Ann Thorac Surg. 2003 Nov;76(5):1614-22.  

Optimal dose and mode of delivery of Na+/H+ exchange-1 inhibitor are critical
for reducing postsurgical ischemia-reperfusion injury.

Corvera JS, Zhao ZQ, Schmarkey LS, Katzmark SL, Budde JM, Morris CD, Ehring T,
Guyton RA, Vinten-Johansen J.

Cardiothoracic Research Laboratory, Emory University School of Medicine,
Atlanta, Georgia, USA.

BACKGROUND: In clinical trials, perioperative intravenous Na(+)/H(+) exchange
isoform-1 (NHE1) inhibitors were only moderately effective in high-risk patients
undergoing surgical reperfusion (GUARDIAN trial). However, effective myocardial
concentrations of NHE1 inhibitor may not have been achieved by parenteral
administration alone. We tested the hypothesis that increasing doses of NHE1
inhibitor EMD 87580 ((2-methyl-4,5-di-(methylsulfonyl)-benzoyl)-guanidine)
delivered in blood cardioplegia (BCP) and by parenteral route at reperfusion
reduce myocardial injury after surgical reperfusion of evolving infarction.
METHODS: Twenty-six anesthetized dogs underwent 75 minutes of left anterior
descending coronary artery occlusion, followed by cardiopulmonary bypass and 60
minutes of arrest with multidose 10 degrees C BCP. In the control group (n = 8),
BCP was not supplemented. In the three EMD-BCP groups, BCP was supplemented with
10 micromol/L EMD 87580 (EMD-10, n = 5), 20 micromol/L EMD 87580 (EMD-20, n =
5), or 20 micromol/L EMD 87580 combined with an immediate reperfusion bolus (5
mg/kg intravenously) (EMD-20R, n = 8). The left anterior descending coronary
artery occlusion was released just before the second infusion of BCP.
Reperfusion continued for 120 minutes after discontinuation of cardiopulmonary
bypass. RESULTS: Postischemic systolic and diastolic function in the area at
risk was dyskinetic in all groups. Infarct size (percentage of area at risk) was
not significantly reduced in the EMD-10 (26.2% +/- 3.6%) and EMD-20 (22.5% +/-
2.4%) groups versus control (30.7% +/- 2.4%); however, infarct size was
significantly reduced in the EMD-20R group (16.1% +/- 2.8%, p = 0.003). Edema in
the area at risk in the EMD-10 (81.1% +/- 0.5% water content), EMD-20 (81.7% +/-
0.3%), and EMD-20R (81.9% +/- 0.3%) groups was less than in controls (83.2% +/-
0.2%), (p < 0.056). Neutrophil accumulation (myeloperoxidase activity) in
postischemic area-at-risk myocardium was less in the EMD-20R group versus the
control group (5.3 +/- 0.7 versus 8.7 +/- 1.4 absorbance units x min(-1) x
g(-1); p = 0.05), which suggests an attenuated postischemic inflammatory
response. CONCLUSIONS: Optimal delivery of NHE1 inhibitor to the heart through
combined cardioplegia and parenteral routes significantly attenuates myocardial
injury after surgical reperfusion of regional ischemia. Timing, dose, and mode
of delivery of NHE1 inhibitors are important to their efficacy.

Ann Thorac Surg. 2003 Nov;76(5):1471-6; discussion 1476.  

Coronary malperfusion due to type A aortic dissection: mechanism and surgical
management.

