bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac and Skeletal Muscle Myoglobin Release After Reperfusion of Injured Myocardium in Dogs With Systemic Hypotension
Authors: Spangenthal Edward J. , Ellis Avery K.
Published: June 2012

Background
Myoglobin (Mb) is an intramyocardial protein that is released into the systemic circulation and rapidly cleared via the kidneys after myocardial injury. Arterial Mb concentration–time curves have been studied in humans and dogs in the setting of acute coronary artery occlusion, and the rate of rise of Mb is both sensitive and specific as an indicator of successful coronary artery reperfusion. Systemic hypotension may alter Mb kinetics and impact on the utility of this method by causing Mb release from ischemic skeletal muscle and by decreasing renal Mb clearance. This study was undertaken to determine whether analysis of Mb kinetics remains accurate in identifying coronary reperfusion in the setting of systemic hypotension.

Methods and Results
Eighteen chronically instrumented dogs were made hypotensive by being bled via a large-bore femoral artery catheter into a reservoir adjusted to maintain a constant mean arterial pressure of 50 mm Hg for 8 hours. After the first hour of hypotension, each dog was studied under one of the following three protocols: group 1, 2 hours of mid–left anterior descending artery (LAD) occlusion followed by 5 hours of unlimited reperfusion; group 2, 7 hours of mid-LAD occlusion without reperfusion; or group 3, 7 additional hours of hypotension alone. Systemic lactate extractions demonstrated a shift to anaerobic metabolism in skeletal muscle and confirmed that shock was established in all animals. Regional arteriovenous Mb differences in group 1 animals demonstrated release of large amounts of Mb from reperfused myocardium; in contrast, smaller amounts of Mb were released both from skeletal muscle rendered ischemic by hypotension and from myocardium rendered ischemic by coronary occlusion without reperfusion. In group 1 dogs, arterial Mb rose rapidly immediately after reperfusion, with peak Mb occurring 108±24 minutes (mean±SEM) after vessel reopening. In group 2 and group 3 dogs, arterial Mb rose more slowly, such that peak Mb was not reached within 8 hours in 11 of 12 animals. The linear rate of rise of arterial Mb over the first hour of reperfusion in group 1 dogs was 51±16 ng · mL
−1
· min
−1
. This slope was significantly greater than slopes determined over the same time period in dogs occluded and not reperfused (group 2, 1.2±0.6 ng · mL
−1
· min
−1
) and in those hypotensive alone (group 3, 0.8±0.5 ng · mL
−1
· min
−1
). All the slopes of group 2 and group 3 dogs fell below the range of slopes of group 1 dogs. In contrast to slopes of the Mb concentration–time curves, linear creatine kinase slopes were significantly less sensitive in predicting reperfusion.

Conclusions
Analysis of plasma Mb kinetics allows early identification of coronary reperfusion after myocardial injury even in the presence of significant systemic hypotension.
Serial Echocardiographic-Doppler Assessment of Left Ventricular Geometry and Function in Rats With Pressure-Overload Hypertrophy
Authors: Litwin Sheldon E. , Katz Sarah E. , Weinberg Ellen O. , Lorell Beverly H. , Aurigemma Gerard P. , Douglas Pamela S.
Published: June 2012

Background
Although chronic pressure overload may progress to left ventricular (LV) failure, the pathophysiology of this transition is not well understood. In addition, the effects of chronic angiotensin-converting enzyme (ACE) inhibition on this transition are largely undefined.

Methods and Results
To examine changes in LV structure and function during the transition to heart failure, rats with LV hypertrophy due to banding of the ascending aorta (LVH, n=22) and age-matched sham-operated rats (n=6) were studied 6, 12, and 18 weeks after aortic banding. Two-dimensionally guided transthoracic M-mode echocardiograms and transmitral Doppler spectra were recorded for assessment of LV geometry and systolic and diastolic functions. LVH rats were randomized to no treatment (n=10) or treatment with the ACE inhibitor fosinopril (50 mg/kg per day, n=12) after the baseline echocardiogram. Six weeks after banding, LVH rats had increased LV wall thickness with normal cavity dimensions and supranormal endocardial systolic shortening. However, midwall shortening was mildly depressed, and a restrictive diastolic filling pattern was present. After 18 weeks of untreated pressure overload, LV wall thickness was unchanged, but cavity dilation, a fall in endocardial shortening, and further deterioration of diastolic filling were evident. In contrast to untreated LVH rats, the fosinopril-treated rats showed no change in LV diastolic cavity dimension, and systolic and diastolic functions did not deteriorate or improved. Closed chest LV systolic pressures at 18 weeks were not different in LVH or LVH-fosinopril rats (197 versus 198 mm Hg), although end-diastolic pressure was higher in the untreated rats (18 versus 11 mm Hg). Calculated LV systolic wall stress was lower in fosinopril-treated than untreated LVH rats. The severity of LV diastolic filling abnormalities correlated strongly with operating LV chamber stiffness (
r
=.88,
P
<.0001).

