bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Coronary Artery Bypass and Age on Clinical Performance After Aortic and Mitral Valve Replacement With Biological and Mechanical Prostheses
Authors: Jamieson W.R. Eric , Munro A. Ian , Burr Lawrence H. , Germann Eva , Miyagishima Robert T. , Ling Hilton
Published: June 2012

Abstract
The influence of prosthetic type, age, and coronary artery bypass grafting (CABG) on valve-related complications by valve position was evaluated in a population of 2353 bioprosthesis patients (mean age, 66.5 years; range, 13 to 89 years) and in a population of 1112 mechanical prosthesis patients (mean age, 59.1 years; range, 13 to 91 years). The follow-up was complete to 96% and 98%, respectively, for the bioprosthesis and mechanical prosthesis groups. The patient groups were evaluated by actuarial assessment of survival and valve complications and composites. Preoperative factors were evaluated for determination of significant independent predictors by multivariate proportional-hazard regression analysis. CABG was an influential factor in the actuarial analysis. Survival was superior for aortic mechanical replacements without CABG and for mitral replacements, both biological and mechanical, without CABG (
P
<.05). The freedom from thromboembolism (TE) and antithromboembolic hemorrhage (ATH) was greater for biological prostheses with and without CABG for aortic replacements (
P
<.05) but not for mitral replacements (
P
=NS). The freedom from valve-related mortality was not influenced by CABG for either position (
P
=NS). The freedom from valve-related reoperation was greater for biological prostheses with CABG than without CABG for both aortic and mitral replacements (
P
<.05). The evaluation of covariates as independent predictors revealed CABG to be a nonpredictor for aortic valve replacement (AVR) (
P
=NS) but a predictor of survival and valve-related reoperation for mitral valve replacement (MVR) (
P
<.05). With AVR, biological prostheses predicted greater freedom from valve-related mortality and TE and ATH (
P
<.05) and for MVR for TE and ATH (
P
<.05). Valve position was not a predictor otherwise (
P
=NS). Advancing age was a significant covariate for AVR for all areas of assessment. Advancing age for MVR provided a lower rate of survival and greater freedom from valve-related mortality and reoperation (
P
<.05). The clinical performance of valvular prostheses is influenced to a greater degree by valve type and age than by CABG.
Interrupted Aortic Arch
Authors: Jacobs Marshall L. , Chin Alvin J. , Rychik Jack , Steven James M. , Nicolson Susan C. , Norwood William I.
Published: June 2012

Abstract
Interrupted aortic arch (IAA) is often related developmentally to subaortic obstruction (SAO). When severe, SAO must be addressed in surgical management of IAA. From 1990 to 1993, 25 neonates presented for initial surgical management of IAA complexes. Associated lesions were ventricular septal defect (VSD) with or without atrial septal defect (19 patients), truncus arteriosus (3 patients), tricuspid atresia with transposition of the great arteries (1 patient), aortic atresia with VSD (1 patient), and d-transposition of the great arteries with VSD (1 patient). Overall hospital mortality was 20% (five deaths). One death was related to sepsis and two to sudden hemodynamic decompensation (a 2-kg premature infant after arch repair and VSD closure and a neonate with IAA–truncus arteriosus after arch repair and truncus repair with aortic root replacement). Two deaths were related to low cardiac output in patients with severe subaortic narrowing (<3 mm by two-dimensional echocardiography), which was not addressed surgically. Of 10 additional patients judged preoperatively to have severe SAO, 1 underwent resection of the infundibular septum together with VSD closure and arch reconstruction, and 9 underwent a modification of Norwood’s operation with arch reconstruction and proximal pulmonary artery to aortic anastomosis (7 with systemic to pulmonary artery shunts and 2 with right ventricle to pulmonary artery outflow tract reconstruction). One patient died 2 months after surgery of staphylococcal sepsis. All 9 others were discharged well. Subaortic narrowing is a physiologically important element of IAA complexes. When SAO is severe, satisfactory initial palliation can be achieved by a modification of Norwood’s operation.
Early Results of a Simplified Method of Mitral Valve Annuloplasty
Authors: Odell John A. , Schaff Hartzell V. , Orszulak Thomas A.
Published: June 2012

Background
We hypothesized that a simple, unmeasured posterior annuloplasty technique (two thirds of a 27-mm Duran ring) offered advantages of standardization and ease of insertion.

Methods and Results
A consecutive series of all patients (n=418; median age, 67 years) having mitral valve repair performed by two surgeons was analyzed to determine the outcome of three different annuloplasty techniques: commissural annuloplasty (n=124), complete ring annuloplasty (n=113), and an unmeasured, posterior, partial ring annuloplasty (n=181). Intraoperatively, before repair, severity of mitral regurgitation as measured by double sampling dye curves and transesophageal echocardiography was similar in all three groups; after mitral valve repair, intraoperative assessment showed a similar degree of reduction in regurgitation in the three annuloplasty groups. Before hospital dismissal, transthoracic echocardiography demonstrated that the mean mitral valve areas and gradients were similar in the three groups; more patients having commissural annuloplasty were classified as having grade II or greater regurgitation. Mortality (n=7, 1.7%) and need for reoperation (n=8, 1.9%) was low in all groups despite the fact that additional procedures were performed in 48.8% of patients. Durations of cardiopulmonary bypass and aortic cross-clamping were significantly less in patients having commissural or posterior annuloplasties compared with those receiving a complete ring annuloplasty.

