J Cardiothorac Vasc Anesth  2002 Dec;16(6):727-30 

Validation of continuous thermodilution cardiac output in patients implanted
with a left ventricular assist device.

Mets B, Frumento RJ, Bennett-Guerrero E, Naka Y.

Departments of Anesthesiology and Surgery, Columbia University, New York, NY.

OBJECTIVE: To assess the accuracy of a continuous cardiac output (CCO) monitor
against an independent, intravascular measurement of flow as can be performed in
patients fitted with a left ventricular assist device (LVAD). DESIGN: A
prospective cohort study. SETTING: Academic tertiary-care center. PARTICIPANTS:
Adult patients (n = 15) presenting for LVAD placement. INTERVENTIONS: Consenting
patients presenting for LVAD placement for end-stage cardiac failure were
anesthetized, and a CCO pulmonary artery catheter was placed (OptiQ, CCO/SvO(2);
Abbott Critical Care, North Chicago, IL). Patients were monitored with
transesophageal echocardiography and excluded from analysis if aortic
regurgitation was found. Cardiac output was determined using a Q-Vue, CCO/SvO(2)
computer with digital readout (Abbott Critical Care, North Chicago, IL). The
LVAD was placed in standard fashion during cardiopulmonary bypass. The Thoratec
vented electric Heartmate (Thoratec Co, Pleasanton, CA) incorporates an LVAD
flow console, which computes LVAD flow within +/- 5% (range, 1.8 to 10 L/min).
MEASUREMENTS AND MAIN RESULTS: Cardiac output flow measurements were made from
both systems at the following time points: 5 minutes and 30 minutes after
protamine administration, at chest closure, and after skin closure. Mean cardiac
output for each device did not differ at any time point. Regression analysis
(Pearson's) showed acceptable correlation (r(2) = 0.79, p < 0.0001), whereas a
bias of 529 mL with limits of agreement of 1,208 mL were shown for CCO
measurement compared with LVAD flow. CONCLUSION: The data indicate that the CCO
system tends to overestimate cardiac output by approximately 500 mL/min when
compared with LVAD flow. Nevertheless, this bias is within the range found by
other less-invasive studies done to assess the accuracy of this system and
further serves to confirm its relative accuracy. Copyright 2002, Elsevier
Science (USA). All rights reserved.

J Cardiovasc Surg (Torino)  2002 Dec;43(6):803-9 

Inhibition of systemic inflammatory response with sodium nitroprusside in open
heart surgery.

Gol MK, Nisanoglu V, Iscan Z, Balci M, Kandemir O, Tasdemir O.

Cardiovascular Surgery Clinic, Turkiye Yuksek I htisas Hospital, Ankara, Turkey.

BACKGROUND: A nitric oxide donor, sodium nitroprusside has been reported to
reduce the inflammatory response during cardiopulmonary bypass (CPB). To
investigate this, a double-blind and prospective study was conducted. METHODS:
Twenty patients with multi vessel coronary disease were randomly chosen to form
study (SNP) and control groups. In the SNP group, 0.5 micro g/kg/min sodium
nitroprusside were administered for 20 min right after the release of the aortic
crossclamp. Mac-1 (CD11b/CD18) leukocyte adhesion molecule expressions,
interleukin-6 levels were measured from radial artery blood as well as leukocyte
and platelet counts in both groups at 6 different time points: a) before
anesthesia, b) after heparin administration, c) after aortic crossclamp release,
d) after protamine administration, e) 3 hours after the termination of CPB, f)
24 hours after the termination of CPB. RESULTS: The increase in Mac-1
expressions were not different between the two groups at any time point except
the measurements after the administration of protamine. At this time point,
Mac-1 expressions were not different between the groups (99.8+/-30.7 vs
134.6+/-95.1%, p=0.076), but higher when compared with the preinduction levels.
IL-6 levels for SNP and control groups was 89+/-43 and 215+/-131 pg/dL,
respectively (p=0.016) 3 hours after the termination of CPB. Twenty-four hours
after the termination of CPB, IL-6 levels were still significantly higher in the
control group (47+/-27 vs 111+/-68 pg/dL, p=0.039). Leukocyte and platelet
counts were not different at any time point between the groups. CONCLUSIONS:
Systemic inflammatory response in patients undergoing CPB can be reduced to a
certain level with sodium nitroprusside, especially the activation of vascular
endothelial cells can be inhibited, but activation of lekocytes still takes
place.

