bluuebunny/crossref_metadata_2025 huggingface dataset:
Postoperative Course and Hemodynamic Profile After the Arterial Switch Operation in Neonates and Infants
Authors: Wernovsky Gil , Wypij David , Jonas Richard A. , Mayer John E. , Hanley Frank L. , Hickey Paul R. , Walsh Amy Z. , Chang Anthony C. , Castañeda Aldo R. , Newburger Jane W. , Wessel David L.
Published: June 2012

Background
The neurological morbidity associated with prolonged periods of circulatory arrest has led some cardiac surgical teams to promote continuous low-flow cardiopulmonary bypass as an alternative strategy. The nonneurological postoperative effects of both techniques have been previously studied only in a limited fashion.

Methods and Results
We compared the hemodynamic profile (cardiac index and systemic and pulmonary vascular resistances), intraoperative and postoperative fluid balance, and perioperative course after deep hypothermia and support consisting predominantly of total circulatory arrest or low-flow cardiopulmonary bypass in a randomized, single-center trial. Eligibility criteria included a diagnosis of transposition of the great arteries and a planned arterial switch operation before the age of 3 months. Of the 171 patients, 129 (66 assigned to circulatory arrest and 63 to low-flow bypass) had an intact ventricular septum and 42 (21 assigned to circulatory arrest and 21 to low-flow bypass) had an associated ventricular septal defect. There were 3 (1.8%) hospital deaths. Patients assigned to low-flow bypass had significantly greater weight gain and positive fluid balance compared with patients assigned to circulatory arrest. Despite the increased weight gain in the infants assigned to low-flow bypass, the duration of mechanical ventilation, stay in the intensive care unit, and hospital stay were similar in both groups. Hemodynamic measurements were made in 122 patients. During the first postoperative night, the cardiac index decreased (32.1±15.4%, mean±SD), while pulmonary and systemic vascular resistance increased. The measured cardiac index was <2.0 L · min
−1
· m
−2
in 23.8% of the patients, with the lowest measurement typically occurring 9 to 12 hours after surgery. Perfusion strategy assignment was not associated with postoperative hemodynamics or other nonneurological postoperative events.

Conclusions
After heart surgery in neonates and infants, both low-flow bypass and circulatory arrest perfusion strategies have comparable effects on the nonneurological postoperative course and hemodynamic profile.
Mechanisms of Ischemic Preconditioning in Rat Hearts
Authors: Hu Keli , Nattel Stanley
Published: June 2012

Background
Ischemic preconditioning attenuates the effects of subsequent sustained ischemia by a mechanism involving adenosine and G proteins in several species. Adenosine is not involved in ischemic preconditioning of rat hearts, the mechanisms of which are poorly understood.

Methods and Results
Reduction of isometric tension development was used as an index of the effects of ischemia in isolated, Langendorff-perfused rat hearts. Two 5-minute periods of ischemia followed by 10 minutes of reperfusion attenuated the reduction of developed tension caused by 30 minutes of ischemia and 15 minutes of reperfusion. Pretreatment with pertussis toxin (PTX), depletion of norepinephrine stores with reserpine, or blockade of α
1
-adrenoceptors with prazosin prevented the effects of ischemic preconditioning. Whereas α
1B
-receptor blockade with chloroethylclonidine blocked ischemic preconditioning, α
1A
-receptor blockade with 5-methylurapadil had no effect. The α-adrenergic agonist phenylephrine mimicked the effects of ischemic preconditioning in a concentration-dependent manner, and pretreatment with PTX prevented the action of maximally effective concentrations of phenylephrine. The protein kinase C activator phorbol 12-myristate 13-acetate mimicked and the protein kinase C inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine and bisindolylmaleimide prevented ischemic preconditioning.

Conclusions
Ischemic preconditioning in isolated, perfused rat hearts is caused by stimulation of α
1B
-adrenoceptors by endogenous catecholamines through the activation of protein kinase C via a PTX-sensitive G protein. The PTX-sensitive inhibitory protein G
i
, which can be activated by adenosine, muscarinic agonists, and α
1
-adrenoceptor agonists, may play a central role in ischemic preconditioning mediated by protein kinase C across a broad range of species.
Vagal Modulation of Epicardial Coronary Artery Size in Dogs
Authors: Kovach Julie A. , Gottdiener John S. , Verrier Richard L.
Published: June 2012

Background
Because the role of tonic vagus nerve activity in regulating conduit coronary artery size remains undefined, we investigated the response of epicardial coronary artery size to changes in resting vagal tone resulting from vagotomy and muscarinic receptor blockade.

Methods and Results
Using intravascular ultrasound to measure left circumflex coronary artery cross-sectional area continuously, we examined the effects of vagotomy on left circumflex cross-sectional area in nine dogs. Lumen area decreased 20% from 8.70±2.81 to 6.92±1.97 mm
2
after right vagotomy, 17% to 7.19±2.80 mm
2
after left vagotomy (both
P
<.05 versus baseline), and 38% to 5.42±2.00 mm
2
after bilateral vagotomy (
P
<.05 versus unilateral vagotomy). Vasoconstriction occurred despite increases in heart rate and an unchanged rate-pressure product. In six additional dogs, after acetylcholine (100 μg/kg IV), lumen area increased by 18%, although heart rate, blood pressure, and rate-pressure product were unchanged. Vasodilation was prevented by prior muscarinic blockade with glycopyrrolate. With glycopyrrolate administration and heart rate control by pacing, lumen area decreased by 26% (
P
=.011). When stellate stimulation was performed in a third group of eight dogs with heart rate, blood pressure, and rate-pressure product controlled by a combination of pacing and exsanguination, there was no change in coronary area, thus precluding reflex sympathetic activation as a contributor to the vasoconstriction produced by vagal withdrawal.

