Pediatr Res. 2008 Feb 27 [Epub ahead of print]

Plasma biomarkers in pediatric patients undergoing cardiopulmonary bypass.

Lull ME, Carkaci-Salli N, Freeman WM, Myers JL, Midgley FM, Thomas NJ, Kimatian
SJ, Vrana KE, Undar A.

Department of Pharmacology [M.E.L., N.C.-S., W.M.F., K.E.V.], Department of
Surgery [J.L.M., F.M.M., S.J.K., A.U.], Department of Pediatrics [J.L.M., F.M.M.,
N.J.T., S.J.K., A.U.], Department Bioengineering [A.U.], Pennsylvania State
University College of Medicine, Penn State Children's Hospital, Hershey
Pennsylvania 17033.

It is critical to identify at-risk patients and minimize the deleterious effects 
of cardiopulmonary bypass (CPB) procedures in pediatric populations. The present 
study screened the plasma proteome of pediatric patients undergoing CPB
procedures to identify potential clinical biomarkers related to tissue damage,
inflammation, or other pathologies. Blood samples were collected at five
different time points from ten children undergoing a CPB procedure. Plasma was
isolated and analyzed using 2-dimensional differential in-gel electrophoresis
(2-DIGE) and matrix-assisted laser desorption ionization time of flight
(MALDI-ToF) mass spectrometry. Levels of differentially regulated proteins
identified by 2-DIGE, and related proteins were then measured in all timepoints
and patients. As well, associated small molecules and ions were measured. The
present study identified 13 proteins and protein isoforms altered in expression, 
including hemopexin, ceruloplasmin, inter-alpha inhibitor H4 (ITI-H4), and
alpha-2-macroglobulin. Immunoblot analysis revealed significant decreases in each
of these proteins during the CPB procedure. Significant changes in the levels of 
copper, iron, hemoglobin, epinephrine, norepinephrine, and serotonin were
observed. The potential markers of pathology (inflammation, oxidative stress)
identified during this preliminary study may illuminate opportunities for
preventative measures and/or treatments during and following CPB procedures in
pediatric patients.

Eur J Cardiothorac Surg. 2008 Feb 26 [Epub ahead of print]

Initial results of a clinical study: adenosine enhanced cardioprotection and its 
effect on cardiomyocytes apoptosis during coronary artery bypass grafting.

Shalaby A, Rinne T, Järvinen O, Saraste A, Laurikka J, Porkkala H, Saukko P,
Tarkka M.

Heart Center, Division of Cardiothoracic Surgery, Tampere University Hospital,
Tampere, Finland; Heart Center, Division of Cardiothoracic Surgery, Affiliated
1st Hospital, Alexandria University, Faculty of Medicine, Egypt.

Objective: Apoptosis has been considered as one of the mechanisms of
cardiomyocyte loss during open heart surgery. Adenosine is cardioprotective
against ischemia-reperfusion injury in experimental models. The aim of this study
was to find out whether the administration of single dose adenosine added to
blood cardioplegia is effective in decreasing the apoptosis process. Methods: In 
a double-blinded randomized control intervention study, 40 patients were enrolled
for elective coronary artery bypass grafting. In the adenosine group (n=20)
patients received 250mug/kg adenosine in the aortic root after cross-clamping
followed by cold blood cardioplegia. In the control group (n=20) patients had
only antegrade cardiolplegia. Left ventricular tissue samples (from apex) were
taken before and after the bypass. The apoptotic cells were identified by dUTP
nick-end labeling (TUNEL) using an apoptosis detection kit. The number of
TUNEL-positive cardiomyocytes was expressed as percentage of the total number of 
cardiomyocytes in histological tissue sections. Results: The groups were closely 
identical in demographic data, cross-clamp time, cardiopulmonary bypass time and 
weaning time. The postoperative cardiac index and other hemodynamic parameters,
including the patterns of CK-MB, did not show statistically significant
differences. In the tissue samples there were an equal number of patients who
developed apoptosis after the cross-clamp. Although the frequency of apoptosis in
the control group was two times higher than in the adenosine group, this was
statistically not significant. Conclusions: Adenosine enhanced blood cardioplegia
could not prevent myocardial apoptosis completely. However, it seems to be that
adenosine might influence the frequency of apoptosis and this needs to be
considered in future investigations.

