J Thorac Cardiovasc Surg. 2003 Dec;126(6):1765-74.  

The influence of hemodilution on outcome after hypothermic cardiopulmonary
bypass: Results of a randomized trial in infants.

Jonas RA, Wypij D, Roth SJ, Bellinger DC, Visconti KJ, Du Plessis AJ, Goodkin H,
Laussen PC, Farrell DM, Bartlett J, McGrath E, Rappaport LJ, Bacha EA, Forbess
JM, Del Nido PJ, Mayer JE Jr, Newburger JW.

BACKGROUND: We hypothesized that cognitive impairment and hemodynamic
instability after infant cardiac surgery with cardiopulmonary bypass might be
exacerbated by hemodilution. METHODS: In a single-center randomized trial with
blinded assessment of outcomes, we compared use of 2 hemodilution protocols
during hypothermic cardiopulmonary bypass with infant cardiac surgery. The
primary perioperative end point was lowest cardiac index in the first 24 hours
postoperatively, and primary end points at age 1 year were scores on the
Psychomotor Development Index and Mental Developmental Index of the Bayley
Scales. RESULTS: Among 147 subjects, 74 were assigned to the lower-hematocrit
strategy (21.5% +/- 2.9%, mean +/- SD at onset of low-flow bypass) and 73 to the
higher-hematocrit strategy (27.8% +/- 3.2%). In intent-to-treat analyses the
lower-hematocrit group had lower nadirs of cardiac index (P =.02), higher serum
lactate levels 60 minutes after cardiopulmonary bypass (P =.03), and a greater
percentage increase in total body water on the first postoperative day (P
=.006). Blood product use and adverse events were similar in the 2 groups. At
age 1 year (113 children), the lower-hematocrit group had worse scores on the
Psychomotor Development Index (81.9 +/- 15.7 vs 89.7 +/- 14.7, P =.008), as well
as more Psychomotor Development Index scores at least 2 SDs below the population
mean (16/56 [29%] vs 5/53 [9%], P =.01). The groups had similar Mental
Developmental Index scores and findings on neurologic examination. Inferences
using hematocrit as a continuous variable were similar to those based on
intent-to-treat analyses. CONCLUSIONS: Hemodilution to a hematocrit level in
wide use for cardiopulmonary bypass and thought to be safe is associated with
adverse perioperative and developmental outcomes in infants.

Di Yi Jun Yi Da Xue Xue Bao. 2003 Dec;23(12):1317-8.  

Effects of open heart surgery under normothermic and hypothermic cardiopulmonary
bypass on cytokines and complements.

Han PL, Fu QL, Dong JF, Zhang J, Qin YX, Cui Y, Li Q.

Department of Thoracic Surgery, First Affiliated Hospital, Xinxiang Medical
College, Weihui 453100, China.

OBJECTIVE: To explore the detrimental influence of normothermic and hypothermic
cardiopulmonary bypass during open heart surgery on cytokines and complements.
METHOD: Forty patients with congenital or rheumatic heart disease were
randomized into 2 groups to receive normothermic cardiopulmonary bypass (CPB,
study group, n=20) or hypothermic CPB (control group, n=20). Venous blood
samples were respectively collected at scheduled time points preoperatively, at
the end of CPB, and 1,4,7,14 d postoperatively to examine the level of
interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, C3, and C4. RESULTS: IL-2
in both groups decreased significantly at the end of CPB, postoperative day 1
and 4, but recovered the normal level at day 7 postoperatively. IL-2 in control
group was significantly lower than that in the study group at each time points
at the end of CPB and day 1 and 4 postoperatively. TNF-alpha in two groups was
both elevated at the time points cited above, and in the study group, recovery
of normal TNF-alpha level occurred at day 7 postoperatively, whereas in the
control group, the recovery was not achieved until postoperative day 14. C3 in
the study group was significantly lower at the time points of the end of CPB,
day 1, 7 postoperatively than that in control group, but both elevated above
normal at the end of CPB, day 1, and 4 postoperatively; in the study group, C3
became normal at day 7 postoperatively, which occurred in the control group only
till day 14 postoperatively. At the end of CPB and day 1 postoperatively, C4 was
significantly lower in the study group than in the control group, both below the
level measured preoperatively at the time points of the end of CPB, day 1 and 4
postoperatively. CONCLUSION: Open-heart surgery under normothermic CPB has less
detrimental influence on cytokines and complements than the operation under
hypothermic CPB for better recovery of the patient.

 Am J Surg. 2003 Dec;186(6):636-9; discussion 639-40.  

Clinical benefits of leukocyte filtration during valve surgery.

Patel AN, Sutton SW, Livingston S, Patel A, Hunley EK, Hebeler RF, Henry AC 3rd,
Hamman BL, Wood RE, Urschel HC Jr.

