Thorac Cardiovasc Surg  2002 Feb;50(1):16-20 

Right Ventricular Performance During Left Ventricular Unloading Conditions: The
Contribution of the Right Ventricular Free Wall.

Omoto T, Tanabe H, LaRia PJ, Guererro J, Vlahakes GJ.

Department of Surgery, Massachusetts General Hospital and Harvard Medical
School, Boston, Massachusetts.

Abstract. AIM: Right ventricular (RV) dysfunction is a significant complication
following implantation of left ventricular assist device (LVAD). However, RV
performance after LVAD implantation remains unclear. We have studied the effects
of preload and afterload on RV performance under left ventricular (LV)
unloading. METHODS: Six adult mongrel dogs were subjected to cardiopulmonary
bypass. RV preload and afterload were independently regulated. Dynamic
pressure-length analysis of RV free walls was performed using micromanometer
catheter and sonomicrometric dimension transducers. Global RV systolic function
was evaluated by the relationship between stroke volume vs. end-diastolic length
(EDL) or end-diastolic pressure (EDP). We also examined the afterload dependency
of RV performance at constant stroke volume. RESULTS: Stroke volume vs. EDP and
stroke volume vs. EDL demonstrated a linear relationship (r(2) = 0.849 [plus
minus] 0.147 and 0.776 [plus minus] 0.121, respectively). At constant stroke
volume, RV systolic peak pressure vs. EDL or EDP were shown to have a linear
relationship (r(2) = 0.906 [plus minus] 0.050 vs. 0.909 [plus minus] 0.047,
respectively). Conclusion: The Frank-Starling relationship for RV performance
was shown in this animal model. Without interventricular interaction, RV preload
is dependent on RV afterload.

Thorac Cardiovasc Surg  2002 Feb;50(1):5-10 

Cardiopulmonary Bypass Copolymer Surface Modification Reduces Neither Blood Loss
Nor Transfusions in Coronary Artery Surgery.

Sudkamp M, Mehlhorn U, Reza Raji M, Hekmat K, Easo J, Geissler HJ, Sindhu D, de
Vivie R.

Clinic for Cardiothoracic Surgery, University of Cologne, Germany.

Abstract. OBJECTIVE: Surface-modifying additives (SMA) have been suggested for
improving cardiopulmonary bypass (CPB) circuit biocompatibility, potentially
minimizing inflammatory complications and bleeding associated with CPB. The
purpose of this prospective, randomized clinical study was to compare a novel
copolymer surface-modified CPB circuit (SMARXT[TM]; COBE[reg] Cardiovascular)
against the unmodified circuit. METHODS: We randomized 122 patients with
isolated coronary artery disease subjected to first-time surgery on CPB into
either the SMA (n = 62) or the control group (n = 60). Exclusion criteria
included renal insufficiency, liver disease, coagulopathy, anticoagulation
therapy < 6 days preop, carotid artery stenosis > 70 %, and a history of stroke.
We collected perioperative clinical data including drainage blood loss,
transfusion requirements, duration of mechanical ventilation, and ICU stay.
Platelet function was determined pre- and post-CPB. RESULTS: SMA patients
received 3.2 [plus minus] 0.9 (SD) grafts during 48 [plus minus] 16 min of
aortic cross clamp and 91 [plus minus] 30 min CPB (Control: 3.0 [plus minus] 0.9
grafts; p = 0.33, 46 [plus minus] 14 min AXC; p = 0.36, and 84 [plus minus] 23
min CPB; p = 0.14). In the SMA group, 23 patients (37 %) received red blood-cell
transfusions, 9 patients (15 %) fresh frozen plasma, and 3 patients (5 %)
received platelets (control: n = 27 [46 %], p = 0.44; n = 10 [17 %], p = 0.91;
and n=4 [7 %], p = 0.71, respectively). Platelet count on CPB fell to the same
level in both groups. In SMA patients, platelet function decreased from 94.2
[plus minus] 24.9 % pre-CPB to 79.5 [plus minus] 32.8 % post-CPB (p = 0.043)
(control: from 87.7 [plus minus] 25.6 % to 69.4 [plus minus] 34.7 %; p = 0.001).
Postoperative drainage blood loss, mechanical ventilation duration, and ICU stay
were similar in both groups (p > 0.3). One patient of the control group was
excluded due to surgical bleeding, and one SMA patient died. CONCLUSIONS: Our
results show that the surface-modified CPB circuit decreased neither blood loss
nor transfusions despite slightly better platelet function preservation compared
to the unmodified circuit. This type of CPB circuit surface modification does
not appear to improve clinical outcome in low-risk coronary artery surgery
patients.