Heart Lung Circ. 2008 Feb 20 [Epub ahead of print]

Anaortic Techniques Reduce Neurological Morbidity After Off-Pump Coronary Artery 
Bypass Surgery.

Vallely MP, Potger K, McMillan D, Hemli JM, Brady PW, Brereton RJ, Marshman D,
Mathur MN, Ross DE.

Department of Cardiothoracic Surgery, Royal North Shore Hospital, Sydney, NSW,
Australia.

BACKGROUND: Stroke remains one of the most devastating complications of cardiac
surgery. Advocates of off-pump coronary revascularisation (OPCAB) maintain that
post-operative neurologic morbidity is reduced by avoiding aortic cannulation and
cross-clamping, and by eliminating the systemic effects of cardiopulmonary
bypass. We sought to determine whether completing off-pump coronary surgery
without any aortic manipulation ("anaortic" technique) afforded any additional
neurological protection, as compared to off-pump grafting in which the aorta was 
utilised for graft inflow. METHODS: A comprehensive review of prospectively
collected data was undertaken of all patients undergoing OPCAB in our institution
between January 2002 and December 2006. Cases requiring intra-operative
conversion to cardiopulmonary bypass were excluded from further analysis.
Patients having OPCAB surgery with aortic manipulation were compared to those
having OPCAB surgery without aortic manipulation. Multiple logistic regression
was used to identify possible predictors of post-operative neurologic morbidity, 
with particular focus on the role of aortic manipulation. RESULTS: During the
period of review, 1758 patients underwent OPCAB, of which 1201 (68.3%) were
completed without aortic manipulation, constituting the "anaortic" cohort. This
group was compared with the remaining 557 patients, which included fashioning at 
least one aorto-conduit anastomosis, utilising either a side-biting aortic clamp 
or a no-clamp proximal anastomotic device. The two groups of patients were
well-matched with respect to risk factors for adverse neurologic outcomes. Nine
patients sustained focal neurological deficits (transient or permanent) in the
peri-operative period, constituting a stroke rate of 0.51% for the entire series.
The incidence of peri-operative neurological deficit in the anaortic group was
0.25% compared with 1.1% in the aortic manipulation group (odds ratio (OR) 0.23, 
95% confidence interval (CI) 0.06-0.92, p=0.037). Advanced age was also
associated with peri-operative neurological injury (OR 1.1, 95% CI 1.01-1.20,
p=0.017). CONCLUSIONS: Off-pump coronary artery surgery is associated with a low 
incidence of peri-operative stroke. Completing the surgical procedure without
manipulating the ascending aorta in any way ("anaortic" technique) offers
additional neurological protection and should be the goal in all suitable
off-pump coronary cases.

Ann Thorac Cardiovasc Surg. 2008 Feb;14(1):22-4.

Left axillary artery perfusion in surgery of type A aortic dissection.

Kano M, Chikugo F, Shimahara Y, Urata M, Hayamizu T.

Department of Cardiovascular Surgery, Tokushima Prefectural Central Hospital,
Tokushima, Japan.

