bluuebunny/crossref_metadata_2025 huggingface dataset:
Pretransplant Risk Factors and Causes of Death or Graft Loss After Heart Transplantation During Early Infancy
Authors: Chinnock Richard E. , Larsen Ranae L. , Emery Janet R. , Bailey Leonard L.
Published: June 2012

Background
This study was performed to report causes of death or graft loss and to identify possible pretransplant risk factors for death or graft loss in infants after heart transplantation.

Methods and Results
Pretransplant risk factors were compared for 153 infants registered for heart transplantation within 90 days of life and transplanted from November 1985 to June 1994. Factors assessed were diagnosis, age at transplantation, race, weight, blood type, sex, donor/recipient blood type match, sex match, weight ratio, fetal registration, locale of pretransplant waiting period, mechanical ventilation, ischemic time, and the need for atrial septostomy or septectomy pretransplantation. No factor was associated with death or graft loss at 1 month or 1 year. Causes of death or graft loss were determined using clinical course and pathology data when available. Death or grafts lost at 1 month, 1 year, and >1 year were 14, 13, and 15, respectively. Causes of death or graft loss expressed as a percent (at 1 month, 1 year, and >1 year, respectively) were acute rejection (14, 23, 27), chronic rejection and posttransplant coronary disease (0, 8, 47), infectious causes (21, 15, 13), early graft failure (21, 0, 0), technical issues (21, 23, 0), chronic graft dysfunction (0, 15, 0), and miscellaneous (21, 15, 13). The graft loss rate at 1 year was significantly correlated (linear regression,
r
2
=.66;
P
<.05) with the year of transplantation. Actuarial survival in this population was 91% at 1 month, 81% at 1 year, and 73% at 3 years.

Conclusions
Heart transplantation in the young infant can be performed with acceptable short-term and midterm results. Causes of death or graft loss and survival are similar to adult data. No pretransplant risk factors were identified. The experience level of the transplant team members affects survival. The diagnosis and management of rejection remain a major challenge.
Peak Oxygen Consumption and Resting Left Ventricular Ejection Fraction Changes After Cardiomyoplasty at 6-Month Follow-up
Authors: Bocchi Edimar Alcides , Guimarães Guilherme Veiga , Moreira Luiz Felipe P. , Bacal Fernando , de Moraes Alvaro Vilela , Barreto Antonio Carlos Pereira , Wajngarten Mauricio , Bellotti Giovanni , Stolf Noedir , Jatene Adib , Pileggi Fulvio
Published: June 2012

Background
The effects of cardiomyoplasty on cardiopulmonary exercise test characteristics are not fully known.

Methods and Results
We determined in 19 patients who underwent cardiomyoplasty for treatment of refractory heart failure (New York Heart Association [NYHA] functional class III) before (pre) and at 6-month follow-up (post) maximum oxygen consumption (peak V̇
o
2
), NYHA functional class, and resting left ventricular ejection fraction (LVEF) (MUGA). We analyzed the results according to pre peak V̇
o
2
< or >14 mL/kg per minute and the correlation between the changes in absolute values of LVEF and peak V̇
o
2
. Pre– and post–peak V̇
o
2
values were 15.9±4.4 and 18.6±6.4 mL/kg per minute, respectively (
P
=.059). In the subgroup with pre–peak V̇
o
2
<14 mL/kg per minute, the peak V̇
o
2
increased from 11.1±1.9 to 16.4±6.2 mL/kg per minute (
P
=.02). The subgroup with peak V̇
o
2
>14 mL/kg per minute showed pre– and post–peak V̇
o
2
of 19.2±2.6 and of 20.1±7 mL/kg per minute, respectively (
P
=.06). The pre–total exercise time of the entire group increased from 688.4±222.1 to 833.7±241.6 seconds (
P
<.04). For the subgroup with preoperative peak V̇
o
2
<14 mL/kg per minute, exercise time improved from 585±76.9 to 825±186.3 seconds (
P
<.01). In the subgroup with preoperative V̇
o
2
>14 mL/kg per minute, the preexercise and postexercise time was 763.6±264.4 and 840±282 seconds, respectively (
P
=.4). Pre- LVEF increased from 20.6±3.3% to 24.2±7.8% at 6 months of follow-up (
P
=.02). At 6 months of follow-up, 9 patients were in NYHA functional class I and 10 were in class II. There was no correlation between LVEF values and absolute values of peak V̇
o
2
before (
r
=.123,
P
=.6) and after (
r
=.27,
P
=.2) cardiomyoplasty. A weak correlation was observed between the changes in absolute values of peak V̇
o
2
and LVEF from the preoperative to the postoperative period (
r
=.48,
P
=.048).

Conclusions
Cardiomyoplasty is a useful method for improving NYHA functional class and LVEF in patients with heart failure. Peak V̇
o
2
<14 mL/kg per minute before cardiomyoplasty may be a selection criterion with which to determine improved exercise capacity after surgery. The effects of cardiomyoplasty on LVEF appear to be partially associated with maximum exercise capacity changes.
Discriminating Between Preservation and Reperfusion Injury in Human Cardiac Allografts Using Heart Weight and Left Ventricular Mass
Authors: Slater James P. , Amirhamzeh Mehrdad M.R. , Yano Osvaldo J. , Shah Aamir S. , Starr Joanne P. , Kaplon Richard J. , Burfeind William , Pepino Paolo , Michler Robert E. , Rose Eric A. , Smith Craig R. , Spotnitz Henry M. , Oz Mehmet C.
Published: June 2012

Background
Myocardial edema caused by injury during preservation or reperfusion can affect cardiac function after heart transplantation. This study was designed to distinguish these forms of injury in human allografts.