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

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

BACKGROUND: Coronary malperfusion associated with aortic dissection is
relatively rare, but when it occurs, it is fatal to the patient. To salvage such
moribund patients, aggressive coronary revascularization concomitant with aortic
repair is essential. We review the surgical results and mechanism of
malperfusion in a group of 12 patients with coronary malperfusion caused by type
A aortic dissection, and we discuss our surgical approach. METHODS: Between
March 1990 and March 2003, 12 patients (6.1%) from a total of 196 consecutive
patients with acute type A aortic dissection undergoing surgery suffered
coronary malperfusion associated with the dissection. There were 4 men and 8
women (mean age, 60.8 +/- 8.3 years). Nine patients had acute myocardial
infarction due to dissection before surgery, and 3 patients suffered coronary
malperfusion after aortic declamping. RESULTS: Hospital mortality rate was 33.3%
(4 patients). The mortality rate was higher than that in patients without
coronary malperfusion (33.3% vs. 8.2%, p = 0.019). Three patients could not be
weaned from cardiopulmonary bypass, and 1 patient died of heart failure in the
intensive care unit. Involved coronary arteries included the right coronary
artery (8 patients), left coronary (2 patients), and both (2 patients).
Mechanisms of coronary obstruction were compression (2 patients), coronary
dissection (7 patients), and coronary disruption (3 patients). Coronary artery
bypass grafting was performed concomitant with aortic repair. CONCLUSIONS: Acute
type A aortic dissection with coronary involvement is associated with high
mortality rate, aggressive coronary revascularization and early aortic repair
with simple techniques are necessary to salvage these critically ill patients.

Ann Thorac Surg. 2003 Nov;76(5):1443-9.  

Peritoneal dialysis after surgery for congenital heart disease in infants and
young children.

Chan KL, Ip P, Chiu CS, Cheung YF.

Division of Paediatric Cardiology, Department of Paediatrics and Adolescent
Medicine, Grantham Hospital, The University of Hong Kong, People's Republic of
China.

BACKGROUND: We determined the risk factors for peritoneal dialysis (PD) in young
children undergoing open heart surgery and, in those patients requiring PD,
factors associated with prolonged PD and mortality. METHODS: The clinical
records of 182 children, aged 3 years or younger, who had undergone open heart
surgery during a 2-year period were reviewed. Demographic data, preoperative
risk factors, intraoperative variables, and postoperative complications were
compared between patients requiring PD and those who did not, and between
survivors and nonsurvivors of PD. RESULTS: Of the 182 patients, 31 (17%)
required PD. Patients requiring PD were lighter and more likely to have required
preoperative ventilation; had undergone more complex surgery requiring longer
bypass and circulatory arrest; and had experienced a pulmonary hypertensive
crisis (p < 0.01). Logistic regression identified circulatory arrest (relative
risk, 9.4; p = 0.002), cardiopulmonary bypass duration (relative risk, 1.02; p =
0.028), and low cardiac output syndrome (relative risk, 12.9; p < 0.0001) as
significant determinants. Peritoneal dialysis was effective in achieving
negative fluid balance, although serum urea and creatinine levels remained
static. Prolonged PD was associated with younger age, higher preoperative serum
creatinine, higher postoperative oxygen requirement, postoperative pulmonary
hypertensive crisis, and low cardiac output syndrome (p < 0.05). When compared
with survivors (n = 22), nonsurvivors (n = 9) were more likely to have had
syndrome disorders and required preoperative ventilation and higher
postoperative ventilatory settings (p < 0.05). CONCLUSIONS: Risk factors for PD
in young children undergoing open heart surgery are circulatory arrest,
cardiopulmonary bypass duration, and low cardiac output syndrome. The
preoperative and postoperative cardiopulmonary status has a significant bearing
on PD duration and patient survival.

Shock. 2003 Nov;20(5):427-30.  

First use of hypertonic saline dextran in children: a study in safety and
effectiveness for atrial septal defect surgery.

Rocha-E-Silva R, Caneo LF, Lourenco Filho DD, Jatene MB, Barbero-Marcial M,
Oliveira SA, Rocha-E-Silva M.