Conclusions
This model of pressure overload is characterized initially by concentric LV hypertrophy with compensated LV chamber performance; however, markedly abnormal diastolic filling is present. The transition from compensated hypertrophy to early failure is heralded by LV dilation, impairment of systolic function, and progression of the abnormalities in LV filling. Chronic ACE inhibition in rats with supravalvular aortic banding (1) does not change in vivo LV systolic pressure but prevents increased LV cavity size and increased LV wall stress and (2) attenuates impairment of (or improves) both systolic and diastolic functions. The effects of fosinopril could be explained in part by inhibition of an intracardiac renin-angiotensin system.
Effect of Vasa Vasorum Flow on Structure and Function of the Aorta in Experimental Animals
Authors: Stefanadis Christodoulos , Vlachopoulos Charalambos , Karayannacos Panagiotis , Boudoulas Harisios , Stratos Costas , Filippides Theodoros , Agapitos Manolis , Toutouzas Pavlos
Published: June 2012

Background
It is known that vasa vasorum flow contributes substantially to the nutrition of the outer layers of the thoracic aorta. This investigation was undertaken to test the hypothesis that impairment of vasa vasorum flow would alter the structure of the aortic wall and change the elastic properties of the aorta.

Methods and Results
The periaortic fat that contains the vasa vasorum for the ascending aorta was removed in seven anesthetized dogs, and the results were compared with those obtained from six weight-matched sham-operated control dogs. Aortic pressures, aortic diameters, and aortic distensibility were obtained before and 30 minutes and 15 days after removal of the periaortic vasa vasorum network. Aortic pressures were measured directly with a fluid-filled catheter. Aortic diameters were measured simultaneously with aortic pressures with an elastic, air-filled ring connected to a transducer. Aortic distensibility was calculated by the formula 2×pulsatile change in aortic diameter/(diastolic aortic diameter×pulse pressure). Histology was performed in transverse blocks of aortic wall at the end of the experiment in both groups. The efficacy of the technique for the interruption of vasa vasorum blood supply to the aortic wall was demonstrated by histology in four additional animals that were killed without removal of vasa vasorum (two animals) and immediately after vasa vasorum removal (two animals). At baseline, heart rate, aortic pressures, aortic diameters, and aortic distensibility were similar in the two groups. A significant decrease in aortic distensibility was observed 30 minutes and 15 days after removal of the vasa vasorum in the experimental group (baseline, 3.453±1.023; 30 minutes, 2.521±0.760; 15 days, 1.586±0.488 10
−6
· cm
2
· dyn
−1
; F=9.532,
P
<.001). No changes were observed in aortic distensibility in the control group during the experiment. Histology of the aorta revealed medial necrosis, alterations of the elastin fibers, and a trend (
P
=.055) for altered collagen-to-elastin ratio in a region occupying more than the one (outer) half of the media of the experimental group animals. No changes were observed in the control group.

Conclusions
The findings of the present study demonstrated that interruption of vasa vasorum flow led to an acute decrease in the distensibility of the ascending aorta. Moreover, structural changes of the aortic wall and further deterioration of the elastic properties of the aorta occurred 15 days after vasa vasorum removal.
Suppression of Ventricular Arrhythmias During Ischemia-Reperfusion by Agents Inhibiting Ins(1,4,5)P
3
Release
Authors: Du Xiao-Jun , Anderson Karen E. , Jacobsen Alexander , Woodcock Elizabeth A. , Dart Anthony M.
Published: June 2012

Background
Reperfusion following myocardial ischemia causes a rapid and transient release of inositol (1,4,5)triphosphate [Ins(1,4,5)P
3
]. The aim of this study was to test whether this increased Ins(1,4,5)P
3
release was important for the development of ventricular arrhythmias and whether agents that inhibit this signal transduction pathway, such as aminoglycoside antibiotics, suppress arrhythmias.

Methods and Results
In perfused rat hearts, ventricular tachycardia (VT), ventricular fibrillation (VF), and accumulation of Ins(1,4,5)P
3
were measured during early reperfusion. A number of different compounds, including neomycin, gentamicin, streptomycin, spermine, reserpine, and prazosin, were effective in inhibiting the reperfusion-induced Ins(1,4,5)P
3
release and the onset of VT and VF in parallel. A strong correlation existed between Ins(1,4,5)P
3
content, measured at 2 minutes of reperfusion, and the incidence of reperfusion VT and VF. In addition, intravenous gentamicin suppressed the onset of arrhythmias under ischemic and reperfusion conditions in vivo.

Conclusions
Our results are consistent with the view that Ins(1,4,5)P
3
release plays a pivotal role in mediating arrhythmias during early reperfusion. Agents inhibiting Ins(1,4,5)P
3
release are antiarrhythmic and may have potential use clinically.
Local Delivery of Vascular Endothelial Growth Factor Accelerates Reendothelialization and Attenuates Intimal Hyperplasia in Balloon-Injured Rat Carotid Artery
Authors: Asahara Takayuki , Bauters Christophe , Pastore Christopher , Kearney Marianne , Rossow Susan , Bunting Stuart , Ferrara Napoleone , Symes James F. , Isner Jeffrey M.
Published: June 2012

Background
Most strategies designed to reduce restenosis by the use of pharmacological or biological reagents involve direct inhibition of vascular smooth muscle cell (SMC) proliferation. Alternatively, SMC proliferation might be indirectly inhibited if reendothelialization could be specifically facilitated at sites of balloon-induced arterial injury. Accordingly, we investigated the hypothesis that application of an endothelial cell (EC)-specific mitogen to a freshly denuded intimal surface could accelerate reendothelialization and thereby attenuate intimal hyperplasia.