PURPOSE: A left axillary artery perfusion instead of a femoral perfusion has the 
benefit of avoiding false lumen perfusion and atheroembolization into the brain, 
which is caused by retrograde perfusion in type A aortic dissection surgery. We
performed type A aortic dissection surgery using the left axillary artery
perfusion technique and reviewed this method. PATIENTS AND METHODS: From April
2002 to January 2004, 8 patients with a mean age of 70 years (48 to 81),
underwent axillary artery cannulation with a side graft technique in type A
aortic dissection operations. Six patients had acute type A and 2 had chronic
type A dissections. The surgical procedures were ascending aortic replacement in 
5, hemiarch replacement in 2, and total arch replacement in 1. RESULTS: In all
patients, a cardiopulmonary bypass was established through the left axillary
perfusion. There were no operative deaths and no hospital deaths. All patients
were able to avoid cerebral vascular accidents. One patient required a
femoro-femoro bypass on the 10th postoperative day because of malperfusion of the
left leg, which occurred suddenly. Postoperative hemorrhaging requiring
resternotomy occurred in 2 patients. CONCLUSION: A left axillary artery perfusion
is safe and useful for arterial inflow for type A aortic dissection surgery.

Eur J Cardiothorac Surg. 2008 Feb 12 [Epub ahead of print]

Heart transplantation following cardiomyoplasty: a biological bridge.

Chachques JC, Jegaden OJ, Bors V, Mesana T, Latremouille C, Grandjean PA, Fabiani
JN, Carpentier A.

Department of Cardiovascular Surgery, Georges Pompidou European Hospital, 20 rue 
Leblanc, 75015 Paris, France.

Objective: Dynamic cardiomyoplasty (CMP) was proposed as a treatment for
refractory heart failure; more than 2000 procedures have been performed
worldwide. Heart transplantation was indicated afterwards in some CMP patients
with recurrent heart failure symptoms. This study reviews the multicentric French
experience with CMP followed by heart transplantation. Methods: From 1985 to
2007, 212 patients (mean age 53+/-11 years) with refractory heart failure
(LVEF=22+/-9%, mean NYHA 3.2) underwent CMP in France. Heart transplantation was 
performed in 26 patients (12.3%), mean age: 51+/-11 years, within 2.3+/-3 years
after CMP. Transplantation was indicated for persistent heart failure, i.e. no
immediate improvement after CMP (19%) and for recurring heart failure (81%).
Results: The surgical technique of heart transplantation following
cardiomyoplasty presents few particularities. Routine extracorporeal bypass was
instituted between the vena cavas and the ascending aorta. As in most of these
patients the CMP procedure had been performed without the need of extracorporeal 
circulation, hearts were free of previous cannulations for cardiopulmonary
bypass. The latissimus dorsi muscle flap was divided as far as possible inside
the left pleural cavity and its vascular pedicle was obturated. The proximal
portion of the muscle as well as the muscular pacing electrodes were kept in
place in the pleural cavity. The adhesions between the flap and the heart were
not released so as to achieve an en bloc resection of the heart and the muscle
flap. During removal of the recipient's heart, care was taken not to injure the
left phrenic nerve that was frequently in tight relation with the latissimus
dorsi muscle. Heart transplantation was then performed in a routine manner, the
donor heart being anastomosed to remnant atria and great vessels. Mean follow-up 
was 5.5 years (longest 13.5 years). Survival at 10 years was 40% for early heart 
transplantation (done within 4 months of CMP) and 57% for transplantation
performed at 3+/-2.8 years after CMP. Conclusions: Heart transplantation after
CMP is technically feasible. Hospital mortality was higher when urgent
transplantation was required. Long-term survival results are similar to those for
primary heart transplantation. Cardiomyoplasty, when it fails, does not preclude 
transplantation, and when indicated, CMP could be considered as a biological
bridge to heart transplantation.

Heart Surg Forum. 2008;11(1):E21-3.

Clinical experience with assisted venous drainage cardiopulmonary bypass in
elective cardiac reoperations.

Nyawo B, Botha P, Pillay T, Clark SC, Tocewicz K, Forty J, Hamilton JR, Hill P,
Hasan A.

