pacing-induced ischemia. The more left ventricular contractility decreases, the more the EDPVR shifts downward and rightward.
Cardiac Allograft Survival in Mice Deficient in Intercellular Adhesion Molecule–1
Authors: Schowengerdt Kenneth O. , Zhu Jessica Y. , Stepkowski Stanislaw M. , Tu Yizheng , Entman Mark L. , Ballantyne Christie M.
Published: June 2012

Background
Intercellular adhesion molecule–1 (ICAM-1, CD54) is a cell adhesion molecule that interacts with the leukocyte β2 integrins, lymphocyte function–associated antigen–1, and macrophage antigen–1. ICAM-1 is postulated to play a key role in several cell-cell interactions that are important in allograft rejection, including antigen presentation, transendothelial migration of leukocytes, and leukocyte-mediated myocyte injury.

Methods and Results
Mice homozygous for a gene-targeted mutation of ICAM-1 were used in two different cardiac transplant models to further define the role of ICAM-1 in the process of allograft rejection. In the first model, hearts from newborn mice were implanted in the ear pinnae of
H
-2–incompatible recipients. In the second model, intra-abdominal transplantation by direct vascular anastomosis was performed. Time to rejection was defined by the loss of pulsatile activity assessed by visual inspection in the ear model or by cessation of palpable cardiac impulse in the abdominal model. Allograft survival did not differ significantly between control groups that express normal levels of ICAM-1 and those groups using ICAM-1–deficient mutants as either donors or recipients. Histological examination of rejection of both normal and mutant (ICAM-1-deficient) cardiac allografts revealed similar patterns of infiltration of mononuclear and granulocytic leukocytes and myocyte necrosis. Immunostaining with anti–ICAM-1 antibodies showed ICAM-1–positive infiltrating cells in both mutant (ICAM-1–deficient) and normal allografts, with the graft endothelium negative for ICAM-1 staining in the mutant allografts.

Conclusions
The absence of surface expression of ICAM-1 in the donor allograft or recipient is insufficient to produce a significant impact on cardiac allograft survival. This study highlights the need to understand more precisely the mechanism of action whereby monoclonal antibodies to ICAM-1 prolong cardiac allograft survival before new therapeutic strategies based on gene transfer technology or small molecule inhibitors are developed. Mutant mice with targeted mutations in cell adhesion molecules provide powerful tools to study the complex role that cell adhesion molecules play in the cellular interactions between donor graft tissue and the recipient that culminate in graft rejection.
Role of Blood Doping in the Coronary Vasoconstrictor Response to Cocaine
Authors: Shannon Richard P. , Manders W. Thomas , Shen You-Tang
Published: June 2012

Background
The mechanism by which cocaine induces myocardial ischemia remains controversial. Most prior studies have postulated that cocaine-induced coronary vasoconstriction limits myocardial oxygen delivery during times of increased myocardial oxygen demand.

Methods and Results
To determine the contribution of altered myocardial metabolic demands to the coronary vasoconstrictor effects of intravenous cocaine (COC 1 mg/kg), we studied 13 conscious, chronically instrumented dogs in the intact state and with heart rate held constant with atrial pacing in the presence and absence of β-adrenergic blockade with propranolol (2 mg/kg) to limit the inotropic and chronotropic effects of cocaine on associated increases in myocardial oxygen consumption. In the intact state, COC caused a prompt increase in coronary blood flow (+30±3%,
P
<.01) that returned rapidly to baseline within 10 minutes, whereas coronary vascular resistance did not increase significantly (+17±6%,
P
<.05) until 15 minutes after COC. Notably, myocardial oxygen consumption increased (+57±4%,
P
<.01) to a greater extent than oxygen delivery (+42±3%,
P
<.01) during the first 2.5 minutes, requiring increased oxygen extraction (from 75±1% to 80±1%,
P
<.01), although only transiently. Thereafter, enhanced oxygen delivery matched the required oxygen consumption without further need to extract additional oxygen. Surprisingly, the enhanced oxygen delivery associated with COC in conscious dogs did not depend on persistent increases in coronary blood flow but rather was due to enhanced arterial oxygen content (+22±4%,
P
<.01) as a result of a significant “blood doping” effect with associated increases in circulating hemoglobin from 12.1±0.4 to 14.2±0.6 g/dL (
P
<.01), which persisted for 60 minutes.