Division of Surgery, Sao Paulo University School of Medicine, Sao Paulo, Brazil
05403-900. rors@terra.com.br

Hypertonic saline dextran (7.5% NaCl + 6% Dextran-70) has been used in adults in
several studies and shown beneficial effects in hypovolemic shock, trauma,
cardiogenic shock, and cardiac surgery. There have never been studies of this
solution in children. This work studies its effect in children undergoing
surgery for the correction of atrial septal defects. Twenty-five children
underwent correction of atrial septal defect using cardiopulmonary bypass with
bloodless priming. Children were divided in five groups and each received an
incremental hypertonic saline dextran dose of 0.1, 0.5, 1.0, 2.0, and 4.0 mL/kg,
5 min before the beginning of cardiopulmonary bypass. Collected data were fluid
balance, amount of bleeding, blood/derivative transfusion occurrence, plasma
sodium, and hematocrit. Patients were divided into low-dose (0-1 mL/kg) and
high-dose (2-4 mL/kg) groups. Analysis of variance was used to determine
differences in blood loss between groups. The fluid balance and blood/derivative
requirements were compared through Student's t test and Fisher's exact test
(2-tail), respectively. All patients were discharged from hospital with
corrected atrial septal defect. No hypertonic saline dextran-related
complications occurred. There were no differences in the amount of bleeding. The
high-dose group exhibited a significant decrease in fluid balance and in
blood/derivative requirements in comparison with the low-dose group. In this
study, the use of hypertonic saline dextran in the pediatric population
submitted to cardiopulmonary bypass is safe and does not raise the amount of
bleeding. Its effective doses produce negative fluid balance and reduce
blood/derivative requirements.

Pharmacol Res. 2003 Nov;48(5):519-29.  

A possible cardioprotective effect of heat shock proteins during cardiac surgery
in pediatric patients.

Giannessi D, Caselli C, Vitale RL, Crucean A, Murzi B, Ry SD, Vanini V, Biagini
A.

Laboratory of Cardiovascular Biochemistry, CNR Institute of Clinical Physiology,
Via Moruzzi, 156100 Pisa and G. Pasquinucci Hospital, Massa, Italy.
danielag@ifc.pi.cnr.it

BACKGROUND: Overexpression of heat shock proteins (Hsps) is associated to
myocardial protection and it has been suggested that they could be a marker of
cardiac preservation in conditions such as extracorporeal circulation. Aim of
this study was to evaluate if cardioplegic arrest can modify the expression of
Hsps in the heart and if this alteration is associated to cardiac
preservation.METHOD: The levels of Hsp 27, Hsp 60, and both the constitutive and
the inducible form of Hsp 70 were measured in the cardiac tissue from right
atrium of pediatric patients before and after aortic cross-clamping (ACC) during
cardiopulmonary bypass surgery for correction of congenital heart disease
(n=20). The quantitative evaluation of Hsps was made by Western blotting
analysis after tissue extraction and protein separation. Hsp 72 mRNA expression
was also evaluated in pre- and post-ACC samples of eight subjects by
semiquantitative RT-PCR. Peripheral levels of Troponin I, Myoglobin, LDH, CK,
CK-MB were measured in basal conditions and at 12 and 24h after cardiosurgery as
markers of heart damage.RESULTS: The cardioplegic arrest did not significantly
modify the mean levels of all the Hsps measured. Hsp 72 levels increased after
cardioplegia in the 40% of the patients and all Hsps in the 28% of subjects. The
patients whose levels of Hsps are increased after cardioplegia are associated
with lower post-surgery concentrations of all the markers of cardiac
injury.CONCLUSIONS: This observation suggests a relationship between the
increase of Hsps and the reduction of cardiac injury.

Eur J Cardiothorac Surg. 2003 Nov;24(5):807-16.  

Impact of hypothermic selective cerebral perfusion compared with hypothermic
cardiopulmonary bypass on cerebral hemodynamics and metabolism.

Strauch JT, Spielvogel D, Haldenwang PL, Zhang N, Weisz D, Bodian CA, Griepp RB.

