TOP TEN SELECTED PAPERS - November 2008

1

Ann Thorac Surg. 2008 Nov;86(5):1613-9.

Comparison of two cardioplegia solutions using thermodilution cardiac output in
neonates and infants.

Sinha P, Zurakowski D, Jonas RA.

Department of Cardiovascular Surgery, Children's National Medical Center,
Washington, DC.

BACKGROUND: Information from clinical studies is limited regarding the optimal
method for myocardial protection in immature hearts, and specifically the
benefits of different cardioplegia (CP) formulations. We compared two CP
techniques by evaluation of the cardiac index using thermodilution catheters.
METHODS: The study cohort includes 102 neonates and infants (aged 2 to 269 days) 
undergoing biventricular repair surgery. A total of 52 patients were managed with
commercially available crystalloid CP ("standard CP") and 50 had a custom mix of 
crystalloid CP with dilute blood ("custom CP"). Repeated-measures analysis of
variance was applied to compare the cardiac index every 3 hours during the
24-hour postoperative period between the two groups and stratified by diagnosis. 
Adjustment for possible confounders was used to more objectively compare the
groups. RESULTS: Standard crystalloid CP provided superior myocardial protection 
in patients who had transposition of great arteries (p < 0.001), and this
advantage held after adjusting for age and cross-clamp time. Shorter ventilatory 
times and intensive care unit stays were also noted for the standard CP group (p 
= 0.01). Cardiac index after cardiopulmonary bypass was lower in patients who had
transposition of great arteries and intact ventricular septum compared with the
group who had transposition of great arteries and ventricular septal defect; and 
in both subgroups, the standard CP technique was superior to the custom CP
solution. Age at operation was inversely correlated with the cardiac index.
CONCLUSIONS: Younger patients, particularly neonates, have a significantly higher
postoperative cardiac index with standard CP than with custom CP. The advantage
is not apparent beyond the neonatal period.

Ann Thorac Surg. 2008 Nov;86(5):1576-83.

Endothelin-a receptor inhibition after cardiopulmonary bypass: cytokines and
receptor activation.

Ford RL, Mains IM, Hilton EJ, Reeves ST, Stroud RE, Crawford FA Jr, Ikonomidis
JS, Spinale FG.

Division of Cardiothoracic Surgery and Anesthesia, Medical University of South
Carolina, and Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South
Carolina.

BACKGROUND: Basic studies have suggested that cross-talk exists between the
endothelin-A receptor (ET-AR) and tumor necrosis factor signaling pathway. This
study tested the hypothesis that administration of an ET-AR antagonist at the
separation from cardiopulmonary bypass would alter the tumor necrosis factor
activation in the early postoperative period. METHODS: Patients (n = 44) were
randomly allocated to receive bolus infusion of vehicle, 0.1, 0.5, 1, or 2 mg/kg 
of the ET-AR antagonist (sitaxsentan), at the separation from cardiopulmonary
bypass (n = 9, 9, 9, 9, and 8, respectively). Plasma levels of tumor necrosis
factor-alpha and soluble tumor necrosis factor receptor 1 and 2 were measured.
RESULTS: Compared with the vehicle group at 24 hours, plasma levels of tumor
necrosis factor-alpha and tumor necrosis factor receptor 2 (indicative of
receptor activation) were reduced in the 1 mg/kg ET-AR antagonist group (by
approximately 13 pg/mL and approximately 0.5 ng/mL, respectively; p < 0.05).
Plasma tumor necrosis factor receptor I levels also decreased (by approximately 1
ng/mL) after infusion of the higher doses of the ET-AR antagonist and remained
lower (by approximately 3 ng/mL) at 24 hours after infusion (p < 0.05). In
addition, a dose effect was observed between the ET-AR antagonist and these
indices of tumor necrosis factor activation (p < 0.01). CONCLUSIONS: This study
demonstrated a mechanistic relationship between the ET-AR and tumor necrosis
factor receptor activation in the post-cardiac surgery period. Thus, in addition 
to the potential cardiovascular effects, a selective ET-AR antagonist can modify 
other biological processes relevant to the post-cardiac surgery setting.