Department of Cardiothoracic Surgery, Freeman Hospital, Newcastle upon Tyne,
United Kingdom. bcnyano@yahoo.co.uk

Reoperative cardiac surgery is associated with substantial morbidity and
mortality due to technical problems at sternal reentry, which can result in
laceration of the right ventricle, innominate vein injury, or embolization from
patent grafts. To minimize the risk associated with reentry, we adopted the
method of assisted venous drainage in the cardiopulmonary bypass circuit with
peripheral cannulation for cardiac reoperations. From March 1999 to May 2003, a
series of 52 patients (38 males; mean age 48.7 years, range 4 months to 78 years)
underwent cardiac reoperations performed with centrifugal pump venous-assisted
cardiopulmonary bypass. EuroSCORE was 7.34 +/- 3.9 (range, 4-19). The
reoperations were coronary artery bypass graft (25 patients), valve
replacement/repair (18 patients), and complex pediatric procedures (11 patients).
The studied adverse events were structural damage at reentry, mortality, blood
loss, stroke, and hemolysis. Complications at sternotomy were damage to the
innominate vein (1 patient) and aorta (1 patient) with blood loss of 625 and 225 
mL, respectively. Four patients required intraaortic balloon pump or
extracorporeal membrane oxygenation (n = 1) for hemodynamic support on weaning
off cardiopulmonary bypass. Three patients died in the postoperative period. Our 
experience with centrifugal pump-assisted venous drainage in cardiac reoperations
has shown excellent results, with reduced risk of damage to vital structures on
sternal reentry. In cases in which structural damage did occur, blood loss was
minimal.

Am J Nephrol. 2008 Feb 8;28(4):576-582 [Epub ahead of print]

Increased Incidence of Acute Kidney Injury with Aprotinin Use during Cardiac
Surgery Detected with Urinary NGAL.

Wagener G, Gubitosa G, Wang S, Borregaard N, Kim M, Lee HT.

Department of Anesthesiology, College of Physicians and Surgeons, Columbia
University, New York, N.Y., USA.

Background: Use of aprotinin has been associated with acute kidney injury after
cardiac surgery. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel,
very sensitive marker for renal injury. Urinary NGAL may be able to detect renal 
injury caused by aprotinin. This study determined if the use of aprotinin is
associated with an increased incidence of acute kidney injury and increased
levels of urinary NGAL. Methods: In this prospective, observational study 369
patients undergoing cardiac surgery were enrolled. 205 patients received
aprotinin and 164 received epsilon amino-caproic acid intraoperatively. Urinary
NGAL was measured before and immediately after cardiac surgery and 3, 18 and 24 h
later. The association of aprotinin use with the incidence of acute kidney injury
(increase of serum creatinine >0.5 mg/dl) and NGAL levels was determined using
logistic and linear regression models. Results: 51 of 205 patients (25%) who
received aprotinin developed acute kidney injury compared to 19 of 164 patients
(12%) who received epsilon amino-caproic acid (p = 0.0013). Aprotinin use was
associated with a two-fold higher risk of acute kidney injury when adjusted for
potential confounders (age, Parsonnet score, preoperative serum creatinine,
cardiopulmonary bypass and cross-clamp times; multiple logistic regression: OR = 
2.164; CI (95%) = 1.102 to 4.249; p = 0.0249. Urinary NGAL was 19 times higher
immediately after cardiopulmonary bypass and 18 times higher 3 h later in
patients who had received aprotinin (postoperative: 19.23; CI (95%) = 12.60 to
29.33; p < 0.0001; 3 h post-cardiopulmonary bypass 18.67; CI (95%) = 11.45 to
30.43; p < 0.0001). Conclusions: Postoperative urinary NGAL - a novel marker for 
renal injury - is increased in cardiac surgical patients receiving aprotinin
compared to patients receiving epsilon amino-caproic acid. These results further 
support the hypothesis that aprotinin may cause renal injury. The substantial
rise of urinary NGAL associated with aprotinin use may in part be due to
aprotinin blocking the uptake of NGAL by megalin/gp330 receptors in the proximal 
tubules. Copyright (c) 2008 S. Karger AG, Basel.