Conclusions
Vagus nerve activity maintains tonic dilation of the left circumflex coronary artery by muscarinic receptor activation. Each vagus nerve contributes approximately equally to the tonically dilated state. Vagotomy-induced vasoconstriction occurs independently of local metabolic factors and coronary distending pressure and is a result of cholinergic withdrawal rather than reflex sympathetic activation.
Intramural Delivery of Agent via a Novel Drug-Delivery Sleeve
Authors: Moura Alvaro , Lam Jules Y.T. , Hébert Daniel , Kermode James R. , Grant Gordon W. , Robitaille Danielle , Klein Enrique J. , Yock Paul G. , Simpson John B. , Kaplan Aaron V.
Published: June 2012

Background
The infusion sleeve is a novel drug-delivery catheter system designed to deliver an agent under controlled conditions into the arterial wall at the site of angioplasty. The purpose of the present study was to characterize the delivery agent via the infusion sleeve in ex vivo and in vivo models.

Methods and Results
The delivery of horseradish peroxidase via the infusion sleeve was studied in a porcine explanted heart model. Under physiological conditions, arteries underwent balloon injury (≈10% overstretch), after which horseradish peroxidase (2.5 mL) was delivered at specific pressures. Cross-sectional analysis demonstrated greater staining when the agent was delivered at increasing pressures. The infusion sleeve was evaluated in an in vivo canine coronary model. With an infusion sleeve loaded over a standard dilatation catheter through a 9F guide, overstretch balloon injury was performed, after which fluoresceinated heparin was delivered. Animals were killed 2 hours after delivery. Fluoresceinated heparin–treated segments demonstrated high fluorescence signals, localizing with smooth muscle cell nuclei with less activity in the interstitium. The functional significance of intramural heparin delivery was studied in a porcine carotid model. In the presence of
111
In-labeled platelets, arteries underwent overstretch injury followed by delivery of heparin (50 or 100 units/kg) or vehicle. Platelet deposition was reduced at 30 minutes (57%,
P
<.01) and 12 hours (39%,
P
=.06) compared with saline controls.

Conclusions
Agent delivery via the infusion sleeve is pressure dependent; transmural delivery is possible with minimal disruption of arterial wall architecture; the infusion sleeve is compatible with standard angioplasty equipment; and heparin delivery at the site of balloon injury significantly reduces platelet deposition in a porcine model for a minimum of 12 hours.
Our Preoccupation With Coronary Luminology
Authors: Topol Eric J. , Nissen Steven E.
Published: June 2012

Abstract
Nearly 40 years after its invention, the angiogram is still considered by most physicians to be the “gold standard” for defining coronary anatomy. Careful investigations have revealed many deficiencies inherent in this approach. The purpose of this article is to outline the evidence that our current preoccupation with coronary “luminology” may be misguided and to propose a rational paradigm for future practice and investigation. Angiography depicts coronary anatomy from a planar two-dimensional silhouette of the lumen. Angiography is limited in resolution to four or five line pairs per millimeter. Confounding factors include vessel tortuosity, overlap of structures, and the effects of lumen shape. After intervention, a hazy, broadened silhouette may overestimate the actual gain in lumen size. Studies show marked disparity between the apparent severity of lesions and their physiological effects. After myocardial infarction, cardiologists too often do not make an attempt to demonstrate the physiological significance of the stenosis before performing percutaneous coronary revascularization. Similarly, the allure of a better, more gratifying angiogram with new interventional devices appears to be a dominant factor in their popularity. Interventional cardiologists should be aware that techniques yielding marked angiographic benefit may also generate important but unrecognized hazards. The dissociation between the angiogram and clinical outcome should influence future research efforts. Our review of the literature indicates that we may benefit from shifting the current focus and preoccupation with coronary luminology to achieving the desired clinical end point: promoting survival and long-term freedom from myocardial infarction and the disabling symptoms of coronary heart disease.
Long-term Clinical and Echocardiographic Follow-up After Surgical Correction of Hypertrophic Obstructive Cardiomyopathy With Extended Myectomy and Reconstruction of the Subvalvular Mitral Apparatus
Authors: Schoendube Friedrich A. , Klues Heinrich G. , Reith Sebastian , Flachskampf Frank A. , Hanrath Peter , Messmer Bruno J.
Published: June 2012

Background
The standard surgical approach to hypertrophic obstructive cardiomyopathy (HOCM) was modified in the present series with a combination of extended myectomy with partial excision and mobilization of the papillary muscles.

Methods and Results
Between 1979 and 1992, 58 patients (38 men and 20 women; mean age, 49±24 years) with HOCM were operated on with the use of this different technique. Their intraventricular gradients were 79±33 (±SD) mm Hg at rest and increased to 147±48 mm Hg with provocative maneuvers. Mild-to-moderate mitral regurgitation was present in 60% of the patients, and severe regurgitation was present in 5%. Ten patients required additional aortocoronary bypass graft surgery. Follow-up (mean, 84 months) was complete (100%). Hemodynamic improvement was documented by a significant (
P
<.01) decrease in left ventricular end-diastolic pressure from 19±9 to 14±6 mm Hg and reduction of basal outflow tract gradients to 5±7 mm Hg at rest and 16±24 mm Hg after provocation. Late mortality was 1.4% per patient-year, and no sudden cardiac deaths occurred during follow-up. Functional status was excellent for 84% of the patients; 8 patients were in New York Heart Association functional class III, and none were in class IV. Echocardiography revealed no outflow tract obstruction.