Ann Thorac Surg  2002 Feb;73(2):601-8; discussion 608-9 

Cytokine balance in infants undergoing cardiac operation.

Hovels-Gurich HH, Schumacher K, Vazquez-Jimenez JF, Qing M, Huffmeier U, Buding
B, Messmer BJ, von BG, Seghaye MC.

Department of Pediatric Cardiology, Aachen University of Technology, Germany.
hhoevels-guerich@ukaachen.de

BACKGROUND: The control of the systemic inflammatory response taking place
during cardiac operations depends on adequate antiinflammatory reaction. In this
prospective study we tested the hypothesis that cytokine balance during
pediatric cardiac surgical procedures would be influenced by the patients'
preoperative clinical condition, defined as hypoxemia or heart failure. METHODS:
Twenty infants (median age, 8 months) with hypoxemia owing to intracardiac
right-to-left shunt (group 1, n = 10) or with heart failure because of
intracardiac left-to-right shunt (group 2, n = 10), scheduled for elective
primary corrective operation, were enrolled. Plasma levels of the
proinflammatory cytokine interleukin (IL) 6, the natural antiinflammatory
cytokine IL-10, and the markers of the acute-phase response, C-reactive protein
and procalcitonin, were sequentially measured before, during, and after cardiac
operation up to the 10th postoperative day. The ratio of IL-10 to IL-6 levels
served as a marker for the individual's antiinflammatory cytokine balance.
RESULTS: Group 1 showed higher preoperative IL-6 (p < 0.001), lower IL-10 levels
(p < 0.02), and lower ratio of IL-10 to IL-6 levels (p < 0.001) than group 2.
Preoperative C-reactive protein and procalcitonin were not detectable. In group
1, preoperative IL-6 levels inversely correlated with preoperative oxygen
saturation (Spearman correlation coefficient, -0.74, p < 0.02). During
cardiopulmonary bypass, IL-6 levels were higher, whereas IL-10 and ratio of
IL-10 to IL-6 levels were lower in group 1 than in group 2. In all patients,
postoperative IL-6 levels were positively correlated with duration of inotropic
support and serum creatinine value and inversely correlated with oxygenation
index and diuresis. CONCLUSIONS: Infants with hypoxemia show a preoperative
inflammatory state with low antiinflammatory cytokine balance in contrast to
those with heart failure. This in turn is associated with lower perioperative
antiinflammatory cytokine balance and might contribute to postoperative
morbidity.

Ann Thorac Surg  2002 Feb;73(2):546-8 

And hemolysis goes on: ventricular assist device in combination with veno-venous
hemofiltration.

Luckraz H, Woods M, Large SR;  The Papworth VAD Group.

The Transplant Unit Papworth Hospital, Papworth Everard, Cambridgeshire, United
Kingdom. heyman.luckraz@papworth-tr.anglox.nhs.uk

