Kazuaki Fukahara

Long-term results of simultaneous carotid endarterectomy and myocardial revascularization with cardiopulmonary bypass used for both procedures.

OBJECTIVE Controversy continues about the treatment of patients with a concomitant occlusive disease of the coronary and carotid arteries. Our operative strategy in these patients is to do simultaneous carotid endarterectomy and myocardial revascularization in conjunction with cardiopulmonary bypass with mild hypothermia. We report our experience with this kind of one-stage procedure and its retrospective long-term results. METHODS From February 1985 to September 1998, 340 patients underwent simultaneous carotid endarterectomy and myocardial revascularization. The average age of the patients was 65.3 years; 45.6% were neurologically symptomatic, and 44.4% had bilateral carotid stenosis. The indication for carotid endarterectomy was lumen diameter reduction of more than 75%, angiographic signs of thrombogenic endovascular morphology, or both. Carotid endarterectomy was performed in conjunction with cardiopulmonary bypass with mild hypothermia, hemodilution, systemic heparinization, and controlled hemodynamics under pulsatile perfusion for additional cerebral protection. RESULTS There were 16 perioperative neurologic complications (4.7%), 11 permanent deficits (3.2%), and 9 cardiac complications (2.6%). Early mortality was 2.6% (SE 0.8%): 2 patients had a stroke and 2 had a myocardial infarction. The 5-year survival was 78.9% (SE 2.6%), and freedom from ipsilateral stroke and cardiac event were 93.2% (SE 1.5%) and 87.5% (SE 2.1%), respectively. The predictor for early death was age over 70 years, and predictors for late death were age over 70 years, previous myocardial infarction, previous stroke, and bilateral carotid stenosis of greater than 90%. CONCLUSION On the basis of our long-term results, we believe that simultaneous carotid endarterectomy and myocardial revascularization in conjunction with cardiopulmonary bypass is a method safe enough to prefer its routine use with acceptable low operative risk and satisfactory long-term morbidity.

Additive Effect of Beraprost on Pulmonary Vasodilation by Inhaled Nitric Oxide in Children With Pulmonary Hypertension

Combined administration of inhaled nitric oxide and beraprost sodium resulted in a more intense decrease in pulmonary vascular resistance than nitric oxide given alone (mean -33% vs -45%, p <0.05), without serious systemic hypotension. Combined therapy with nitric oxide and beraprost sodium is highly desirable in treating primary and secondary pulmonary hypertension in children.

Chronic effects of oral prostacyclin analogue on thromboxane A2 and prostacyclin metabolites in pulmonary hypertension.

Abnormal biosynthesis of thromboxane and prostacyclin has been implicated in patients with primary pulmonary hypertension and secondary pulmonary hypertension associated with congenital heart disease, and could be involved in the pathogenesis of pulmonary vascular disease. The chronic effects of an oral prostacyclin analogue, beraprost sodium, on thromboxane and prostacyclin biosynthesis and on pulmonary circulation were investigated in 15 children with pulmonary hypertension. The plasma concentrations of thromboxane B, and 6‐keto‐prostaglandin F1α were measured, as was the urinary excretion of 11‐dehydro‐thromboxane B, and 2.3‐dinor‐6‐keto‐prostaglandin F1α, which are stable metabolites of thromboxane A, and prostacyclin, respectively. In patients with pulmonary hypertension, the plasma concentration of thromboxane B. and the ratio of thromboxane B, to 6‐keto‐prostaglandin F1α were greater than in healthy controls: 210 ± 49 versus 28 ± 4 pg/mL (P<6.05) and 32.6 ± 8.9 versus 5.7± 1.8 (p<0.01), respectively. After 3 months of administration of beraprost. the plasma concentration of thromboxane B, and the ratio of thromboxane B, to 6‐keto‐prostaglandin F were reduced significantly: 210 ± 49 to 98 ± 26 pg/mL (P < 0.01) and 32.6 ± 8.9 to 18.0 ± 6.7 (P < 0.05). respectively. In contrast, the plasma concentrations of 6‐keto‐prostaglandin F in patients were slightly but not significantly higher than in controls, and did not change significantly after administration of beraprost. The concentrations of 11‐dehydro‐thromboxane B, and 2.3‐dinor‐6‐keto‐prostaglandin F, in urine correlated significantly with thromboxane B, and 6‐keto‐prostaglandin F . respectively, in plasma. Beraprost improved the imbalance of thromboxane and prostacyclin biosynthesis and has a potential efficacy for preventing the progressive development of pathological changes in pulmonary vasculature.