Methods and Results
In 15 donor hearts preserved in University of Wisconsin solution, heart weight (HW) was obtained immediately after explantation and after transport before implantation. Left ventricular mass (LVM) was calculated separately in 18 patients with the use of epicardial two-dimensional echocardiograms obtained both before explantation from the donor and after transplantation and weaning from cardiopulmonary bypass. While changes in LVM could be due to preservation or reperfusion injury, changes in HW can only be due to edema occurring during transport. HW averaged 339±24 g (mean±SE) before and 340±24 g after transport (
P
=NS); however, LVM increased 14 g, from 164±8 to 178±11 g (
P
<.05, paired
t
test). LVM increased in 10 of 18 patients (56%). No correlation was demonstrated between duration of ischemia (mean, 172±13 minutes) and changes in HW or LVM. Two patients died as a result of primary graft failure. In the first, HW increased 54 g, 2 SD above the mean. In the second, LVM increased 66 g, 2 SD above the mean, but HW changed minimally.

Conclusions
While current preservation methods result in minimal change in HW during transport, reperfusion injury frequently increases LVM. LVM determination by two-dimensional echocardiography may prove valuable in detecting allograft injury.
Transient Myocardial Contrast After Initial Exposure to Diagnostic Ultrasound Pressures With Minute Doses of Intravenously Injected Microbubbles
Authors: Porter Thomas R. , Xie Feng
Published: June 2012

Background
We have observed a transient but significant increase in myocardial contrast intensity with intravenously injected perfluorocarbon-exposed sonicated dextrose albumin (PESDA) microbubbles that occurs on initial exposure to pulsed ultrasound (transient-response imaging). The characteristics and magnitude of this response were examined in the present study.

Methods and Results
In 14 dogs, the myocardial contrast intensity produced by transient-response imaging (TRI) was compared with conventional 30-Hz imaging (CI) after a 0.005 to 0.030 mL/kg intravenous injection of PESDA. TRI was produced either by measuring myocardial contrast during triggered (1 pulse per cardiac cycle) ultrasound or by withholding real time ultrasound transmission until after microbubbles had entered the myocardium after intravenous injection. Both first-harmonic imaging (2.0 to 3.5 MHz) and second-harmonic imaging (2.0 to 2.5 MHz fundamental, 4.0 to 5.0 MHz received) were used. TRI produced over three times the anterior myocardial contrast intensity of CI (36±12 U TRI versus 11±11 U CI;
P
<.01), with visually better anterior and posterior myocardial contrast. The spatial extent of myocardial ischemia was easily visualized after intravenous PESDA by use of TRI and correlated closely with risk area as measured with Monastral blue (
r
=.99,
P
=.002).

Conclusions
TRI produces significantly greater myocardial contrast than CI and may dramatically enhance the ability of intravenous ultrasound contrast agents to identify myocardial perfusion abnormalities.
Blood Pressure and Mortality Among Men With Prior Myocardial Infarction
Authors: Flack John M. , Neaton James , Grimm Richard , Shih Joanna , Cutler Jeffrey , Ensrud Kristine , MacMahon Stephen
Published: June 2012

Background
The purpose of the present study was to describe the relation between blood pressure (systolic [SBP] and diastolic [DBP]) and death from coronary heart disease (CHD) and all causes for men with a history of myocardial infarction (MI).

Methods and Results
The study cohort consisted of men aged 35 to 57 years screened for the Multiple Risk Factor Intervention Trial (MRFIT) in 1973 through 1975 and followed for survival for an average of 16 years through 1990. There were 5362 men who reported prior hospitalization for a heart attack of at least 2 weeks’ duration at the initial screening of MRFIT. There was a J-shaped relation between SBP and DBP with both CHD and all-cause mortality during the first 2 years of follow-up in older (age, 45 to 57 years) men only. Risk nadirs for SBP were 152 and 145 mm Hg, respectively, for CHD death and all-cause mortality; corresponding DBP risk nadirs were 94 and 90 mm Hg. After the first 2 years, there was a positive association between SBP and death from CHD and all causes. By 15 years, cumulative CHD mortality percentages for men with screening SBP <120, 120 to 139, 140 to 159, and ≥160 mm Hg were 19.7%, 21.3%, 27.5%, and 32.0%, respectively. When deaths only after year 2 were considered, although the linear DBP coefficient was significant, the quadratic term for DBP was no longer significant (
P
>.05). However, the relation still appeared J-shaped as cumulative mortality for those with DBP <70, 70 to 79, 80 to 89, 90 to 99, and ≥100 mm Hg was 24.3%, 20.8%, 21.1%, 25.5%, and 29.7%, respectively. When the joint relation of SBP and DBP was considered, there were no survival differences among the four cohorts (SBP ≥140 and DBP <80, SBP ≥140 and DBP ≥80, SBP ≤140 and DBP <80, and SBP ≤140 and DBP ≥80) during the first 2 years. After 2 years, both CHD and all-cause mortality rates were approximately 40% higher for participants with SBP ≥140 mm Hg versus <140 mm Hg regardless of DBP level (<80 or ≥80 mm Hg).

Conclusions
In this large cohort of men with prior MI, the association of SBP and DBP with CHD and all-cause mortality varied over the 16-year follow-up period. During early follow-up, in older men only, J- or U-shaped relations were evident. However, after 2 years, these same relations had become positive and graded. Given the substantial excess mortality risk in this cohort associated with high blood pressure, particularly SBP, efforts to gradually lower blood pressure should receive high priority among hypertensive men with prior MI.
Relation of Coronary Angioscopic Findings at Coronary Angioplasty to Angiographic Restenosis
Authors: Bauters Christophe , Lablanche Jean-Marc , McFadden Eugène P. , Hamon Martial , Bertrand Michel E.
Published: June 2012

Background
Discordant results have been reported regarding morphological predictors of restenosis after percutaneous transluminal coronary angioplasty (PTCA). These discrepancies may be related to the limitations of angiography in the study of plaque morphology.