Conclusions
These early results indicate that the posterior annuloplasty method is reproducible and expeditious. Postoperative valve function as assessed by degree of regurgitation, transvalvular gradient, and valve area was similar to that obtained by measured, complete ring annuloplasty and superior to that found in patients having commissural annuloplasty.
Early Changes in Regional and Global Left Ventricular Function After Aortic Valve Replacement
Authors: Jin Xu Y. , Gibson Derek G. , Pepper John R.
Published: June 2012

Background
The clinical effects of different cardioplegic methods on left ventricular (LV) function have not been fully elucidated, particularly in the setting of myocardial hypertrophy.

Methods and Results
Sixty-four patients (mean age, 62±12 years; 41 men, 23 women) who were undergoing elective aortic valve replacement (stenosis, 49; regurgitation, 15; concomitant coronary artery bypass grafting, 22), with LV mass index 230±70 g/m
2
, were randomized to the following groups: antegrade crystalloid cardioplegia (CCP, 21 patients), antegrade/retrograde cold blood cardioplegia (CBP, 23 patients), or continuous retrograde warm (37°C) blood cardioplegia (WBP, 20 patients). Mean aortic cross-clamp and cardiopulmonary bypass times were 100±20 and 126±24 minutes. Positive inotropic drug therapy was required postoperatively in 9 patients after CBP, 14 after CCP, and 18 after WBP. Perioperative LV function was assessed using transesophageal M-mode echocardiography, combined with high-fidelity LV pressure recording and thermodilution cardiac output, before bypass and 0.5, 1, 3, 6, 12, and 20 hours after cross-clamp removal. There was a similar fall in LV peak circumferential wall stress at constant LV end-diastolic dimension in each group after aortic valve replacement. The increase in contraction velocity was significant from 0.5 hour with CBP; however, no significant increase occurred until 12 hours with CCP and until 20 hours with WBP. The rate and extent of LV pressure fall and early diastolic filling rate both increased with CBP, and only in this group did ventricular coordination improve. LV stroke work index was maintained with CBP throughout the postoperative period with less inotropic support than with the other two methods.

Conclusions
In the hypertrophied LV, CBP offers the best preservation of myocardial physiological response and ventricular function with less inotropic support.
Effects of Cholesterol Lowering on the Progression of Coronary Atherosclerosis in Women
Authors: Waters David , Higginson Lyall , Gladstone Peter , Boccuzzi Stephen J. , Cook Thomas , Lespérance Jacques
Published: June 2012

Background
Although coronary disease is the leading cause of death in women and its clinical features differ from those in men, very few women have been included in angiographic trials of cholesterol lowering.

Methods and Results
Sixty-two women with diffuse but not necessarily severe coronary atherosclerosis documented on a recent angiogram and with fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a double-blind, placebo-controlled trial. More than one half had a history of hypertension, approximately one quarter were diabetics, and one third were current smokers. All women received dietary counseling. Lovastatin or placebo was begun at 20 mg/d and was titrated if necessary to 40 and then to 80 mg during the first 16 weeks to attain a fasting LDL cholesterol ≤130 mg/dL. The mean lovastatin dose was 34 mg/d. Total and LDL cholesterol decreased by 24% and 32%, respectively, in lovastatin-treated women but by <3% in women receiving placebo. Coronary arteriography was repeated after 2 years in 54 women (87%), and their 394 lesions were measured “blindly” on pairs of film with an automated computerized quantitative system. Progression, defined as a worsening in minimum diameter of one or more stenoses by ≥0.4 mm, occurred in 7 of 25 lovastatin-treated women and 17 of 29 placebo-treated women (28% versus 59%,
P
=.031). New coronary lesions developed in 1 lovastatin-treated woman and 13 placebo-treated women (4% versus 45%,
P
<.001). The outcome for each of the angiographic end points was not significantly different between the women and the 245 men who completed the trial.

Conclusions
Lovastatin slows the progression of coronary atherosclerosis and prevents the development of new coronary lesions in women.
Reduction in Cardiovascular Events During Pravastatin Therapy
Authors: Byington Robert P. , Jukema J. Wouter , Salonen Jukka T. , Pitt Bertram , Bruschke Albert V. , Hoen Helena , Furberg Curt D. , Mancini G. B. John
Published: June 2012

Background
It has been documented that the HMG coenzyme A reductase inhibitors, or statins, can decrease cardiovascular events and mortality in patients with clinical coronary disease and moderately to severely elevated lipid levels. Additional data are required to demonstrate a reduction of vascular events in coronary patients with less than severely elevated lipid levels and in subgroups of this population.

Methods and Results
Clinical data from four atherosclerosis regression trials that evaluated pravastatin were pooled for a predetermined analysis of the effect of that agent on the risk of coronary events. All trials were double-masked, placebo-controlled designs that used pravastatin as monotherapy for 2 to 3 years. The 1891 participants in the trials had evidence of atherosclerosis and mildly to moderately elevated lipid levels. For fatal or nonfatal myocardial infarction, there was a 62% reduction in events attributable to pravastatin (
P
=.001). This effect was evident in younger and older patients, men and women, and patients with and without histories of hypertension and prior infarction. There was a 46% reduction in all-cause mortality (
P
=.17), which, although not statistically significant, is consistent with the results of other statin trials. There also was a 62% reduction in the risk of fatal or nonfatal stroke (
P
=.054).