Conclusions
Extended myectomy and reconstruction of the subvalvular mitral apparatus in HOCM result in excellent functional improvement with relief of outflow tract obstruction. The technique can be performed safely despite its more aggressive surgical nature and allows an individualized strategy depending on the patient’s extent and distribution of left ventricular hypertrophy.
Early and Late Mortality of Patients Undergoing Aortic Valve Replacement After Previous Coronary Artery Bypass Graft Surgery
Authors: Fighali Sayid F. , Avendaño Amilcar , Elayda MacArthur A. , Lee Vei Vei , Hernandez Cesar , Siero Valentina , Leachman Robert D. , Cooley Denton A.
Published: June 2012

Background
In a small number of patients who undergo coronary artery bypass graft surgery (CABG), a hemodynamically significant aortic valve lesion requiring aortic valve replacement (AVR) develops as they grow older. In a limited number of studies in small patient groups, high mortality has been shown in patients undergoing AVR after CABG. We undertook this study to determine the mortality risk factors for patients who undergo AVR after CABG procedures.

Methods and Results
The outcome of 104 patients treated at our institution between January 1983 and December 1993 was retrospectively reviewed. The initial surgery was CABG in all patients. The patient population included 86 men (83%) and 18 women (17%); their mean age was 67 years. Overall, 70% of patients had congestive heart failure, and 96% had multivessel coronary artery disease. The diagnosis was aortic stenosis in 68% of patients, aortic insufficiency in 16%, and combined aortic stenosis and aortic insufficiency in 16%. Postoperative complications included worsening congestive heart failure (35%), perioperative myocardial infarction (13%), and bleeding (28%). The early mortality was 14%, and the late mortality was 17% (mean follow-up, 35 months). The risk factors for early mortality were number of diseased vessels (
P
=.028), renal failure (0.000), and prior myocardial infarction (
P
=.028). A perioperative predictor of early mortality was cardiopulmonary bypass time (
P
=.000). The risk factors for late mortality included preoperative diabetes mellitus (
P
=.007), postoperative acute respiratory distress syndrome (
P
=.011), and ventricular arrhythmias (
P
=.0001). The survival at 1, 5, and 10 years was 96%, 75%, and 49%, respectively.

Conclusions
Risk factors were identified for early and late mortality in patients undergoing AVR after previous CABG. Although early morbidity and mortality were high, the long-term outcome of the survivors was favorable.
Use of the Bidirectional Glenn Procedure in the Presence of Forward Flow From the Ventricles to the Pulmonary Arteries
Authors: Uemura Hideki , Yagihara Toshikatsu , Kawashima Yasunaru , Okada Kenji , Kamiya Tetsuro , Anderson Robert H.
Published: June 2012

Background
Relative regression of the pulmonary arterial size has been reported after a conventional bidirectional Glenn procedure. Maintaining a supplemental pulmonary flow could be of surgical value unless the option also militates against the efficacy of the partial right heart bypass.

Methods and Results
Twenty-seven patients considered unsuitable for a Fontan-type procedure underwent a bidirectional Glenn procedure in the presence of forward flow from the ventricles to the pulmonary arteries, the flow being maintained through the pulmonary trunk in 22 or a systemic-to-pulmonary shunt in 5. There was one surgical death due to atrioventricular valvular regurgitation. Subsequently, 9 patients have successfully undergone a total cavopulmonary connection 2.6±1.9 years after the initial procedure. Preoperative and postoperative catheterizations revealed changes in arterial oxygen saturation (75±11% compared with 83±7%,
P
<.001) and end-diastolic volumes of the systemic ventricles (from 238±92% to 188±97% of the expected normal volume,
P
<.01), whereas no difference was detected in the mean cross-sectional area of the right and left pulmonary arteries compared with the expected normal value for the right pulmonary artery (from 76±21% to 81±20%) or in the ventricular ejection fraction (from 53±8% to 50±14%). The relative regression or growth of the pulmonary arterial size was statistically related to the size of the channel for forward flow.

Conclusions
Maintenance of forward flow from the ventricle provides a feasible means, when performing a bidirectional Glenn procedure, of protecting against regression of pulmonary arterial size as well as off-loading the ventricles and improving arterial oxygen saturation.
Intracoronary Heparin Delivery in Humans
Authors: Camenzind Edoardo , Kint Peter-Paul , Di Mario Carlo , Ligthart Jürgen , van der Giessen Wim , Boersma Eric , Serruys Patrick W.
Published: June 2012

Background
Inefficacy of systemic drug administration for restenosis prevention may partially relate to insufficient local drug concentration. This study aimed to evaluate the acute feasibility and long-term outcome of using an infusion-perfusion coil balloon, Dispatch.

Methods and Results
In 22 patients after balloon angioplasty, the coil balloon was studied for (1) feasibility of local heparin delivery, (2) symptoms and signs of ischemia during prolonged deployment compared with angioplasty balloon occlusion, (3) coronary pressure and flow distal to the inflated device, and (4) long-term clinical and angiographic results. During prolonged intracoronary deployment of the coil balloon (29±8 minutes), 5 of 22 patients developed mild chest pain versus 20 of 22 during angioplasty (275±283 seconds). Neither hemodynamic nor vectorcardiographic signs of ischemia were detected, in contrast to angioplasty balloon occlusion. Baseline flow across the coil balloon was 44±31 mL/min, increasing by a factor of 1.8±0.7 during pharmacologically induced hyperemia. A mean volume of 14.2±6.1 mL containing 1416±608 IU of heparin was infused locally at a pressure of 122±54 mm Hg. At 7±1-month follow-up, 1 asymptomatic patient had died, and of the remaining 21, 17 (81%) were asymptomatic. Angiographic follow-up was obtained in 15 of 21 patients (71%), including all 4 symptomatic patients. Mean minimal luminal diameter after the procedure was 2.16±0.49 mm and at follow-up, 1.89±0.45 mm, which corresponds to a restenosis rate (diameter stenosis ≥50%) of 7% (1/15).