Anadolu Kardiyol Derg. 2008 Feb;8(1):22-6.

Obesity and open-heart surgery in a developing country.

Discigil G, Ozkisacik EA, Badak MI, Günes T, Discigil B.

Department of Family Medicine, Faculty of Medicine, Adnan Menderes University,
Aydin, Turkey. guzeld@yahoo.com

OBJECTIVE: The aim of the present study was to assess obesity as a risk of
adverse outcomes following cardiac surgery. METHODS: The data of 324 consecutive 
patients who underwent elective procedures requiring cardiopulmonary bypass in a 
single cardiac center in South-Western Anatolia were retrospectively analyzed.
There were 250 males and 74 females. Median age was 58.8 years (range 17 to 90
years). A body mass index (BMI)> or =30 kg/m2 was defined as obesity. Adverse
outcomes analyzed included in-hospital mortality, chest tube drainage, reopening,
inotropic support, arrhythmias, deep sternal wound infection, superficial
surgical site infection and hospital stay duration. Multiple logistic regression 
analysis was performed to assess the relationship of obesity with clinical
outcomes after cardiac surgery. Covariates considered in the logistic model
included age, gender, pulmonary disease, cerebrovascular disease, smoking,
hypertension, and diabetes. RESULTS: Fourteen percent of patients (47/324) were
obese and this ratio is quite smaller than reported for industrialized countries.
The results of multiple regression analysis demonstrated that obesity was a risk 
factor only for superficial sternal or harvesting site infection (odds
ratio--4.5, 95% CI--1.404-14.679, p=0.012). CONCLUSION: Obesity was associated
with increased risk of superficial surgical wound infections following cardiac
surgery. In comparison with industrialized countries, obesity may account for
fewer adverse events in patients undergoing open-heart surgical procedures in
South-Western Anatolia, a developing country sample.

J Cardiothorac Vasc Anesth. 2008 Feb;22(1):53-9. Epub 2007 Aug 22.

Cardiopulmonary bypass parameters and hemostatic response to cardiopulmonary
bypass in infants versus children.

Eisses MJ, Chandler WL.

Department of Anesthesiology and Pain Medicine, University of Washington School
of Medicine, Seattle, WA, USA. michael.eisses@seattlechildrens.org

OBJECTIVE: Because infants have relatively more blood loss (mL/kg) than older
children during cardiac surgery involving cardiopulmonary bypass (CPB), the
authors compared hemostatic activation between infants and older children
undergoing cardiac surgery. DESIGN: Observational study. SETTING:
University-affiliated children's hospital. PARTICIPANTS: Twenty-eight children
(18 infants <1 year and 10 children >1 year) undergoing cardiac surgery with CPB.
INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Markers of coagulation and
fibrinolysis were evaluated at 9 sample points before, during, and after CPB in
the 28 children. Infants had greater chest tube output, longer CPB times, and a
larger drop in platelet counts during CPB than children. Active tissue
plasminogen activator (tPA) increased during CPB in both groups, with infants
showing lower levels than children (p < 0.001). In both groups, active
plasminogen activator inhibitor type 1 (PAI-1) first decreased during CPB and
then increased above baseline postoperatively. Infants had higher PAI-1 than
children near the end of CPB (p = 0.01). Thrombin-antithrombin complex levels
increased during and after CPB, with infants showing lower levels only during CPB
(p = 0.01). D-dimer and prothrombin activation peptide (F1.2) levels increased in
a similar pattern for both groups during and after CPB. The length of aortic
cross-clamp time and the level of F1.2 after protamine administration correlated 
significantly and independently with 12-hour chest tube output. CONCLUSIONS:
Compared with children, infants had greater blood loss (mL/kg), greater drop in
platelets during CPB, lower active tPA, and higher active PAI-1. Cumulative
thrombin generation after CPB, indicated by F1.2 levels, correlated with early
blood loss.