Department of Cardiothoracic Surgery, Baylor University Medical Center, Dallas,
TX 75236, USA. anpatel72@hotmail.com

BACKGROUND: The accumulation of activated leukocytes in the pulmonary
circulation plays an important role in the pathogenesis of lung dysfunction
associated with cardiopulmonary bypass (CPB). Patients undergoing valve surgery
have prolonged CPB owing to the complexity of the surgery. The goal of this
study is to determine if arterial leukocyte filters during CPB improve clinical
outcomes after valve surgery. METHODS: A prospective analysis of all patients
receiving only valve surgery with leukocyte arterial filters from June 1999 to
June 2002 was compared with a case matched cohort during the same time period.
Two hundred fifty patients were identified and compared with a cohort who did
not have leukocyte filters used during CPB. The following study points were
evaluated preoperatively and postoperatively: white blood cell count, platelet
count, arterial blood gas, time to extubation, intensive care unit stay, and
total length of hospital stay. RESULTS: There were 500 patients in the study.
The following valve operations were performed: 92 mitral valve replacements, 168
aortic valve replacements, 152 mitral valve repairs, 80 combined valve
repair/replacements, and 8 tricuspid valve repairs, all evenly divided between
the two treatment limbs. Patients with leukocyte filters had the following
findings compared with nonfilter patients: The time to extubation 10.3 versus
16.2 hours (P = 0.009), postoperative respiratory quotient 407 versus 320 (P =
0.02), total length of stay 5.4 versus 7.2 days (P = 0.04). CONCLUSIONS: The use
of arterial leukocyte filters in patients undergoing valve surgery leads to
earlier extubation, improved oxygenation, and a decreased length of stay.
Leukocyte filters should be used during CPB for patients having valve surgery.

Thorac Cardiovasc Surg. 2003 Dec;51(6):306-11.  

Adequacy of Perfusion during Hypothermia: Regional Distribution of
Cardiopulmonary Bypass Flow, Mixed Venous and Regional Venous Oxygen Saturation
- Hypothermia and Distribution of Flow and Oxygen -.

Schmid FX, Philipp A, Foltan M, Jueckstock H, Wiesenack C, Birnbaum D.

Department of Cardiothoracic and Vascular Surgery.

BACKGROUND: Hypothermia during CPB is used to reduce metabolic activity, thus
protecting organs and tissues. The aim of this study was to investigate the
relationship between regional and mixed venous oxygen saturation and
distribution of pump flow with respect to hypothermia. METHODS: Twenty-five
patients undergoing a Ross procedure were included in a prospective, controlled
study. During standard CPB, temperature was reduced stepwise to 28 degrees C.
Blood gases (a-stat regimen) were analysed in samples from the inferior (IVC)
and the superior vena cava (SVC), arterial and mixed venous blood. Flow was
detected separately in the SVC, IVC, arterial, and collecting venous line.
Samples were taken, and flows were measured before CPB, during hypothermia,
during rewarming, and 30 min after CPB discontinuation. RESULTS: Oxygen
saturation in the IVC was lower than in the SVC and in mixed venous blood at all
times (max. difference - 17.3 +/- 3.0 % during hypothermia, - 23.8 +/- 2.9 %
during rewarming, p < 0.01). There was a statistical correlation of mixed and
IVC venous oxygen saturation (r = 0.79, p < 0.001) but not of SVC venous blood.
Hypothermia had a major influence on pump flow distribution as backflow from the
SVC decreased significantly in favour of IVC flow with increasing degree of
hypothermia (increase of flow difference from 1.15 +/- 0.23 l/min to 1.49 +/-
0.36 l/min, p < 0.01). Temperature profiles were similar when detected in aorta,
pulmonary artery, tympanum and nasopharygeum, but differed significantly from
other sites. CONCLUSIONS: During hypothermic CPB, regional deoxygenation occurs
in spite of normal mixed venous saturation. The level of hypothermia has a major
impact on bypass flow distribution with cerebral perfusion reduction. Methods of
regional oxygenation assessment are needed, and altered strategies during

Ann Thorac Surg. 2003 Dec;76(6):2121-31.  

Heparin-induced thrombocytopenia and cardiac surgery.

Warkentin TE, Greinacher A.

Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
twarken@mcmaster.ca

Unfractionated heparin given during cardiopulmonary bypass is remarkably
immunogenic, as 25% to 50% of postcardiac surgery patients develop
heparin-dependent antibodies during the next 5 to 10 days. Sometimes, these
antibodies strongly activate platelets and coagulation, thereby causing the
prothrombotic disorder, heparin-induced thrombocytopenia. The risk of
heparin-induced thrombocytopenia is 1% to 3% if unfractionated heparin is
continued beyond the first postoperative week. When cardiac surgery is urgently
needed for a patient with acute or subacute heparin-induced thrombocytopenia,
options include an alternative anticoagulant (bivalirudin, lepirudin, or
danaparoid) or combining unfractionated heparin with a platelet antagonist
(epoprostenol or tirofiban). As heparin-induced thrombocytopenia antibodies are
transient, unfractionated heparin alone is appropriate in a patient with
previous heparin-induced thrombocytopenia whose antibodies have disappeared.

Ann Thorac Surg. 2003 Dec;76(6):1911-6; discussion 1916.  

Cavopulmonary assist: circulatory support for the univentricular Fontan
circulation.

Rodefeld MD, Boyd JH, Myers CD, LaLone BJ, Bezruczko AJ, Potter AW, Brown JW.

Section of Cardiothoracic Surgery, Department of Surgery, Indiana University
School of Medicine and James Whitcomb Riley Hospital for Children, Indianapolis,
Indiana 46202, USA. rodefeld@iupui.edu

BACKGROUND: Following Fontan palliation, the univentricular circulation is
notable for coexisting systemic venous hypertension and pulmonary arterial
hypotension. Assisted cavopulmonary blood flow to overcome this pressure
gradient would restore the circulation to one more closely resembling normal
two-ventricle physiology. We hypothesized that mechanical augmentation of
cavopulmonary blood flow would provide physiologic stability in a model of
cavopulmonary diversion and univentricular circulation. METHODS: Yearling sheep
(n = 13, mean weight 56.5 kg) underwent total cavopulmonary diversion on
cardiopulmonary bypass. The superior and inferior vena cavae were anastomosed
directly to the right pulmonary artery. Axial flow pumps were positioned within
both vena cavae to assist blood flow from the systemic venous circulation into
the pulmonary vasculature. Baseline ventilation was resumed, cardiopulmonary
bypass was weaned, and pump support was titrated to obtain normal physiologic
measurement. Cardiopulmonary data were collected for 6 hours. RESULTS: All
animals demonstrated hemodynamic stability without need for volume loading,
inotropic support, or pulmonary vasodilator therapy. Cardiac output, pulmonary
vascular resistance, pulmonary arterial pressure, inferior vena caval pressure,
and arterial pCO(2) and pO(2) values 6 hours after intervention were similar to
baseline values. Arterial lactate levels steadily decreased throughout the
cavopulmonary assist period. CONCLUSIONS: Cavopulmonary assist with a
percutaneous pump provides physiologic stability in a model of total
cavopulmonary diversion and univentricular Fontan circulation without altering
regional volume distribution or cardiac output. This mode of circulatory support
may have potential to benefit patients with marginal Fontan hemodynamics in both
the early and late time periods.

Circ Res. 2003 Dec 1 [Epub ahead of print].  

Hemoglobin Scavenger Receptor CD163 Mediates Interleukin-10 Release and Heme
Oxygenase-1 Synthesis. Antiinflammatory Monocyte-Macrophage Responses In Vitro,
in Resolving Skin Blisters In Vivo, and After Cardiopulmonary Bypass Surgery.

Philippidis P, Mason JC, Evans BJ, Nadra I, Taylor KM, Haskard DO, Landis RC.

British Heart Foundation Cardiac Surgery Unit and British Heart Foundation
Cardiovascular Medicine Unit, National Heart and Lung Institute, Faculty of
Medicine, Imperial College, Hammersmith Hospital, London, UK.

The recently described hemoglobin scavenger receptor CD163 mediates the
endocytosis of hemoglobin:haptoglobin (Hb:Hp) complexes and thereby counters
Hb-induced oxidative tissue damage after hemolysis. Although CD163 has been
indirectly associated with antiinflammatory and atheroprotective activity, no
ligand-receptor-effector pathway has yet been described for this receptor. To
understand the significance of CD163 and more clearly define downstream pathways
linked to inflammatory resolution, we studied the expression and function of
CD163 in human monocytes/macrophages using both in vitro and in vivo models.
Differentiation of human blood monocytes into macrophages either by in vitro
culture or in resolving cantharidin-induced skin blisters led to an equivalent
increase (>15x) in CD163 expression. Elevated CD163 levels were also noted on
circulating monocytes in cardiac surgical patients during the resolution phase
of the systemic inflammatory response to cardiopulmonary bypass surgery. In each
case, binding of Hb:Hp to CD163-bearing cells elicited potent interleukin-10
secretion, and this was inhibited by the anti-CD163 antibody RM3/1. Release of
interleukin-10, in turn, induced heme oxygenase-1 stress protein synthesis via
an autocrine mechanism. Such induction of heme oxygenase-1 was observed in vivo
24 to 48 hours after the onset of cardiopulmonary bypass surgery. These results
identify novel antiinflammatory and cytoprotective effector pathways in human
monocytes/macrophages related to Hb scavenging and metabolism, which may have
relevance in atheroprotection, wound healing, and patient recovery
postoperatively.