Conclusions
These pooled results provide strong evidence that pravastatin reduces the risk of cardiovascular events in patients with atherosclerotic disease and mildly to moderately elevated lipid levels. The benefit for reducing myocardial infarction is evident in older and younger patients, men and women, and patients with and without histories of hypertension and prior infarction.
Reduced Contraction and Altered Frequency Response of Isolated Ventricular Myocytes From Patients With Heart Failure
Authors: Davies C.H. , Davia K. , Bennett J.G. , Pepper J.R. , Poole-Wilson P.A. , Harding S.E.
Published: June 2012

Background
Previous work has failed to demonstrate reduced maximal contraction of isolated ventricular myocytes from failing human hearts compared with nonfailing control hearts. The effect of alterations in stimulation frequency and temperature on the contraction of isolated ventricular myocytes has been investigated. Left ventricular myocytes were isolated from the hearts of patients with severe heart failure undergoing heart transplantation and compared with myocytes isolated from myocardial biopsies from patients with coronary disease but preserved left ventricular systolic function or from myocytes from rejected donor hearts.

Methods and Results
Myocytes were exposed to either a maximally activating level of extracellular calcium at 37°C or to 2 mmol/L calcium at 32°C. There was no significant difference in the contraction amplitude between myocytes from failing and nonfailing hearts at 0.2 Hz. With increasing stimulation frequency, there was a reduction in contraction amplitude in cells from failing hearts relative to control hearts in both maximal calcium from 0.33 Hz (4.5% versus 6.6%) to 1.4 Hz (3.9% versus 8.8%) (ANCOVA,
P
<.001) and at 2 mmol/L calcium from 0.50 Hz (2.3% versus 3.5%) to 1.4 Hz (1.8% versus 3.9%) (ANCOVA,
P
<.001). The time to peak contraction and the times to 50% and 90% relaxation were prolonged in myocytes from failing hearts at stimulation rate of 0.2 Hz (
P
<.01), but only the time to 50% relaxation was prolonged at 1.0 Hz (
P
<.05).

Conclusions
Reduced contraction, slowed relaxation, and impaired frequency response occurring at the level of the individual ventricular myocyte can be demonstrated in human heart failure. This demonstrates that disruption of myocyte function can contribute to both the systolic and the diastolic abnormalities that occur in the failing human heart.
Cytomegalovirus Antigen Expression, Endothelial Cell Proliferation, and Intimal Thickening in Rat Cardiac Allografts After Cytomegalovirus Infection
Authors: Lemström Karl , Koskinen Petri , Krogerus Leena , Daemen Mat , Bruggeman Cathrien , Häyry Pekka
Published: June 2012

Background
Cardiac allograft arteriosclerosis is the primary cause of late death in heart transplant recipients. Clinical studies have suggested that humoral and cellular immune response, hyperlipidemia, and cytomegalovirus (CMV) infection may amplify the disease. In this study, the role of CMV infection in the development of rat cardiac allograft arteriosclerosis is investigated.

Methods and Results
Heterotopic rat cardiac allografts were performed from the DA to the WF rat strains. To prevent rejection, the recipients received triple-drug (cyclosporine A 20 mg · kg
−1
· d
−1
, azathioprine 2 mg · kg
−1
· d
−1
, and methylprednisolone 0.5 mg · kg
−1
· d
−1
) immunosuppression postoperatively. Recipient rats were infected intraperitoneally (n=21) with 10
5
plaque-forming units of rat CMV (RCMV) 1 day after transplantation or were left uninfected and used as controls (n=18). The grafts were removed 7 and 14 days and 1 and 3 months after transplantation. In 42% (9 of 21) of cardiac allografts in RCMV-infected rats, an intramural, mononuclear cell inflammation of small intramyocardial arterioles was observed compared with none in uninfected rats (
P
=.005). Acute RCMV infection was associated with an early perivascular inflammatory cell response of helper T (W3/25), cytotoxic T (OX8), and NK (3.2.3) cells, macrophages (OX42), and major histocompatibility complex class II expression around small intramyocardial arterioles and capillaries. No upregulation of interleukin-2 receptor expression was seen. In arteries and small intramyocardial arterioles, RCMV infection was associated with a significant endothelial cell proliferation and a clear increase in intimal thickening. Significant endothelial cell proliferation was also observed in the capillaries after RCMV infection. Immunohistochemistry revealed specific focal RCMV early and late antigen expression in epicardial and interstitial ED1–immunoreactive mononuclear cell infiltrates and around small arterioles of RCMV-infected cardiac allografts. Occasionally, media cells of stenosed small intramyocardial arterioles also showed strong focal RCMV antigen expression. In addition, infectious RCMV could be recovered by plaque assay in cardiac allografts expressing RCMV antigens.

Conclusions
These results demonstrate a productive RCMV infection in cardiac allograft structures and suggest that RCMV infection accelerates cardiac allograft arteriosclerosis, particularly in small intramyocardial arterioles mediated by inflammatory responses in the vascular wall and perivascular space.
Long-term Treatment With Angiotensin I–Converting Enzyme Inhibitors Attenuates the Loss of Cardiac β-Adrenoceptor Responses in Rats With Chronic Heart Failure
Authors: Sanbe Atsushi , Takeo Satoshi
Published: June 2012

Background
Cardiac contractile force in response to β-adrenoceptor agonists and β-adrenergic receptor density are decreased in failing human hearts. The effects of angiotensin I–converting enzyme (ACE) inhibitor on cardiac responsiveness to β-adrenergic stimulation in failing hearts are not established. The present study was undertaken to determine whether ACE inhibitor may improve cardiac β-adrenergic responsiveness in animals with chronic heart failure (CHF).

