J Surg Res. 2008 Apr 8. [Epub ahead of print]

Role of Cardiopulmonary Bypass and Arrested Heart Status in the Early Cell
Distribution after Intracoronary Infusion of Bone Marrow Stromal Cells.

Song P, Zhang H, Lu MJ, Li J, Liu XW, Wei YJ, Hu SS.

Research Center for Cardiac Regenerative Medicine, the Ministry of Health and
Department of Surgery, Fu Wai Hospital, Chinese Academy of Medical Sciences and
Peking Union Medical College Beijing, China.

BACKGROUND: Systemic distribution of bone marrow stromal cells (BMSCs) after
intracoronary infusion (ICI) and the role of cardiopulmonary bypass (CPB) in cell
distribution still remain unclear. This study was designed o analyze the cell
distribution after ICI in variations of heart status in a swine myocardial
infarction model. MATERIALS AND METHODS: After inducing a myocardial infarction, 
iron oxide labeled male cells (1 x 10(8)) were infused through the coronary
artery of the beating swine heart in Group 1. In Group 2, CPB was set up and then
the same volume of cells was infused after cardioplegic arrest. In Groups 3 and
4, the animals underwent either beating or arrested ICI with the same volume of
saline. Three days later, cell distribution was assessed by T2* change with
magnetic resonance imaging and sex-determining region on Y-chromosome with
quantitive polymerase chain reaction. RESULTS: Only a few transplanted cells were
localized in the heart and no difference was found between Groups 1 and 2. The
majority of BMSCs would be trapped in extracardial organs, and more cells resided
in the spleen in arrested heart status. CONCLUSIONS: The majority of BMSCs
transplanted by ICI would be entrapped by the extracardial organs. The arrested
heart with CPB during ICI does not favor more cell retention in the injured
myocardium. The optimal approach of delivery of BMSCs still needs further
investigation.

Acta Med Okayama. 2008 Apr;62(2):69-74.

Preoperative oral administration of pentoxifylline ameliorates respiratory index 
after cardiopulmonary bypass through decreased production of IL-6.

Otani S, Kuinose M, Murakami T, Saito S, Iwagaki H, Tanaka N, Tanemoto K.

Division of Cardiovascular Surgery, National Hospital Organization, Iwakuni
Clinical Center, Iwakuni, Yamaguchi 740-0041, Japan.

Activation of inflammatory response during cardiopulmonary bypass (CPB) may lead 
to considerable post-operative mortality. Recently, pentoxifylline (PTX), a
methylxanthine derivative, has been reported to be effective in inhibiting
proinflammatory cytokine production. This study aimed to determine whether or not
PTX prevented CPB-induced systemic inflammatory response syndrome (SIRS) in
patients undergoing cardiovascular surgery. Thirty adult patients were randomly
separated into 2 experimental groups and 1 control group of 10 patients each. The
experimental group received peroral PTX administration (Group 1: 600 mg/day,
Group 2: 900 mg/day), while the control group did not. In Group 1 and Group 2,
PTX administration was started on preoperative day 5 and continued for 5 days.
Serum levels of PTX and IL-6 were measured just before and at 4 h after CPB using
HPLC and ELISA, respectively. Respiratory index (RI) before and at 4 h after CPB 
was calculated, and serum levels of C-reactive protein (CRP) and fibrinogen on
postoperative day 1 were also determined. There were no significant differences
in age, body weight, sex, surgical procedures, CPB time, haemodynamics or risk
factors among the 3 groups. Serum IL-6 level and RI index after CPB in Group 2
were significantly decreased compared with those in Group 1 and the control
group. These results, therefore, suggested that preoperative daily administration
of 900 mg/day PTX contributed to the attenuation of CPB-induced SIRS and had a
beneficial effect on the postoperative course after cardiovascular surgery.

Eur J Cardiothorac Surg. 2008 Apr 30. [Epub ahead of print]

Effects of the heart-lung machine on melatonin metabolism and mood disturbances.

Chenevard R, Suter Y, Erne P.