Department of Cardiothoracic Surgery, Mount Sinai School of Medicine/New York
University, One Gustave L. Levy Place, P.O. Box 1028, 10029, New York, NY, USA

OBJECTIVE: Hypothermic selective cerebral perfusion (SCP) is widely used for
cerebral protection during aortic arch surgery, but the effect of the absence of
systemic perfusion on cerebrovascular dynamics it has never been established.
This study explored the physiology of prolonged SCP compared to hypothermic
cardiopulmonary bypass (HCPB) in pigs. METHODS: In this blinded protocol, 29
juvenile pigs (20-23 kg) were randomized after cooling on cardiopulmonary bypass
(CPB) to 20 degrees C. Group I pigs (n=14) underwent 90 min of SCP, while group
II (HCPB, n=15) underwent total body perfusion. Fluorescent microspheres were
injected during perfusion and recovery, enabling calculation of total and
regional cerebral blood flow (CBF). Cerebrovascular resistance (CVR), oxygen
consumption and intracranial pressure (ICP) were also monitored. RESULTS: CBF
decreased significantly (P=0.0001) during cooling, but remained at significantly
higher levels with SCP than with HCPB throughout perfusion and recovery
(P<0.0001). CVR was significantly lower with SCP than with HCPB throughout
perfusion (P=0.04). Oxygen consumption fell significantly with cooling
(P=0.0001), remained low during perfusion, and rebounded promptly with
rewarming; with SCP it was significantly higher than with HCPB throughout the
perfusion interval (P=0.03), and remained higher thereafter. ICP rose
significantly less with SCP than with HCPB (P=0.02). CONCLUSION: We conclude
that, compared with HCPB, SCP results in beneficial cerebral vasodilatation, as
evidenced by significantly higher CBF and oxygen consumption during SCP, by
prompt recovery of oxygen consumption after rewarming, and by significantly
lower ICP during perfusion and in the post-bypass period.

J Surg Res. 2003 Nov;115(1):56-62.  

Activation of pulmonary mitogen-activated protein kinases during cardiopulmonary
bypass.

Khan TA, Bianchi C, Araujo EG, Ruel M, Voisine P, Sellke FW.

Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center,
Boston, Massachusetts, USA.

PURPOSE: Cardiopulmonary bypass (CPB) produces an inflammatory response
associated with pulmonary dysfunction. Mitogen-activated protein kinases (MAPK)
have been shown to mediate pulmonary injury. We hypothesized that MAPK are
activated during CPB and potentially contribute to lung injury. METHODS: Pigs
were placed on CPB (n = 6) for 90 min, which included 80 min of cardioplegic
arrest, followed by 180 min of post-CPB reperfusion. Control animals (n = 6)
underwent sternotomy and heparinization only. Lung samples were collected at
baseline, during CPB, and during post-CPB reperfusion. Activated forms of
extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 were measured by
Western blot. Immunohistochemistry was used for tissue localization of activated
MAPK. Pulmonary inflammation was determined by histology. Pulmonary edema was
estimated by tissue water percentage. RESULTS: Activated ERK1/2 and p38 were
increased after 90 min of CPB compared with controls (3.94 +/- 0.61- and 2.49
+/- 0.15-fold increase, respectively; both P < 0.01). At 180 min of post-CPB
reperfusion, ERK1/2 activity was increased by nearly 5-fold compared with
controls (P < 0.01), whereas p38 activity returned to baseline levels. By
immunohistochemistry, activated ERK1/2 and p38 in the CPB group were localized
to alveolar epithelial cells, vascular endothelial cells, and bronchial smooth
muscle. Histologic signs of lung injury included leukocyte infiltration in the
CPB group. Tissue water percentage was increased with CPB (89.9 +/- 1.5% versus
82.5 +/- 1.0%, CPB versus control, P < 0.05). CONCLUSIONS: The results of our
study demonstrate that CPB increases pulmonary p38 activity and causes sustained
activation of ERK1/2. MAPK activation thus may in part mediate the pulmonary
inflammatory response and provide a potential site of intervention to prevent
pulmonary dysfunction due to CPB.

Br J Anaesth. 2003 Nov;91(5):656-61.  

Cerebral embolization during cardiac surgery: impact of aortic atheroma burden.

Mackensen GB, Ti LK, Phillips-Bute BG, Mathew JP, Newman MF, Grocott HP;
Neurologic Outcome Research Group (NORG).

Division of Cardiothoracic Anesthesiology and Critical Care Medicine, Department
of Anesthesiology, Box 3094, Duke University Medical Center, Durham, NC 27710,
USA.

