Asian Cardiovasc Thorac Ann. 2008 Jan;16(1):4-6.

Di(2-ethylhexyl) Phthalate Exposure During Cardiopulmonary Bypass.

Takahashi Y, Shibata T, Sasaki Y, Fujii H, Bito Y, Suehiro S.

, Department of Cardiovascular Surgery, Osaka City University Graduate School of 
Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
ysk@msic.med.osaka-cu.ac.jp.

Di(2-ethylhexyl) phthalate is an excellent plasticizer for polyvinyl chloride but
a known endocrine disrupting chemical. To investigate whether tubing containing
no diethylhexyl phthalate reduces the overall extraction of this plasticizer
during cardiopulmonary bypass, 16 patients undergoing coronary artery bypass
grafting were randomly divided into 2 groups of 8 each. Group A had tubing
containing diethylhexyl phthalate in the circuit, and group B had no diethylhexyl
phthalate in the tubing. The plasma diethylhexyl phthalate level at the end of
cardiopulmonary bypass was significantly increased compared to before anesthesia 
in both groups (group A: 103 +/- 60 to 2,094 +/- 1,046 ng.mL(-1); group B: 135
+/- 60 to 472 +/- 141 ng.mL(-1)), and it was significantly higher in group A than
group B. This study demonstrates that using tubing free from diethylhexyl
phthalate significantly reduces the release of this agent during cardiopulmonary 
bypass, which may minimize exposure to diethylhexyl phthalate.

Eur J Cardiothorac Surg. 2008 Jan 31 [Epub ahead of print]

Moderate versus deep hypothermia for the arterial switch operation - experience
with 100 consecutive patients.

Rastan AJ, Walther T, Alam NA, Daehnert I, Borger MA, Mohr FW, Janousek J,
Kostelka M.

Department of Cardiac Surgery, Heart Center, University of Leipzig,
Struempellstr. 39, 04289 Leipzig, Germany.

Objectives: To evaluate the impact of moderate versus deep perioperative
hypothermia on postoperative morbidity in patients receiving the arterial switch 
operation (ASO). Methods: One hundred consecutive patients received the ASO from 
9/98 to 4/06 using temperature-corrected full-flow moderate (M>24 degrees C,
n=51) or deep hypothermic cardiopulmonary bypass (CPB) (D, <20 degrees C, n=49). 
Complex TGA morphology was present in 33 patients (M: 27.4%, D: 38.8%, n.s.).
Median age was 9 days (M) versus 10 days (D) and body weight was 3.5+/-0.7kg (M) 
versus 3.6+/-0.9kg (D) (both p=n.s.). Follow-up was 3.7+/-2.1 years. Results:
Lowest perioperative rectal temperature was 25.3+/-1.1 degrees C (M) versus
19.0+/-0.8 degrees C (D), p<0.001. Intraoperative blood transfusion (M:
231+/-47ml, D: 252+/-112ml, p=0.04) and postoperative lactate level (M:
3.2+/-1.3mmol/l, D: 3.8+/-2.4mmol/l, p=0.02) were lower under moderate
hypothermia. One patient (D) suffered myocardial ischemia, required ECMO support 
and died. All other patients were safely weaned from CPB using dopamine (M:
3.0mug/kgmin, D: 3.4mug/kgmin, n.s.) and dobutamine (M: 5.6mug/kgmin, D:
6.7mug/kgmin, p=0.048). Secondary chest closure was performed in 41% (M) versus
59% (D, p=0.04). Patients were extubated after 89h (M) versus 126h (D) (p=0.03). 
Under moderate hypothermia ICU stay (M: 8.4+/-4.7 days, D: 12.0+/-13.8 days,
p=0.03) and hospital stay (M: 12.8+/-6.8 days, D: 20.7+/-15.5 days, p=0.001) were
shorter. Five-year freedom from reoperation was 97.0% for simple and 85.2% for
complex TGA with RVOT reconstruction in 4/6 patients. Conclusions: The ASO under 
full-flow moderate compared to deep hypothermia was advantageous regarding length
of procedure and primary chest closure rate. Moderate hypothermia seemed to be
beneficial for pulmonary recovery, length of chest tube drainage treatment and
inotropic support. No worse early or long-term effects of moderate hypothermia
were found.

