J Thorac Cardiovasc Surg 2001 Apr;121(4 Pt 1):773-81

Inactivation of the MEK/ERK pathway in the myocardium during cardiopulmonary
bypass.

Araujo EG, Bianchi C, Sato K, Faro R, Li XA, Sellke FW.

Division of Cardiothoracic Surgery, Department of Surgery, Beth Israel Deaconess
Medical Center, and Harvard Medical School, Boston, Mass, and the Department of
Cellular Biology, University of Brasilia, Brasilia, DF, Brazil.

OBJECTIVES: A general pro-inflammatory response after cardiopulmonary bypass
(CPB) may involve changes in signal transduction and in part be responsible for
arrhythmias and myocardial dysfunction after cardiac surgery. The MEK/ERK
(mitogen-activated protein kinase kinase/extracellular regulated kinase) pathway
is common to many stimuli and may play a pivotal role in morbidity associated
with CPB. We investigated the changes in MEK/ERK pathway and related enzymes
after CPB in pigs. METHODS: We examined ventricular and atrial tissue from pigs
before 90 minutes of normothermic CPB and after 90 minutes of post-CPB
perfusion. The activities and protein levels of kinases MEK1/2, ERK1/2, a
cellular tyrosine kinase (c-Src), protein kinase B (Akt), and the protein levels
of mitogen-activated protein kinase phosphatase (MKP-1) were studied by
immunoblotting ventricular and atrial myocardium lysates and labeling sections
with antibodies that recognize the activated forms of the kinases and the
phosphatase. Control pigs were subjected to sternotomy and heparinization but
not CPB. RESULTS: We found a consistent inactivation of MEK/ERK pathway in both
ventricular and atrial myocardium with an increase in MKP-1, a negative
regulator of ERK1/2. The activities and protein levels of c-Src and Akt were not
significantly modified before or after CPB, suggesting a certain degree of
specificity for the MEK/ERK pathway. Such changes were not observed in controls.
The decrease of ERK1/2 and MEK1/2 phosphorylation 90 minutes after termination
of CPB (as well as the increase of nuclear MKP-1 protein levels) was also
apparent by confocal microscopy. CONCLUSIONS: These results collectively reveal
a prevalence of inhibitory mechanisms in the MEK/ERK signal transduction
machinery in myocardium subjected to CPB.

Basic Res Cardiol 2001 Apr;96(2):198-205

Influence of mild hypothermia on myocardial contractility and circulatory
function.

Weisser J, Martin J, Bisping E, Maier LS, Beyersdorf F, Hasenfuss G, Pieske B.

Abteilung Kardiologie und Pneumologie, Zentrum Innere Medizin,
Georg-August-Universitat Gottingen, Germany.

Myocardial contractility depends on temperature. We investigated the influence
of mild hypothermia (37-31 degrees C) on isometric twitch force, sarcoplasmic
reticulum (SR) Ca2+-content and intracellular Ca2+-transients in ventricular
muscle strips from human and porcine myocardium, and on in vivo hemodynamic
parameters in pigs. In vitro experiments: muscle strips from 5 nonfailing human
and 8 pig hearts. Electrical stimulation (1 Hz), simultaneous recording of
isometric force and rapid cooling contractures (RCCs) as an indicator of SR
Ca2+-content, or intracellular Ca2+-transients (aequorin method). In vivo
experiments: 8 pigs were monitored with Millar-Tip (left ventricle) and
Swan-Ganz catheter (pulmonary artery). Hemodynamic parameters were assessed at
baseline conditions (37 degrees C), and after stepwise cooling on
cardiopulmonary bypass to 35, 33 and 31 degrees C. Hypothermia increased
isometric twitch force significantly by 91 +/- 16 % in human and by 50 +/- 9 %
in pig myocardium (31 vs. 37 degrees C; p < 0.05, respectively). RCCs or
aequorin light emission did not change significantly. In anesthetized pigs, mild
hypothermia resulted in an increase in hemodynamic parameters of myocardial
contractility. While heart rate decreased from 111 +/- 3 to 73 +/- 1 min(-1),
cardiac output increased from 2.4 +/- 0.1 to 3.1 +/- 0.31/min, and stroke volume
increased from 21 +/- 1 to 41 +/- 3 ml. +dP/dtmax increased by 25 +/- 8% (37 vs.
31 degrees C; p < 0.05 for all values). Systemic and pulmonary vascular
resistance did not change significantly during cooling. Mild hypothermia exerts
significant positive inotropic effects in human and porcine myocardium without
increasing intracellular Ca2+-transients or SR Ca2+-content. These effects
translate into improved hemodynamic parameters of left ventricular function.