Conclusions
Intracoronary use of the coil balloon after balloon angioplasty proved to be feasible and subjectively as well as objectively well tolerated during prolonged deployment by virtue of its perfusion properties. High volumes of heparin solution can be infused locally at very low pressure. No unfavorable clinical or angiographic long-term effects were observed.
Congestive Heart Failure After Surgical Correction of Mitral Regurgitation
Authors: Enriquez-Sarano Maurice , Schaff Hartzell V. , Orszulak Thomas A. , Bailey Kent R. , Tajik A. Jamil , Frye Robert L.
Published: June 2012

Background
In patients with mitral regurgitation, surgical intervention produces immediate improvement in symptoms, but the long-term incidence and significance of postoperative congestive heart failure are unknown.

Methods and Results
The long-term outcome of 576 operative survivors of surgical correction of pure mitral regurgitation performed between 1980 and 1989 was analyzed. Survival was 77±2% and 56±3% at 5 and 10 years, respectively. Cumulative incidence of congestive heart failure was 23±2%, 33±3%, and 37±3% at 5, 10, and 14 years, respectively. Survival after the first episode of congestive heart failure was dismal, 44±4% at 5 years. Cause of congestive heart failure was left ventricular dysfunction in two thirds of the patients and valvular dysfunction in the other third. With multivariate analysis, the independent predictors of postoperative heart failure were preoperative ejection fraction (
P
=.0001), coronary artery disease (
P
=.0017), and New York Heart Association functional class (
P
=.012), with borderline value for atrial fibrillation (
P
=.10). The performance of valve repair was independently predictive of a lower incidence of the combined end point of death and heart failure (
P
=.001), compared with valve replacement.

Conclusions
Congestive heart failure frequently occurs late after surgical correction of mitral regurgitation and portends dismal prognosis. This complication is due most often to left ventricular dysfunction; its main determinant is decreased left ventricular function preoperatively. These data should lead to earlier indication of surgical correction of mitral regurgitation, before left ventricular dysfunction occurs.
Noninvasive Assessment of Left Internal Mammary Artery Graft Patency Using Transthoracic Echocardiography
Authors: Crowley James J. , Shapiro Leonard M.
Published: June 2012

Background
Cardiac catheterization is the only practical method of assessing internal mammary artery graft patency. A noninvasive method would be useful in patients with recurrence of anginal symptoms after coronary artery bypass graft surgery. We hypothesized that transthoracic echocardiography could provide information on blood velocity and anatomy and therefore has the potential to allow measurement of blood flow.

Methods and Results
High-frequency (5 MHz) transthoracic echocardiography was performed on 41 consecutive patients (mean age, 67±6 years) who had had left internal mammary artery grafts to the left anterior descending coronary artery (LAD) and were undergoing coronary angiography because of recurrence of anginal symptoms. The results were compared with those from 19 patients (mean age, 58±11 years) in whom an ungrafted left internal mammary artery was assessed and with those from 15 patients (mean age, 61±12 years) who had angiographically normal coronary arteries in whom the LAD was studied. Doppler velocity profiles of the left internal mammary graft were obtained in 35 of the 41 study patients (81%). In all cases, a biphasic pattern of blood flow was recorded that corresponded to systole and diastole. Two different flow patterns were observed. In 25 patients with a normal graft or moderate (<70%) stenosis (group A), blood flow velocity was maximal during diastole. This pattern was also seen in the LAD control group. In 10 patients with severe (>70%) graft stenosis (group B), blood velocity was maximal during systole, and low velocities were recorded during diastole. This pattern was also seen in the ungrafted internal mammary artery control group. The diastolic fraction of the velocity time integrals for group A was 0.77±0.07 and for group B was 0.27±0.01 (
P
<.05). A diastolic velocity time integral fraction <0.5 predicted severe stenosis with a sensitivity and specificity of 100%. The ratio of systolic-to-diastolic peak velocities for group A was 0.54±0.26 and for group B was 3.45±0.74 (
P
<.05). A systolic-to-diastolic peak velocity ratio >1 predicted severe stenosis with a sensitivity of 100% and specificity of 85%. Mean graft blood flow was 63±21 mL/min. There was no significant difference in mean blood flow between any of the patient groups studied.

Conclusions
High-frequency transthoracic echocardiography allows identification of the left internal mammary grafts and measurement of blood flow. Compared with patent grafts or those with moderate lesions, severe stenoses demonstrated different Doppler velocity patterns. Use of this technique may allow noninvasive detection of significant stenoses of the left internal mammary artery graft.
Dilated Cardiomyopathy Associated With Hepatitis C Virus Infection
Authors: Matsumori Akira , Matoba Yoshiki , Sasayama Shigetake
Published: June 2012

Background
Myocarditis is thought to be commonly caused by various viruses, and accumulating evidence links viral myocarditis with the eventual development of dilated cardiomyopathy. In many cases, however, the evidence is only circumstantial, and direct conclusive proof is not available. Polymerase chain reaction (PCR) has been used to detect enterovirus RNA in myocardial tissue, but the wide discrepancy in results emphasizes the need for further study.