J Cardiothorac Surg. 2008 Jan 29;3(1):4 [Epub ahead of print]

How I do it: transapical cannulation for acute type-A aortic dissection.

Sosnowski AW, Jutley RS, Masala N, Alexiou C, Swanevelder J.

ABSTRACT: Aortic dissection is the most frequently diagnosed lethal disease of
the aorta. Half of all patients with acute type-A aortic dissection die within 48
hours of presentation. There is still debate as to the optimal site of arterial
cannulation for establishing cardiopulmonary bypass in patients with type-A
aortic dissection. Femoral artery cannulation with retrograde perfusion is the
most common method but because of the risk of malperfusion of vital organs and
atheroembolism related to it different sites such as the axillary artery, the
innominate artery and the aortic arch are used. Cannulation of these sites is not
without risks of atheroembolism, neurovascular complications and can be time
consuming. Another yet to be popularised option is the transapical aortic
cannulation (TAC) described in this article. TAC consists of the insertion of the
arterial cannula through the apex of the left ventricle and the aortic valve to
lie in the sinus of Valsalva. Trans-oesophageal guidance is necessary to ensure
correct placement of the cannula. TAC is an excellent method of establishing
cardiopulmonary bypass as it is quick, provides a more physiological method of
delivering antegrade arterial flow and is the only method to assure perfusion of 
the true lumen.

J Cardiovasc Pharmacol. 2008 Jan;51(1):11-17.

Differential Effects of Inhaled and Intravenous Sildenafil in the Prevention of
the Pulmonary Endothelial Dysfunction Due to Cardiopulmonary Bypass.

Aubin MC, Laurendeau S, Mommerot A, Lamarche Y, Denault A, Carrier M, Perrault
LP.

From the *Department of Pharmacology, Université de Montréal, Montreal, Quebec,
Canada; †Department of Surgery, Montreal Heart Institute and Université de
Montréal, Montreal, Quebec, Canada; ‡Department of Cardiovascular Surgery,
University Hospital, Strasbourg, France; and §Department of Anesthesiology,
Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada.

The objective of the present study was to evaluate the effects of inhaled and
intravenous sildenafil on the pulmonary endothelium-dependent relaxations, the
hemodynamic profile and oxygenation after cardiopulmonary bypass. Five groups of 
Landrace swine were compared: 1) control; 2) cardiopulmonary bypass: 90 min of
normothermic cardiopulmonary bypass; 3) precardiopulmonary bypass sildenafil
nebulization; 4) postcardiopulmonary bypass sildenafil nebulization; 5)
intravenous sildenafil administration prior to cardiopulmonary bypass. All groups
underwent a 60-min period of pulmonary reperfusion after cardiopulmonary bypass. 
Vascular reactivity of second-degree pulmonary arteries was evaluated in response
to acetylcholine and bradykinin. Cardiopulmonary bypass caused a significant
decrease in endothelium-dependent relaxations to both agonists; this dysfunction 
was prevented by administration of sildenafil, both intravenous and inhaled (P < 
0.05). Both administration routes prevented the significant increase in mean
pulmonary arterial pressure with a safe hemodynamic profile. Moreover,
intravenous and inhaled sildenafil after cardiopulmonary bypass also prevented
the increase in alveoloarterial gradient (P < 0.05). Both sildenafil formulations
of administration prevent the occurrence of pulmonary endothelial dysfunction.
Depending on the administration moment and the route, the administration of
sildenafil improves the hemodynamic profile and post-cardiopulmonary bypass
oxygenation.

J Pediatr Surg. 2008 Jan;43(1):46-52; discussion 52.

A 22-year experience in global transport extracorporeal membrane oxygenation.

Coppola CP, Tyree M, Larry K, DiGeronimo R.