Circulation. 2003 Dec 23;108(25):3079-83. Epub 2003 Dec 01. 

Angiotensin-converting enzyme inhibition alters the fibrinolytic response to
cardiopulmonary bypass.

Pretorius M, Murphey LJ, McFarlane JA, Vaughan DE, Brown NJ.

Department of Anesthesiology, Vanderbilt University, Nashville, Tenn, USA.
mias.pretorius@vanderbilt.edu

BACKGROUND: Increased plasminogen activator inhibitor-1 (PAI-1) concentrations
after coronary artery bypass grafting (CABG) are associated with increased risk
of vein graft occlusion. Because angiotensin II stimulates PAI-1 expression, we
tested the hypothesis that preoperative angiotensin-converting enzyme (ACE)
inhibition decreases PAI-1 expression after CABG. METHODS AND RESULTS: We
measured the effects of cardiopulmonary bypass (CPB) on PAI-1 antigen and
tissue-type plasminogen activator (tPA) antigen and activity in 31 patients
taking an ACE inhibitor (ACEI) who were randomized to continue ACEI until the
morning of surgery (ACEI group, n=19) or to discontinue it 48 hours before
surgery (No-ACEI group, n=12). Arterial blood samples were taken at baseline
before CPB, twice during CPB, after separation from CPB, and on postoperative
day 1 (POD1). CPB caused an early decrease in PAI-1 antigen, followed by an
increase in PAI-1 antigen on POD1 (P<0.001 for effect of time). ACE inhibition
attenuated the increase in PAI-1 antigen such that both PAI-1 antigen on POD1
(P=0.013) and the change in PAI-1 antigen from baseline to POD1 (P=0.009) were
higher in the No-ACEI group (from 17.0+/-5.0 to 48.7+/-8.8 ng/mL) versus the
ACEI group (from 19.9+/-3.4 to 33.1+/-6.2 ng/mL). There was no significant
difference between the 2 groups in intraoperative tPA activity (P=0.259);
however, the increase in tPA activity was significantly greater in the ACEI
group than in the No-ACEI group (P=0.030). CONCLUSIONS: Preoperative ACEI
attenuates the increase in PAI-1 after CABG, suggesting a role for ACE
inhibition in reducing the risk of acute graft thrombosis.

Eur J Cardiothorac Surg. 2003 Dec;24(6):953-60.  

Myocardial revascularization with and without cardiopulmonary bypass:
advantages, disadvantages and similarities.

Calafiore AM, Di Mauro M, Canosa C, Di Giammarco G, Iaco AL, Contini M.

Division of Cardiac Surgery, University "G. D'Annunzio", S. Camillo de' Lellis
Hospital, via C. Forlanini 50, 66100, Chieti, Italy. calafiore@unich.it

OBJECTIVES: Off-pump coronary artery bypass surgery is becoming increasingly
popular although its effectiveness remains controversial. Our goal was to
investigate the effectiveness of on-pump and off-pump coronary artery bypass
surgery on early (30 days) and long-term (5 years) clinical outcome in two
groups of patients selected using propensity scores. METHODS: From November 1994
to December 2001, 4381 patients underwent isolated coronary surgery. Applying
propensity score matching, 1922 patients were selected (off-pump n=961, on-pump
n=961). RESULTS: Stepwise logistic regression analysis showed that the use of
cardiopulmonary bypass was an independent predictor for early death, cerebral
vascular accident, early negative primary endpoints (ENPEP), and early major
events (EME). Five years freedom from both events was similar in the two groups.
However, freedom from acute myocardial infarction (AMI) in grafted areas was
higher in the off-pump than in the on-pump patients, a possible explanation
being the lower postoperative creatine kinase myocardial band (CKMB) release.
Grouping all patients according to CKMB peak release also showed that patients
with normal release values had higher freedom from all cardiac events
investigated. A subgroup analysis of 59 patients converted from off-pump to
on-pump showed higher early mortality, ENPEP, and EME. Conversion, however, did
not affect late clinical outcome. CONCLUSIONS: These results suggest that
off-pump surgery reduces early mortality and morbidity. Conversion to on-pump
carries high in-hospital mortality and morbidity. Long-term clinical outcome is
similar in the two groups; however, off-pump patients seemed to have a higher
freedom from AMI in the grafted area which might be related to the lower CKMB
peak release when compared with patients undergoing on-pump surgery.