Conclusions
The myocardial oxygen requirements associated with COC administration have a significant impact on both the magnitude and the mechanism of the coronary vasoconstrictor effects of COC in conscious dogs. Furthermore, the enhanced myocardial oxygen delivery associated with COC administration is not dependent solely on coronary blood flow responses but is due to a significant “blood doping” effect associated with COC.
Gene Polymorphism but not Catalytic Activity of Angiotensin I–Converting Enzyme Is Associated With Coronary Artery Disease and Myocardial Infarction in Low-Risk Patients
Authors: Gardemann Andreas , Weiß Tanja , Schwartz Oliver , Eberbach Andreas , Katz Norbert , Hehrlein Friedrich Wilhelm , Tillmanns Harald , Waas Wolfgang , Haberbosch Werner
Published: June 2012

Background
An insertion/deletion (I/D) polymorphism of the angiotensin I–converting enzyme (ACE) gene has been postulated to be associated with an increased risk of coronary artery disease (CAD) and myocardial infarction (MI).

Methods and Results
In the present study, the effects of I/D gene polymorphism and of ACE activity on CAD and MI were investigated in 920 individuals who underwent coronary angiography for diagnostic purposes. In the total population and in all CAD and MI groups, a strong association was observed between the gene polymorphism and ACE activities; DD genotypes had approximately twofold higher ACE activities than II genotypes. Although classic risk and protective factors of CAD and MI were identified, associations of ACE genotype and of ACE activity to CAD and MI were not detected in the total population. Among subjects defined to be at lower risk of MI by low body mass index and low cigarette consumption, however, an association of the DD genotype with MI was found. Exclusion of individuals with triglyceride levels >140 mg/dL and cholesterol levels >180 mg/dL revealed an association of the DD genotype with CAD. An association of the ACE activity with CAD or MI could not be demonstrated in any of the low-risk populations.

Conclusions
Increased ACE activity obviously is not a risk factor of CAD or MI. The importance of the deletion polymorphism for the development of CAD and MI may be restricted to individuals without classic risk factors.
Antiarrhythmic Activity of Quinine in Humans
Authors: Sheldon Robert , Duff Henry , Koshman Mary Lou
Published: June 2012

Background
Quinine is the diastereomer of quinidine. In dogs, it has similar effects on conduction time but does not prolong epicardial repolarization time or ventricular refractoriness. It has antiarrhythmic effects in both cats and dogs. We assessed the antiarrhythmic potential of quinine in suppressing ventricular arrhythmias in humans.

Methods and Results
Patients underwent open-label, dose-ranging trials of quinine with daily doses of 600, 1200, and 1800 mg in a twice-daily dosing regimen. In 17 patients with frequent spontaneous ventricular ectopy, oral quinine suppressed arrhythmia in 11 of 12 patients who finished the study and was not tolerated by 4 patients, and 1 patient withdrew from the study. The mean effective daily dosage was 927 mg, the mean effect trough serum level was 11 μmol/L (range, 4 to 17 μmol/L), and the half-life was 20±7 hours. In a second open-label, dose-ranging trial in 10 patients with inducible ventricular tachycardia and reduced left ventricular systolic function (left ventricular ejection fraction, 35±16%), quinine suppressed inducibility of ventricular tachycardia in 3 of 10 patients. At a basic pacing cycle length of 500 milliseconds, ventricular effective refractory period was prolonged (279±21 versus 247±10 milliseconds, quinine versus drug free,
P
=.003). In the remaining patients, ventricular tachycardia cycle length was prolonged (373±48 versus 253±30 milliseconds, quinine versus drug free,
P
<.001). The corrected QT interval was not prolonged.

Conclusions
Quinine is an effective and convenient antiarrhythmic drug for the suppression of ventricular arrhythmias in humans.
Role of Transesophageal Echocardiography in the Diagnosis and Management of Traumatic Aortic Disruption
Authors: Vignon Philippe , Guéret Pascal , Vedrinne Jean-Marc , Lagrange Philippe , Cornu Elisabeth , Abrieu Olivier , Gastinne Hervé , Bensaid Julien , Lang Roberto M.
Published: June 2012

Background
Traumatic disruption of the aorta (TDA) is a life-threatening injury that requires rapid diagnosis and treatment. Emergency aortography, which is the current standard diagnostic imaging modality, is invasive, time-consuming, and difficult to perform in hemodynamically unstable patients with multiple trauma. We performed transesophageal echocardiography (TEE) in patients with suspected TDA to determine the diagnostic accuracy and impact on patient management of this alternative, portable imaging modality.

Methods and Results
Thirty-two consecutive trauma patients (mean age, 40±16 years) with suspected TDA (violent deceleration accident and mediastinum >8 cm on admission chest x-ray) prospectively underwent a TEE examination in the emergency room. Findings during TEE were compared with those encountered during aortography, surgery, or necropsy. Two subsets of traumatic aortic injuries with distinct echocardiographic signs were observed: (1) subadventitial TDA (n=10) and (2) traumatic intimal tears (n=3). Eighteen patients had normal TEE confirmed by aortography. One 2-mm medial tear was missed by TEE (necropsy). The sensitivity and specificity of TEE for the diagnosis of subadventitial TDA were 91% and 100%, respectively. Patients with subadventitial TDA were taken to surgery immediately, whereas patients with intimal aortic tears were treated conservatively. Eighteen patients (mean age, 57±15 years) with confirmed acute aortic dissection involving the aortic isthmus were also included to establish the echocardiographic differential diagnostic criteria between this entity and TDA.