Department of Surgery, Wilford Hall Medical Center, San Antonio, Lackland AFB, TX
78236, USA. ccoppola@pol.net

BACKGROUND/PURPOSE: Transport extracorporeal membrane oxygenation (ECMO) is
currently available at 12 centers. We report a 22-year experience from the only
facility providing global transport ECMO. Indications for transport ECMO include 
lack of ECMO services, inability to transport conventionally, inability to wean
from cardiopulmonary bypass, extracorporeal cardiopulmonary resuscitation, and
need to move a patient on ECMO for specialized services such as organ
transplantation. METHODS: Retrospective database review of children undergoing
inhouse and transport ECMO from 1985 to 2007. RESULTS: Sixty-eight children
underwent transport ECMO. Fifty-six were transported on ECMO into our facility.
The remaining 12 were moved between 2 outside locations. Ground vehicles and
fixed-wing aircraft were used. Distance transported was 8 to 7500 miles (13-12070
km), mean 1380 miles (2220 km). There were 116 inhouse ECMO runs. No child died
during transport. Survival to discharge after transport ECMO was 65% (44/68) and,
for inhouse ECMO, was 70% (81/116). CONCLUSIONS: Transport ECMO is feasible and
effective, with survival rates comparable to inhouse ECMO. We have used transport
ECMO to help children at non-ECMO centers with pulmonary failure who have not
improved with inhaled nitric oxide and high-frequency ventilation. We have also
transported a child after extracorporeal cardiopulmonary resuscitation, which may
represent an emerging indication for transport ECMO. Transport ECMO often is the 
only option for children too unstable for conventional transport or those already
on ECMO and requiring a specialized service at another facility, such as organ
transplantation.

ASAIO J. 2008 Jan-Feb;54(1):78-88.

Systemic leukofiltration does not attenuate pulmonary injury after
cardiopulmonary bypass.

Warren OJ, Tunnicliffe CR, Massey RM, Wallace S, Smith AJ, Alcock EM, Darzi A,
Vincent CA, Athanasiou T.

Department of BioSurgery and Surgical Technology, Imperial College, London,
United Kingdom.

Pulmonary injury mediated by activated leukocytes is a recognized complication of
cardiopulmonary bypass. The aim of this paper is to systematically analyze the
effects of systemic leukofiltration within the cardiopulmonary bypass circuit on 
pulmonary injury and related clinical outcomes. We performed a systematic search 
to identify randomized controlled trials reporting on the effects of systemic
leukofiltration on respiratory parameters. Random effect meta-analytical
techniques were applied to identify differences in outcomes between the two
groups. Sensitivity and subgroup analyses were undertaken to evaluate study
heterogeneity. Incorporating 995 patients, 21 studies satisfied the inclusion
criteria. Systemic leukofiltration significantly increased the PaO2/FiO2 ratio
within 12 hours of bypass cessation, (weighted mean difference (WMD), 25.97; 95% 
confidence interval (CI), 3.41-48.53; p = 0.02) but this effect was lost by 24
hours (WMD, 12.98; 95% CI, -7.93-33.89; p = 0.22). Leukofiltration significantly 
reduced the duration of ventilatory support postoperatively (WMD, -2.11 hours;
95% CI, -0.65 to -3.58; p = 0.005), but had no impact on postoperative chest
infection, intensive care length of stay or hospital length of stay. The
heterogeneity of the included studies was high, due to poor quality study design 
and failure to include patients at high risk of pulmonary complications. Systemic
leukofiltration may attenuate bypass-related lung injury in the early
postoperative period, but this does not seem to translate to clinically
significant differences in outcomes.

ASAIO J. 2008 Jan-Feb;54(1):73-7.

Influence of normothermic cardiopulmonary bypass on body oxygen metabolism during
lung transplantation.

Sato K, Tsuchida M, Saito M, Koike T, Hayashi J.

Division of Thoracic and Cardiovascular Surgery, Niigata University Graduate
School of Medical and Dental Sciences, Niigata, Japan.