BACKGROUND: Aortic atheromatous disease is known to be associated with an
increased risk of perioperative stroke in the setting of cardiac surgery. In
this study, we sought to determine the relationship between cerebral microemboli
and aortic atheroma burden in patients undergoing cardiac surgery. METHODS:
Transoesophageal echocardiographic images of the ascending, arch and descending
aorta were evaluated in 128 patients to determine the aortic atheroma burden.
Transcranial Doppler (TCD) of the right middle cerebral artery was performed in
order to measure cerebral embolic load during surgery. Using multivariate linear
regression, the numbers of emboli were compared with the atheroma burden.
RESULTS: After controlling for age, cardiopulmonary bypass time and the number
of bypass grafts, cerebral emboli were significantly associated with atheroma in
the ascending aorta (R2=0.11, P=0.02) and aortic arch (P=0.013). However, there
was no association between emboli and descending aortic atheroma burden
(R2=0.05, P=0.20). CONCLUSIONS: We demonstrate a positive relationship between
TCD-detected cerebral emboli and the atheromatous burden of the ascending aorta
and aortic arch. Previously demonstrated associations between TCD-detectable
cerebral emboli and adverse cerebral outcome may be related to the presence of
significant aortic atheromatous disease.

Anesth Analg. 2003 Nov;97(5):1222-9.  

Mannitol and dopamine in patients undergoing cardiopulmonary bypass: a
randomized clinical trial.

Carcoana OV, Mathew JP, Davis E, Byrne DW, Hayslett JP, Hines RL, Garwood S.

Department of Anesthesiology, Yale University School of Medicine, New Haven,
Connecticut 06520-8051, USA .

In this prospective, randomized, placebo-controlled, double-blinded study, we
determined the effects of two commonly used adjuncts, mannitol and dopamine, on
beta(2)-microglobulin (beta(2)M) excretion rates in patients undergoing coronary
artery bypass graft surgery with cardiopulmonary bypass (CPB). beta(2)M
excretion rate has been described as a sensitive marker of proximal renal
tubular function. One-hundred patients with a preoperative serum creatinine
level <or=1.5 mg/dL were prospectively randomized into 4 groups: 1). placebo,
2). mannitol 1 g/kg added to the CPB prime, 3). dopamine 2 microg kg(-1x.
min(-1) from the induction of anesthesia to 1 h post-CPB, or 4). mannitol plus
dopamine. The primary outcome measure was beta(2)M excretion rate at 1 h
post-CPB. Secondary outcome measures included beta(2)M excretion rate at 6 and
24 h post-CPB; urinary flow rate and creatinine clearance at 1, 6, and 24 h
post-CPB; and the highest postoperative serum creatinine level. Length of
intensive care stay and hospitalization, as well as adverse events, were also
considered secondary outcomes. Dopamine significantly increased beta(2)M
excretion rate at 1 h post-CPB (2.48 +/- 3.61 microg/min) compared with placebo
(0.59 +/- 1.04 microg/min; P = 0.001). This effect was not ameliorated by the
addition of mannitol (beta(2)M excretion rate, 2.05 +/- 2.77 microg/min; P =
0.007 compared with placebo). beta(2)M excretion rate was similar in patients
given placebo or mannitol alone (P = 0.831). Rather than being a protective drug
in the setting of CPB, dopamine alone or in combination with mannitol increases
beta(2)M excretion rate, which may be a measure of renal tubular dysfunction.
The clinical implications of this increase and whether it is also seen in
patients with established renal dysfunction undergoing CPB require additional
investigation. IMPLICATIONS: In many clinical settings, an increased
beta-2-microglobulin (beta(2)M) excretion rate indicates renal tubular injury.
In this cardiopulmonary bypass (CPB) study, a dopamine infusion (alone or with
mannitol) resulted in an increased beta(2)M excretion rate. It is unclear
whether this dopamine-related increase implies renal injury after CPB, and
further investigations are required to examine the mechanism/clinical relevance
of this observation.