Methods and Results
We studied 117 consecutive patients who underwent successful PTCA and who underwent coronary angioscopy before and immediately after the procedure. Angiographic follow-up was performed in 99 (85%) patients. We analyzed the relationship between angioscopic variables at the time of PTCA and the occurrence of restenosis assessed by quantitative coronary angiography. Plaque shape and color had no effect on late loss in luminal diameter (late loss: smooth lesions, 0.55±0.68 mm; complex lesions, 0.76±0.60 mm; white plaques, 0.51±0.56 mm; yellow plaques, 0.65±0.72 mm;
P
=NS). An angioscopic protruding thrombus at the PTCA site was associated with significantly greater loss in luminal diameter (late loss: no thrombus, 0.47±0.54 mm; lining thrombus, 0.59±0.67 mm; protruding thrombus, 1.07±0.77 mm;
P
<.05). Dissection assessed by angioscopy immediately after PTCA had no effect on late loss in luminal diameter (late loss: no dissection, 0.60±0.60 mm; simple dissection, 0.82±0.75 mm; complex dissection, 0.57±0.80 mm;
P
=NS).

Conclusions
These results show that coronary angioscopy may be helpful in predicting the risk of restenosis after PTCA. The high rate of angiographic recurrence observed when PTCA is performed at thrombus-containing lesions supports a role for thrombus in the process of luminal renarrowing after PTCA.
Activation of Blood Coagulation After Cardiac Arrest Is Not Balanced Adequately by Activation of Endogenous Fibrinolysis
Authors: Böttiger Bernd W. , Motsch Johann , Böhrer Hubert , Böker Thomas , Aulmann Michael , Nawroth Peter P. , Martin Eike
Published: June 2012

Background
Animal studies have demonstrated that hemostatic disorders occurring after cardiac arrest affect outcome. We investigated hemostatic changes during and after cardiopulmonary resuscitation (CPR) in humans.

Methods and Results
The prospective study included 23 patients (29 to 86 years) who underwent out-of-hospital CPR for nontraumatic causes. Blood samples were drawn immediately and 15 and 30 minutes after initiation of CPR. In the case of restoration of spontaneous circulation (ROSC; n=7), additional blood samples were taken immediately, 30 minutes, and 2, 8, 24, 48, and 72 hours after ROSC. A marked activation of blood coagulation was found in all patients. The specific markers of activated blood coagulation and fibrin formation, thrombin-antithrombin complex (TAT; median during CPR, 260 μg/L; median after ROSC, 57 μg/L; normal range, 1.0 to 4.1 μg/L), and fibrin monomers (FM; median during CPR, 34.3 μg/mL; median after ROSC, 65.4 μg/mL; normal range, 0 to 3.6 μg/mL) were markedly increased during and in the early phase after CPR. When patients survived for 48 hours, TAT and FM values returned to the normal range. In most patients, the plasma levels of
d
-dimer, an indicator of endogenous fibrinolytic activity, were not markedly increased during CPR (median, <0.25 μg/mL; normal range, <0.25 μg/mL) but increased moderately after ROSC (median, 0.56 μg/mL). Levels of plasminogen activator inhibitor type 1 (normal range, 0.3 to 3.5 U/mL), a marker for endogenous inhibition of fibrinolytic activity, were moderately increased in most patients (median during CPR, 4.22 U/mL; median after ROSC, 8.08 U/mL).

Conclusions
Our data clearly demonstrate that there is a marked activation of blood coagulation and fibrin formation after prolonged cardiac arrest and CPR in humans that is not balanced adequately by concomitant activation of endogenous fibrinolysis. These changes may contribute to reperfusion disorders, such as the cerebral “no-reflow” phenomenon, by inducing fibrin deposition and formation of microthrombi.
Timing of Magnesium Therapy Affects Experimental Infarct Size
Authors: Herzog William R. , Schlossberg Matthew L. , MacMurdy Karen S. , Edenbaum Lisa R. , Gerber Matthew J. , Vogel Robert A. , Serebruany Victor L.
Published: June 2012

Background
Controversy exists regarding the use of magnesium in the treatment of acute myocardial infarction (AMI) because of apparent conflicting results from clinical trials. One hypothesis to explain the various clinical observations proposes that the timing of magnesium administration significantly influences its therapeutic effect; ie, supraphysiological levels of Mg
2+
must be present at the time of reperfusion for magnesium to produce clinical benefit.

Methods and Results
These experiments evaluated the effect of varying the timing of magnesium administration during AMI. Female Yorkshire swine (34 to 42 kg) underwent thoracotomy and 50 minutes of left anterior descending coronary artery (LAD) occlusion, followed by 3 hours of reperfusion. In the first group, MgSO
4
(250 mg of magnesium diluted in 60 cm
3
saline) was infused into the LAD over 12 minutes, beginning immediately with the onset of reperfusion (n=6, Mg-early group). In the second group, MgSO
4
was given after 1 hour of reperfusion (n=6, Mg-late group). Six pigs received saline instead of magnesium and served as the control group. Lethal arrhythmias were significantly reduced in the Mg-early group. Infarct size was determined by vital staining. Infarct size was 0.16±0.05 g/kg body wt (Mg-early), 0.35±0.08 g/kg (Mg-late), and 0.42±0.04 g/kg for the control group. Compared with the control group, significant (
P
=.029) reduction in infarct size occurred in the Mg-early group but not in the Mg-late group.