Cardiology, Kantonsspital Luzern, Luzern, Switzerland.

Objective: Cardiothoracic surgery using the heart-lung machine (HLM) provokes a
pronounced endocrine-metabolic response leading to circadian rhythm disturbances 
that affect postoperative morbidity. Focus has been laid on changes in melatonin 
metabolism. The effects of an extra-corporal artificial circulation have not been
adequately addressed. Methods: Seventeen patients scheduled for open heart
surgery using the HLM were compared with 15 patients undergoing major surgery
without cardiopulmonary bypass (non-HLM). Late afternoon and night urinary
6-sulfatoxymelatonin were measured at baseline, immediately after the operation
and on return to the normal ward. Mood disturbances were assessed at baseline and
final sampling times using a standardized questionnaire (arbitrary units).
Results: Vital signs were comparable between groups. The difference (delta)
between day and night melatonin levels was similar at baseline (HLM group
1.1ng/ml, non-HLM group 1.4ng/ml, p=0.25). Immediately following surgery
melatonin day-night deltas were unchanged to baseline (HLM 1.0ng/ml, p=0.67;
non-HLM 0.8ng/ml, p=0.46) but at final sampling normal circadian melatonin
profile was abolished (-0.3ng/ml, p=0.001 and 0.0ng/ml, p=0.07). However, this
effect was not different between the two studied groups (p=0.17). No mood
disorders were detectable at baseline (HLM 8.0 vs non-HLM 7.0, p=0.97) and no
changes occurred after surgery (7.0 vs 6.5, p=0.33). Overall, patients with a
worsening psychological score had pronounced postoperative washout of
afternoon-night melatonin delta (p=0.04). Conclusions: We found no relevant
influence of the HLM on perioperative circadian melatonin profiles. Additionally,
no alterations in mood assessment before and after surgery were observed.
However, worsening of psychological score was associated with a pronounced
disruption of the normal circadian melatonin profile.

Kidney Int Suppl. 2008 Apr;(108):S81-6.

Clinical outcome in children with acute renal failure treated with peritoneal
dialysis after surgery for congenital heart disease.

Pedersen KR, Hjortdal VE, Christensen S, Pedersen J, Hjortholm K, Larsen SH,
Povlsen JV.

Department of Cardio Thoracic and Vascular Surgery, Aarhus University Hospital,
Skejby, Denmark.

The present single-center cohort study was based on a clinical intensive care
unit database containing data on 1128 consecutive children undergoing their first
operation for congenital heart disease between 1993 and 2002 at Aarhus University
Hospital, Skejby, Denmark. A total of 130 (11.5%) children developed
postoperative acute renal failure (ARF) managed with peritoneal dialysis (PD).
Logistic regression analysis was used to examine risk factors for complications
related to PD and to compare mortality between ARF and non-ARF patients
controlling for potential confounding factors. A total of 43 complications
related to PD were registered in 27 (20.8%) patients. Major complications were
seen in eight (6.2%) patients, and only two (1.5%) patients were switched to
hemodialysis after peritonitis and hemicolectomy due to bowel perforation. The
main risk factors for complications to PD were duration of PD, high RACHS-1 score
(Risk Adjusted Classification for Congenital Heart Surgery), and hyperkalemia at 
initiation of PD. Overall, in-hospital mortality was 6.8% (76/1128). Mortality of
ARF patients was 20.0% compared to 5.0% among non-ARF patients (adjusted odds
ratio=1.91, 95% confidence interval=1.10-3.36). After stratification, ARF was
strongly associated with increased mortality in the subgroups of patients with
the lowest overall risk of dying (age> or =1 year, body weight> or =5 kg, RACHS-1
score <3, and no preoperative cyanosis). For patients at high risk of dying (age 
<1 year, body weight <5 kg, RACHS-1 score> or =3, cardiopulmonary bypass time> or
=60 min, and preoperative cyanosis), the association between ARF and mortality
was substantially weaker. In conclusion, postoperative ARF was associated with
increased mortality in children operated for congenital heart disease. Major
complications to PD were few, and our data strongly support that PD is a simple, 
safe, feasible, and robust dialysis modality for the management of ARF in
children.