Pediatrics. 2008 Dec;122(6):1292-8.

Frequency, predictors, and neurologic outcomes of vaso-occlusive strokes
associated with cardiac surgery in children.

Domi T, Edgell DS, McCrindle BW, Williams WG, Chan AK, MacGregor DL, Kirton A,
deVeber GA.

Department of Child Health and Evaluative Sciences, Hospital for Sick Children,
and Institute of Medical Sciences, University of Toronto, 555 University Ave,
Toronto, Ontario, Canada M5G 1X8.

OBJECTIVE: Our aim was to define the frequency, predictors, and outcomes of
stroke associated with cardiac surgery in children with congenital heart disease.
METHODS: We performed a case-control study of children (term birth to 18 years)
with congenital heart disease who underwent cardiac surgery at the Hospital for
Sick Children between January 1, 1992, and March 1, 2001. Case subjects
experienced stroke within 72 hours after cardiac surgery, and control subjects (2
for each case subjects) had cardiac surgery and no stroke. The frequency of
arterial ischemic stroke/cerebral sinovenous thrombosis was calculated among
children who underwent cardiac surgery during the study period. Predictors for
stroke, including age, gender, simple versus complex procedure, reoperation,
bypass duration, circulatory arrest, postoperative hematocrit level, and
intraoperative activated clotting time, were tested. The presence of clinical and
radiologically defined stroke was the main outcome. Neurologic outcomes were
assessed in case subjects with the Pediatric Stroke Outcome Measure. RESULTS:
During the study period, 30 children with stroke (28 with arterial ischemic
stroke and 2 with cerebral sinovenous thrombosis) were identified among 5526
children undergoing cardiac surgery. This yielded a risk for arterial ischemic
stroke/cerebral sinovenous thrombosis of 5.4 strokes per 1000 children undergoing
a cardiac operation. Univariate analysis revealed that older age at the time of
the procedure, longer duration of cardiopulmonary bypass, number of days in the
hospital postoperatively, and reoperation were associated with stroke. In
multivariate analyses, only reoperation was associated with stroke. CONCLUSIONS: 
The frequency of vaso-occlusive stroke in children with congenital heart disease 
undergoing cardiac surgery was 5.4 cases per 1000 children. Age, duration of
bypass, and reoperation may be associated with stroke risk.

J Biomech Eng. 2008 Dec;130(6):061012.

Neonatal aortic arch hemodynamics and perfusion during cardiopulmonary bypass.

Pekkan K, Dur O, Sundareswaran K, Kanter K, Fogel M, Yoganathan A, Undar A.

Department of Biomedical Engineering, Carnegie Mellon University, 2100 Doherty
Hall, Pittsburgh, PA 15213-3890.

The objective of this study is to quantify the detailed three-dimensional (3D)
pulsatile hemodynamics, mechanical loading, and perfusion characteristics of a
patient-specific neonatal aortic arch during cardiopulmonary bypass (CPB). The 3D
cardiac magnetic resonance imaging (MRI) reconstruction of a pediatric patient
with a normal aortic arch is modified based on clinical literature to represent
the neonatal morphology and flow conditions. The anatomical dimensions are
verified from several literature sources. The CPB is created virtually in the
computer by clamping the ascending aorta and inserting the computer-aided design 
model of the 10 Fr tapered generic cannula. Pulsatile (130 bpm) 3D blood flow
velocities and pressures are computed using the commercial computational fluid
dynamics (CFD) software. Second order accurate CFD settings are validated against
particle image velocimetry experiments in an earlier study with a complex
cardiovascular unsteady benchmark. CFD results in this manuscript are further
compared with the in vivo physiological CPB pressure waveforms and demonstrated
excellent agreement. Cannula inlet flow waveforms are measured from in vivo
PC-MRI and 3 kg piglet neonatal animal model physiological experiments,
distributed equally between the head-neck vessels and the descending aorta.
Neonatal 3D aortic hemodynamics is also compared with that of the pediatric and
fetal aortic stages. Detailed 3D flow fields, blood damage, wall shear stress
(WSS), pressure drop, perfusion, and hemodynamic parameters describing the
pulsatile energetics are calculated for both the physiological neonatal aorta and
for the CPB aorta assembly. The primary flow structure is the high-speed canulla 
jet flow ( approximately 3.0 m/s at peak flow), which eventually stagnates at the
anterior aortic arch wall and low velocity flow in the cross-clamp pouch. These
structures contributed to the reduced flow pulsatility (85%), increased WSS
(50%), power loss (28%), and blood damage (288%), compared with normal neonatal
aortic physiology. These drastic hemodynamic differences and associated intense
biophysical loading of the pathological CPB configuration necessitate urgent
bioengineering improvements-in hardware design, perfusion flow waveform, and
configuration. This study serves to document the baseline condition, while the
methodology presented can be utilized in preliminary CPB cannula design and in
optimization studies reducing animal experiments. Coupled to a lumped-parameter
model the 3D hemodynamic characteristics will aid the surgical decision making
process of the perfusion strategies in complex congenital heart surgeries.