J Cardiothorac Vasc Anesth. 2008 Feb;22(1):6-15. Epub 2007 Nov 7.

Perioperative renal outcome in cardiac surgical patients with preoperative renal 
dysfunction: aprotinin versus epsilon aminocaproic acid.

Maslow AD, Chaudrey A, Bert A, Schwartz C, Singh A.

Department of Anesthesiology, Brown University Medical School, Rhode Island
Hospital, Providence, RI, USA. amaslow@rcn.com

OBJECTIVE: The administration of aprotinin to patients with pre-existing renal
dysfunction who are undergoing cardiac surgery is controversial. Therefore, the
authors present their experience with the use of aprotinin for patients with
preoperative renal dysfunction who underwent elective cardiac surgery requiring
cardiopulmonary bypass (CPB). DESIGN: Retrospective analysis. SETTING: University
hospital. PARTICIPANTS: Consecutive cardiac surgical patients with preoperative
serum creatinine (SCr) > or =1.8 mg/dL undergoing nonemergent cardiac surgery
requiring CPB. INTERVENTIONS: None. METHODS: One hundred twenty-three patients
either received epsilon aminocaproic acid (EACA, n = 82) or aprotinin (n = 41) as
decided by the attending anesthesiologist and surgeon. Data were collected from
the Society of Thoracic Surgeons database and from automated intraoperative
anesthesia records. Renal function was assessed from measured serum creatinine
(SCr) and calculated creatinine clearances (CrCls). Acute perioperative renal
dysfunction was defined as a worsening of perioperative renal function by > or
=25% and/or the need for hemodialysis (HD). ANALYSIS: Data were recorded as mean 
and standard deviation or percentage of population depending on whether the data 
were continuous or not. Data were compared by using an analysis of variance,
chi-square analysis, Student paired and unpaired t tests, Fisher exact test,
Wilcoxon rank sum test, and Mann-Whitney U test. A p value <0.05 was considered
significant. RESULTS: Overall, 32% and 41% of patients had acute perioperative
renal dysfunction measured by CrCl and SCr, respectively. Seven patients required
HD (5.7%). Six of these 7 had complicated postoperative courses. Of all the
variables measured, only the duration of the aortic crossclamp (AoXCl) and CPB
were significantly associated with acute perioperative renal dysfunction. Acute
perioperative renal dysfunction was associated with increased intensive care unit
and hospital stays, postoperative blood transfusion, dialysis, and major
infection. Aprotinin patients were significantly older (75.2 v 70.2 years, p <
0.05), had lower left ventricular ejection fraction (44.4% v 49.2%, p < 0.05), a 
greater preoperative history of congestive heart failure (63 v 44%, p < 0.05), a 
greater renal risk score (5.8 v 4.9, p < 0.05), and underwent more nonisolated
coronary artery bypass graft surgeries (77% v 29%, p < 0.0001). CPB time (126.0 v
96.5 minutes, p < 0.001) and AoXCl duration (100.9 v 78.0 minutes, p < 0.005)
were longer in the aprotinin group. Diabetes (60.5% v 41.5%, p < 0.05) and
hypertension (90.1% v 73.2%, p < 0.05) were more prevalent in the EACA group.
Baseline renal function and renal outcomes were not significantly different
between the aprotinin and EACA groups. Six of the 7 patients who required HD
received EACA (p = 0.1). The earliest SCr recorded > or =3 months after surgery
was significantly lower in the aprotinin group compared with the EACA group (1.8 
v 2.2 mg/dL, p < 0.05). CONCLUSION: Acute perioperative renal dysfunction was
associated with worse patient outcome and longer CPB and AoXCl times. Demographic
and surgical variables indicated that the sicker patients undergoing more complex
surgeries were more likely to be treated with aprotinin. Although aprotinin
patients had a higher renal risk score, the administration of aprotinin did not
negatively impact renal outcome.