Conclusions
We conclude that intracoronary MgSO
4
delivered during reperfusion can significantly diminish infarct size in swine, but the timing of administration is critical.
Postextrasystolic Mechanical Restitution in Closed-Chest Dogs
Authors: Prabhu Sumanth D. , Freeman Gregory L.
Published: June 2012

Background
Postextrasystolic mechanical restitution (MR
PES
) is thought to be an expression of intracellular Ca
2+
handling by cardiac sarcoplasmic reticulum (SR). Since congestive heart failure is characterized by abnormal intracellular Ca
2+
homeostasis, we sought to delineate MR
PES
behavior before and after the production of heart failure to obtain insights into the relation between altered mechanical performance and Ca
2+
handling.

Methods and Results
Ten dogs instrumented with left ventricular (LV) micromanometers and piezoelectric dimension crystals were studied under control conditions; 6 dogs also were studied after tachycardia heart failure (THF) produced by rapid LV pacing for 4 weeks. After priming at a basic cycle length of 375 ms, test pulses were delivered at fixed extrasystolic intervals (ESIs; 300, 375, or 450 ms) and graded postextrasystolic intervals (PESIs). Postextrasystolic mechanical response was assessed using single-beat elastance. MR
PES
curves were constructed by expressing normalized mechanical response as a function of the PESI. Control MR
PES
was a monoexponential function whose time constant (TC) and PESI–axis intercept (PESI
0
) increased significantly (
P
<.01) with increases in the antecedent ESI. THF significantly slowed MR
PES
kinetics at each antecedent ESI (
P
<.025), increased normalized maximal contractile response (CR
max
,
P
<.01), and shortened PESI
0
(
P
<.025). Increases in the TC and CR
max
were most pronounced with the smallest antecedent ESI (percent control postextrasystolic TC 363.7±60.5%, ESI of 300 ms versus 139.0±15.1%, ESI of 450 ms,
P
<.005; percent control CR
max
128.6±4.9%, ESI of 300 ms versus 104.9±1.0%, ESI of 450 ms;
P
<.005).

Conclusions
MR
PES
is much less dynamic in THF: The failing heart operates at lower levels of contractile performance after higher stimulation frequencies and cannot increase its speed of contractile recovery to compensate for higher heart rate. Prolongation of MR
PES
kinetics is consistent with depression of SR Ca
2+
release mechanisms in THF and implicates this site in the loss of the capacity of the failing heart to maintain mechanical performance with tachycardia.
Enhancement of Left Ventricular Relaxation in the Isolated Heart by an Angiotensin-Converting Enzyme Inhibitor
Authors: Anning Peter B. , Grocott-Mason Richard M. , Lewis Malcolm J. , Shah Ajay M.
Published: June 2012

Background
ACE inhibitors exert both acute and chronic beneficial effects on cardiac function (eg, remodeling, diastolic dysfunction) in experimental studies and in patients. They inhibit the formation of angiotensin II as well as the degradation of endogenous bradykinin. We recently reported that bradykinin induces selective left ventricular (LV) relaxant effects in isolated hearts via the release of nitric oxide. The present study examined the direct effects of interaction between the ACE inhibitor captopril and endogenous bradykinin on cardiac contractile function.

Methods and Results
Isolated ejecting guinea pig hearts were studied under conditions of constant loading and heart rate. LV pressure was monitored by a 2F micromanometer-tipped catheter. Captopril (1 μmol/L, n=9) caused a progressive acceleration of LV relaxation without significantly affecting early systolic parameters (eg, LV dP/dt
max
) or coronary flow. These effects were inhibited by the nitric oxide scavenger hemoglobin (1 μmol/L, n=5) or by the B
2
-kinin receptor antagonist HOE140 (10 nmol/L, n=5). In the presence of captopril, bradykinin (0.1 nmol/L, n=6) markedly accelerated LV relaxation (significantly more than captopril alone), whereas bradykinin alone (0.1 nmol/L, n=6) had no effect.

Conclusions
These data indicate that the ACE inhibitor captopril causes an acute and selective enhancement of LV relaxation independent of changes in coronary flow, probably via an endogenous bradykinin/nitric oxide pathway.
Hemodynamic Characteristics of Neonates Following First Stage Palliation for Hypoplastic Left Heart Syndrome
Authors: Mosca Ralph S. , Bove Edward L. , Crowley Dennis C. , Sandhu Santinder K. , Schork M. Anthony , Kulik Thomas J.
Published: June 2012

Background
It is widely held that the postoperative course of patients with hypoplastic left heart syndrome (HLHS) after stage 1 palliation is characterized by hemodynamic instability, which in part may be due to excessive pulmonary blood flow. Hence, avoidance of alkalosis and the use of minimally oxygen-enriched inspiratory gas are thought by many to be important, although there is little pertinent published data. This study was undertaken to characterize the postoperative course and to determine whether the F
io
2
and blood pH are related to indices of hemodynamic stability in these infants.

Methods and Results
The postoperative course of 25 consecutive infants undergoing first stage palliation for HLHS were retrospectively reviewed and the following data were obtained: arterial pressure, arterial blood gas measurements, the inotropic agents used, and multiple respiratory parameters. There was one operative death, and 2 patients died within 2 days, but 22 were extubated (mean, 5.2±4.1 days after surgery). Hospital mortality was 24%. Mean pH was ≥7.51 for the first 9 hours after surgery and was ≥7.45 for the entire period. The mean F
io
2
was ≥50% for the first 18 hours. The Pa
o
2
was appropriate (37±6 mm Hg at 1 hour after surgery, increasing to 45±5 mm Hg by hour 73). Only modest inotropic support was needed to maintain appropriate blood pressure.