Methods and Results
CHF was induced by left coronary artery ligation in rats. Cardiac output and stroke volume indices decreased 12 weeks after the operation. In sham-operated rats, dobutamine and isoprenaline increased cardiac output and stroke volume indices. In contrast, cardiac output and stroke volume responses to dobutamine and isoprenaline were severely blunted in the CHF rat. Cardiac β
1
-adrenergic receptor density was decreased while its dissociation constant (
K
d
) was not altered in the viable tissue of the left ventricle of the CHF rat, which is consistent with β-adrenergic receptor downregulation. Cardiac norepinephrine content decreased in the CHF rats. Rats were treated orally with ACE inhibitors, 3 mg/kg trandolapril or 10 mg/kg enalapril once daily, or 5 mg/kg captopril twice daily from the 2nd to the 12th weeks after the operation. Treatment with ACE inhibitors attenuated the reduction in cardiac output and stroke volume indices and improved the inotropic response to dobutamine and isoprenaline and reversed partially the cardiac norepinephrine content in the CHF rat. ACE inhibitor treatment also attenuated the reduction in β
1
-adrenergic receptor density in the viable tissue of the left ventricle of the CHF rat.

Conclusions
The results suggest that ACE inhibitor treatment attenuates the blunting of cardiac responses to β-adrenergic agonists in the CHF rat and that one of the mechanisms underlying this effect is prevention of cardiac β
1
-adrenergic receptor downregulation.
Combining Monophasic Action Potential Recordings With Pacing to Demonstrate Delayed Afterdepolarizations and Triggered Arrhythmias in the Intact Heart
Authors: de Groot S.H. Marieke , Vos Marc A. , Gorgels Anton P.M. , Leunissen Jet D.M. , van der Steld Bert J. , Wellens Hein J.J.
Published: June 2012

Background
In the intact heart, methodological difficulties hamper the direct visualization of delayed afterdepolarizations (DADs) responsible for triggered arrhythmias. Therefore, we tested the hypothesis that a combination of pacing and the recording of a monophasic action potential (MAP) could facilitate the recognition of ouabain-induced DADs and triggered arrhythmias by demonstrating an increase in the diastolic baseline slope (dV/dT) of the MAP recording at the end of a pacing train.

Methods and Results
In anesthetized dogs with chronic atrioventricular block, a right ventricular endocardial MAP was recorded during (1) control (n=11), (2) 15 to 45 minutes after administration of ouabain (45±10 μg/kg, n=11), (3) 10 minutes after administration of lidocaine (3 mg/kg, n=5), and (4) during lidocaine washout (n=3). Pacing was performed with the MAP catheter. Also, the protocol was performed in 3 dogs with conducted sinus rhythm during control and ouabain circumstances. During control, the slope value was 2±2 mV/s (mean±SD), the incidence of DADs after the stimulation train was 6%, and no ventricular tachycardias (VTs) were induced in dogs with atrioventricular block. During ouabain administration, the slope and DAD incidences increased to, respectively, 26±14 mV/s and 74% (
P
<.05 for both). VTs were induced frequently. Lidocaine prevented VT induction by decreasing the slope and the incidence of DADs. This effect disappeared after lidocaine washout. During conducted sinus rhythm, similar results were found.

Conclusions
By combining pacing and MAP recordings, the diastolic slope observed on MAP recordings in ouabain-intoxicated hearts can be used as a marker for DADs and triggered arrhythmias. This finding may be helpful in identifying triggered activity in the intact heart.
Effects of Elevated Coronary Sinus Pressure on Coronary Blood Flow and Left Ventricular Function
Authors: Miura Takuya , Hiramatsu Takeshi , Forbess Joseph M. , Mayer John E.
Published: June 2012

Background
After the Fontan operation there is elevated systemic venous pressure, and the coronary sinus pressure (CSP) may also be elevated depending on the operative technique. Elevated CSP can potentially alter coronary perfusion and thereby be a cause for postoperative left ventricular (LV) dysfunction.

Methods and Results
The effects of elevated CSP on coronary blood flow (CBF) and LV function were evaluated in 14 isolated blood-perfused juvenile lamb hearts. After baseline measurements were made, CSP was elevated by a 10-minute inflation of a balloon catheter inserted into the coronary sinus via the hemiazygos vein in 7 hearts (CSHT group) to cause moderate (phase I, ≈15 mm Hg) and severe (phase II, ≈30 mm Hg) elevations of mean CSP at a constant coronary perfusion pressure (80 mm Hg). The results were compared with results from 7 hearts continuously perfused without elevation of CSP (C group). Mean CSP in the CSHT group was elevated from 0.4±1.9 to 16.4±2.4 mm Hg during phase I and to 32.6±3.6 mm Hg during phase II. CBF in the CSHT group decreased to 89.7±5.2% in phase I and to 79.0±13.2% in phase II, and these values were significantly lower than those in the C group (98.5±6.7% in phase I and 106.8±16.0% in phase II;
P
<.05 each). There were no significant differences in maximum developed pressure (DP), max+dP/dt, max−dP/dt, or LV end-diastolic pressure (LVEDP) at a fixed volume between the CSHT group and the C group either in phase I or phase II. The time constant of pressure decline during LV isovolumic relaxation (tau) showed no significant difference in phase I, but in phase II tau was significantly higher in the CSHT group (116.2±7.8%) than that in the C group (106.3±8.5%;
P
<.05).