BACKGROUND: Ventricular Assist Device (VAD) is an accepted treatment as a bridge
to cardiac transplantation, and may be of help in patients as destination
therapy for end-stage cardiac failure. The low output state associated with
end-stage cardiac failure predisposes patients to renal dysfunction and the need
for short-term renal support. The use of cardiopulmonary bypass for VAD
insertion, VAD, and hemofiltration expose the blood to mechanical trauma and
activated inflammatory cascades that can result in hemolysis. This produces free
hemoglobin, a known nephrotoxin; this is a further renal insult. This study
assesses the effect of VAD alone and in combination with continuous veno-venous
hemofiltration (CVVHF) on hemolysis. METHODS AND RESULTS: From July 1999 to
December 2000, Thoratec VAD was used in 11 patients. Nine (all males) were
included in this study as all had laboratory profiles. Hemolysis was quantified
by plasma free hemoglobin (PFHb) and hydroxybuterate dehydrogenase (HBD) levels
measured daily, defined as PFHb level greater than 40 mg/L and HBD greater than
250 IU/L. Data relate to the following time intervals while the VAD was still in
situ: T1 = 24 hours post-VAD insertion, T2 = 24 hours post-CVVHF start, T3 = 48
to 72 hours with the same CVVHF circuit, T4 = 24 hours post-stopping of CVVHF,
and T5 = CVVHF off for over 48 hours. The mean (SD) PFHb levels were 19.6 (10.9)
at T1, 31.7 (0.6) at T2, 93.7 (16.4) at T3 (p < 0.05), 32.5 (20.9) at T4, and
14.2 (3.8) at T5 (p < 0.05). These changes were paralleled by the mean (SD) HBD
levels: T1 = 1,337 (616), T2 = 2,025 (509), T3 = 2,676 (1,170) (p < 0.05), T4
1,780 (618), and T5 = 1,310 (436). CONCLUSIONS: Thoratec VAD was associated with
a mild degree of hemolysis. This was worsened by concomitant use of CVVHF. The
effect was accentuated if the same CVVHF circuit was used for over 48 hours but
was reversible within 24 hours of stopping the hemofilter.

Am Surg  2002 Feb;68(2):154-8 

Cardiac surgery after renal transplantation.

Reddy VS, Chen AC, Johnson HK, Pierson RN 3rd, Christian KJ, Drinkwater DC Jr,
Merrill WH.

Department of Cardiac and Thoracic Surgery, Vanderbilt University Medical
Center, Nashville, Tennessee 37232, USA.

Renal transplantation remains a mainstay of therapy for end-stage renal disease.
Cardiac disease has a high prevalence in this patient population. This study
reviews the factors and outcomes associated with cardiac surgery in renal
transplant recipients. We performed a retrospective review of all patients at
our institution with a functioning renal allograft at the time of their cardiac
surgical procedure. Between June 1971 and April 2000, 2343 patients underwent
renal transplantation at Vanderbilt University Medical Center. Twenty-six
patients with a functioning renal allograft subsequently underwent a cardiac
procedure requiring cardiopulmonary bypass. There were 11 women and 15 men.
Twenty-four patients underwent coronary bypass, one had a double valve
replacement, and one had a combined coronary bypass/valve replacement. The
interval from renal transplant to heart surgery ranged between 0.6 and 227
months (mean 79.1). Operative mortality was zero but there were two hospital
deaths: one due to multisystem organ failure and one due to pulmonary embolism.
Six additional patients died late with only one due to heart disease. Four
patients required perioperative dialysis, and one of these went on to require
permanent dialysis. Two additional patients returned to dialysis late
postoperatively. The requirement for acute perioperative dialysis was predicted
by preoperative creatinine, hematocrit, and intraoperative urine output. The
overall survival is 69 per cent (18 of 26) with a median follow-up of 38 months.
The majority of long-term survivors have minimal cardiac symptoms. Standard
cardiac surgery procedures can be performed with relative safety in patients
with functioning renal allografts. The incidence of perioperative and late
development of renal failure requiring dialysis is low. The long-term survival
and symptomatic improvement achieved are favorable and warrant continued
performance of cardiac surgery in patients with functioning renal allografts.

Circulation  2002 Feb 12;105(6):685-90 

Inflammatory response after open heart surgery: release of heat-shock protein 70
and signaling through toll-like receptor-4.

Dybdahl B, Wahba A, Lien E, Flo TH, Waage A, Qureshi N, Sellevold OF, Espevik T,
Sundan A.