Conclusions
These data suggest that neither alkalosis nor relatively high inspired oxygen necessarily cause hemodynamic instability in these patients. To what extent these results are generalizable is unclear, but they suggest that there is nothing inherent with HLHS that mandates postoperative hemodynamic instability or unacceptable mortality.
Detection of Regional Left Ventricular Dysfunction in Early Pacing-Induced Heart Failure Using Ultrasonic Integrated Backscatter
Authors: Nozaki Shiro , DeMaria Anthony N. , Helmer Gregory A. , Hammond H. Kirk
Published: June 2012

Background
It has been demonstrated that cyclic variation of ultrasonic integrated backscatter (CVIBS) may be useful in detecting altered physical conditions in the heart. However, no previous study has examined serial changes of CVIBS in the myocardium during the development of left ventricular dysfunction.

Methods and Results
We examined alterations of CVIBS in pacing-induced cardiac dysfunction. Eight pigs (36±2 kg) were studied before and sequentially during sustained rapid ventricular pacing (225±9 beats per minute). CVIBS was measured in the IVS and left ventricular PLW before pacing and daily for 4 days after onset of pacing. Five additional pigs (35±10 kg) were examined after 14 days of pacing. Regional function and CVIBS were assessed with pacemakers inactivated. A quantitative integrated backscatter imaging system (two-dimensional format) was used. Over 4 days of pacing, the magnitude of CVIBS progressively decreased in the PLW but was unchanged in the IVS, findings that persisted at 14 days. Percent wall thickening in the PLW progressively decreased to a greater degree than percent wall thickening in the IVS. A linear relation between the magnitude of CVIBS and percent wall thickening was found. At 14 days, blood flow to the two regions was similar but regional differences in CVIBS persisted.

Conclusions
Rapid left ventricular pacing produces abnormalities of regional myocardial function within 48 hours of pacing. Regional myocardial dysfunction is accompanied by a reduction in CVIBS in the same region.
Synergistic Effect of Vascular Endothelial Growth Factor and Basic Fibroblast Growth Factor on Angiogenesis In Vivo
Authors: Asahara Takayuki , Bauters Christophe , Zheng Lu P. , Takeshita Satoshi , Bunting Stuart , Ferrara Napoleone , Symes James F. , Isner Jeffrey M.
Published: June 2012

Background
Recent studies have suggested that vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) may have synergistic effects on the induction of angiogenesis in vitro. Therefore, we investigated the hypothesis that the simultaneous administration of VEGF and bFGF, each having been previously shown to independently enhance collateral development in an animal model of hind limb ischemia, could have a synergistic effect in vivo.

Methods and Results
Ten days after surgical induction of unilateral hind limb ischemia, New Zealand White rabbits were randomized to receive either VEGF 500 μg alone (n=6), bFGF 10 μg alone (n=7), VEGF 500 μg, immediately followed by 10 μg bFGF (n=7), or vehicle only (control animals, n=8) in each case administered intra-arterially via a catheter in the internal iliac artery of the ischemic limb. BP ratio (BPR, ischemic/healthy limb) at day 10 for the VEGF+bFGF group was 0.82±0.01, much superior (
P
<.0005) to that of either the VEGF group (0.52±0.02) or the bFGF group (0.57±0.02). This outcome persisted at day 30: BPR in the VEGF+bFGF group (0.91±0.02) exceeded that of the control group (0.49±0.05,
P
<.0001), the VEGF group (0.65±0.03,
P
<.0005), or the bFGF group (0.66±0.03,
P
<.0005). Serial angiography demonstrated a progressive increase in luminal diameter of the stem collateral artery and the number of opacified collaterals in the thigh of the ischemic limbs in all groups. Stem artery diameter with VEGF+bFGF (1.34±0.07 mm) on day 30 was significantly (
P
<.05) greater than with either VEGF (1.09±0.09) or bFGF (1.18±0.06) alone. Capillary density was significantly greater (
P
<.05) in VEGF+bFGF animals (275±20 mm
2
) compared with VEGF (201±8) or bFGF (209±15).

Conclusions
Combined administration of VEGF and bFGF stimulates significantly greater and more rapid augmentation of collateral circulation, resulting in superior hemodynamic improvement compared with either VEGF or bFGF alone. This synergism of two angiogenic mitogens with different target cell specificities may have important implications for the treatment of severe arterial insufficiency in patients whose disease is not amenable to direct revascularization.
Left Ventricular Function After Extended Hypothermic Preservation of the Heart Is Dependent on Functional Coronary Capillarity
Authors: Manciet Lorraine H. , Fox Kenneth A. , Copeland Jack G. , Wilson Donald S. , Reimer Paulette R. , McDonagh Paul F.
Published: June 2012

Background
A growing body of knowledge has led to the hypothesis that injury to the microcirculation during hypothermic myocardial preservation may result in decreased contractility of hearts upon reperfusion.

Methods and Results
To test this hypothesis, we examined the relationship between no-reflow and left ventricular function after hypothermic cardiac preservation after reperfusion with solutions containing dilute whole blood (DWB) or washed red blood cells (K2RBC). Rat hearts were arrested with high-potassium cardioplegia, then flushed and stored for 6 hours in low-potassium cardioplegia at 4°C. Hearts were reperfused at a constant flow rate (4 mL/min) with K2RBC for 60 minutes (group 1, n=5) or DWB for 7 minutes followed by 53 minutes of K2RBC (group 2, n=5). Left ventricular developed pressure (LVDP) was measured with an intraventricular balloon. Immediately after functional assessment, hearts were perfused with an india ink solution to mark flow, then glutaraldehyde. Morphometric techniques were used to determine the degree of capillary compression [Δd̄(c)], perfused capillary number per fiber area [Q
A
(0)
P
], and perfused capillary surface area per fiber volume [S
V
(c,f)
P
]. Capillaries were moderately compressed in both groups after reperfusion (group 1, 19±1%; group 2, 20±1%). Q
A
(0)
P
and S
V
(c,f)
P
were highly correlated with Δd̄(c) in hearts reperfused with K2RBC (
r
=.92 and
r
=.92;
P
<.01). Although statistically significant, the correlation was not as strong in DWB-reperfused hearts (
r
=.66 and
r
=.67;
P
<.05). LVDP was correlated to Q
A
(0)
P
and S
V
(c,f)
P
(
r
=.86 and
r
=.87, respectively) for groups 1 and 2.