Methods and Results
The left carotid artery of 31 Sprague-Dawley rats was subjected to balloon injury, after which 16 rats were treated with a 30-minute incubation with 100 μg of vascular endothelial growth factor (VEGF), an EC-specific mitogen. Control animals (n=15) received a 30-minute incubation with 0.9% saline. At 2 weeks after balloon injury, carotid artery reendothelialization was markedly superior in the VEGF-treated group compared with the control group (14.59±1.12 versus 7.96±0.51 mm
2
,
P
<.0005). The extent of reendothelialization measured at 4 weeks after balloon injury remained superior for arteries treated with VEGF (18.04±0.90 mm
2
) versus saline (13.42±0.84 mm
2
,
P
<.005). Neointimal thickening was correspondingly attenuated to a statistically significant degree in arteries treated with VEGF versus the control group at both the 2-week and 4-week time points. Immunostaining for proliferating cell nuclear antigen (PCNA) disclosed a threefold increase in PCNA-positive cells in the neointima of control arteries versus VEGF-treated arteries at 2 weeks after injury.

Conclusions
Application of VEGF, an EC-specific growth regulatory molecule, may be effectively used in vivo to promote reendothelialization and thereby indirectly attenuate neointimal thickening due to SMC proliferation.
Characteristics of the β-Adrenergic Receptor Complex in the Epicardial Border Zone of the 5-Day Infarcted Canine Heart
Authors: Steinberg Susan F. , Zhang HongLu , Pak Elena , Pagnotta Geraldine , Boyden Penelope A.
Published: June 2012

Background
The effect of isoproterenol on increasing the peak amplitude of the L-type calcium current is reduced in myocytes dispersed from the epicardial border zone (EBZ) of the 5-day infarcted canine heart when compared with control cells from noninfarcted hearts. This suggests that specific alterations in the β-adrenergic receptor complex develop in this setting. The present study is an examination of individual components of the β-adrenergic receptor complex with the aim of elucidating the biochemical defect(s) that might be responsible for the diminished β-adrenergic receptor responsiveness in the myocytes that survive in the infarcted heart.

Methods and Results
We compared components of the β-adrenergic receptor signaling pathway in membranes prepared from the EBZ of the 5-day infarcted heart and a remote, noninfarcted region (RZ) of the same ventricle as well as the corresponding regions of noninfarcted ventricles. Defects in multiple components of the β-adrenergic receptor complex were confined to the EBZ of the 5-day infarcted heart. These include a decrease in β-adrenergic receptor density; diminished basal, guanine nucleotide–, isoproterenol-, forskolin-, and manganese-dependent adenylyl cyclase activities; an increase in the EC
50
for isoproterenol-dependent activation of adenylyl cyclase; a diminished level of the α-subunit of the G
s
protein; and an elevated level of the α-subunit of the G
i
protein.

Conclusions
Defects in multiple components of the membrane β-adrenergic receptor complex were identified in the EBZ of the 5-day infarcted canine heart. This constellation of abnormalities would be predicted to impair functional β-adrenergic responsiveness and contribute to the defect in isoproterenol-dependent stimulation of the L-type calcium current in myocytes isolated from this tissue.
Long-term Outcome of Women Compared With Men After Successful Coronary Angioplasty
Authors: Bell Malcolm R. , Grill Diane E. , Garratt Kirk N. , Berger Peter B. , Gersh Bernard J. , Holmes David R.
Published: June 2012

Background
Women who undergo coronary angioplasty have a higher in-hospital mortality than men, although much of this difference can be accounted for by their poorer clinical characteristics at the time of their procedures. However, whether or not there are important long-term differences in outcome between women and men after coronary angioplasty is not clear.

Methods and Results
A retrospective analysis was performed of 3027 consecutive patients (824 women and 2203 men) who underwent successful angioplasty and who have been followed continuously for a mean of 5.5 years (range, 0.5 to 14 years). Follow-up is 100% complete. Event-free survival was assessed by the Kaplan-Meier method, and clinical end points were also examined by Cox proportional-hazards models to account for important baseline differences when appropriate. There was a trend toward lower survival among women during follow-up, but this was not significant (
P
=.06). The relative risk of death among women compared with men after adjustment for baseline differences was 0.94 (CI, 0.76 to 1.15;
P
=NS). No significant sex differences in occurrence of Q-wave myocardial infarction were observed. Women were less likely to remain free of angina after 10 years (34% versus 37%, respectively;
P
=.008), but after adjustment for baseline differences, this difference was not significant (relative risk of angina, 1.07; CI, 0.95 to 1.21). Women tended to have less coronary artery bypass surgery performed during follow-up (
P
=.06); adjusting for baseline differences made this difference more significant (relative risk, 0.79; CI, 0.64 to 0.96;
P
=.02). Among patients who were not treated in the setting of acute infarction, no sex differences in survival and freedom from myocardial infarction were noted.

Conclusions
After successful coronary angioplasty, the long-term prognosis for women is excellent and is similar to that observed in men. Risk-adjusted survival did not differ significantly between the sexes, but less frequent use of subsequent surgical revascularization was observed in women.
Effect of Acute and Long-term Smoking on Myocardial Blood Flow and Flow Reserve
Authors: Czernin Johannes , Sun Karl , Brunken Richard , Böttcher Morten , Phelps Michael , Schelbert Heinrich
Published: June 2012

Background
Cigarette smoking is a major preventable risk factor for coronary artery disease and sudden cardiac death. However, the effect of acute and long-term cigarette smoking on coronary vasodilatory capacity and myocardial flow reserve has not been quantified in humans.