Faculty of Medicine, Institute of Cancer Research and Molecular Biology,
Norwegian University of Science and Technology, Trondheim, Norway.
brit.dybdahl@medisin.ntnu.no

BACKGROUND: Coronary artery bypass grafting with the use of cardiopulmonary
bypass is known to mediate an inflammatory response. The stress-inducible
heat-shock protein (HSP) 70 has been detected in myocardial cells after CABG,
and toll-like receptors (TLRs) are suggested as putative signaling receptors for
the HSPs, mediating synthesis of inflammatory cytokines. The main aims of our
study were to explore the release of HSP70 and the regulation of monocyte TLR-2
and TLR-4 expression after CABG. METHODS AND RESULTS: Twenty patients referred
for elective CABG were included in this study. Using immunoassays, we detected
HSP70 in plasma after CABG, with peak concentration immediately after surgery.
Interleukin-6 in plasma reached peak concentration 5 hours after surgery.
Monocyte CD14, TLR-2, and TLR-4 expression, as analyzed by flow cytometry, was
initially downregulated. On day 1, CD14 expression normalized, whereas TLR-2 and
TLR-4 expression was upregulated. TLR-4 was significantly upregulated even on
postoperative day 2. Additional experiments revealed that peritoneal macrophages
from control (C3H/HeN) mice responded to HSP70 with release of tumor necrosis
factor, whereas macrophages from mutated TLR-4 (C3H/HeJ) mice were unresponsive.
In vitro, human adherent monocytes responded to recombinant HSP70 with
interleukin-6 and tumor necrosis factor release. CD14 and TLR-4 monoclonal
antibodies inhibited the cytokine response. CONCLUSIONS: In this study, we
observed an immediate release of HSP70 into the circulation and a modulation of
monocyte TLR-2 and TLR-4 expression after CABG. TLR-4 and CD14 appear to be
involved in an HSP70-mediated activation of innate immunity.

J Thorac Cardiovasc Surg  2002 Feb;123(2):218-224 

Leukocyte depletion attenuates expression of neutrophil adhesion molecules
during cardiopulmonary bypass in human beings.

Chen YF, Tsai WC, Lin CC, Lee CS, Huang CH, Pan PC, Chen ML, Huang YS.

Divisions of Cardiovascular Surgery, Cardiology, and Immunology and the
Department of Public Health, Kaohsiung Medical University Hospital, Kaohsiung,
Taiwan.

BACKGROUND: On the basis of scanty information, the effects of a leukocyte
filter during cardiac operations in human beings have been examined from the
viewpoint of the expression of neutrophil adhesion molecules. This study was
therefore designed to determine whether leukocyte depletion during
cardiopulmonary bypass may interfere with neutrophil adhesion properties.
METHODS: Twenty-four patients undergoing elective heart operations were randomly
allocated to a leukocyte-depletion group or a control group. Blood samples were
collected at 7 points: before sternotomy, at 10, 30, and 60 minutes of
cardiopulmonary bypass, at termination of cardiopulmonary bypass, 5 minutes
after protamine administration, and 2 hours after cardiopulmonary bypass. The
expression of the neutrophil surface adhesion molecules L-selectin and
[beta](2)-integrins was determined by flow cytometric analysis in whole blood.
RESULTS: (1) CD11a expression did not change significantly in either group.
There were no significant differences between control and leukocyte-depletion
groups (P =.63). (2) There was a significantly higher expression of CD11b on the
neutrophils during cardiopulmonary bypass in the control group than in the
leukocyte-depletion group (P =.01). (3) CD11c expression was initially
up-regulated from the onset of cardiopulmonary bypass, reaching a peak at 60
minutes after bypass in the control group (P =.02). The expression of CD11c did
not differ significantly between groups (P =.23). (4) L-selectin expression was
significantly lower in the leukocyte-depletion group than in the control group
(P =.03). CONCLUSIONS: The major findings of the present study in human subjects
undergoing elective cardiac operations with cardiopulmonary bypass are as
follows: (1) bypass was associated with an up-regulation of the adhesion
molecules L-selectin, CD11b, and CD11c but with no significant change in CD11a
expression, and (2) the clinical use of a leukocyte-depleting filter could
down-regulate the expression of CD11b and L-selectin.