Conclusions
TEE should be considered the first-line imaging modality for the evaluation of trauma patients with suspected injuries of the thoracic aorta because of its portability, safety, diagnostic accuracy, and potential impact on patient management.
Effects of EMD 57033 on Contraction and Relaxation in Isolated Rabbit Hearts
Authors: Hgashiyama Akihiro , Watkins Matthew W. , Chen Zengyi , LeWinter Martin M.
Published: June 2012

Background
Ca
2+
sensitizers are reported to enhance contractility with modest effects on energy utilization. In the present study we assessed the effects of the relatively “pure” Ca
2+
sensitizer EMD 57033 on mechanical performance and energy consumption in the beating heart.

Methods and Results
In 10 isolated, red blood cell–perfused rabbit hearts the effects of EMD 57033 (5.0 to 5.8 μmol/L) on left ventricular (LV) pressure and O
2
consumption (V̇
o
2
) were examined at heart rates of 100 and 150 beats per minute (bpm) and perfusate [Ca
2+
] ([Ca
2+
]
o
) of 2.5 and 1.0 mmol/L (isovolumic contractions). LV developed pressure and maximum dP/dt increased, but less so at 150 bpm or 1.0 mmol/L [Ca
2+
]
o
. End-diastolic pressure also increased, more so at 150 bpm or 1.0 mmol/L [Ca
2+
]
o
. EMD 57033 decreased time to peak isovolumic pressure (T
max
) and prolonged time to 50% pressure decline (T
1/2
). These changes were greater at slower heart rate or lower [Ca
2+
]
o
. The magnitude of increased V̇
o
2
with EMD 57033 was greater at 100 bpm than 150 bpm but unaffected by [Ca
2+
]
o
. We then investigated the influence of ejection on the response to EMD 57033 (n=7). The increase in developed pressure with EMD 57033 was greater for ejecting than isovolumic beats (25.5±10.2 versus 14.7±7.5 mm Hg at 100 bpm,
P
<.01), while the increase in end-diastolic pressure was less (
P
=NS). The increase in V̇
o
2
was significantly greater for ejecting than isovolumic beats (0.027±0.013 versus 0.020±0.009 mL O
2
/beat per 100 g at 100 bpm,
P
<.01).

Conclusions
EMD 57033 enhances contractility and prolongs relaxation. Its effects are modulated by heart rate, [Ca
2+
]
o
, and contraction mode, with positive inotropic effects being more prominent for ejecting beats.
Tissue Factor Mediates Prolonged Procoagulant Activity on the Luminal Surface of Balloon-Injured Aortas in Rabbits
Authors: Speidel Christopher M. , Eisenberg Paul R. , Ruf Wolfram , Edgington Thomas S. , Abendschein Dana R.
Published: June 2012

Background
Activation of coagulation has been implicated in both acute thrombotic occlusion and restenosis after balloon angioplasty. However, concomitant administration of antithrombotic agents has thus far failed to prevent these complications. Importantly, the factors contributing to procoagulant activity of balloon-injured arteries over time have not been defined. This study was designed to determine the duration of procoagulant activity on the luminal surface of balloon-injured arteries and the relative roles of tissue factor and thrombin in this response.

Methods and Results
Abdominal aortas in rabbits were subjected to repetitive balloon hyperinflations sufficient to disrupt the internal elastic lamina. Aortas were excised at <1, 2, 4, 8, 16, 24, 48, and 72 hours and 1, 2, and 4 weeks after injury; divided into segments; and perfused with recalcified human pooled plasma (n=58) or plasma depleted of vitamin K–dependent coagulation factors (n=27) or first incubated with a monoclonal antibody to rabbit tissue factor (n=33) followed by perfusion with human plasma. Samples of the effluent and plasma perfusate were collected over 10 minutes and assayed for fibrinopeptide A (FPA) as an index of the rate of thrombin-induced fibrin formation. FPA in the effluent from segments perfused with recalcified plasma, expressed as a percentage of FPA in the perfusate, was elevated for 16 hours after balloon-induced injury and exhibited two distinct increases occurring <1 hour (1297±473%, mean±SD, n=5) and 8 hours (1052±330%, n=6) after injury (
P
≤.000001 versus uninjured vessels). Preincubation of segments at these intervals with an antibody to tissue factor markedly attenuated the increases in FPA, as did perfusion of segments with plasma depleted of vitamin K–dependent coagulation factors, indicating that the observed increases in FPA in whole plasma did not result from preformed thrombin bound to the injured vessel wall.

Conclusions
Tissue factor–mediated coagulation appears to be primarily responsible for prolonged procoagulant activity of balloon-injured arteries.