Methods and Results
To examine the effect of short-term and long-term smoking, myocardial blood flow was quantified at rest and during dipyridamole-induced hyperemia (0.56 mg/kg) in 12 smokers (10 males and 2 females; mean age, 27±4 years) under baseline conditions (reflecting the effect of long-term smoking) and during short-term cigarette smoking with
13
N ammonia, positron emission tomography, and a two-compartment model. Twelve sex- and age-matched nonsmokers served as control subjects. Smoking significantly increased the rate-pressure product at rest from 7525±1290 to 9160±1125 (
P
<.001 versus baseline), which was paralleled by a proportional increase in myocardial blood flow at rest (0.70±0.17 versus 0.88±0.17 mL · g
−1
· min
−1
;
P
<.05 versus baseline). In contrast, hyperemic blood flow declined from 2.23±0.35 at baseline (
P
=NS versus control) to 1.98±0.32 mL · g
−1
· min
−1
during smoking (
P
<.01 versus baseline). Accordingly, the myocardial flow reserve declined from 3.36±0.83 in smokers at baseline to only 2.28±0.28 during smoking (
P
<.0001 versus baseline). Thus, myocardial blood flow and flow reserve were similar in young, long-term smokers and young, healthy nonsmokers.

Conclusions
Short-term smoking increases the coronary vasomotor tone during dipyridamole-induced hyperemia and markedly reduces the myocardial flow reserve. In contrast, long-term smoking does not attenuate the coronary vasodilatory capacity in young individuals with a relatively short smoking history. It might be speculated that the short-term reduction in the coronary vasodilatory capacity during smoking could lower the ischemic threshold in smokers with coronary artery disease and contribute to the increased risk for sudden cardiac death.
Importance of Initial Coronary Artery Flow After Heart Procurement to Assess Heart Viability Before Transplantation
Authors: Ferrera René , Forrat Rémi , Marcsek Peter , de Lorgeril Michel , Dureau Georges
Published: June 2012

Background
The objective of this study was to evaluate different tests of heart viability in a pig model of warm ischemia.

Methods and Results
Pig hearts (n=30) were submitted to 0 (= group I), 10 (group II), 20 (group III), 30 (group IV), and 60 (group V) minutes of in situ warm ischemia (animal exsanguination). Hearts were removed, then flushed with cardioplegic solution for 3 minutes at a fixed pressure of 60 cm H
2
O, and edema formation, initial coronary flow, and ionic composition (Na
+
, K
+
, and Ca
++
) of coronary sinus effluent were evaluated. Hearts were then stored for 2 hours in a cold (4°C) preservation solution. Myocardial biopsies (and evaluation of energetic index) were performed, then the hearts were reperfused for 30 minutes with whole blood with an in vitro functional testing system. No edema occurred during cardioplegic flush in the hearts in groups I through IV, but a 37±11% weight increase (
P
<.001) occurred in hearts in group V. There was a progressive decrease in initial coronary flow with the increase in the duration of warm ischemia (70±14 mL/min per 100 g of tissue in group I and 52±9, 41±16, 25±11, and 23±5 mL/min per 100 g, respectively, in groups II through V (
P
<.01 to
P
<.001 versus group I). Initial coronary flow was positively correlated with the energetic index (
r
=.84,
P
<.001), and the left ventricle developed pressure at reperfusion (
r
=.90,
P
<.001). Finally, there were significant differences between hearts in the control group and those in group V for calcium and sodium release (lower in the control group;
P
<.001 and
P
<.01, respectively) and for potassium removal (lower in group V,
P
<.05).

Conclusions
These data suggest that early measurement of coronary flow after removal of the heart may help to assess heart viability before transplantation. This approach may provide a comprehensive clinical evaluation to increase the number of hearts available for transplantation among those that are rejected in the absence of accurate criteria of viability.
Comparison of Clinical and Angiographic Outcomes After Saphenous Vein Graft Angioplasty Using Coronary Versus ‘Biliary’ Tubular Slotted Stents
Authors: Wong S. Chiu , Popma Jeffrey J. , Pichard Augusto D. , Kent Kenneth M. , Satler Lowell F. , Mintz Gary S. , Chuang Ya Chien , Hong Mun K. , Ditrano Christine J. , Leon Martin B.
Published: June 2012

Background
Saphenous vein graft (SVG) angioplasty using 15-mm articulated, tubular slotted stents results in low (0% to 20%) residual diameter stenoses and infrequent (<5%) major complications. A “biliary” stent design with greater radial compressive strength, enhanced visibility, and more variable sizing (diameter and length) has been approved for noncoronary indications. A comparison of outcomes after coronary versus biliary stent placement in SVG stenoses has not been performed. The purpose of this study was to compare the angiographic and clinical results after SVG angioplasty using these two balloon-expandable, tubular slotted stent designs.

Methods and Results
During a 3-year period, 231 patients with 305 SVG lesions were treated using Palmaz-Schatz coronary (n=108) or biliary (n=123) stents. Cineangiograms were reviewed using qualitative morphological and quantitative angiographic methods. Time-dependent clinical outcome (freedom from death, Q-wave myocardial infarction, or the need for repeat coronary bypass surgery or SVG angioplasty) was assessed using Kaplan-Meier life-table methods. Unstable angina (
P
<.001) and recent myocardial infarction (
P
=.001) were present more often in patients undergoing biliary stent versus coronary stent placement. Biliary stent–treated SVG lesions were more frequently de novo (
P
=.001), ostial in location (
P
=.002), ≥10 mm in length (
P
=.009), thrombus containing (
P
=.001), and ulcerated (
P
<.001) than coronary stent–treated SVG lesions. Angiographically, biliary stent–treated lesions had larger reference vessel diameter (3.43±0.59 mm versus 3.10±0.64 mm,
P
<.001), higher balloon-to-artery ratio (1.15±0.16 mm versus 1.07±0.19,
P
=.0001), and lower residual diameter stenosis (6±17% versus 14±11% in coronary stent–treated patients;
P
<.001). Procedural success rates were high (95%), in-hospital major complications were uncommon (<3%), and follow-up clinical outcomes were favorable (6-month event-free survival ≈80%) in both groups.