Conclusions
The weaker correlation between capillary perfusion and capillary compression in DWB-reperfused hearts suggests that factors other than compression contribute to no-reflow after hypothermic preservation. Regardless of the composition of the reperfusate, recovery of left ventricular function after hypothermic ischemia is directly related to coronary capillary perfusion upon reperfusion.
Enrollment in the Health Alliance Plan HMO Is Not an Independent Risk Factor for Coronary Artery Bypass Graft Surgery
Authors: Paone Gaetano , Higgins Robert S.D. , Spencer Trey , Silverman Norman A.
Published: June 2012

Background
Henry Ford Hospital is the sole provider of cardiac surgical services for the Health Alliance Plan, a health maintenance organization (HMO) that presently serves 450 000 enrollees.

Methods and Results
To determine the effect of managed care referral patterns on the outcome of coronary artery bypass graft (CABG) surgery, we retrospectively reviewed two concurrent groups of patients, 569 HMO patients and 225 patients with fee-for-service (FFS) insurance, who had undergone isolated primary CABG surgery between January 1, 1990 and January 31, 1994. The 605 patients with Medicare operated on during the same time frame were excluded to obviate age bias. Age, sex, use of cardiac medications, history of prior percutaneous transluminal coronary angioplasty or thrombolytic therapy, history of recent and remote myocardial infarction, extent of coronary disease, presence of preexisting comorbid conditions, and incidence of unstable clinical syndromes and left ventricular dysfunction (ejection fraction<40%) were comparable for both groups. Inhospital mortality (HMO group, 1.9%; FFS group, 2.2%), mean ICU stay (HMO, 2.6±0.3 days; FFS, 2.3±0.3 days), and total hospital length of stay (HMO, 9.8±0.8 days; FFS, 8.6±0.6 days) were likewise similar.

Conclusions
These data refute the notion that the gatekeeper mentality often associated with managed-care health insurance vehicles results in delayed referral of patients with coronary artery disease and results in suboptimal outcome.
The Protective Dose of the Potent GPIIb/IIIa Antagonist SC-54701A Is Reduced When Used in Combination With Aspirin and Heparin in a Canine Model of Coronary Artery Thrombosis
Authors: Frederick Leo G. , Suleymanov Osman D. , King Lucy W. , Salyers Anita K. , Nicholson Nancy S. , Feigen Larry P.
Published: June 2012

Background
Fibrinogen receptor antagonists block the fibrinogen-platelet interaction at the GPIIb/IIIa receptors and inhibit thrombus formation. SC-54701 is the active metabolite of SC-54684A, an orally active fibrinogen receptor antagonist. We compared the efficacy of SC-54701A (SCa, hydrochloride salt) with that of aspirin (ASA) or heparin and with combination therapy in a canine model of continuous current injury.

Methods and Results
Sixty-six dogs were used (6 per treatment). SCa (15-minute loading dose followed by [//] infusion [μg/kg per minute]: (0.87//0.39=1×SCa; 0.52//0.23=0.6×SCa; and 0.425//0.20=0.5×SCa), ASA (2.8 mg/kg), heparin (200 U/kg plus 1000 U/h), or saline (0.1 mL/kg) was administered intravenously. Experimental time was 180 minutes of current. Time to occlusion was increased (
P
<.05) by SCa (T=incidence of thrombosis) (1×SCa, >180 minutes [T=0]; 0.6×SCa, 158±15 minutes [T=2]; 0.5×SCa, 130±22 minutes [T=4]), heparin (114±16 minutes [T=5]), and ASA plus heparin (130±11 minutes [T=5]) relative to saline (58±7 minutes [T=6]). Time to occlusion for the SCa treatments was increased compared with ASA (64±7 minutes [T=6]). When 0.5×SCa was administered with ASA plus heparin, time to occlusion was >180 minutes [T=0]. SCa provided complete protection at ≥90% inhibition of ex vivo collagen-induced platelet aggregation. Cyclic flow variations were minimal with SCa or any treatment involving 0.5×SCa and ASA.

Conclusions
SCa has dose-dependent antithrombotic efficacy and inhibits ex vivo platelet aggregation. ASA, heparin, or saline was ineffective in this model. SCa (0.5×) plus ASA and heparin maximized the antithrombotic effect of this lower dose of SCa.
Progression of Coronary Artery Disease Predicts Clinical Coronary Events
Authors: Azen Stanley P. , Mack Wendy J. , Cashin-Hemphill Linda , LaBree Laurie , Shircore Anne M. , Selzer Robert H. , Blankenhorn David H. , Hodis Howard N.
Published: June 2012

Background
Progression of coronary artery disease is assumed to be a surrogate end point for clinical coronary events. Because no single method or measure for a coronary angiographic end point is uniformly accepted as optimal, the utility and validity of surrogate end points for predicting clinical coronary events remain unsettled.

Methods and Results
The Cholesterol Lowering Atherosclerosis Study randomized 162 nonsmoking, 40- to 59-year-old men with previous coronary artery bypass graft surgery to colestipol/niacin plus diet or placebo plus diet. Atherosclerosis change on 2-year coronary angiograms was evaluated by a consensus panel and by quantitative coronary angiography (average per-subject change in percent diameter stenosis [%S] and minimum lumen diameter [MLD]). With all three end points, the benefit of colestipol/niacin treatment on coronary artery atherosclerosis has been reported. Annual follow-up for an average of 7 years (range, 6.3 months to 10 years) has been carried out on all subjects who completed the 2-year angiogram. Clinical coronary events (need for revascularization, nonfatal acute myocardial infarction, and coronary death) have been documented. Risk of clinical coronary events was positively related to coronary lesion progression for all three surrogate end points (
P
<.05). New lesion formation in bypass grafts (
P
=.02) and progression of mild/moderate lesions (<50%S) were predictive of clinical coronary events (
P
<.01). Change in MLD contributed significantly to the prediction of clinical coronary events beyond a model with %S alone (
P
<.05).