Methods and Results
We investigated hepatitis C virus infection in patients with dilated cardiomyopathy. The presence, type, and quantity of hepatitis C virus RNA were evaluated in the sera, and the presence of positive and negative strands of hepatitis C virus RNA in the heart was investigated with the PCR technique. Anti–hepatitis C virus antibody was present in the sera of 6 of 36 patients (16.7%) with dilated cardiomyopathy and in 1 of 40 patients (2.5%) with ischemic heart disease, showing a statistically significant (
P
<.05) difference. At an earlier time, acute myocarditis was suspected in 3 patients who had developed acute onset of heart failure, and the diagnosis was confirmed by endomyocardial biopsy in 1 patient. Hepatitis C virus RNA was present in the sera of 4 of the 6 patients, and all 4 had hepatitis C virus type II. The copy number of hepatitis C virus RNA in the serum was 8×10
2
to 2×10
3
genomes per 1 mL serum. Positive strands of hepatitis C virus were found in the hearts of 3 patients, and negative strands of hepatitis C virus were detected in the heart of 1 patient.

Conclusions
The results suggest that hepatitis C virus infection is frequently found in patients with dilated cardiomyopathy and that hepatitis C virus is an important causal agent in the pathogenesis of the disease. Antiviral therapy against hepatitis C virus may be indicated in these patients.
Sternotomy Approach for the Modified Blalock-Taussig Shunt
Authors: Odim Jonah , Portzky Michael , Zurakowski David , Wernovsky Gil , Burke Redmond P. , Mayer John E. , Castaneda Aldo R. , Jonas Richard A.
Published: June 2012

Background
Since 1990, sternotomy has been the preferred approach for construction of a modified Blalock-Taussig shunt (MBTS) at Children’s Hospital, Boston, Mass. In retrospect, we sought to test the hypothesis that this approach yields less mortality and morbidity than the traditional thoracotomy approach.

Methods and Results
One hundred four primary MBTSs with polytetrafluoroethylene grafts were constructed in patients from January 1988 through December 1992. Fifty-two shunts were constructed by thoracotomy approach and 52 by sternotomy approach. Fifteen of the thoracotomy patients were less than one month of age (8 less than 7 days), while 36 of the sternotomy patients were less than 1 month of age (20 less than 7 days). There were 10 shunt failures and 3 hospital deaths in the thoractomy group and 4 shunt failures with 6 hospital deaths in the sternotomy group. The overall hospital mortality rate for the group was 8.7% (9 of 104). The operative route was not a significant predictor of hospital mortality (
P
=.30). However, there was a significant difference between the two operative approaches in shunt failure, with shunts that were created by thoracotomy four times more likely to fail than those created by the sternotomy route (odds ratio, OR, 3.88; 95% CI, 1.01 to 15.03;
P
=.049). The side of the shunt was also a significant predictor of failure with left-side MBTSs four times more prone to failure (OR, 4.02; 95% CI, 1.19 to 15.25;
P
=.025).

Conclusions
The sternotomy route is technically less challenging and is associated with fewer shunt failures than the classic thoracotomy approach. The potential theoretical disadvantages of this method for future sternal reentry for subsequent procedures was not apparent but requires prospective analysis.
Effects on Coagulation and Fibrinolysis With Reduced Versus Full Systemic Heparinization and Heparin-Coated Cardiopulmonary Bypass
Authors: Øvrum Eivind , Brosstad Frank , Åm Holen Einfrid , Tangen Geir , Abdelnoor Michel
Published: June 2012

Background
Extracorporeal circulation with circuits coated with surface-bound heparin has allowed reduced levels of systemic heparinization. Clinical benefits have included reduced postoperative bleeding and less homologous blood usage. However, the effects on the hemostatic and fibrinolytic systems have remained in part unknown.

Methods and Results
Indications of thrombin generation, platelet activation, and fibrinolytic activity were investigated in patients undergoing coronary artery bypass surgery. Two groups were perfused with cardiopulmonary bypass (CPB) circuits completely coated with surface-bound heparin: one group with low systemic heparin dose (activated clotting time [ACT] >250 seconds; n=17) and a second group having a full heparin dose (ACT >480 seconds; n=18). A third control group was perfused with ordinary uncoated circuits and full heparin dose (n=17). The plasma level of thrombin-antithrombin complex and prothrombin fragment 1.2 increased in all groups during bypass, and somewhat more in both the heparin-coated groups toward the end of CPB, compared with the control group (
P
<.01). However, the increase during CPB was minimal compared with the major elevation observed 2 hours after surgery in all groups. Platelet release of β-thromboglobulin increased in all groups (
P
<.01) during CPB and significantly more in the high-dose group compared with the other two groups (
P
=.03). Fibrinolytic activities were similar in all groups, and there were no indications of major consumption of coagulation factors.

Conclusions
Reduced systemic heparinization (ACT >250 seconds) in patients having extracorporeal circulation with completely heparin-coated circuits did not lead to increased thrombogenicity. Thrombin formation remained within low ranges during CPB compared with patients receiving a full heparin dose and with the major elevations observed after surgery.
Chronic Inhibition of Endothelium-Derived Nitric Oxide Synthesis Causes Coronary Microvascular Structural Changes and Hyperreactivity to Serotonin in Pigs
Authors: Ito Akira , Egashira Kensuke , Kadokami Toshiaki , Fukumoto Yoshihiro , Takayanagi Tsuneo , Nakaike Ryuichi , Kuga Takeshi , Sueishi Katsuo , Shimokawa Hiroaki , Takeshita Akira
Published: June 2012

Background
Endothelium-derived nitric oxide (NO) is believed to regulate myocardial perfusion and structural changes in the vascular wall. Our objective was to determine whether chronic inhibition of NO synthesis causes structural and functional changes in coronary arteries.