J Cardiovasc Surg (Torino). 2008 Dec;49(6):801-8.

The systemic inflammatory response in coronary artery bypass grafting: what is
the role of the very low ejection fraction (EF =/<30%)?

Karfis EA, Papadopoulos G, Matsagas M, Pantazi D, Lekka M, Kitsiouli I,
Siminelakis S, Anagnostopoulos C, Drossos G.

Department of Cardiac and Thoracic Surgery, University Hospital of Ioannina,
School of Medicine, Ioannina, Greece hkarfis@yahoo.gr.

AIM: Patients with depressed left ventricular function are more susceptible to
develop postoperative complications after cardiac surgery. The aim of the present
study was to examine the effect of severe left ventricular dysfunction on the
activation of systemic inflammatory reaction during and after coronary artery
bypass grafting (CABG). METHODS: Clinical prospective study; 32 selected patients
underwent CABG; 16 patients had depressed left ventricular function before the
operation (low ejection fraction [EF] <30%) Low EF group (study group). Sixteen
patients had normal left ventricular function (normal EF, >50%) Normal EF group
(control group). The levels of inflammatory mediators TNF-alfa, IL-6, IL-8 and
IL-10 were measured preoperatively, during and after cardiopulmonary bypass (CPB)
and 24 hours postoperatively. RESULTS: Higher levels of almost all of
inflammatory mediators were detected in patients with depressed left ventricular 
function compared with patients of normal EF group. IL-6 levels were found
statistically significant higher in Low EF group before the induction of
anesthesia (P=0.039) and after the administration of protamine (P=0.02). IL-8
levels were found statistically significant higher in Low EF group before the
induction of anesthesia (P=0.05), 30 min after the start of CPB (P=0.02), after
the administration of protamine (P=0.015) and 24 hours after the end of the
operation (P=0.05). No statistically significant differences were demonstrated
between the 2 groups of study relative to TNF-alfa and IL-10. CONCLUSION: A
greater activation of systemic inflammatory reaction occurred in patients with
depressed left ventricular function than in patients with normal cardiac function
when they underwent CABG with extracorporeal circulation.

J Surg Res. 2008 Dec;150(2):304-30. Epub 2008 Jan 22.

Remote ischemic preconditioning: a novel protective method from ischemia
reperfusion injury--a review.

Tapuria N, Kumar Y, Habib MM, Abu Amara M, Seifalian AM, Davidson BR.

Institute-Hepatobiliary Pancreatic and Liver Transplant Unit, University
Department of Surgery, Royal Free and University College School of Medicine, UCL,
London, United Kingdom.