Cardiology. 2008 Apr 25;111(3):181-187. [Epub ahead of print]

Nitric Oxide Synthase Inhibitor (MTR-105) during Open-Heart Surgery. A Pilot
Double-Blind Placebo-Controlled Study of Hemodynamic Effects and Safety.

Sasson L, Ureche A, Manolache G, Ciubotaru A, Borer JS, Schachner A.

Angela and Sami Shamoon Cardiothoracic Surgery Department, Edith Wolfson Medical 
Center, Holon, affiliated with the Sackler School of Medicine, Tel Aviv
University, Tel Aviv, Israel.

Objectives: Hypotension is common immediately following cardiopulmonary bypass.
Experimentally, MTR-105 (S-ethylisothiuronium diethylphosphate), a fast-acting
synthetic nitric oxide synthase inhibitor, rapidly increases blood pressure. The 
purpose of the current study was to assess the influence of MTR-105 on
hemodynamics early after cardiopulmonary bypass in patients undergoing open-heart
surgery. Methods:Thirty-six patients with an ejection fraction >50% undergoing
open-heart surgery were randomly assigned to either 50 mug kg(-1) min(-1) MTR-105
(M50, n = 12), 10 mug kg(-1) min(-1) MTR-105 (M10, n = 12) or buffered phosphate 
solution (placebo control, n = 12). Half suffered from atrial fibrillation and
75% had severe tricuspid regurgitation. Patients received the drug for 6 h after 
cross-clamp removal. Hemodynamic variables were measured before drug
administration until 24 h after operation. Adverse events were recorded from
study drug initiation through 30 days after the operation. Results:Compared with 
control, both MTR-105 doses were associated with an immediate increase in
systemic blood pressure (16%) and systemic vascular resistance and a decrease in 
cardiac index. Half-life time of MTR-105 was calculated to be 4.1 +/- 0.8 h (M10)
and 4.45 +/- 0.92 h (M50). Three patients died during hospitalization, unrelated 
to the study medication. Conclusions:At the doses employed, MTR-105 appears
hemodynamically active in increasing both blood pressures. Copyright © 2008 S.
Karger AG, Basel.

J Cardiovasc Surg (Torino). 2008 Apr;49(2):261-7.

Is use of temporary pacing wires following coronary bypass surgery really
necessary?

Imren Y, Benson AA, Oktar GL, Cheema FH, Comas G, Naseem T.

Cardiovascular Surgery Department, Gazi University Medical Faculty, Ankara,
Turkey yimren@gmail.com.

AIM: Temporary epicardial pacing wires (TEPW) which are routinely used after
coronary bypass grafting may result in significant complications. We sought to
identify variables that predict TEPW implantation and thereby limit their use.
METHODS: This prospective study enrolled 564 patients (296 underwent coronary
artery bypass grafting with cardiopulmonary bypass [ONCAB] and 268 underwent
off-pump coronary artery bypass grafting, OPCAB). TEPW were placed in patients
with the intraoperative presence of one or more of the following criteria: sinus 
bradycardia, sinus arrest, nodal/junctional rhythms, atrioventricular block,
bundle branch block, ventricular tachycardia, or onset of atrial fibrillation.
RESULTS: Only 31 (5.5%) patients [ONCAB: 20 (6.8%) (ventricular: 14, bichamber:
6); OPCAB: 11 (4.1%) (ventricular: 9, bichamber: 2)] had temporary epicardial
pacing wires implanted intraoperatively. Indications for using temporary
epicardial pacing wires for ONCAB were sinus bradycardia (8), nodal/junctional
rhythms (3), atrioventricular block (3), atrial fibrillation (4), and bundle
branch block (2), and for OPCAB were sinus bradycardia (8), nodal/junctional
rhythms (2), and atrioventricular block (1). Mean duration for pacing was 22.4 h 
for the ONCAB group and 11.3 h for the OPCAB group. There were no temporary
epicardial pacing wires associated complications. One paced OPCAB patient
required a permanent pacemaker and 2 non-paced OPCAB patients required
transvenous pacing wires. Univariate and multivariate analyses were also
conducted to determine risk factors for TEPW. CONCLUSION: TEPW implantation is
overused in cardiac surgery and by identifying independent predictors for pacing 
we conclude that TEPW use should be limited to a select few.