J Thorac Cardiovasc Surg  2002 Feb;123(2):213-217 

Antithrombin III concentrate to treat heparin resistance in patients undergoing
cardiac surgery.

Lemmer JH Jr, Despotis GJ.

Northwest Surgical Associates, Portland, Ore, and the Department of
Anesthesiology, Washington University School of Medicine, St Louis, Mo.

OBJECTIVE: The purpose of this report is to describe the clinical use of
antithrombin III concentrate in 53 patients who were found, in the operating
room before cardiopulmonary bypass, to be heparin resistant. METHOD: Resistance
to heparin was determined to be present when greater than 600 U/kg body weight
of heparin failed to prolong the kaolin-activated clotting time to more than 600
seconds in 53 aprotinin-treated patients. Blood samples were obtained for
subsequent antithrombin III activity determination. Patients were then
administered 500 U of antithrombin III concentrate, and the activated clotting
time was remeasured. If the activated clotting time remained less than 600
seconds, a second 500-U dose was given. RESULTS: Of the 53 patients, 45 (85%)
had subnormal measured antithrombin III activity, and the mean plasma
antithrombin III activity level for the entire group was 67% (normal 80%-120%).
Administration of antithrombin III concentrate (500 U in 45 patients and 1000 U
in 8 patients) resulted in prolongation of the mean activated clotting time from
492 to 789 seconds without additional heparin. The mean heparin dose response
increased from 36.5 to 69.3 s.U(--1).mL(--1) with antithrombin III treatment.
Only one patient did not achieve the target activated clotting time, despite
administration of greater than 600 U/kg heparin and 1000 U of antithrombin III
concentrate, and was treated with fresh-frozen plasma. CONCLUSIONS: On the basis
of the criterion used in this report, most of the patients defined as being
heparin resistant had subnormal plasma antithrombin III activity. Treatment with
antithrombin III concentrate resulted in potentiation of the heparin effect to
meet predetermined activated clotting time thresholds and allow for
cardiopulmonary bypass.

J Cardiovasc Surg (Torino)  2002 Feb;43(1):31-6 

Clinical evaluation of normothermic cardiopulmonary bypass and cold
cardioplegia.

Nappi G, Torella M, Romano G.

Department of Cardiac Surgery, Second University of Naples Medical School, V.
Monaldi Hospital, Naples, Italy.

BACKGROUND: To evaluate the validity of normothermic cardiopulmonary bypass
(CPB) associated with topical hypothermia and cold cardioplegia technique.
METHODS: In a clinical prospective trial, a consecutive series of 100 patients,
homogeneous for demographics, clinical and operative data, undergoing coronary
artery bypass surgery were randomized for hypothermic CPB (rectal temperature
28-32 inverted exclamation markC group A, 50 patients) and normothermic CPB
(rectal temperature 35-37 inverted exclamation markC, group B, 50 patients). In
both groups of patients cold crystalloid cardioplegic solution and topical
hypothermia was used. RESULTS: During CPB group B patients had lower systemic
vascular resistance (p=0.0001); they needed a significant (p=0.0001) increase in
vasocostrictive. At the removal of aortic cross-clamp, a spontaneous sinus
rhythm resumed in 48% of patients in group A and in 95% of group B patients
(p=0.001). To disconnect CPB, vasoconstrictive drugs were used in 10% of
patients in group B and in none of patients in group A (p=0.0001); vasodilating
drugs were infused in 96% of patients in group A and in 40% of patients in group
B (p=0.0001). In the immediate postoperative period, positive inotropic agents
were used in 67% of patients in group A and in 22% of patients in group B (p=
0.0003); group B patients showed a more physiological rewarming, reduced periods
of mechanical ventilation and an easier regulation of the volemia. CONCLUSIONS:
In our clinical experience the technique of cold heart and warm body proved to
be safe and effective in simplifying surgical procedures and facilitating
postoperative management.