Artif Organs 2001 Apr;25(4):263-7

Coronary artery bypass grafting in patients with dialysis-dependent renal
failure.

Higashiue S, Nishimura Y, Shinbo M, Hatada A, Yokoi Y.

Department of Cardiovascular Surgery, and Department of Cardiology, Kishiwada
Tokushukai General Hospital, Osaka, Japan.

The aim of this study was to define short- and long-term results of coronary
artery bypass grafting (CABG) in dialysis patients. A retrospective review was
carried out on 73 consecutive patients dependent on chronic dialysis who
underwent CABG. In 63 isolated CABGs, 9 operations were performed under normal
beating heart because of severe atherosclerotic changes in the ascending aorta
or carotid arteries. The operative mortality (30 days' mortality) was 4.1%, and
causes of death were closely related to cardiopulmonary bypass use. In the last
29 operations after introduction of the beating heart bypass, no hospital deaths
occurred. The actual survival rates dropped to 45% at 70 months mainly for
noncardiac late death. CABG for dialysis patients as undertaken with an
acceptable operative risk. Extended application of beating heart bypass to these
patients may produce further positive early results.

Artif Organs 2001 Apr;25(4):252-5

Immediate and long-term results of coronary artery bypass operation in
hemodialysis patients.

Osaka SI, Osawa H, Miyazawa M, Honda J.

The Cardiovascular Center, Teikyo University Ichihara Hospital, Ichihara City;
and Department of Cardiovascular Surgery, Sakakibara Heart Institute, Tokyo,
Japan.

This study evaluated the early and late results of coronary artery bypass
grafting (CABG) in patients on long-term maintenance hemodialysis (chronic HD)
at Teikyo University Ichihara Hospital between January 1996 and June 2000.
Thirty-six patients on chronic HD underwent CABG. There were 26 males (72%) and
10 females (28%) ranging from 41 to 81 years (mean +/- SD, 61.8 +/- 9.2 years)
of age. Twenty-one patients (58%) had unstable angina, 14 (39%) stable angina,
and 1 acute myocardial infarction. Eleven patients (31%) had urgent or emergency
CABG. The average graft number was 2.5 +/- 0.8 (arterial graft 1.3 +/-
0.7/patient). Six patients had concomitant cardiac operations. Three patients
underwent re- or a second re-CABG. Five patients underwent off-pump CABG.
Principally, HD was performed during cardiopulmonary bypass and was followed by
continuous hemodiafiltration in the early postoperative period. The early
mortality was 11%; 25% in emergency and urgent CABG and 4% in elective CABG. In
the follow-up period between 1 and 53 months (mean +/- SD 21.9 +/- 15.1 months),
4 patients died, and 9 patients developed recurrence of angina pectoris (6,
occlusion of saphenous vein graft and 3, native coronary progression). Six
patients had coronary intervention. The postoperative angiogram showed that all
arterial grafts were patent, but the patency of the vein grafts was only 61.5%.
The early results of CABG in patients on chronic HD was satisfactory. The late
recurrence of angina pectoris mostly was caused by occlusion of the saphenous
vein graft. In conclusion, the aggressive use of arterial grafts is crucial in
CABG for patients on chronic HD.

J Cardiothorac Vasc Anesth 2001 Apr;15(2):210-5

Effects of hypertonic saline (7.5%) on extracellular fluid volumes compared with
normal saline (0.9%) and 6% hydroxyethyl starch after aortocoronary bypass graft
surgery.

Jarvela K, Koskinen M, Kaukinen S, Koobi T.

Departments of Anaesthesia and Intensive Care and Clinical Physiology, Tampere
University Hospital, Tampere, Finland.