Conclusions
Elevated CSP on a short-term basis did not affect the LV systolic function indexes (max DP, max+dP/dt), max−dP/dt, or LVEDP at a fixed volume, but tau did appear to worsen and CBF decreased during CSP elevation. These actions might have deleterious effects on the LV over a longer time period.
Determinants of Cerebral Oxygenation During Cardiac Surgery
Authors: Nollert Georg , Möhnle Patrick , Tassani-Prell Peter , Reichart Bruno
Published: June 2012

Background
Neuropsychological deficits after cardiac surgery are attributed to the side effects of cardiopulmonary bypass (CPB). To protect the brain from ischemic damage, the influences of temperature, blood pressure, blood gases, acid-base status, and hemodilution on cerebral oxygenation have to be elucidated and quantified.

Methods
Forty-one consecutive patients were investigated during cardiac surgery while on CPB. Operative management included moderate hypothermia of 26°C and the alpha-stat pH management. With near-infrared spectrophotometry, changes in oxygenated hemoglobin (Hb
o
2
, representing oxygen delivery) and oxidized cytochrome a,a3 (Ct
o
2
, cellular oxygenation) in brain tissue were obtained noninvasively. In addition, venous saturation of the brain was measured via a catheter in the jugular bulb (S
BJ
o
2
). The influence of operative management parameters on cerebral oxygenation was calculated by univariate and multiple regression analyses.

Results
Before and after CPB there was no significant multivariate determinant of cerebral oxygenation. During CPB, Hb
o
2
depended solely on P
co
2
(
P
<.01;
r
=.89). Ct
o
2
was determined by pH (
P
<.01), esophageal temperature (
P
<.01), P
co
2
(
P
<.01), and Hb (
P
<.01). These parameters explained nearly all changes of the cytochrome measurements during CPB (
r
=.99). Arterial P
co
2
(
P
<.01) and pH (
P
<.01) influenced brain venous oxygen saturation (S
BJ
o
2
;
r
=.98).

Conclusions
Cerebral oxygenation is autoregulated during cardiac surgery before and after CPB. During CPB, Hb, temperature, pH, and P
co
2
determine at least 85% of all changes in cerebral oxygenation. The main causes of impaired cerebral oxygenation are the decrease in Hb with hemodilution, vasoconstriction due to hypocapnia, and the leftward shift of the Hb binding curve in alkalosis and hypothermia.
Influence of Temperature on Neutrophil Trafficking During Clinical Cardiopulmonary Bypass
Authors: Menasché Philippe , Peynet Jacqueline , Haeffner-Cavaillon Nicole , Carreno Marie-Paule , de Chaumaray Thierry , Dillisse Valentine , Faris Bouchaı̂b , Piwnica Armand , Bloch Gérard , Tedgui Alain
Published: June 2012

Background
The adhesion of neutrophils to endothelial cells and their subsequent transendothelial migration play a major role in inflammatory damage elicited by cardiopulmonary bypass (CPB) because these events are linked to the release of cytotoxic proteases and oxidants. However, the patterns of neutrophil trafficking in relation to systemic temperature during clinical CPB have not yet been characterized.

Methods and Results
Twenty case-matched patients undergoing warm (31.8±0.4°C) or cold (26.3±0.5°C,
P
<.0001 versus warm) bypass were studied. Blood samples were simultaneously collected from the right and left atria before, at the end of, and 30 minutes after CPB. Plasma levels of C3a, P- and E-selectins, elastase, and interleukin-8 were determined by immunoassays. The results demonstrate: (1) a rise in C3a, reflecting complement activation, (2) a fall in soluble E-selectin consistent with an increased adhesiveness of activated neutrophils, (3) a rise in soluble P-selectin expected to enhance endothelial adhesion of these neutrophils, (4) a rise in elastase, suggesting an adhesion-triggered neutrophil degranulation, and finally (5) a rise in interleukin-8 that is likely to promote transendothelial migration of adherent neutrophils. All of these changes occurred in the two groups of patients and were significant compared with prebypass values. However, in none of the groups was there a significant difference between right and left atrial values for any of the markers. The single difference between cold and warm bypass patients was a significant reduction of elastase release in the cold group (
P
<.001 versus the warm group).

Conclusions
Clinical CPB is associated with biological changes suggesting the occurrence of neutrophil trafficking. Hypothermia provides only partial protection through a reduced release of elastase. Overall, these results reinforce the rationale for the development of therapeutic strategies targeted at blunting the neutrophil-mediated component of bypass-induced inflammatory damage.
Intermittent Warm Blood Cardioplegia
Authors: Lichtenstein Samuel V. , Naylor C. David , Feindel Christopher M. , Sykora Kathy , Abel James G. , Slutsky Arthur S. , Mazer C. David , Christakis George T. , Goldman Bernard S. , Fremes Stephen E.
Published: June 2012

Background
Warm heart surgery implies continuous perfusion with normothermic blood cardioplegia. Interruption of cardioplegia, however, facilitates construction of distal coronary anastomoses and is the method practiced by many surgeons. To determine whether intermittency is harmful, we present results from 720 coronary bypass patients, protected with intermittent antegrade warm blood cardioplegia, that were derived from a previous study of normothermic versus hypothermic cardioplegia.