Cytokine. 2008 Apr 14. [Epub ahead of print]

Risk stratification in neonates and infants submitted to cardiac surgery with
cardiopulmonary bypass: A multimarker approach combining inflammatory mediators, 
N-terminal pro-B-type natriuretic peptide and troponin I.

Carmona F, Manso PH, Vicente WV, Castro M, Carlotti AP.

Division of Pediatric Critical Care Medicine, Department of Pediatrics, Hospital 
das Clinicas, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo,
Avenida dos Bandeirantes, 3900, Campus Universitario, Ribeirao Preto, SP, CEP
14049-900, Brazil.

Low cardiac output syndrome (LCOS) is a common problem following cardiac surgery 
with cardiopulmonary bypass (CPB) in neonates and infants, and its early
recognition remains a challenging task. We aimed to test whether a multimarker
approach combining inflammatory and cardiac markers provides complementary
information for prediction of LCOS and death in children submitted to cardiac
surgery with CPB. Forty-six children younger than 18 months with congenital heart
defects were prospectively enrolled. No intervention was made. Blood samples were
collected pre-operatively, during CPB and post-operatively (PO) for measurement
of interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-alpha, cardiac
troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP).
Clinical data and outcome variables were recorded. Logistic regression was used
to identify predictors of LCOS and death. Multivariate logistic regression
identified pre-operative NT-proBNP and IL-8 4h PO as independent predictors of
LCOS, while cTnI 4h PO and CPB length were independent predictors of death. The
use of inflammatory and cardiac markers in combination improved sensitivity,
negative predictive value and accuracy of the models. In conclusion, the combined
assessment of inflammatory and cardiac biochemical markers can be useful for
identifying young children at increased risk for LCOS and death after heart
surgery with CPB.

Masui. 2008 Apr;57(4):471-3.

[Heparin resistance associated with elevated factor VIII]

[Article in Japanese]

Kumano N, Ikeda S, Arimori Y, Ono T, Saeki S.

Department of Anesthesiology, National Hospital Organization, Iwakuni Clinical
Center, Iwakuni 740-8510.

An 84-year-old female patient was scheduled to undergo AVR, CABG, and Maze
procedure. She had a history of hypertension, cerebral infarction, and branch
retinal vein occlusion. Warfarin was administered preoperatively. Before the
cardiopulmonary bypass (CPB), heparin 5,000 units was administered. Activated
coagulation times (ACTs) before and after CPB were 123 sec and 157 sec,
respectively. Additional heparin of 5,000 units extended ACT to 221 seconds,
which was not enough for the CPB. Heparin 10,000 units was added, and ACT was 157
sec. AntithrombinIII (ATIII) and platelet counts were 75% and 270,000 mm(-3),
respectively. ATIII 1,500 units was administered. ACT and ATIII became 133 sec
and 123%, respectively. Because heparin resistance did not respond to ATIII, the 
operative method was changed to off-pump CABG. A postoperative examination
revealed high factor VIII activity of 263%. Other results were as follows:
protein C antigen, 40%; protein S antigen, 65%; factor VII, 50%; platelet factor 
4, 12%; heparin cofactor II, 104%; von Willebrand factor antigen, 181%;
heparin-PF4-IgG antibody, negative; factor VIII inhibitor, negative. The low
values of protein C, protein S, and factor VII may have been caused by warfarin. 
Other values were normal, except for the von Willebrand factor antigen.

Gen Thorac Cardiovasc Surg. 2008 Apr;56(4):163-9. Epub 2008 Apr 10.

Pharmacokinetic analysis of flomoxef in children undergoing cardiopulmonary
bypass and modified ultrafiltration.

Masuda Z, Kurosaki Y, Ishino K, Yamauchi K, Sano S.