J Cardiovasc Surg (Torino)  2002 Dec;43(6):793-7 

The role of plasma endothelin in the Fontan circulation.

Yamagishi M, Kurosawa H, Hashimoto K, Nomura K, Kitamura N.

Department of Pediatric Cardiovascular Surgery, Children's Research Hospital,
Kyoto Prefectural University of Medicine, Kyoto, Japan.

BACKGROUND: Various vasoactive substances are released during cardiopulmonary
bypass. They may deteriorate pulmonary circulation after the Fontan operation.
Effects of plasma endothelin-1 (ET-1), a vasoconstricting peptide, on the Fontan
circulation have not been investigated. METHODS: Eleven patients (aged
11.1+/-7.5 years) who underwent the modified Fontan operation (group F) and
seven patients (aged 9.9+/-6.0 years) who underwent the biventricular repair
(group C) were studied. Plasma samples were obtained for measuring ET-1 on the
first postoperative day (Early I), on returning to floor care from the intensive
care unit (Early II), and during postoperative cardiac catheterization (Late).
RESULTS: Plasma concentrations of ET-1 increased in group F (Early I,
4.37+/-1.78 pg/ml; Early II, 4.07+/-1.90 pg/ml) as compared with the basal value
of 1.0+/-0.5 pg/ml. The central venous pressure, which reflects the pulmonary
circulatory state, soon after the Fontan operation correlated significantly with
the increased ET-1 concentration (y=1.809 x+6.484; r=0.809; p=0.0026). Although
the Late ET-1 concentrations in group F were significantly decreased, the
central venous pressure and the ET-1 concentrations demonstrated a significant
correlation (y=3.074 x +5.427; r=0.740; p=0.0227). CONCLUSIONS: The increased
humoral vasoactive substances such as ET-1, which induces pulmonary
vasoconstriction following the Fontan operation, may have important implications
for the Fontan circulation.

Crit Care Med  2002 Dec;30(12):2762-4 

Inhaled prostacyclin for the treatment of pulmonary hypertension after cardiac
surgery.

Lowson SM, Doctor A, Walsh BK, Doorley PA.

OBJECTIVE To describe the effects of inhaled prostacyclin administered after
cardiopulmonary bypass (CPB) to a patient with severe pulmonary
hypertension.DESIGN Case report and literature review.SETTING Cardiac surgical
operating rooms and postoperative recovery unit.PATIENTS A 63-yr-old female who
had undergone mitral and aortic valve replacement for rheumatic heart
disease.INTERVENTIONS Administration of inhaled prostacyclin to decrease
pulmonary artery pressures and to permit discontinuation of CPB.MEASUREMENTS AND
MAIN RESULTS The patient was unable to be removed from CPB because of severe
pulmonary hypertension precipitating acute right heart failure, despite
administration of milrinone, norepinephrine, and nitroglycerin infusions.
Inhaled prostacyclin was started at a dosage of 50 ng/kg/min, and the patient
was able to be weaned from CPB. The inhaled prostacyclin was continued for 4
days postoperatively, with no signs of tolerance or systemic effects.CONCLUSION
Inhaled prostacyclin is an effective and selective pulmonary vasodilator at the
dosage given in this report. Prolonged use is not associated with tolerance or
systemic effects. The apparatus required for the delivery of inhaled
prostacyclin is simple, inexpensive, and readily available in most hospitals. A
review of the literature suggests that inhaled prostacyclin is effective in a
number of clinical settings and displays comparable efficacy and hemodynamic
effects to inhaled nitric oxide.