Methods and Results
Mean±SD age was 60.8±9.0 years; 27% of cases were urgent; 16% of patients had >50% left main stenosis, and 19% had grade III or IV ventricles. A mean of 3.2±0.9 grafts was constructed. The average aortic cross-clamp time was 61.8±22.2 minutes. The longest single time off cardioplegia (LTOC) averaged 11.4±4.0 minutes per patient. The cumulative time off cardioplegia as a percentage of the cross-clamp time (PTOC) was 48.2±18.6% per patient. LTOC and PTOC were divided into quartiles (LTOC, <10, 10 to 11, 12 to 13, and >13 minutes; PTOC, <36%, 36% to 49%, 50% to 62%, and >62%) and related to the prespecified composite outcome of mortality, myocardial infarction according to serial CK-MB sampling, and low-output syndrome (LOS). Longer LTOC was harmful (event rates per quartile, 13.5%, 10.3%, 10.9%, and 19.0%;
P
=.046), whereas longer PTOC was protective (16.1%, 17.2%, 9.4%, and 10.6%;
P
=.07). Stepwise logistic regression was performed, controlling for demographic and angiographic predictors. In the multivariate models, LTOC remained detrimental (
P
=.07) and PTOC remained beneficial (
P
=.053). Additional modeling after entering surgeon identity (
P
<.001) into the risk equation eliminated the PTOC effect, whereas LTOC remained predictive of adverse outcomes (
P
=.053; odds ratio, 1.06; 95% CI, 1.00, 1.13).

Conclusions
The data indicate that a reasonable margin of safety exists with intermittent, antegrade warm blood cardioplegia. Repeated interruptions of warm blood cardioplegia are unlikely to lead to adverse clinical results if single interruptions are ≤13 minutes.
Effects of Endothelin-1 and Endothelin-A Receptor Antagonist on Recovery After Hypothermic Cardioplegic Ischemia in Neonatal Lamb Hearts
Authors: Hiramatsu Takeshi , Forbess Joseph , Miura Takuya , Roth Stephen J. , Cioffi MAT Mark A. , Mayer John E.
Published: June 2012

Background
Prior studies suggest an important role for coronary endothelium in ischemia/reperfusion (I/R) injury. Decreased endothelial release of the vasodilator nitric oxide occurs after I/R, but the role of the endothelium-derived vasoconstrictor endothelin-1 (ET-1) in I/R is unknown.

Methods and Results
We measured plasma ET-1 concentrations by radioimmunoassay in isolated blood-perfused neonatal lamb hearts before and after 2 hours of 10°C cardioplegic ischemia and examined the effects of ET-1 and the endothelin-A (ET-A) receptor antagonist BE-18257B on the postischemic recovery of isolated hearts. ET-1 levels in coronary sinus blood before ischemia and at 0 and 30 minutes of reperfusion in 8 control hearts were constant (2.2±1.2 fmol/L, 2.2±1.3 fmol/L, and 2.5±1.0 fmol/L, respectively). In group 2 (n=6), 10 μmol/L of BE-18257B was given just before reperfusion. In group 3 (n=8), 10 pmol/L ET-1 was given just before the start of reperfusion. At 30 minutes of reperfusion, the ET-A antagonist hearts had significantly greater recovery of LV systolic (positive dP/dt and dP/dt at V10) and diastolic function (negative dP/dt), coronary blood flow (CBF), and MV̇
o
2
compared with controls (
P
<.05). The ET-1 hearts showed significantly reduced recovery of LV systolic (positive maximum and volume-normalized dP/dt) and diastolic (negative maximum dP/dt) function, CBF, and myocardial oxygen consumption compared with controls (
P
<.05).

Conclusions
These results, combined with prior studies, suggest that I/R causes reduced production of endogenous vasodilators (eg, nitric oxide), leaving unopposed the vasoconstriction that is caused by the continued presence of ET-1. This imbalance may contribute to I/R injury. ET-A receptor antagonists may be useful therapeutic agents in reducing the injury that results from I/R.
Left Ventricular Function, Twist, and Recoil After Mitral Valve Replacement
Authors: DeAnda Abe , Komeda Masashi , Nikolic Srdjan D. , Daughters George T. , Ingels Neil B. , Miller D. Craig
Published: June 2012

Background
Preservation of the mitral subvalvular apparatus during mitral valve replacement (MVR) has become more popular, in part because of the clinically and experimentally demonstrated more optimal left ventricular (LV) performance after surgery; the mechanisms responsible for this beneficial influence, however, have not been clearly elucidated.

Methods and Results
Fourteen dogs underwent placement of 26 myocardial markers into the LV and septum. One week later, the animals were studied while awake, sedated, and atrially paced (120 beats per minute) both under baseline conditions and after inotropic stimulation (calcium). The animals then underwent MVR and were randomized into either chord-sparing (MVR-Intact) or chord-severing (MVR-Cut) techniques. Two weeks later, the animals were studied under the same conditions. LV systolic function was assessed by the slope of the end-systolic pressure-volume relation (E
es
); early LV diastolic filling was analyzed by the pressure-time constant of relaxation (τ). The instantaneous longitudinal gradient of torsional deformation for the LV (twist) was also calculated, as were the changes in twist with respect to time during systole and early diastole (LV recoil). Intergroup comparison showed a trend toward increased contractility (E
es
,
P
=.061, before versus after MVR), as well as faster relaxation for the MVR-Intact group. Concurrent analysis of LV systolic function and the rate of systolic twist revealed a significant inverse relation, which disappeared after MVR when the chordae were severed.

Conclusions
These observations suggest that the mitral subvalvular apparatus acts as a modulator of LV systolic torsional deformation into LV pump (or ejection) performance.
Efficiency of In Vivo Gene Transfection Into Transplanted Rat Heart by Coronary Infusion of HVJ Liposome
Authors: Sawa Yoshiki , Suzuki Ken , Bai Hong-Zhi , Shirakura Ryota , Morishita Ryuichi , Kaneda Yasufumi , Matsuda Hikaru
Published: June 2012

Background
Current methods of in vivo gene transfer into myocardium are limited by low efficiency. To improve in vivo gene transfer, a gene transfer method using hemagglutinating virus of Japan (HVJ) as a viral vector can be an alternative.