BACKGROUND: Restoration of blood supply to an organ after a critical period of
ischemia results in parenchymal injury and dysfunction of the organ referred to
as reperfusion injury. Ischemia reperfusion injury is often seen in organ
transplants, major organ resections and in shock. Ischemic preconditioning (IPC) 
is an adaptational response of briefly ischemic tissues which serves to protect
against subsequent prolonged ischemic insults and reperfusion injury. Ischemic
preconditioning can be mechanical or pharmacological. Direct mechanical
preconditioning in which the target organ is exposed to brief ischemia prior to
prolonged ischemia has the benefit of reducing ischemia-reperfusion injury (IRI) 
but its main disadvantage is trauma to major vessels and stress to the target
organ. Remote (inter organ) preconditioning is a recent observation in which
brief ischemia of one organ has been shown to confer protection on distant organs
without direct stress to the organ. Aim: To discuss the evidence for remote IPC
(RIPC), underlying mechanisms and possible clinical applications of RIPC. METHODS
OF SEARCH: A Pubmed search with the keywords "ischemic preconditioning," "remote 
preconditioning," "remote ischemic preconditioning," and "ischemia reperfusion"
was done. All articles on remote preconditioning up to September 2006 have been
reviewed. Relevant reference articles from within these have been selected for
further discussion. RESULTS: Experimental studies have demonstrated that the
heart, liver, lung, intestine, brain, kidney and limbs are capable of producing
remote preconditioning when subjected to brief IR. Remote intra-organ
preconditioning was first described in the heart where brief ischemia in one
territory led to protection in other areas. Translation of RIPC to clinical
application has been demonstrated by the use of brief forearm ischemia in
preconditioning the heart prior to coronary bypass and in reducing endothelial
dysfunction of the contra lateral limb. Recently protection of the heart has been
demonstrated by remote hind limb preconditioning in children who underwent
surgery on cardiopulmonary bypass for congenital heart disease. The RIPC stimulus
presumably induces release of biochemical messengers which act either by the
bloodstream or by the neurogenic pathway resulting in reduced oxidative stress
and preservation of mitochondrial function. Studies have demonstrated endothelial
NO, Free radicals, Kinases, Opioids, Catecholamines and K(ATP) channels as the
candidate mechanism in remote preconditioning. Experiments have shown suppression
of proinflammatory genes, expression of antioxidant genes and modulation of gene 
expression by RIPC as a novel method of IRI injury prevention. CONCLUSION: There 
is strong evidence to support RIPC. The underlying mechanisms and pathways need
further clarification. The effective use of RIPC needs to be investigated in
clinical settings.

J Cardiovasc Pharmacol. 2008 Nov 19. [Epub ahead of print]

Protective Effect of Ambroxol on Pulmonary Function After Cardiopulmonary Bypass.

Ulas MM, Hizarci M, Kunt A, Ergun K, Kocabeyoglu SS, Korkmaz K, Lafci G, Gedik S,
Cagli K.

From the *Departments of Cardiovascular Surgery; and daggerCardiology, Turkiye
Yuksek Ihtisas Hospital, Ankara, Turkey.

BACKGROUND:: To evaluate whether ambroxol administered orally during the
perioperative period has a protective effect against postoperative pulmonary
dysfunction in on-pump coronary artery bypass surgery. METHODS:: Fifty younger
patients without known pulmonary disease were randomly assigned into 2 groups. In
ambroxol group (n = 25), patients were given ambroxol for a week before and after
the elective coronary artery bypass grafting. In control group (n = 25), placebo 
was given. Groups were compared with respect to pulmonary function tests (PFTs), 
lecithin/sphingomyelin (L/S) ratio in the bronchoalveolar lavage fluid, arterial 
blood gases, and incidence of perioperative morbidity. PFTs were performed before
medication and repeated on the postoperative seventh day. Bronchoalveolar lavage 
fluid was obtained just before cardiopulmonary bypass and within the first
postoperative hour. Room air arterial blood gases were checked before and 2 days 
after the operation. RESULTS:: Postoperative lecithin/sphingomyelins were
significantly lower than the preoperative values in both groups, but differences 
between the groups in either preoperative or postoperative measurements were not 
significant. Although preoperative PaO2 in both groups was similar, it was
significantly lower in control group on postoperative second day (62.4 +/- 7.1
vs. 55.2 +/- 6.4 mm Hg, P < 0.05). In either groups, postoperative forced vital
capacity and forced expiratory volume in 1 second were significantly lower than
preoperative values with a more prominent decrease in control group.
Perioperative morbidity was similar. CONCLUSIONS:: In on-pump coronary artery
bypass grafting, ambroxol improves postoperative PFTs and PaO2 levels without any
significant clinical implication, and it exerts these effects possibly in ways
other than surfactant modulation.