Conclusions
In this population of nonsmoking men with previous bypass surgery, both the consensus panel– and quantitative coronary angiography–based end points of coronary artery disease progression predict clinical coronary events. Subjects who demonstrate greater coronary artery lesion progression have an increased risk of future clinical coronary events. Design of shorter, smaller trials of antiatherosclerotic agents is justified.
Undetected Ventricular Fibrillation in Transvenous Implantable Cardioverter-Defibrillators
Authors: Natale Andrea , Sra Jasbir , Axtell Kathi , Akhtar Masood , Newby Keith , Kent Virginia , Geiger Mary J. , Brandon M. Joan , Kearney Margaret M. , Pacifico Antonio
Published: June 2012

Background
The purpose of this study was to prospectively analyze redetection problems after unsuccessful shock with different lead systems and devices.

Methods and Results
We prospectively analyzed detection and redetection characteristics among transvenous implantable cardioverter-defibrillators (ICDs) using standard bipolar and integrated bipolar sensing. Monophasic and biphasic ICDs were included. Subthreshold shocks were intentionally delivered, and redetection of ventricular fibrillation (VF) was assessed before discharge and at 1, 3, 6, and 12 months later. Sensing of VF resulting from antitachycardia pacing and low-energy cardioversion (≤2 J) also was analyzed. Before inclusion in the study, each patient underwent subthreshold shock testing at three different time intervals. Among the 160 ICDs with standard bipolar sensing, 530 VF inductions were analyzed. After the failed shocks, undersensing was more frequent (3% versus 20%,
P
<.01) but did not remarkably prolong redetection (3.1±0.8 versus 3.3±1.1 seconds). Among the 201 ICDs with integrated bipolar sensing, 80 were connected to a CPI device (60 Ventak 1600–Endotak 60 series and 20 PRx II 1715–Endotak 70 series) and 121 to the Ventritex defibrillator (91 Endotak 60 series, 14 TVL systems, and 16 Endotak 70 series). After 252 failed shocks, redetection was prolonged with the CPI system (3.1±1.4 versus 4.6±3.6 seconds,
P
<.05) but did not change after 396 failed shocks with the Ventritex ICD (5.4±1.9 versus 4.9±2.2 seconds). This may reflect different nominal settings for detection and redetection. In 9 of 121 patients with Ventritex and 1 of 80 with the CPI ICDs, the devices failed to redetect VF. However, redetection malfunction was never observed in patients with integrated bipolar systems with >6-mm electrode separation. After antitachycardia pacing in 1 patient and a 2-J shock in 1 patient, ventricular tachycardia turned into VF, which was undetected. Both patients used the Endotak 60 series–Cadence combination. None of the patients showing VF undersensing had sudden death at follow-up. Only 3 of the 12 patients with sensing malfunction were on antiarrhythmia drugs at the time of testing. Analysis of endocardial electrograms showed that failure to redetect VF is not associated with a uniform reduction but with a rapid and repetitive change of electrogram amplitude.

Conclusions
Standard bipolar sensing redetects VF more effectively than integrated bipolar sensing. Endocardial electrogram analysis provides insights into the understanding of the mechanism of undersensing, and certain lead-device combinations result in a higher occurrence of VF undersensing. The clinical relevance of this phenomenon remains unknown.
Comparison of Sudden and Nonsudden Coronary Deaths in the United States
Authors: Escobedo Luis G. , Zack Matthew M.
Published: June 2012

Background
The present study was designed to compare risk factor prevalences in coronary heart disease deaths in persons dying within 1 hour of onset of cardiovascular symptoms (sudden coronary death), those dying without such sudden symptoms (nonsudden coronary death), and those with unknown duration of symptoms before death (other coronary death).

Methods and Results
Data from the 1986 National Mortality Followback Survey and the US Bureau of the Census were examined to assess death rates for sudden, nonsudden, and other coronary deaths. Multivariate logistic regression methods were used to calculate the odds ratio (OR), compared with nonsudden and other coronary deaths, for sudden coronary death associated with socioeconomic status variables, the person’s location at death, and coronary heart disease risk factors. Mortality rates for all coronary deaths increased with age, were higher for men than women, and increased with decreasing years of schooling. The rate of sudden coronary death was highest for Hispanics. In 1986, an estimated 251 000 sudden coronary deaths (95% CI=238 000 to 263 000) occurred in the United States. Sudden coronary deaths were less likely than nonsudden coronary deaths to occur at home (OR=0.5, 95% CI=0.4 to 0.6), but individuals who died of sudden coronary death were more likely to have been current cigarette smokers (OR=1.3, 95% CI=1.0 to 1.8). No other modifiable risk factors for coronary heart disease distinguished sudden coronary deaths from nonsudden coronary deaths.

Conclusions
Contrary to the commonly held view, coronary deaths in the home are more likely to be nonsudden than sudden. Cigarette smoking more likely results in sudden than nonsudden coronary death, perhaps because of nicotine-induced ventricular arrhythmias.
Association Between an Angiotensinogen Microsatellite Marker in Children and Coronary Events in Their Grandparents
Authors: Badenhop Renee F. , Wang Xing Li , Wilcken David E.L.
Published: June 2012

Background
Recently we found that the deletion (D) allele of the insertion/deletion (I/D) polymorphism of the ACE gene in 404 children was associated with a history of coronary artery disease (CAD) in their grandparents. This led us to explore polymorphisms in other genes of the renin-angiotensin system in this same population.