Blood  2002 Dec 12; [epub ahead of print] 

Estimating the rate of thrombin and fibrin generation in vivo during
cardiopulmonary bypass.

Chandler WL, Velan T.

Laboratory Medicine, University of Washington, Seattle, WA, USA.

Our objective was to estimate the in vivo rates of thrombin and fibrin
generation to better understand how coagulation is regulated. Nine males
undergoing cardiopulmonary bypass (CPB) were studied. The rates of thrombin,
total fibrin and soluble fibrin generation in vivo were based on measured levels
of prothrombin activation peptide F1.2, thrombin-antithrombin complex,
fibrinopeptide A and soluble fibrin combined with a computer model of the
patient's vascular system that accounted for marker clearance, hemodilution,
blood loss and transfusion. Prior to surgery, the average thrombin generation
rate was 0.24+/-0.11 picomoles/sec. Each thrombin molecule in turn generated
about 100 fibrin molecules of which 1% was soluble fibrin. The thrombin
generation rate did not change after sternotomy or administration of heparin,
then rapidly increased 20-fold to 5.60+/-6.65 pmol/s after 5 minutes of CPB (p =
0.00005). Early in CPB each new thrombin generated only 4 fibrin molecules of
which 35% were soluble fibrin. The thrombin generation rate was 2.14+/-1.88
pmol/s during the remainder of CPB, increasing again to 5.47+/-4.08 pmol/s after
reperfusion of the ischemic heart (p = 0.00008). After heparin neutralization
with protamine, thrombin generation remained high (5.34+/-4.01 pmol/s, p =
0.0002) and total fibrin generation increased, but soluble fibrin generation
decreased. By two hours after surgery thrombin and fibrin generation rates were
returning to baseline levels. We conclude that cardiopulmonary bypass and
reperfusion of the ischemic heart results in bursts of non-hemostatic thrombin
generation and dysregulated fibrin formation, not just a steady increase in
thrombin generation as suggested by previous studies.

Croat Med J  2002 Dec;43(6):660-4 

Right ventricle failure and outcome of simple and complex arterial switch
operations in neonates.

Kiraly L, Hartyanszky I, Prodan Z.

Hungarian Institute of Cardiology, Pediatric Cardiac Centre, Szent Laszlo Ter
22, H-1102 Budapest, Hungary, kiraly@kardio.hu

AIM. To analyze the causes and role of right ventricle failure in the morbidity
and mortality after arterial switch operation for transposition of the great
arteries in neonates. METHOD. Between January 1999 and December 2001, 62
neonates underwent arterial switch operation. The simple transposition group was
comprised of 39 patients with transposition of the great arteries and intact
ventricular septum. The complex transposition group included 23 patients with
large ventricular septal defects, accompanied with left ventricle outflow tract
obstruction in 6 cases and dextrocardia in 1 case. Arterial switch operation was
performed on elective basis in all but 3 patients who underwent emergency
operation. RESULTS. Patients with complex heart defects had significantly lower
body weight (p=0.008) than patients with simple trasposition of great arteries.
The usual coronary artery pattern (ie, the left anterior descending artery and
circumflex artery arising from the right aortic sinus; the right coronary artery
arising from the left aortic sinus) was found in 74% of the neonates in the
simple transposition group and 65% of the neonates in the complex transposition
group. Age, weight, coronary artery anatomy, cardiopulmonary bypass, duration of
aortic cross-clamp, bleeding, and the need for delayed chest closure did not
influence the outcome of surgery. Low cardiac output after surgery was more
common in the complex transposition group (p=0.0001), although it was not a
predictor of fatal outcome. Preoperative hypoxia coupled with acidosis (odds
ratio (OR), 5.70; 95% confidence intervals (CI), 4.45-7.44), and emergency
operations (OR, 3.62; 95% CI, 2.22-5.59) were strong predictors of unfavourable
outcome. We lost 4 patients out of 62 (6.5%) because of right ventricle failure
caused by persistent pulmonary hypertension. Right ventricle failure on the
second postoperative day, e.g., sustained increased central venous pressure >15
mm Hg (p<0.001) and high velocity tricuspid regurgitation >4 m/s (p=0.002),
indicated bad prognosis. CONCLUSION. Difficult coronary anatomy was not a risk
factor for morbidity and mortality after arterial switch operation. Poor
preoperative health condition, hypoxia (despite effective balloon
atrioseptostomy), and acidosis contributed to persistent pulmonary hypertension.
Operation on the emergency basis and tricuspid valve insufficiency with right
ventricle failure were strong predictors of unfavorable outcome.