Conclusions
Despite frequent short-term ischemic syndromes and unfavorable lesion characteristics, both biliary and coronary cohorts have similarly favorable short-term procedural results and long-term clinical outcomes. The increased strut thickness of the biliary stent confers greater fluoroscopic visibility and radial compressive strength in exchange for decreased stent flexibility and added technical demand in stent deployment. Extreme caution is recommended with biliary stent placement in the treatment of SVG lesions as clinical results are highly operator dependent.
PQ Segment Depression in Acute Q Wave Inferior Wall Myocardial Infarction
Authors: Nagahama Yo , Sugiura Tetsuro , Takehana Kazuya , Tarumi Noritaka , Iwasaka Toshiji , Inada Mitsuo
Published: June 2012

Background
PQ segment deviation is almost as characteristic as the classic ST segment deviation and is detected in most patients with pericarditis. However, as infarction-associated pericarditis remains over the infarct zone, PQ segment depression is observed much less often in patients with acute myocardial infarction.

Methods and Results
We designed this study to examine the clinical significance of PQ segment depression in acute Q wave inferior myocardial infarction. We examined 171 consecutive patients with acute Q wave inferior myocardial infarction by means of auscultation, ECG, and two-dimensional echocardiography. The diagnosis of pericarditis was made on the basis of pericardial rub detected by more than two observers during the first 3 days after admission. At least 0.5 mm of PQ segment depression from the TP segment lasting more than 24 hours in both limb and precordial leads was considered diagnostic of PQ segment depression.

Conclusions
PQ segment depression was present in 14 patients and absent in 157 patients. Eleven patients with and 55 patients without PQ segment depression had advanced asynergy (akinesis or dyskinesis) in the posterior segments, whereas 9 patients with and 20 patients without PQ segment depression had pericardial rub. When multivariate analysis was performed to determine the important variables related to the occurrence of PQ segment depression, pericardial rub was selected with advanced asynergy of the posterior segment as significant factors related to PQ segment depression. Major complications (ventricular fibrillation, sustained ventricular tachycardia, cardiogenic shock, need for pacing) were present in 63 patients; 9 with (64%) and 54 without (34%) PQ segment depression. PQ segment depression was one of the clinical signs of more extensive damage extending to the posterior segments and increased incidence of major complications.
Effect of Enalapril on Ventricular Remodeling and Function During Healing After Anterior Myocardial Infarction in the Dog
Authors: Jugdutt Bodh I. , Khan Mohammad I. , Jugdutt S. Joanne , Blinston Gordon E.
Published: June 2012

Background
Ventricular remodeling after myocardial infarction involves changes in ventricular size, shape, structure, and matrix that impact on function. Prolonged angiotensin-converting enzyme inhibition after infarction with captopril reduces ventricular enlargement and improves clinical outcome, but whether enalapril produces similar benefits is controversial.

Methods and Results
The effect of enalapril during healing between 1 day and 6 weeks after myocardial infarction on in vivo changes in ventricular size, shape, mass, and function (asynergy, or akinesis and dyskinesis, and ejection fraction), as determined by serial two-dimensional echocardiography, hemodynamics, postmortem topography (planimetered short- and long-axis ventricular contours), and collagen content (determined by levels of hydroxyproline, a marker for collagen), was measured in 25 instrumented dogs. The dogs were randomized 1 day after left anterior descending coronary artery ligation to a control group (no treatment) and a group receiving oral enalapril (2.5 mg BID). Compared with no treatment, enalapril produced a sustained lowering of left atrial pressure but no difference in heart rate and mean blood pressure over the 6 weeks. Also compared with no treatment, enalapril modified in vivo remodeling parameters between 1 day and 6 weeks, with less elongation of the asynergy-containing segment, a lower expansion index (ratio of endocardial lengths of infarct to non–infarct-containing segments demarcated by papillary muscle landmarks), less scar wall thinning, a lower thinning ratio (ratio of average thickness of infarcted wall to average thickness of the normal wall), smaller ventricular volume, less regional bulging and aneurysm frequency, prevention of the increase in ventricular mass, less total extent of asynergy, and higher volume ejection fraction. At postmortem examination, scar mass was similar in the two groups, but topographic maps with enalapril revealed less infarct bulging, flatter infarct scars, and less noninfarct wall thickness. In addition, postmortem collagen content was similar in noninfarct zones of the two groups but lower in infarct zones of the dogs given enalapril.