Am Heart J. 2008 Dec;156(6):1095-102. Epub 2008 Sep 30.

Off-pump coronary artery bypass graft surgery in California, 2003 to 2005.

Li Z, Yeo KK, Parker JP, Mahendra G, Young JN, Amsterdam EA.

Department of Internal Medicine, University of California, Davis Medical Center, 
Sacramento, CA 95817, USA.

BACKGROUND: The impact of off-pump coronary artery bypass graft surgery (OPCAB)
on operative mortality compared to conventional coronary artery bypass graft
surgery (CABG) with cardiopulmonary bypass (CCB) has not been clarified. METHOD: 
Patient clinical characteristics were compared between OPCAB and CCB for isolated
CABG surgeries in 2003 to 2005 using data from the California CABG outcomes
reporting program. A propensity score method and logistic regression models were 
used to compute propensity-adjusted operative mortality for patients undergoing
OPCAB or CCB. RESULTS: Of 57,284 isolated CABGs, 13,515 (22.9%) were OPCAB.
Compared to CCB, OPCAB patients were older, more females/nonwhite, and had a
higher prevalence of certain noncardiac risk factors but were fewer with
diabetes, acute myocardial infarction, New York Heart Association class IV heart 
failure or angina, cardiogenic shock, prior cardiac surgery, left main coronary
disease, or > or =3-vessel coronary disease (all P < .01). Overall, the
propensity-adjusted operative mortalities (PAOMRs) were significantly lower in
OPCAB patients compared to CCB patients (OPCAB 2.59% [95% CI 2.52%-2.67%] vs CCB 
3.22% [95% CI 3.17%-3.27%]). Off-pump CABG had a protective advantage for all
quintile subgroups (all P < .05). However, within the OPCAB cohort, those who
converted to CCB intraoperately had higher PAOMR (converters 3.47% [95% CI
3.16%-3.77%] vs nonconverters 2.53% [95% CI 2.46%-2.61%]). Age, female sex,
nonwhite race, diabetes, congestive heart failure, prior cadiac surgery, left
main disease, and with > or =3 diseased coronary arteries were associated with a 
higher risk of intraoperative conversion from OPCAB to CCB (all <0.05).
CONCLUSION: OPCAB and CCB patients had significantly different preoperative risk 
profiles, and OPCAB was associated with lower operative mortality compared to
CCB.

J Thorac Cardiovasc Surg. 2008 Nov;136(5):1237-42. Epub 2008 Jul 17.

The bidirectional Glenn operation: a risk factor analysis for morbidity and
mortality.

Kogon BE, Plattner C, Leong T, Simsic J, Kirshbom PM, Kanter KR.

Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta,
GA, USA. Brian_kogon@emoryhealthcare.org