Hematology  2002 Dec;7(6):359-69 

Thrombus formation with rehydrated, lyophilized platelets.

Fischer TH, Merricks EP, Bode AP, Bellinger DA, Russell K, Reddick R, Sanders
WE, Nichols TC, Read MS.

Department of Pathology and Laboratory Medicine, CB #3114 Francis Owen Blood
Research Laboratory, 350 Old Fayetteville Road, University of North Carolina at
Chapel Hill, Chapel Hill, NC, 27599 USA.

Stored human platelets are frequently used in hemorrhagic emergencies, but have
limited immediate utility for controlling bleeding due to storage lesion and are
frequently contaminated with microorganisms. The development of
paraformaldehyde-treated, lyophilized and rehydrated (RL) platelets, which are
sterile and have a prolonged shelf life (years), ameliorate the efficacy and
sterility problems with stored platelets. RL platelets have been shown to have
many native functions of fresh platelets in vitro and to mediate hemostasis in
vivo in large animal models of hemorrhagic shock and cardiopulmonary bypass
induced platelet dysfunction. To further evaluate the functional properties of
this transfusion product, we studied the role of RL platelets in three aspects
of thrombus formation and lysis. First, the interaction between RL platelets and
fibrinogen was investigated. The surface density of unligated GPIIb-IIIa on RL
and fresh platelets were, respectively 30,000 and 70,000 molecules per cell as
detected with the monoclonal antibody 10E-5. Freezing, lyophilization and
rehydration steps in the preparation of RL platelets resulted in the surface
presentation of 120,000 molecules of fibrinogen per cell from alpha granule
sources. After ADP activation, RL platelets bound exogenous 125I-labeled
fibrinogen in a dose-dependent manner with an affinity that is similar to that
of fresh platelets and was inhibited by RGD peptides. 125I-Labeled fibrinogen
binding to RL and fresh platelets, respectively, saturated at 14,000 and 32,000
molecules per cell. Scanning electron microscopic ultrastructural analysis
showed that fibrin strands interacted with the surface of RL platelets in a
normal manner. The second set of studies investigated the ability of RL
platelets to catalyze and amplify the clot formation process in an
activation-dependent manner. We showed that RL platelets undergo degranulation
in fibrin in clots and functioned as thrombogenic surfaces for the generation of
activated coagulation factors and fibrin generation. A final set of studies was
performed to investigate fibrin of clots that contained RL platelets. RL
platelet clots were lysed in the presence of tissue plasminogen activator with a
similar time course as clots without platelets, and lysis occurred faster than
when fresh platelets were included in the fibrin mass. The results of these
three studies demonstrate that RL platelets are capable of mediating thrombus
formation and do not inhibit lysis. Our results help explain how RL platelets
restore hemostasis in vivo, and indicate that these cells might be a viable
alternative to fresh stored platelets in transfusion medicine.

Eur J Cardiothorac Surg  2002 Dec;22(6):879-84 

Thyroid hormones levels in infants during and after cardiopulmonary bypass with
ultrafiltration.

Bartkowski R, Wojtalik M, Korman E, Sharma G, Henschke J, Mrowczynski W.