Conclusions
Prolonged enalapril therapy, in a dose that did not lower blood pressure, during healing after anterior infarction produced prolonged reduction of left ventricular preload in dogs. This diastolic unloading was associated with limitation of remodeling parameters (infarct expansion and thinning, progressive ventricular dilation and hypertrophy, and regional bulging), less total asynergy, and improved left ventricular ejection fraction. Although angiotensin-converting enzyme inhibition was associated with lower collagen content in the infarct area and altered scar topography, these effects did not impact negatively on overall remodeling and function.
Current Spectrum of Cardiogenic Shock and Effect of Early Revascularization on Mortality
Authors: Hochman Judith S. , Boland Jean , Sleeper Lynn A. , Porway Mark , Brinker Jeffrey , Col Jacques , Jacobs Alice , Slater James , Miller David , Wasserman Hal , Menegus Mark A. , Talley J. David , McKinlay Sonja , Sanborn Timothy , LeJemtel Thierry
Published: June 2012

Background
Cardiogenic shock remains the leading cause of death of patients hospitalized with acute myocardial infarction (MI). This study was conducted to examine (1) the current spectrum of cardiogenic shock, (2) the proportion of patients who are potential candidates for a trial of early revascularization, and (3) the apparent impact of early revascularization on mortality.

Methods and Results
Nineteen participating centers in the United States and Belgium prospectively registered all patients diagnosed with cardiogenic shock. Two hundred fifty-one patients were registered. The mean age was 67.5±11.7 years, and 43% were women. Acute mitral regurgitation or ventricular septal rupture was the cause of shock in 8%. Concurrent conditions contributing to the development of shock were noted in 5%, and 2% had isolated right ventricular shock. Among the remaining 214 patients, nonspecific findings on the ECG associated with “nontransmural” MI were seen in 14%. The median time to shock diagnosis after MI was 8 hours. The overall in-hospital mortality was 66%. Patients clinically selected to undergo cardiac catheterization were significantly younger and had a lower mortality than those not selected (51% versus 85%,
P
<.0001) even if they were not revascularized (58%). Mortality for patients undergoing percutaneous transluminal coronary angioplasty (PTCA) was 60% (n=55) and 19% (n=16) for coronary artery bypass graft surgery (CABG). Sixty percent (n=150) of registered patients were judged eligible for a trial of early revascularization. Trial-eligible patients were significantly younger (65.4±11.0 versus 70.6±11.9 years,
P
<.001), had an earlier median time to shock onset after MI (6.5 versus 17.5 hours,
P
=.003), and had lower mortality (62% versus 73%,
P
=.077) than ineligible patients.

Conclusions
Patients diagnosed with cardiogenic shock complicating acute MI are a heterogeneous group. Those eligible for a trial of early revascularization tended to have lower mortality. Patients selected to undergo cardiac catheterization had lower mortality whether or not they were revascularized. Emergent PTCA and CABG are promising treatment modalities for cardiogenic shock, but biased case selection for treatment may confound the data. Whether PTCA and CABG reduce mortality and which patient subgroups benefit most remain to be determined in a randomized clinical trial.
Hyperdynamic Circulation and Cardiovascular Risk in Children and Adolescents
Authors: Jiang Xiaozhang , Srinivasan Sathanur R. , Urbina Elaine , Berenson Gerald S.
Published: June 2012

Background
Hyperdynamic circulation has been reported to be associated with adverse levels of insulin, blood pressure, adiposity, and lipoproteins in the adult population. Whether this putatively insulin-mediated association also occurs in early life is not known. This aspect was examined in 2229 children and adolescents 8 to 17 years old living in Bogalusa, La.

Methods and Results
Individuals were categorized as hyperdynamic (pulse pressure and heart rate in the upper quartile of the race-sex-age distribution), intermediate, and hypodynamic (pulse pressure and heart rate in the bottom quartile). Systolic blood pressure was significantly greater with a hyperdynamic circulation in both sexes (
P
<.0001), and several measures of obesity were greater with a hyperdynamic circulation. Hyperdynamic circulation was associated with statistically significant increases in triglyceride (
P
<.05) and fasting insulin (
P
<.01) in boys independently of age, race, and obesity. A decreasing trend with HDL cholesterol (
P
=.06) was also observed in boys. A significant association with total cholesterol (
P
<.05) was observed only in girls. In the analysis stratified by percent body fat, many of these features still occurred in obese individuals (top quartile) but not in lean individuals (bottom quartile). Further, when a subset of this cohort (n=1074) was followed over a 3-year period, the above trend persisted significantly in boys.

Conclusions
The present study demonstrates that a hyperdynamic state as defined is associated with increased insulin levels and an adverse cardiovascular risk in early life.
A Novel Variant of Transthyretin, 59
Thr→Lys
, Associated With Autosomal Dominant Cardiac Amyloidosis in an Italian Family
Authors: Booth D. R. , Tan S. Y. , Hawkins P. N. , Pepys M. B. , Frustaci A.
Published: June 2012

Background
Amyloidosis is a disorder of protein metabolism characterized by extracellular accumulation of abnormal protein fibrils. Different proteins form the fibrils in different forms of the disease, and the condition can be acquired or hereditary. Involvement of the heart is quite common, producing a serious and usually fatal cardiomyopathy. Cardiac amyloidosis is often diagnosed late, and cardiac biopsy together with proper histological examination is essential. Contrary to previous perceptions, there is much recent evidence of effective treatment for several different types of systemic and cardiac amyloidosis, including the most common hereditary form caused by mutations in the transthyretin gene. Chemical and genetic typing of amyloid is therefore of considerable clinical importance.

Methods and Results
Seven members in two generations of an Italian family presented with cardiac disease inherited as an autosomal dominant and were found to have systemic amyloidosis. Angina pectoris–like pain, an unusual feature in cardiac amyloidosis, was a prominent symptom, possibly related to partial obliteration of the distal coronary arteries by amyloid infiltration. There were also cases of sudden cardiac death. Peripheral and autonomic neuropathy, which are the usual features of hereditary amyloidosis, were present in only two cases, and a diagnosis of acquired, immunoglobulin light chain (AL type) amyloidosis was suspected in the index case before the family history emerged. In fact, the amyloid fibrils were composed of transthyretin, and the two affected individuals from whom DNA was available were both heterozygotes for a single base change in exon 3 of the transthyretin gene, encoding substitution of Lys for the wild-type Thr residue at position 59 in the mature protein. This mutation has not previously been reported.