OBJECTIVE: Patients with single ventricle heart defects often undergo a
palliative bidirectional Glenn operation. For this operation, we analyzed
potential risk factors for morbidity and mortality. We also evaluated the effects
of a persistent left superior vena cava by comparing the outcomes of unilateral
and bilateral operations. METHODS: We reviewed the clinical records of 270
consecutive patients who underwent a bidirectional Glenn operation between 2001
and 2007. A total of 226 patients underwent unilateral operations and 44 patients
underwent bilateral operations. Patient characteristics included weight and age, 
single ventricle morphology, vena caval anatomy, and previous surgery. Operative 
details included cardiopulmonary bypass technique and duration, pulmonary artery 
management, hemi-Fontan construction, concomitant procedures, and hemodynamics.
Outcome data included duration of chest tube drainage, lengths of intensive care 
unit and hospital stay, morbidity, and mortality (<30 days). RESULTS: The median 
length of chest tube drainage was 2.4 days (range 1-20 days). Risk factors for
prolonged drainage were elevated central venous pressure (P = .015) and
transpulmonary gradient (P = .011). The median lengths of stay in the intensive
care unit and hospital were 50 hours (range 20-1628 hours) and 5 days (range 2-83
days), respectively. Risk factors for both included prolonged cardiopulmonary
bypass time, elevated central venous pressure and transpulmonary gradient, and
right ventricular morphology. Overall, 72 of 270 patients (27%) had 116
postoperative complications. Risk factors included prolonged cardiopulmonary
bypass time (P = .002) and elevated central venous pressure (P = .029). Mortality
was 2 of 270 patients (0.7%). No risk factors for death were identified. Weight
(median 6.8 kg vs 6.2 kg, P = .038) and age (median 186 days vs 159 days, P =
.001) at the time of surgery were significantly greater in the bilateral
bidirectional Glenn group compared with the unilateral group. However, there was 
no difference in any of the outcome variables. CONCLUSION: Outcomes were
adversely affected primarily by prolonged cardiopulmonary bypass time, elevated
central venous pressure and transpulmonary gradient, and right ventricular
morphology. Specifically, outcomes were unaffected by the presence of a left
superior vena cava, cannulation strategy, or antegrade pulmonary blood flow.
There were few differences between the unilateral and bilateral groups, none of
which were postoperative outcomes.

J Cardiothorac Vasc Anesth. 2008 Nov 19. [Epub ahead of print]

Decreased Nitric Oxide Products in the Urine of Patients Undergoing Cardiac
Surgery.

Lema G, Urzua J, Jalil R, Canessa R, Vogel A, Moran S, Fajuri A, Carvajal C,
Aeschlimann N, Jaque MP.

Department of Anesthesiology, Pontificia Universidad Católica de Chile, Santiago,
Chile;

OBJECTIVE: Renal vasoconstriction has been blamed as a cause of perioperative
renal dysfunction after cardiac surgery. Endothelial function is a critical
determinant of vascular tonus, including vasoconstriction. The objective of this 
study was to establish whether the release of the endothelial vasodilator nitric 
oxide (NO) or NO products is altered in patients undergoing surgery with
cardiopulmonary bypass in 3 different clinical conditions. DESIGN: Observational 
and randomized prospective study. SETTING: University hospital. PARTICIPANTS:
Adults and pediatric patients undergoing elective cardiac surgery with
cardiopulmonary bypass. INTERVENTIONS: Three groups of patients were studied:
group 1, 10 patients undergoing elective coronary artery surgery; group 2, 20
patients undergoing elective coronary artery surgery randomized to 2 hematocrit
values during cardiopulmonary bypass, high (27%) and low (23%); and group 3, 10
pediatric patients undergoing surgical repair of noncyanotic cardiac defects.
MEASUREMENTS AND MAIN RESULTS: NO products (NO2 + NO3) and cyclic guanosine
monophosphate (cGMP) in urine were measured before, during hypo- and normothermic
cardiopulmonary bypass, and 1 hour postoperatively. Filtration fraction was
calculated. The glomerular filtration rate and effective renal plasma flow were
measured with inulin and (131)I-hippuran clearances, respectively. Urinary alpha 
glutathione s-transferase was measured pre- and postoperatively in groups 1 and
3. NO products, as well as cGMP, decreased significantly during hypo- and
normothermic cardiopulmonary bypass in all groups. This was not because of urine 
dilution or the degree of hemodilution. Age did not appear to alter this
response. Filtration fraction decreased during cardiopulmonary bypass. Alpha
glutathione s-transferase was normal pre-and postoperatively. CONCLUSIONS:
Cardiac surgery with cardiopulmonary bypass is associated with a significant
decrease of NO products. In the absence of kidney damage, decreased NO products
could represent a physiologic response to cardiopulmonary bypass; however,
endothelial dysfunction cannot be excluded.