Methods and Results
Coronary vasomotor response was studied in pigs before and after chronic oral administration of the NO synthesis antagonist
N
ω
-nitro-
l
-arginine methyl ester (L-NAME) 30 mg · kg
−1
· d
−1
for 2 weeks. Chronic L-NAME treatment increased (
P
<.01) arterial pressure but did not alter baseline coronary blood flow (CBF), epicardial coronary diameter, or heart rate. Chronic L-NAME treatment augmented (
P
<.01) the decrease in CBF in response to intracoronary serotonin (30 μg/kg) from 5±14% to 40±5% but did not alter the CBF response to prostaglandin F
2α
. The serotonin-induced decrease in CBF after acute L-NAME administration was still less before (1.3±0.4%) than after chronic L-NAME treatment (51±6%). Chronic L-NAME treatment attenuated the increase in CBF with bradykinin (100 ng/kg) but did not alter the CBF response to nitroglycerin (10 μg/kg). Compared with intact pigs without L-NAME treatment, L-NAME–treated pigs had significant thickening of the media in the microvessels (diameter, <300 μm) but not in the large epicardial vessels. Chronic intracoronary infusion of L-NAME at 3 mg · kg
−1
· d
−1
for 2 weeks, which did not produce arterial hypertension, caused similar microvascular medial thickening.

Conclusions
These results indicate that chronic administration of L-NAME caused coronary microvascular structural changes and hyperreactivity to serotonin in pigs in vivo, suggesting an important role of defective NO synthesis in coronary microvascular disorders.
Intermediate-Term Outcome After Intracardiac Repair of Associated Cardiac Defects in Patients With Atrioventricular and Ventriculoarterial Discordance
Authors: Sano Tetsuya , Riesenfeld Thomas , Karl Tom R. , Wilkinson James L.
Published: June 2012

Background
Limited information is available concerning long-term results, especially systemic right ventricular (RV) or tricuspid valvular function, after intracardiac repair of anomalies associated with discordant atrioventricular (AV) and ventriculoarterial (VA) connections (“congenitally corrected transposition of the great arteries”).

Methods and Results
We retrospectively reviewed the intermediate-term follow-up of 28 patients, totaling 158 patient-years (median, 60 months), after intracardiac repair involving closure of a ventricular septal defect (VSD) with or without additional surgery. Seven patients had VSD closure alone, 5 had VSD repair with pulmonary stenosis relief, and 16 had VSD closure with conduit insertion between left ventricle and main pulmonary artery. Hospital mortality was 4% (1 of 28 patients; 70% confidence limits, 0.07% to 12%) and the 1-, 5-, and 10-year actuarial survival probabilities were 89%, 83%, and 83%, respectively. Twenty-one of 24 long-term survivors were in New York Heart Association functional class I and 3 were in class II. Sixteen of 24 patients showed increasing tricuspid regurgitation (TR) of more than moderate degree, which occurred within 3 years after surgery in 7 patients. Twelve of 22 patients showed deterioration of RV pump function, mainly (9 of 12 patients) within 3 years postoperatively. The pulmonary to systemic flow ratio at the preoperative cardiac catheter study was significantly (
P
<.05) higher in patients who developed RV dysfunction (2.3±1.0, mean±SD) than in those with well-maintained RV function (1.4±0.6).

Conclusions
Intermediate-term results of intracardiac repair for AV and VA discordance were satisfactory in terms of survival and clinical functional status; however, there is concern about systemic RV dysfunction with development of TR relatively early after the operation. Alternative surgical approaches such as anatomic correction or Fontan repair for cases unsuitable for biventricular repair may improve the long-term results, including ventricular and valvular function.
Loss of Sinus Rhythm After Total Cavopulmonary Connection
Authors: Kavey Rae-Ellen W. , Gaum Winston E. , Byrum Craig J. , Smith Frank C. , Kveselis Daniel A.
Published: June 2012

Background
Total cavopulmonary connection (TCPC) to repair functional single ventricle involves the sinus node area, in contrast to the Fontan procedure. We compared ECG findings after TCPC and Fontan to evaluate the impact of the cavopulmonary connection on sinus rhythm postoperatively.

Methods and Results
The Fontan group consisted of 17 patients repaired at 7.8±3.1 years of age (mean±SD): 11 for tricuspid or pulmonary atresia (TA/PA) and 6 for single ventricle. The TCPC group consisted of 19 patients repaired at 5.1±3.2 years of age (mean±SD) (
P
<.001): 9 for TA/PA, 4 for single ventricle, and 6 for hypoplastic left heart syndrome. Mean follow-up after Fontan was 7.7±2.7 years versus 2.8±1.6 years for TCPC (
P
<.001). Preoperative ECGs on all TCPC patients showed sinus rhythm (SR), whereas 16 of 17 Fontan patients had SR and one had nonsinus atrial rhythm (NSAR) since birth. On the first postdischarge ECG, 12 of 19 TCPC patients (63%) were in SR, 4 were in junctional rhythm (JR), and 3 were in NSAR. In comparison, 15 of 17 Fontan patients (88%) were in SR with 1 of 17 in NSAR and 1 in supraventricular tachycardia (
P
<.05 with χ
2
test). By 2 years postoperatively, only 6 of 15 TCPC patients available for follow-up (40%) were in SR, with 7 of 15 in JR and 2 of 15 in NSAR. By contrast, 13 of 17 Fontan patients (76%) remained in SR, with 1 in NSAR and 3 in JR (
P
<.05 with χ
2
test). TCPC patients with loss of SR did not differ from other patients in the group in age at repair, preoperative diagnosis, or surgeon performing the procedure.