Department of Pediatric Cardiac Surgery, K. Marcinkowski University School of
Medicine, ul. Fredry 10, 61-701, Poznan, Poland

OBJECTIVE: The aim of this study was to find out if infants after
cardiopulmonary bypass develop non-thyroidal illness and if illness severity
after cardiopulmonary bypass depends on hormone concentration in ultrafiltrate.
METHODS: Thyroid hormone status was assessed in 20 infants with congenital heart
defects undergoing cardiac surgery (age range 7 days-11 months). Blood samples
were collected preoperatively, during cardiopulmonary bypass, after
cardiopulmonary bypass, and also postoperatively in 1, 2, 3, and 8 day after
cardiac surgery. Plasma thyrotropin, thyroxine, free thyroxine,
triiodothyronine, free triiodothyronine and reverse triiodothyronine were
measured in blood samples and also in ultrafiltrate. RESULTS: All patients had
reduction in serum thyrotropin, thyroxine, free thyroxine, triiodothyronine,
free triiodothyronine, and elevation of reverse triiodothyronine after cardiac
surgery. In all patients we performed ultrafiltration. Patients were divided in
to two groups. (with and without prolonged recovery). In the group of patients
with prolonged recovery we noticed significantly higher amount of
triiodothyronine per kilogram body weight. One of these patients died. The
average level of total thyroxine decreased from the level 126 nmol/l before
bypass to the minimal level 73 nmol/l after bypass, free thyroxine from the
level 18 pmol/l before bypass to the minimal level 12 pmol/l after bypass. The
average level of total triiodothyronine decreased from the level 1.54 nmol/l
before bypass to the minimal level 0.42 nmol/l after bypass, free
triiodothyronine from the level 6.12 pmol/l before bypass to the minimal level
3.21 pmol/l after bypass. The average level of TSH decreased from the level 4.31
mU/l before bypass to the level 0.64 mU/l after bypass. The average level of
reverse-triiodothyronine increase from the level 0.83 nmol/l before bypass to
the maximal level 1.94 nmol/l after bypass. CONCLUSIONS: We conclude that
non-thyroidal illness occurs in all infants after cardiopulmonary bypass. The
amount of free triiodothyronine that is filtrated during cardiopulmonary bypass
may influence postoperative recovery.

Artif Organs  2002 Dec;26(12):1020-1025 

Adsorption of Inflammatory Cytokines Using a Heparin-Coated Extracorporeal
Circuit.

Fujita M, Ishihara M, Ono K, Hattori H, Kurita A, Shimizu M, Mitsumaru A, Segawa
D, Hinokiyama K, Kusama Y, Kikuchi M, Maehara T.

Cardiopulmonary bypass (CPB) surgeries cause an increase in plasma inflammatory
cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6
(IL-6) along with whole-body inflammatory responses. The inflammatory responses
during a CPB treatment are reduced when using a heparin-coated extracorporeal
circuit. Because many cytokines, growth factors, and complements are known to
interact with heparin, the reduction of inflammatory responses by a
heparin-coated circuit is likely to depend on this heparin-binding nature of the
inflammatory cytokines. In this study, the inflammatory cytokines, TNF-alpha and
IL-6, in fetal bovine serum (FBS) bound to a heparin-agarose beads (heparin
beads)-column and the adsorptions were competitively inhibited on addition of
heparin in a concentration-dependent manner. TNF-alpha in FBS required a higher
concentration of heparin (50% concentration inhibition [IC50] > 20&mgr;g/ml) to
inhibit adsorption to the heparin beads-column compared with IL-6, probably
because of a stronger interaction between TNF-alpha and heparin-beads. TNF-alpha
and IL-6 concentrations in human heparinized blood significantly increased after
a CPB treatment. Although the adsorbed amount of IL-6 onto the heparin-coated
circuit was low (less than 6% of free circulating IL-6), a significant amount of
TNF-alpha adsorbed onto the circuit (23.9-755% of free circulating TNF-alpha).
Therefore, the adsorption of inflammatory cytokines, especially TNF-alpha, onto
the inner heparin-coated surface of an extracorporeal circuit may partly account
for a reduction in inflammatory responses.