Studies have demonstrated that cardiopulmonary bypass (CPB) adversely affects
pulmonary circulation, which is involved in metabolism in the lung, and that
pulmonary circulation after CPB can restore the prostaglandin E2 (PGE2) level
mainly standing for levels of key vasostimulators augmented during CPB, which may
influence systemic tissue perfusion and body oxygen metabolism. However, in lung 
transplantation (Lx), pulmonary circulation is restored to the graft, which might
induce another CPB reaction. We prospectively examined the influence of CPB on
body oxygen metabolism in Lx. Left Lx was successfully performed on 10 dogs
(group-on: with normothermic CPB without cardiac arrest, group-off: without CPB; 
n = 5 vs. 5). At 30 minutes after graft perfusion, the right pulmonary artery and
bronchus were clamped. Body weight, donor-to-recipient body weight ratio, and
clinical parameters were comparable between the two groups, except for the
hematocrit level during CPB. At 90 minutes after graft perfusion, mixed venous
oxygen saturation (SvO2) was lower (p < 0.01) and O2 extraction rate (p < 0.01), 
PGE2 (p = 0.025), and arterial blood ketone body ratio (KBR) (p < 0.01) were
higher in group-on than in group-off, whereas these parameters were comparable
before graft perfusion between the two groups. O2 consumption and acetic acid
were higher in group-on than in group-off, whereas O2 delivery and 3-hydroxy
propioic acid were comparable between the groups. In conclusion, Lx during CPB
may induce a new inflammatory reaction and influence body oxygen metabolism,
contrary to the restoration of pulmonary circulation after CPB.

J Trauma. 2008 Jan;64(1):115-20.

Is distal aortic perfusion in traumatic thoracic aortic injuries necessary to
avoid paraplegic postoperative outcomes?

Whitson BA, Nath DS, Knudtson JR, McGonigal MD, Shumway SJ.

Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.

OBJECTIVES: Traumatic thoracic aorta injuries account for nearly 8,000 deaths
annually in the United States. Clamp-and-sew techniques can lead to high rates of
paraplegia. Use of distal aortic perfusion can lead to heparin-related
complications, particularly with associated head trauma. Our objective was to
evaluate whether or not an individualized approach to operative management
provides acceptable neurologic outcomes. METHODS: A retrospective review
(1991-2004) of patients with a traumatic thoracic aortic injury at a Level I
trauma center was performed. RESULTS: A total of 67 patients fit the study
criteria. Ninety-one percent of patients had concomitant injuries. Median time
from injury to evaluation was 38.0 minutes and from evaluation to operating room 
(OR) 111.0 minutes. Fifty-three percent of patients died before definitive repair
could be undertaken; 29% were in the emergency department and 24% were in the OR.
When definitive repair occurred, distal aortic perfusion was used in 81% of cases
(75% left heart bypass, 6% cardiopulmonary bypass). The remaining 19% underwent
clamp-and-sew technique without heparinization. There were no spinal cord
deficits or adverse cerebral events related to repair. If definitive repair was
completed, the mortality was 16%. Male sex and increasing time, both to
evaluation and to OR, were the only risk factors associated with increased
mortality. CONCLUSIONS: Judicious use of clamp-and-sew techniques can achieve
excellent neurologic outcomes, equivalent to distal aortic perfusion. Prompt
evaluation leads to improved survival. Factors such as age, mechanism of injury, 
site of aortic injury, or operative technique did not affect mortality.

J Thorac Cardiovasc Surg. 2008 Jan;135(1):123-30, 130.e1-2.

Cyclosporine A prevents apoptosis-related mitochondrial dysfunction after
neonatal cardioplegic arrest.

Oka N, Wang L, Mi W, Zhu W, Honjo O, Caldarone CA.

Division of Cardiovascular Surgery, the Hospital for Sick Children, University of
Toronto, Ontario, Canada.