Methods and Results
In vivo gene transfection of FITC-labeled oligonucleotide (F-ODN) and cDNA of β-galactosidase (β-gal) was examined with use of the HVJ liposome (H group) or without it (C group). In the H group, F-ODN or cDNA of β-gal were complexed with liposomes, DNA binding nuclear protein (HMG1), and the viral protein coat of HVJ. After the harvest of donor rat hearts arrested by cardioplegia, the coronary artery was infused with the liposome gene complex. The hearts were transplanted into the abdomens of recipient rats and harvested 3 days after transplantation. Regarding F-ODN, the H group clearly showed FITC staining in the nuclei of the myocytes and endothelial cells in almost all layers of the myocardium as compared with the C group. Regarding the expression of β-gal, the H group showed a clear expression of β-gal on myocytes, whereas very low expression of β-gal was seen in the C group.

Conclusions
The donor hearts were transfected with F-ODN and β-gal gene in almost all layers of the myocardium as a result of coronary infusion of the HVJ liposome during cardioplegic arrest. Our method is seen as a novel in vivo gene transfer technique for the heart and may provide a new tool for both research and therapy of heart transplantation.
Myocardial Revascularization With Laser
Authors: Frazier O.H. , Cooley Denton A. , Kadipasaoglu Kamuran A. , Pehlivanoglu Seckin , Lindenmeir Matthias , Barasch Eddy , Conger Jeff L. , Wilansky Susan , Moore W.H.
Published: June 2012

Background
We assessed the transmyocardial laser revascularization (TMLR) as sole therapy in patients with symptomatic coronary artery disease refractory to interventional or medical treatment.

Methods and Results
Thirty-one patients were evaluated with positron emission tomography (PET), dobutamine echocardiography,
201
Tl single–photon emission computed tomography (
201
Tl-SPECT), and multigated acquisition radionuclide ventriculography (MUGA). TMLR was performed in 21 patients who had demonstrable ischemia in viable myocardium. The mean Canadian Cardiovascular Society (CCS) angina class was 3.70±0.7 (4 patients with unstable angina). Untreated septal segments were used as controls. At 3 months, (
n
=15 patients), the mean CCS angina class was to 2.43±0.9 (
P
<.05). On dobutamine echocardiography, the mean resting wall motion score index was improved by 16% in lased segments (
P
<.03 vs control), and mean LVEF at peak stress increased by 19% (
P
=NS vs baseline). On
201
Tl-SPECT, perfusion of lased and nonlased segments did not change. On PET, the mean ratio of subendocardial to subepicardial perfusion (SEn/SEp) increased 14% over baseline (
P
<.001 vs control). At 6 months (n=15 patients), the mean CCS angina class was 1.7±0.8 (
P
<.05). The mean resting wall motion score index was up by 13% in lased segments (
P
<.05 vs control). Resting LVEF was unchanged. Stress LVEF increased 21% (
P
=NS vs baseline). Myocardial perfusion remained unchanged by
201
Tl-SPECT. On PET, 36% of the lased segments were better, and 25% were worse compared with baseline. The resting SEn/SEp by PET was up 21% (
P
<.001 vs control). All deaths (two perioperative and three late) occurred in patients with preoperative congestive heart failure. Two patients required repeat revascularization of new coronary lesions.

Conclusions
These results suggest that TMLR improves anginal status, relative endocardial perfusion, and cardiac function in patients who do not have preoperative congestive heart failure.
Unilateral Versus Bilateral Internal Mammary Revascularization
Authors: Dewar Leith R.S. , Jamieson W.R. Eric , Janusz Michael T. , Adeli-Sardo Manouchehr , Germann Eva , MacNab Joan S. , Tyers G. Frank O.
Published: June 2012

Background
The influence of unilateral (UL) and bilateral (BL) mammary artery revascularization, within age groups ≤60 years and >60 years, on patient survival, ischemic-related events, and interventional management was studied in 1142 patients who had coronary artery bypass graft surgery between 1984 and 1992.

Methods and Results
UL revascularization was performed in 765 (67%) and BL in 377 (33%) patients with supplemental vein grafts. The overall early and hospital mortality rate was 2.7%. For UL in the age group ≤60 years, it was 1.1%; for BL ≤60 years, 1.3% (
P
=NS); for UL >60 years, 4.3%; and for BL >60 years, 2.8% (
P
=NS). Twenty-five preoperative patient characteristics representing demographics, extent of disease, concomitant disease, ventricular dysfunction, previous surgery, and status did not differentiate the patient groups (
P
=NS). Patient survival at 5 years was not different: 94% for UL ≤60 years, 95% for BL ≤60 years, 91% for UL >60 years, and 86% for BL >60 years (
P
=NS). The freedom from ischemic-related events was not different at 5 years (
P
=NS). The freedom from recurrent angina was 78% for UL ≤60 years, 88% for BL ≤60 years, 82% for UL >60 years, and 83% for BL >60 years (
P
= NS). The myocardial infarction freedom was 98% for UL ≤60 years, 96% for BL ≤60 years, 99% for UL >60 years, and 97% for BL >60 years (
P
=NS). The freedom from sudden unexpected death and cardiac death did not differentiate the groups (
P
=NS). The freedom from angioplasty and reoperation did not differentiate the groups (
P
=NS). The freedom from all ischemic-related and interventional events was 76% for UL ≤60 years, 84% for BL ≤60 years, 81% for UL >60 years, and 79% for BL >60 years (
P
=NS). A trend exists for less angina pectoris in the bilateral population ≤60 years, which reflects in the trend in the freedom from overall events.