Conclusions
We have identified a novel mutation in the transthyretin gene encoding 59
Thr→Lys
associated with autosomal dominant hereditary systemic amyloidosis in an Italian kindred in whom cardiac involvement was the major feature. This family illustrates the difficulty in diagnosis of cardiac amyloid, the variable clinical phenotype in hereditary amyloidosis even within a family, and the importance of precise fibril typing for correct management in this condition.
Elevated Serum Lipoprotein(a) Is a Risk Factor for Clinical Recurrence After Coronary Balloon Angioplasty
Authors: Desmarais Rene L. , Sarembock Ian J. , Ayers Carlos R. , Vernon Sarah M. , Powers Eric R. , Gimple Lawrence W.
Published: June 2012

Background
Elevated lipoprotein (Lp) (a) concentrations are associated with coronary artery disease and myocardial infarction. Lp(a) is structurally related to proteins involved in lipid transport, fibrinolysis, coagulation, and cellular mitogenesis and is known to have important physiological interactions with the coagulation and fibrinolytic systems. Because these processes may be important to arterial healing after balloon injury, we hypothesized that elevated Lp(a) concentrations may be associated with recurrence of symptoms and restenosis after balloon angioplasty.

Methods and Results
We assessed 240 consecutive patients undergoing coronary balloon angioplasty with measurements of Lp(a), total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein A-I, and apolipoprotein B-100 concentrations from fresh specimens. Patients were evaluated 4 to 6 months after angioplasty for clinical recurrence by repeat angiography if angina had returned or by maximal exercise treadmill testing with thallium imaging if patients remained asymptomatic. Ninety-seven patients (40%) had clinical recurrence; 143 (60%) did not. Patients with recurrence had significantly greater Lp(a) concentrations compared with those without (median, 29 versus 14;
P
<.0001). Each patient quintile stratified by increasing Lp(a) concentrations had incrementally greater recurrence rates ranging from 27% (lowest quintile) to 60% (highest quintile). By multivariate logistic regression analysis, Lp(a) concentration was the only predictor of recurrence (
P
<.0001). A subset of frozen, stored serum samples showed a significant decrease in measured Lp(a) concentration over time (mean, 605 days;
P
<.01).

Conclusions
An elevated Lp(a) concentration was a risk factor for clinical recurrence after percutaneous transluminal balloon coronary angioplasty. Other lipid levels or clinical characteristics were not significantly associated with recurrence. When serum was frozen and stored for a prolonged period, Lp(a) concentration decreased over time.
Inhibition of Nitric Oxide Synthesis Reduces Infarct Size by an Adenosine-Dependent Mechanism
Authors: Woolfson Robin G. , Patel Vanlata C. , Neild Guy H. , Yellon Derek M.
Published: June 2012

Background
Nitric oxide (NO) is both a potent endogenous vasodilator with potential to attenuate ischemia-reperfusion injury and a mediator of tissue injury. The aim of the present study was to investigate the mechanism by which prior inhibition of NO synthesis can lessen ischemia-reperfusion injury in the isolated rabbit heart.

Methods and Results
We examined the effects of inhibition of NO synthesis on infarct size using a model of coronary artery ligation in isolated rabbit hearts perfused at a constant flow rate of 35 mL/min. Infarct size averaged 65% of the zone at risk after 45 minutes of ischemia and 180 minutes of reperfusion. The addition of 30 μmol/L
N
G
-nitro-
l
-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, to the perfusate reduced the infarct-to-risk (I/R) ratio to an average of 41% (
P
<.05 versus control). This effect was abolished by pretreatment with 75.5 μmol/L 8-
p
-sulfophenyl theophylline (SPT), an adenosine receptor antagonist (I/R ratio, 63%). Ischemic preconditioning (5 minutes of ischemia and 10 minutes of reperfusion) before 45 minutes of ischemia and 3 hours of reperfusion reduced the I/R ratio to an average of 21%, and this was not augmented by pretreatment with L-NAME (I/R ratio, 20%). However, all protection due to preconditioning and L-NAME was lost in hearts pretreated with SPT (I/R ratio, 59%). In a separate set of experiments, adenosine concentration in the coronary perfusate and myocardial lactate concentrations were measured. Treatment with L-NAME increased the average adenosine concentration in the perfusate from 5.7 μmol/L per 100 g of heart (control) to a peak of 24.0 μmol/L per 100 g of heart; however, there was no effect on average myocardial lactate concentration (control, 4.6 μmol/g dry wt; L-NAME, 5.5 μmol/g dry wt). In contrast, after 5 minutes of global ischemia, the average adenosine concentration peaked at 139.0 μmol/L per 100 g of heart, and the average myocardial lactate concentration increased to 27.1 μmol/g dry wt.