OBJECTIVE: Mitochondrial permeability transition pore opening plays a critical
role in mediating the mitochondrial response to ischemia/reperfusion injury and
initiation of apoptosis. We tested whether inhibition of mitochondrial
permeability transition pore opening with cyclosporine A prevented
apoptosis-related alterations in mitochondrial structure and function after
cardioplegic arrest. METHODS: Newborn piglets (age approximately 14 days)
underwent cardiopulmonary bypass, cardioplegic arrest (60 minutes), weaning from 
bypass, and 6-hour reperfusion. Comparison was made among cold crystalloid
cardioplegia (n = 5), cold crystalloid cardioplegia with cyclosporine A
pretreatment (n = 5), and noncardiopulmonary bypass (n = 5) groups. RESULTS:
Early apoptosis signaling events (Bax translocation to the mitochondria) were
prominent in cold crystalloid cardioplegia and prevented in cold crystalloid
cardioplegia + cyclosporine A myocardium. Mitochondrial release of cytochrome c, 
determined by Western blot of cytosolic fractions and confocal quantitative
colocalization analysis, was also prominent in cold crystalloid cardioplegia but 
prevented in cold crystalloid cardioplegia + cyclosporine A myocardium. Electron 
microscopy of isolated mitochondria demonstrated subjective alterations in
mitochondrial architecture in cold crystalloid cardioplegia mitochondria, which
were prevented by cyclosporine A. Deficiency of isolated mitochondrial oxygen
consumption at Complex I was present in cold crystalloid cardioplegia
mitochondria and prevented by cyclosporine A (P < .01). The frequency of
deoxyuride-5'-triphosphate biotin nick end labeling-positive myocytes was
diminished in cold crystalloid cardioplegia + cyclosporine A myocardium (P <
.05). Mitochondrial resistance to calcium-mediated mitochondrial permeability
transition pore opening was not different in cold crystalloid cardioplegia and
noncardiopulmonary bypass mitochondria, suggesting that calcium overload is not
solely responsible for the observed deficits in mitochondrial function.
CONCLUSIONS: Cyclosporine A pretreatment prevents postcardioplegia alterations in
mitochondrial structure and function in a clinically relevant model of neonatal
cardiac surgery. Prevention of mitochondrial permeability transition pore opening
and apoptosis signaling events (Bax translocation and mitochondrial
permeabilization) are associated with superior mitochondrial preservation.

J Am Coll Surg. 2008 Jan;206(1):33-41. Epub 2007 Oct 1.

Cardiopulmonary bypass with cardioplegic arrest activates protein kinase C in the
human myocardium.

Sodha NR, Clements RT, Bianchi C, Sellke FW.

Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center, Harvard
Medical School, Boston, MA, USA.

BACKGROUND: The protein kinase C (PKC) family consists of 12 isoforms, 6 of which
have been found in human myocardium (PKC alpha, beta I/beta II, delta, epsilon,
eta, and lambda/iota). These kinases function in regulation of contractility, ion
channels, and in cellular protection or damage during ischemia-reperfusion
injury. This study investigated the effects of controlled ischemia-reperfusion
injury through cardioplegic arrest on PKC activity in patients undergoing cardiac
surgery. STUDY DESIGN: Myocardium and skeletal muscle were harvested from
patients before and after cardiopulmonary bypass and cardioplegic arrest. Total
PKC (n=12) was isolated and specifically, the PKC delta (n=8) and PKC epsilon
(n=8) isoforms were immunoprecipitated for use in functional kinase assays.
Cellular fractions (n=4) were separated by differential ultracentrifugation and
analyzed by Western blotting for membrane translocation (an indirect indicator of
increased activity). Immunofluorescent staining for PKC delta and PKC epsilon was
performed on myocardial sections. An in vitro assay of hypoxic cardioplegic
arrest followed by reoxygenation was performed using isolated cardiomyocytes, and
apoptosis was assessed. RESULTS: Cardioplegic arrest was associated with a 24.4% 
+/- 4.6% increase (p < 0.05) in total PKC activity, a 26.7% +/- 4.9% increase (p 
< 0.05) in PKC delta activity, and a 35.3% +/- 14% increase (p < 0.05) in PKC
epsilon activity in myocardium. Cardioplegic arrest induced migration of PKC
delta and epsilon to the z-line of the cardiomyocyte. Inhibition of PKC delta in 
the in vitro studies demonstrated a considerable reduction in apoptotic cells.
CONCLUSIONS: PKC delta and epsilon have previously been shown to mediate and
protect, respectively, from ischemia-reperfusion injury after myocardial
ischemia. Demonstration of increases in their activity after cardioplegic arrest 
provides support for their possible role in myocardial function after cardiac
surgery. Isoform-specific modulators may be of potential therapeutic value in
treating postoperative myocardial dysfunction.