Department of Cardiovascular Surgery, Okayama University Graduate School of
Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
zenyan@aol.com

OBJECTIVE: Cardiopulmonary bypass (CPB) induces changes in the pharmacokinetics
of drugs. The purpose of this study was to model the pharmacokinetics of
flomoxef, a cephalosporin antibiotic, in pediatric cardiac surgery. METHODS: Each
patient received a flomoxef dose of 30 mg/kg as a bolus after the induction of
anesthesia and an additional dose (1 g for a child weighing < 10 kg, 2 g for > or
= 10 kg) was injected into the CPB prime. Modified ultrafiltration (MUF) was
routinely performed. Blood samples, urine, and ultrafiltrate were collected. In
seven patients (group I), serum flomoxef concentration-time courses were analyzed
by a modified two-compartment model. Utilizing the estimated parameters, serum
concentrations were simulated in another eight patients (group II). RESULTS: The 
initiation of CPB resulted in an abrupt increase in serum flomoxef concentrations
in group I; however, concentrations declined biexponentially. The amount of
excreted flomoxef in the urine and by MUF was 47% +/- 8% of the total
administered dose. In group II, an excellent fit was found between the values
calculated by the program and the observed serum concentrations expressed; most
of the performance errors were <1.0. There was no difference in any kinetic
parameter between group I and groups I + II (n = 15). CONCLUSION: The
pharmacokinetics of flomoxef in children undergoing CPB and MUF were well fitted 
to a modified two-compartment model. Using the kinetic data from this study, the 
individualization of dosage regimens for prophylactic use of flomoxef might be
possible.

J Am Coll Surg. 2008 Apr;206(4):645-53. Epub 2008 Feb 1.

Postoperative hyperbilirubinemia is an independent predictor of longterm outcomes
after cardiopulmonary bypass.

Kraev AI, Torosoff MT, Fabian T, Clement CM, Perez-Tamayo RA.

School of Medicine, Oregon Health & Science University, Portland, OR, USA.

BACKGROUND: Two decade-old studies of cardiopulmonary bypass (CPB) patients
documented a 25% to 35% incidence of postoperative hyperbilirubinemia, associated
with increased in-hospital morbidity and mortality. Longterm consequences of this
complication are unknown. STUDY DESIGN: Medical records of CPB patients were
reviewed. Mortality was ascertained through the National Death Index.
Proportional hazards determined important factors in post-CPB survival. Logistic 
regression delineated predictors of hyperbilirubinemia. Kaplan-Meier and
Mantel-Cox log-rank survival analyses compared hyperbilirubinemia groups.
RESULTS: Bilirubin levels were followed in 826 (59.7%) patients. Bilirubin was
normal in 570 (69.0%) patients (group 1), it was 1.4 to 2.8 mg/dL in 184 (22.3%) 
patients (group 2), and it exceeded 2.8 mg/dL in 72 (8.7%) patients (group 3).
Elevated bilirubin was associated with decreased body mass index, congestive
heart failure, heparin before operation, postoperative transfusion requirement,
bleeding, and renal failure. In-hospital mortality was 4.3% in group 2 and 25.0% 
in group 3, compared with 0.9% in group 1 (p<0.001). Two-year crude survival was 
95.8% in group 1, 84.8% in group 2, and 62.5% in group 3 (p<0.001). Multivariable
predictors of longterm mortality were older age, history of stroke, emergency
operation, increased duration of cardiopulmonary bypass, respiratory failure, and
elevated bilirubin. Compared with survival in group 1, there was a 1.7-fold
decrease in group 2 2-year survival (95% CI 0.9 to 3.0; p=0.09) and a 3.8-fold
decrease in group 3 survival (95% CI 2.0 to 7.2; p<0.001). CONCLUSIONS:
Postoperative bilirubin elevation in CPB patients is common and deadly. The
predictive power of hyperbilirubinemia is similar to that of respiratory failure.
The cause of postbypass hyperbilirubinemia is unknown and is probably
multifactorial. Additional prospective studies are warranted.