OBJECTIVE: To compare the effects of hypertonic (7.5%) saline (HS), normal
(0.9%) saline (NS), and 6% hydroxyethyl starch (HES) on extracellular fluid
volumes in the early postoperative period after cardiopulmonary bypass. DESIGN:
A prospective, randomized, double-blind study. SETTING: University teaching
hospital. PARTICIPANTS: Forty-eight patients scheduled for elective coronary
artery bypass graft surgery. INTERVENTIONS: Patients were randomly allocated to
receive 4 mL/kg of HS, NS, or HES during 30 minutes when volume loading was
needed during the postoperative rewarming period in the intensive care unit.
Plasma volume was measured using a dilution of iodine-125-labeled human serum
albumin. Extracellular water and cardiac output were measured by whole-body
impedance cardiography. Measurements and Main Results: Plasma volume had
increased by 19 +/- 7% in the HS group and by 10 +/- 3% in the NS group (p =
0.001) at the end of the study fluid infusion. After 1-hour follow-up time, the
plasma volume increase was greatest (23 +/- 8%) in the group receiving HES (p <
0.001). The increase of extracellular water was greater than the infused volume
in the HS and HES groups at the end of the infusion. One-hour diuresis after the
study infusion was greater in the HS group (536 +/- 280 mL) than in the NS (267
+/- 154 mL, p = 0.006) and HES groups (311 +/- 238 mL, p = 0.025). CONCLUSION:
The effect of HS on plasma volume was short-lasting, but it stimulated excretion
of excess body fluid accumulated during cardiopulmonary bypass and cardiac
surgery. HS may be used in situations in which excess free water administration
is to be avoided but the intravascular volume needs correction. Copyright 2001
by W.B. Saunders Company

J Cardiothorac Vasc Anesth 2001 Apr;15(2):197-203

Effect of low-dose milrinone on gastric intramucosal pH and systemic
inflammation after hypothermic cardiopulmonary bypass.

Yamaura K, Okamoto H, Akiyoshi K, Irita K, Taniyama T, Takahashi S.

Department of Anesthesiology and Critical Care Medicine, Graduate School of
Medical Sciences, Kyushu University, Fukuoka, Japan.

OBJECTIVE: To investigate the usefulness of low-dose milrinone on gastric
intramucosal pH (pHi) and systemic inflammation in patients undergoing
hypothermic cardiopulmonary bypass (CPB). DESIGN: Prospective randomized study.
SETTING: University hospital. PARTICIPANTS: Twenty patients scheduled for
cardiac surgery. INTERVENTIONS: Ten patients were administered a low dose of
milrinone, 0.25 ?g/kg/min, from the initiation of CPB to 1 hour after admission
to the intensive care unit. The other patients were administered saline.
Supplemental inotropes and intravenous fluid were given to obtain adequate mean
arterial blood pressure and pulmonary artery occlusion pressure. Measurements
and Main Results: Gastric pHi and carbon dioxide pressure (PCO(2)) were assessed
by capnometric air tonometry. The difference between PCO(2) and arterial carbon
dioxide pressure (PaCO(2)), PCO(2)-gap, was also examined. Systemic inflammatory
responses were evaluated by serum interleukin-6 and leukocyte counts.
Hemodynamics, oxygen delivery index, and oxygen uptake index were monitored with
catheters in the radial and pulmonary arteries (thermodilution). The hepatic
venous blood flow and left ventricular flow were measured using transesophageal
echocardiography. Milrinone prevented gastric intramucosal acidosis, detected as
a decrease in pHi or an increase in PCO(2)-gap, without affecting hepatic venous
blood flow. Increases in interleukin-6, leukocyte count, and oxygen uptake
index, all of which developed after CPB, were significantly less in the
milrinone group than in the control group. CONCLUSION: These results suggest
that in patients undergoing hypothermic CPB, supplemental low-dose milrinone
prevents gastric intramucosal acidosis and increases in some markers of systemic
inflammation. 

Ann Thorac Surg 2001 Apr;71(4):1267-71; discussion 1271-2

Assisted venous drainage cardiopulmonary bypass in congenital heart surgery.

Ojito JW, Hannan RL, Miyaji K, White JA, McConaghey TW, Jacobs JP, Burke RP.

Division of Cardiovascular Surgery, Miami Children's Hospital, Florida
33155-4069, USA.

BACKGROUND: A novel active venous drainage perfusion circuit was designed to
achieve effective venous return through small venous cannulas. The efficacy and
safety of this new system was investigated and compared with a conventional
gravity drainage system. METHODS: Four hundred consecutive patients undergoing
open heart repair of congenital heart lesions by one surgeon were studied. The
first 200 patients were supported by gravity drainage and the next 200 patients
were supported by assisted venous drainage. No patient in the time period was
excluded from the study. RESULTS: The two groups did not differ significantly in
weight, bypass time, or cross-clamp time. Priming volumes were less in the
assisted group than in the gravity group (576+/-232 mL versus 693+/-221 mL, p <
0.001). Venous cannula size was smaller in the assisted group when compared with
the gravity group (33.2F+/-7.4F versus 38.5F+/-7.1F, p < 0.001). There was a
trend to lower operative mortality in the assisted drainage group (5 of 200,
2.5% versus 11 of 200, 5.5%; p = 0.10). Hospital stay and pulmonary, infectious,
and neurologic complications were comparable in both groups. Cardiac
complications were less common in the assisted group than in gravity group (22
of 200, 11% versus 38 of 200, 19%; p = 0.017). Hematologic complications were
less common in the assisted group than the gravity group (6 of 200, 3% versus 19
of 200, 9.5%; p < 0.01). CONCLUSIONS: These findings suggest that assisted
venous drainage is safe in congenital heart operations and facilitates the use
of smaller venous cannulas.