Conclusions
This significant incidence of loss of SR temporally related to surgery suggests that operative compromise of the sinus node area is common with TCPC.
Hypothermia During Cardiopulmonary Bypass Delays but Does Not Prevent Neutrophil– Endothelial Cell Adhesion
Authors: Le Deist Françoise , Menasché Philippe , Kucharski Christophe , Bel Alain , Piwnica Armand , Bloch Gérard
Published: June 2012

Background
An accurate evaluation of warm heart surgery cannot be limited to the assessment of the myocardial effects of warm blood cardioplegia but should also address the effects of systemic normothermia on the inflammatory response to cardiopulmonary bypass. A major component of this response is the endothelial adhesion of neutrophils, because it is linked to the release of cytotoxic compounds. This study was designed (1) to characterize the bypass-induced changes in the expression of neutrophil adhesion molecules (L-selectin and β
2
-integrins) and (2) to assess the influence of bypass temperature on these changes.

Methods and Results
Twenty case-matched patients undergoing open-heart procedures were divided into two equal groups according to the core temperature during cardiopulmonary bypass: warm (33.4±0.3°C) or cold (27.1±0.4°C,
P
<.0001 versus warm). Arterial blood samples were collected before, during, and 30 minutes after bypass and processed for the expression of L-selectin and β
2
-integrins (CD11a, CD11b, and CD11c) with flow cytometry. Warm bypass was associated with an early and sustained upregulation of CD11b. In contrast, hypothermia resulted in a strikingly less pronounced CD11b upregulation during bypass. However, CD11b expression sharply increased thereafter so that 30 minutes after bypass, it was no longer significantly different between the two groups. Changes in CD11c expression grossly paralleled those described for CD11b. Neither CD11a nor L-selectin changed significantly from baseline values in either group.

Conclusions
Clinical cardiopulmonary bypass is associated with a marked upregulation of the neutrophil CD11b and CD11c integrins. Hypothermia delays but does not prevent the increased expression of these adhesion molecules, which could consequently represent logical targets for interventions designed to blunt the neutrophil-mediated component of bypass-induced inflammatory tissue damage.
Supplement of Nitric Oxide Attenuates Neutrophil-Mediated Reperfusion Injury
Authors: Fukuda Hirotsugu , Sawa Yoshiki , Kadoba Keishi , Taniguchi Kazuhiro , Shimazaki Yasuhisa , Matsuda Hikaru
Published: June 2012

Background
Nitric oxide (NO) derived from the endothelial cell has been identified as a constitutive chemical mediator that regulates the function of the endothelial cell in association with neutrophil (PMN) adhesion and activation. However, its role in the pathogenesis of myocardial reperfusion injury is not clear.

Methods and Results
Fifteen isolated rat hearts were perfused with modified Krebs-Henseleit solution and subjected to 20 minutes of global and normothermic ischemia. Then the hearts were reperfused for 45 minutes with different protocols: the control (C) group was reperfused without PMNs, the P group was reperfused with PMNs, and the N group was reperfused with PMNs and nitroprusside (10
−5
mol/L). The ozone chemiluminescence method was used for direct measurement of NO in the coronary effluent during reperfusion. NO in the coronary effluent in the C group decreased at reperfusion after normoxic perfusion, and this decrease in NO continued for the first 15 minutes of reperfusion. Percentage recovery of left ventricular developed pressure and coronary flow was significantly lower in the P group than that in the N group. Also, the N group had a significantly lesser Luminol-elicited chemiluminescence of the coronary effluent and ratio of PMN adherence to myocardial vasculature compared with the P group.

Conclusions
This study demonstrated directly the decrease in NO production during reperfusion and showed that supplement of NO with NO donor attenuated the injury in which PMNs were involved. The results suggest that NO plays a significant role in reperfusion injury and that supplement of NO during reperfusion appears to be useful to attenuate this injury.
Direct Effects of Protamine Sulfate on Myocyte Contractile Processes
Authors: Hird R. Barry , Wakefield Thomas W. , Mukherjee Rupak , Jones Blanding U. , Crawford Fred A. , Andrews Philip C. , Stanley James C. , Spinale Francis G.
Published: June 2012

Background
Administration of the arginine-rich, highly charged protamine (PROT) molecule has been associated with episodes of acute left ventricular (LV) dysfunction. The objective of the present study was to test the hypothesis that PROT has direct effects on isolated LV myocyte contractile processes and sarcolemmal transduction systems.

Methods and Results
Exposure of porcine LV myocytes (n=305) to 40 μg/mL PROT (reflecting a dose of 2.5 mg/kg) decreased basal contractile function and β-adrenergic responsiveness. For example, myocyte percent shortening was 4.3±0.1% in control myocytes and decreased to 2.8±0.2% in the presence of 40 μg/mL PROT (
P
<.05). Myocyte percent shortening was 9.3±0.7% after β-adrenergic receptor stimulation (isoproterenol; 25 nmol/L) and was significantly reduced in the presence of 40 μg/mL PROT (5.7±0.7%,
P
<.05). PROT reduced myocyte responsiveness to forskolin (100 μmol/L), which directly activates adenylate cyclase, by >40% from forskolin. In addition, PROT abolished the inotropic effects of ouabain on myocyte contractile function. To determine contributory mechanisms for the effects of PROT on myocyte sarcolemmal systems, β-receptor– and cardiac glycoside–binding characteristics were determined in sarcolemmal preparations. β-receptor binding was 175±10 fmol/mg and was reduced to 140±6 fmol/mg in the presence of PROT (
P
<.05). Ouabain receptor binding was 7.1 pmol/mg and decreased to 2.6±0.4 pmol/mg in the presence of PROT. In addition, cAMP production after stimulation with isoproterenol and forskolin was significantly blunted in the presence of PROT. Variants of the PROT molecule were constructed by specific amino acid substitutions and deletions, which provided a means to vary charge as well as structure. Substitution of arginine with lysine in the PROT peptide sequence ameliorated the negative effects on myocyte contractile processes; despite identical overall charge (21+). However, a PROT variant with an 18+ charge but different amino acid sequence induced significant negative effects on myocyte function and inotropic responsiveness. Thus, the effects of PROT on myocyte contractile processes are not due simply to the high positive charge of the molecule. To further establish that PROT can contribute to changes in LV function in the clinical setting, fluorescein-labeled PROT was circulated in antegradely perfused rabbit hearts. Microscopic examination revealed that PROT could traverse the vascular compartment of the myocardium and come in direct contact with the myocyte.