Methods and Results
We determined the genotypes for three microsatellite markers located near or in the angiotensinogen, angiotensin II (type-1) receptor, and renin genes in the children and related the allele frequencies to grandparental CAD. We found a significant association between the angiotensinogen marker in children and grandparental CAD (χ
2
=42.2,
P
=.00001) with these children having an excess of the 125-bp and 129-bp alleles (odds ratio, 2.5; 95% confidence interval, 1.7 to 3.7). Greatest grandparental risk was when their grandchildren had the 125-bp/125-bp, 129-bp/129-bp, or 125-bp/129-bp genotypes (odds ratio, 7.75; 95% confidence interval, 2.2 to 27). There was no association between the microsatellites at either the angiotensin II (type-1) receptor (
P
=.8) or renin (
P
=.2) genes in children and grandparental CAD and none between the angiotensinogen and ACE polymorphisms in relation to CAD family history.

Conclusions
This study identifies a significant association between an angiotensinogen marker in children and grandparental CAD. There was no association between the microsatellites at either the angiotensin II (type-1) receptor or renin genes and CAD in this population. We conclude that the angiotensinogen polymorphism as well as the ACE polymorphism may explain a part of the risk related to a family history of CAD.
Diabetics With Coronary Disease Have a Prevalence of Asymptomatic Ischemia During Exercise Treadmill Testing and Ambulatory Ischemia Monitoring Similar to That of Nondiabetic Patients
Authors: Caracciolo Eugene A. , Chaitman Bernard R. , Forman Sandra A. , Stone Peter H. , Bourassa Martial G. , Sopko George , Geller Nancy L. , Conti C. Richard
Published: June 2012

Background
There are conflicting data as to whether diabetics have a higher prevalence of asymptomatic ST-segment depression during exercise treadmill testing (ETT) and ambulatory ECG (AECG) monitoring. This study was conducted to determine whether diabetic patients with coronary disease enrolled in the Asymptomatic Cardiac Ischemia Pilot (ACIP) have more episodes of asymptomatic ischemia during ETT and 48-hour AECG monitoring than nondiabetic patients and to compare differences in angiographic variables and the magnitude of ischemia as measured by standard ETT and AECG criteria.

Methods and Results
Angiographic variables and the prevalence and magnitude of ischemia during the qualifying ETT and 48-hour AECG were compared by the presence and absence of diabetes mellitus in 558 randomized ACIP patients. Seventy-seven patients had a history of diabetes and were taking oral hypoglycemics or insulin (diabetic group); 481 patients did not meet these criteria (nondiabetic group). Multivessel disease (87% versus 74%,
P
=.01) was more frequent in the diabetic group. The percentages of patients without angina during the ETT were similar in the diabetic and nondiabetic groups (36% and 39%, respectively). Time to onset of ≥1-mm ST-segment depression and time to onset of angina were similar in both groups. The percentages of patients with only asymptomatic ST-segment depression during the 48-hour AECG were similar in the diabetic and nondiabetic groups (94% versus 88%, respectively). However, total ischemic time per 24 hours (15.0±21.4 versus 23.6±31.1 minutes,
P
=.02), ischemic time per episode (6.3±4.6 versus 9.0±8.7 minutes,
P
<.01), and the maximum depth of ST-segment depression tended to be less in the diabetic group.

Conclusions
Patients enrolled in ACIP were selected on the basis of an abnormal ETT and 48-hour AECG and ability to undergo coronary revascularization. When patients with diabetes mellitus were compared with those without diabetes, there was a similar prevalence of asymptomatic ischemia during ETT and 48-hour AECG monitoring. Despite more extensive and diffuse coronary disease, diabetic ACIP patients tended to have less measurable ischemia during the 48-hour AECG.
Temporal Relation Between Ischemic Episodes and Activation of the Coagulation System in Unstable Angina
Authors: Biasucci Luigi M. , Liuzzo Giovanna , Caligiuri Giuseppina , Quaranta Gaetano , Andreotti Felicita , Sperti Giovanni , van de Greef Willy , Rebuzzi Antonio G. , Kluft Cornelis , Maseri Attilio
Published: June 2012

Background
Although a major role of coronary thrombosis in the pathogenesis of unstable angina has been demonstrated, the results of a series of studies have suggested that activation of the hemostatic system may not be confined to ischemic episodes. The purpose of this study was to investigate the temporal relation between ischemic episodes and activation of the coagulation system in unstable angina.

Methods and Results
Thrombin–antithrombin III (TAT) and prothrombin fragment 1+2 (F
1+2
) levels were measured in 13 patients during spontaneous ischemic episodes (time 0, 5, and 15 minutes and 1 hour) to evaluate the time course of the activation of the coagulation system associated with the development of ischemia (protocol A). TAT and F
1+2
levels were also measured in 28 patients with unstable angina on admission to hospital (every 6 hours for 24 hours and daily for 3 days) to assess their temporal relation with ischemic episodes (protocol B). In protocol A, TAT and F
1+2
levels were elevated in 10 of 13 patients (77%) in at least 1 sample. The median value of TAT showed a peak at 5 minutes and returned to baseline within 15 minutes (
P
<.05), consistent with its plasma half-life of 5 minutes, whereas the median value of F
1+2
showed no significant changes, possibly because of its longer half-life, which tends to dampen sudden bursts of thrombin production. In protocol B, activation of the clotting system was found in 10 of 33 samples (30%) temporally related to ischemia and also in 23 of 150 (15%,
P
=.07) of those not temporally related to ischemia.

Conclusions
Our study demonstrates that patients with active unstable angina develop frequent bursts of thrombin production not necessarily associated with ischemic episodes and that, conversely, some ischemic episodes are not associated with evidence of thrombin activation.