Ann Thorac Surg 2001 Apr;71(4):1239-43

Preoperative risk factors for hospital mortality in acute type A aortic
dissection.

Kawahito K, Adachi H, Yamaguchi A, Ino T.

Department of Cardiovascular Surgery, Omiya Medical Center, Jichi Medical
School, Saitama, Japan. kawahito@omiya.jichi.ac.jp

BACKGROUND: Acute type A dissection is associated with postoperative
complications and a high mortality rate. This study was performed to determine
the perioperative risk factors leading to hospital mortality in patients with
acute type A aortic dissection. METHODS: One hundred twenty-two patients with
acute type A aortic dissection treated surgically within 48 hours after onset
were enrolled in this study. Thirty-two perioperative risk factors were used in
statistical analysis for prediction of mortality. Risk factors for hospital
death were investigated with univariate and multiple logistic regression
analysis. RESULTS: The in-hospital mortality rate including operative death was
12.3% (15 of 122 patients) and the actuarial survival rate (including
in-hospital death) was 72%+/-6% at 5 years. Univariate analysis revealed 10 risk
factors to be statistically significant predictors of hospital death: age, year
of operation (1990 to 1995), Marfan syndrome, preoperative ST segment elevation,
heart failure from aortic regurgitation, preoperative shock, preoperative coma,
long operation time (> 6 hours), long cardiopulmonary bypass time (> 4 hours),
and massive blood transfusion (> 20 units) (p < 0.05). Multiple logistic
regression analysis confirmed preoperative ST-T segment elevation and massive
blood transfusion to be statistically significant independent risk factors for
hospital death (p < 0.05). CONCLUSIONS: Preoperative ST-T elevation and massive
blood transfusion during operation were identified as significant independent
risk factors for hospital mortality after operation for acute type A aortic
dissection. Our findings should contribute to estimation of operative risk in
individual patients.

Eur J Cardiothorac Surg 2001 Apr;19(4):507-11

Smart suction device for less blood trauma: a comparison with Cell Saver.

Mueller XM, Tevaearai HT, Horisberger J, Augstburger M, Boone Y, von Segesser
LK.

Clinic for Cardiovascular Surgery and Surgical Intensive Care Unit, CHUV (Centre
Hospitalier Universitaire Vaudois), CH-1011, Lausanne, Switzerland

Objective: The major source of hemolysis during cardiopulmonary bypass remains
the cardiotomy suction and is primarily due to the interaction between air and
blood. The Smart suction system involves an automatically controlled aspiration
designed to avoid the mixture of blood with air. This study was set-up to
compare this recently designed suction system to a Cell Saver system in order to
investigate their effects on blood elements during prolonged intrathoracic
aspiration. Methods: In a calf model (n=10; mean weight, 69.3+/-4.5 kg), a
standardized hole was created in the right atrium allowing a blood loss of 100
ml/min, with a suction cannula placed into the chest cavity into a fixed
position during 6 h. The blood was continuously aspirated either with the Smart
suction system (five animals) or the Cell Saver system (five animals). Blood
samples were taken hourly for blood cell counts and biochemistry. Results: In
the Smart suction group, red cell count, plasma protein and free hemoglobin
levels remained stable, while platelet count exhibited a significant drop from
the fifth hour onwards (prebypass: 683+/-201*10(9)/l, 5 h: 280+/-142*10(9)/l,
P=0.046). In the Cell Saver group, there was a significant drop of the red cell
count from the third hour onwards (prebypass: 8.6+/-0.9*10(12)/l, 6 h:
6.3+/-0.4*10(12)/l, P=0.02), of the platelet count from the first hour onwards
(prebypass: 630+/-97*10(9)/l, 1 h: 224+/-75*10(9)/l, P<0.01), and of the plasma
protein level from the first hour onwards (prebypass: 61.7+/-0.6 g/l, 1 h:
29.3+/-9.1 g/l, P<0.01). Conclusions: In this experimental set-up, the Smart
suction system avoids damage to red cells and affects platelet count less than
the Cell Saver system which induces important blood cell destruction, as any
suction device mixing air and blood, as well as severe hypoproteinemia with its
metabolic, clotting and hemodynamic consequences.