Conclusions
The unique findings from the present study suggest that a fundamental contributory mechanism for the changes in LV function observed after protamine administration may be the direct effect of unbound protamine on myocyte contractile processes.
Myocardial β-Adrenergic Receptor Function and High-Energy Phosphates in Brain Death– Related Cardiac Dysfunction
Authors: Bittner Hartmuth B. , Chen Edward P. , Milano Carmelo A. , Kendall Simon W.H. , Jennings Robert B. , Sabiston David C. , Van Trigt Peter
Published: June 2012

Background
Cardiac failure remains an important problem after heart transplantation and may be associated with events that occur during brain death (BD) before transplantation. In this study, cardiac function is studied after BD, and biochemical evaluation of myocardial high-energy phosphates and the β-adrenergic receptor system is presented.

Methods and Results
The hearts of 17 mongrel dogs (23 to 31 kg) were instrumented with flow probes, micromanometers, and ultrasonic dimension transducers to measure ventricular pressure and volume relationships. In a validated canine BD model, systolic right and left ventricular (RV/LV) function was analyzed by load-insensitive measurements during caval occlusion (preload-recruitable stroke work, PRSW). The β-adrenergic receptor (BAR) density, adenylate cyclase (AC) activity, and myocardial ATP and creatine phosphate (CP) were measured before and 6 to 7 hours after BD. Results are expressed as mean±SEM (*
P
<.05 versus baseline, paired two-tailed Student’s
t
test). Myocardial function deteriorated significantly from baseline PRSW (RV, 22±1 erg×10
3
; LV, 75±4 erg×10
3
) by 37±10% for the RV (
P
<.001) and 22±7% for the LV (
P
<.001). BAR density increased from 282±42 to 568±173 fmol/mg for the RV and from 291±64 to 353±56 fmol/mg for the LV. Isoproterenol-stimulated AC activity was also significantly enhanced after BD. ATP and CP, however, remained unchanged after BD compared with baseline values before BD.

Conclusions
BD causes significant systolic biventricular dysfunction. The loss of ventricular function after BD was more prominent in the right ventricle and may contribute to early postoperative RV failure in the recipient. These injuries occurred despite BAR system upregulation after BD. Global myocardial ischemia is unlikely, since ATP and CP remained normal before and after BD.
Transmural Channels Can Protect Ischemic Tissue
Authors: Whittaker Peter , Rakusan Karel , Kloner Robert A.
Published: June 2012

Background
We previously found that transmural laser channels failed to acutely increase myocardial blood flow. Nevertheless, this method is being used to treat patients with coronary artery disease who are unable to undergo angioplasty or bypass graft surgery and in cases in which previous surgery has failed. To reconcile the lack of an acute increase in blood flow with beneficial effects claimed in patients, our hypothesis was that the channel-making process might, over time, stimulate a protective effect, possibly by the growth of new vessels linking channels to the existing circulation. We tested this hypothesis in rat hearts, which have little native collateral circulation.

Methods and Results
We made six transmural channels in the left ventricle of each heart using a 400-μm-diameter optic fiber coupled to a holmium:yttrium-aluminum-garnet laser or a 400-μm-diameter syringe needle. Two months after the channels were made, rats were randomized to either an infarct-size study or analysis of myocardial capillary density. We challenged any induced protective mechanism by acutely occluding the left coronary artery for 90 minutes, followed by 4.5 hours of reperfusion. The artery was then reoccluded, and pigment was injected into the circulation to delineate tissue perfused by the occluded vessel and to detect perfusion via the channels. We used triphenyltetrazolium staining to determine the amount of muscle necrosis and the location of muscle protection. Infarct size in needle-treated hearts was smaller than in controls (15±6% versus 40±3% of the left ventricle,
P
<.01). Infarct size in laser-treated hearts (27±5%) did not differ significantly from controls; however, all eight laser-treated hearts showed evidence of muscle protection in areas adjacent to channels. We found that the laser-made channels were associated with more fibrosis than the needle-made channels (mean width of fibrosis 430±50 versus 180±30 μm,
P
<.0001), and, in tissue remote from channels, fibrosis was increased more in laser-treated hearts (3.6±0.3%) versus both control (2.5±0.2%) and needle-treated (2.5±0.3%) hearts (
P
<.05). In addition, muscle disarray was seen adjacent to channel-associated fibrosis. We observed injected pigment within fibrosis associated with the channels and in surrounding myocardium. We also found vessels that appeared to be connected to channels; however, there was no overall increase in capillary density.

Conclusions
We were able to protect the heart against coronary artery occlusion by making transmural channels 2 months before occlusion. Channels created by a needle provided greater protection than channels created by a laser, probably because they caused less initial injury. Our results are consistent with the concept that the channels were able to provide blood flow to the tissue directly from the ventricular cavity; however, we cannot rule out the possibility that other mechanisms of protection may be involved.