Conclusions
Infarct size limitation after inhibition of NO synthesis shares a common mechanism with that of ischemic preconditioning and is dependent on the release of adenosine. However, in this model, adenosine release after inhibition of NO synthesis is not secondary to myocardial ischemia. The protection of the heart against ischemic injury by adenosine appears to be concentration dependent.
Angiotensin-Converting Enzyme Genotype in Children and Coronary Events in Their Grandparents
Authors: Badenhop Renee F. , Wang Xing Li , Wilcken David E.L.
Published: June 2012

Background
It has been suggested that the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene is an independent risk factor for coronary artery disease. The D/D genotype, which is associated with higher levels of circulating ACE than the I/D or I/I genotype, has been found significantly more frequently in patients with myocardial infarction and also in individuals with a parental history of myocardial infarction.

Methods and Results
We explored the distribution of the ACE genotype in 404 school children, aged 6 to 13 years, and related the distribution to the number of their grandparents who had had vascular events. We found a significant association between the number of grandparents who had had coronary events and the ACE genotype (
P
=.01). In children with two or more grandparents who had had coronary events, there was an excess of both D/D (odds ratio=2.8 [95% confidence interval=1.16-6.56]) and I/D (odds ratio=1.4 [95% confidence interval=0.62-3.25]) genotypes compared with I/I genotypes. In addition, there was an association between the ACE genotype and lipoprotein(a) levels in children (
P
=.07). Both the ACE genotype and lipoprotein(a) were found to contribute significantly (
P
=.0042) and independently to family history of coronary artery disease, with the ACE genotype proving to be more predictive than lipoprotein(a) levels.

Conclusions
We conclude that the I/D polymorphism of the ACE gene is an important independent risk factor for coronary artery disease and is more predictive that lipoprotein(a). The I/D polymorphism is not only associated with a parental history of myocardial infarction but also with coronary artery disease in second-degree relatives. A further study to explore the relation between the I/D polymorphism and circulating levels of lipoprotein(a) is indicated.
Long-term Effects of Angiopeptin Treatment in Coronary Angioplasty
Authors: Emanuelsson Håkan , Beatt Kevin J. , Bagger Jens-Peder , Balcon Raphael , Heikkilä Juhani , Piessens Jan , Schaeffer Marc , Suryapranata Harry , Foegh Marie , Group for the European Angiopeptin Study
Published: June 2012

Background
Angiopeptin is a cyclic octapeptide analogue of somatostatin that has been shown to limit myointimal thickening of arteries in balloon injury models and to restore the vasodilating response to acetylcholine. A randomized, double-blind placebo controlled trial was conducted to assess the effect of angiopeptin in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA).

Methods and Results
Patients received a continuous infusion of either placebo or angiopeptin subcutaneously 6 to 24 hours before PTCA and for 4 days after PTCA (3 mg per 24 hours before PTCA followed by 6 mg per 24 hours after PTCA and for the remaining period). A 1.5-mg bolus dose of placebo or angiopeptin was given at PTCA. Aspirin (acetylsalicylic acid, 150 mg/d) was administered throughout the study period. Coronary angiograms obtained before and after PTCA and at 6-month follow-up were subjected to computerized quantification. Clinical follow-up was performed after 12 months. Primary clinical end points were death, myocardial infarction, coronary artery bypass surgery, or repeat PTCA. In total, 553 patients with 742 lesions were randomized. Clinical follow-up was available for all 553 patients. Angiopeptin decreased the clinical events during 12 months of follow-up from 36.4% in the placebo-treated group to 28.4% in the angiopeptin-treated patients (
P
=.046). Quantitative angiography after PTCA and at follow-up was available in 423 of 455 patients who underwent successful PTCA. The minimal lumen diameter at follow-up was 1.52±0.64 mm in the angiopeptin-treated group compared with 1.52±0.64 mm in the placebo-treated patients (
P
=.96). The late losses were 0.31±0.59 and 0.30±0.62 mm (
P
=.81) and the restenosis rates (>50% diameter stenosis at follow-up) were 36% and 37% (
P
=.85) in the angiopeptin- and placebo-treated groups, respectively.

Conclusions
In this study, angiopeptin significantly decreased the incidence of clinical events, principally the rate of revascularization procedures. In contrast, no significant effect was seen on angiographic variables.
Papillary Muscle Perfusion Pattern
Authors: Voci Paolo , Bilotta Federico , Caretta Quintilio , Mercanti Corrado , Marino Benedetto
Published: June 2012

Background
The pathogenesis of posterior papillary muscle dysfunction is poorly understood. We hypothesized that papillary muscle perfusion pattern may explain the higher prevalence of posterior papillary muscle dysfunction after myocardial infarction.

Methods and Results
Twenty patients were monitored by transesophageal echocardiography during coronary surgery. Superselective coronary graft injections of 0.2 to 0.5 mL of sonicated albumin microbubbles were performed to assess graft patency and papillary muscle perfusion. Thirty-five graft injections were analyzed: 13 in the right coronary artery, 15 in an obtuse marginal branch, 1 in the left anterior descending coronary artery, and 6 in the first diagonal branch. The posterior papillary muscle was opacified in 16 patients, 11 from the right coronary artery and 5 from one obtuse marginal branch. In 10 of 16 patients (63%), the papillary muscle was perfused by one vessel, while in 6 of 16 (37%), it was perfused by two vessels. The anterior papillary muscle was opacified in 14 patients. Ten patients (71%) had double-vessel and 4 (29%) had single-vessel supply. In the subgroup of 10 patients with old inferior myocardial infarction, mitral regurgitation was present only among those 6 with single rather than double blood supply (
P
<.05).

Conclusions
Myocardial infarction may cause papillary muscle dysfunction when the blood supply is provided by one rather than two vessels, as is more frequently the case with the posterior rather than the anterior papillary muscle.