Conclusions
UL and BL mammary artery revascularizations have the same early mortality regardless of age but do not reveal any advantage for BL revascularization at 5 to 7 years.
Which Is the Graft of Choice for the Right Coronary and Posterior Descending Arteries?
Authors: Dietl Charles A. , Benoit Charles H. , Gilbert Christian L. , Woods Edward L. , Pharr William F. , Berkheimer Marie D. , Madigan N. Patrick , Menapace Francis J.
Published: June 2012

Background
The graft of choice for the left anterior descending coronary artery is the left internal mammary artery because of superior long-term patency. However, controversy exists regarding the graft of choice for the right coronary artery and for the posterior descending branch.

Methods and Results
Two types of pedicled arterial grafts were used for the right coronary and the posterior descending arteries in patients undergoing coronary bypass surgery between January 1991 and September 1994. Group A comprised 114 patients with a right internal mammary artery (RIMA) graft, and group B consisted of 127 patients with an in situ right gastroepiploic artery (R-GEA) graft. Mean age was 56.9 years in group A and 63.3 years in group B; 7.9% (9 of 114) and 33.9% (43 of 127) were diabetics in groups A and B, respectively. Overall mortality was 2.6% (3 deaths) for group A and 3.9% (5 deaths) for group B (
P
=NS). However, the prevalence of perioperative myocardial infarction in the right coronary artery distribution was significantly higher for group A (5.3%, or 6 of 114) than for group B (0.8%, or 1 of 127;
P
<.05), and the reoperation rate for graft failure (from 0 to 12 months after surgery) was significantly higher for the RIMA (4.4%, or 5 of 114) than for the R-GEA (0%;
P
<.05). Also, the prevalence of deep sternal wound infection in diabetics was significantly higher in group A (22.2%, or 2 of 9) than in group B (4.6%, or 2 of 43;
P
<.05).

Conclusions
Our preliminary results suggest that the failure rate of the RIMA graft is significantly higher, especially if used as a pedicled graft to the posterior descending artery. The risk of sternal wound complications is greater in diabetics if both internal mammary arteries are used for grafting. Therefore, the R-GEA graft is preferred in diabetics and whenever the posterior descending artery is the target vessel.
Comparison of Sustained Antithrombotic Effects of Inhibitors of Thrombin and Factor Xa in Experimental Thrombosis
Authors: Biemond Bart J. , Friederich Philip W. , Levi Marcel , Vlasuk George P. , Büller Harry R. , ten Cate Jan W.
Published: June 2012

Background
In the pathogenesis of (recurrent) thrombosis, clot-associated thrombin appears to play an important role. Antithrombin III–independent thrombin inhibitors have been shown to neutralize clot-bound thrombin effectively. We compared the sustained antithrombotic effects and the effects on endogenous fibrinolysis of several of these agents with recombinant tick anticoagulant peptide (rTAP), a selective factor Xa inhibitor, and low-molecular-weight heparin (LMWH) in an experimental venous thrombosis model.

Methods and Results
Rabbits received either recombinant hirudin (rHir), Hirulog-1, CVS#995 (a novel direct inhibitor of thrombin), rTAP, LMWH, or saline. The effect on thrombus growth was assessed by measuring the accretion of
125
I-labeled fibrinogen onto preformed nonradioactive thrombi, and the effect on endogenous fibrinolysis was assessed by measuring the decline in radioactivity of preformed
125
I-labeled thrombi in rabbit jugular veins. All direct thrombin inhibitors induced a sustained antithrombotic effect compared with either LMWH and rTAP. In addition, CVS#995 also further decreased thrombus size after stopping its infusion, which was due to a significant enhancement of endogenous fibrinolysis.

Conclusions
Direct thrombin inhibition by rHir, Hirulog-1, or CVS#995 induces a sustained antithrombotic effect compared with rTAP and LMWH, which is most likely due to inhibition of clot-bound thrombin. CVS#995 was shown to also enhance the extent of endogenous fibrinolysis to a greater degree compared with rHir and might therefore be an interesting new antithrombotic agent for the treatment of venous and arterial thrombosis.
Relation Between Folate Status, a Common Mutation in Methylenetetrahydrofolate Reductase, and Plasma Homocysteine Concentrations
Authors: Jacques Paul F. , Bostom Andrew G. , Williams Roger R. , Ellison R. Curtis , Eckfeldt John H. , Rosenberg Irwin H. , Selhub Jacob , Rozen Rima
Published: June 2012

Background
Methylenetetrahydrofolate reductase (MTHFR) synthesizes 5-methyltetrahydrofolate, the major carbon donor in remethylation of homocysteine to methionine. A common MTHFR mutation, an alanine-to-valine substitution, renders the enzyme thermolabile and may cause elevated plasma levels of the amino acid homocysteine.

Methods and Results
To assess the potential interaction between this mutation and vitamin coenzymes in homocysteine metabolism, we screened 365 individuals from the NHLBI Family Heart Study. Among individuals with lower plasma folate concentrations (<15.4 nmol/L), those with the homozygous mutant genotype had total fasting homocysteine levels that were 24% greater (
P
<.05) than individuals with the normal genotype. A difference between genotypes was not seen among individuals with folate levels ≥15.4 nmol/L.

Conclusions
Individuals with thermolabile MTHFR may have a higher folate requirement for regulation of plasma homocysteine concentrations; folate supplementation may be necessary to prevent fasting hyperhomocysteinemia in such persons.