Scheduled autologous blood donation at the time of cardiac catheterization in infants and children

Preoperative autologous blood donation is commonly performed to avoid homologous blood transfusion during cardiac operations in adult patients. 1 However, autologous blood donation for children is hampered by technical problems including lack of an adequate blood collection system and acute anemia after blood collection. Given the life span of children, it is most important to avoid the complications of homologous transfusion. 2 We describe a technique of scheduled autologous blood donation during preoperative cardiac catheterization and examine the efficacy and safety of this method for use in infants and children. Technique. Cardiac catheterization was performed about 2 weeks before elective operations in infants and children weighing at least 5 kg. Autologous blood donation was performed in patients with a hematocrit value of 33% or more and a hemoglobin value of 11 gm/dl or more. Sedation was achieved with thiopental sodium and local anesthesia was achieved with lidocaine hydrochloride. Sheaths were inserted into the femoral artery and vein. After hemodynamic measurements, but before contrast angiography, 10 ml/kg of blood was collected via the arterial sheath. The same volume of lactated Ringers solution was infused at the same rate through the venous sheath. Collected blood was stored as packed red cells and plasma or as whole blood. Blood erythropoietin concentrations were measured before and after blood collection, and recombinant human erythropoietin (100 U/kg) was administered intravenously to acyanotic patients on the first and seventh days after blood collection. Cyanotic patients were not treated with recombinant human erythropoietin. Each patient was given ferrous sulfate (2 mg/ kg) orally every day. Results. From October 1995 through September 1997, preoperative autologous blood donation was performed in 27 children, including 13 infants (16 boys and 11 girls). Their ages ranged from 6 months to 6 years, 8 months (average 1.9 -+ 2.1 years). Their body weights ranged from 5.8 kg to 20.2 kg (average 9.7 -+ 5.5 kg). The patients

Impact of preoperative atrial fibrillation on the late outcome of off-pump coronary artery bypass surgery

OBJECTIVE The impact of pre-existing atrial fibrillation on the long-term outcome in patients after off-pump coronary revascularisation is not well known. This study aims to determine the independent effects of preoperative atrial fibrillation on the early and late outcomes of off-pump coronary artery bypass surgery. METHODS A total of 513 patients undergoing isolated coronary artery bypass surgery using off-pump approach between 2000 and 2005 were studied. Twenty-six of them (5.1%) had preoperative atrial fibrillation (15 had paroxysmal atrial fibrillation and 11 had persistent or permanent atrial fibrillation) and the other 487 patients were in normal sinus rhythm. Early and late outcomes were compared retrospectively between patients with preoperative atrial fibrillation and patients in sinus rhythm. The median follow-up period for the entire study population was 3.3 + or - 2.7 years. RESULTS The baseline characteristics of the patients with preoperative atrial fibrillation were generally similar to those of patients in sinus rhythm. However, the patients with atrial fibrillation had a significantly lower left ventricular ejection fraction compared with those in sinus rhythm (50 + or - 15 vs 56 + or - 12%, p=0.03). The mean age of the atrial fibrillation group was almost 3 years more than that of the sinus rhythm group. Operative mortality was similar in patients with atrial fibrillation (3.8%) and those in sinus rhythm (1.0%). Ten patients developed cerebral infarction within 7 days after surgery, including one patient (3.8%) from the atrial fibrillation group and nine patients (1.8%) from the sinus rhythm group. Long-term survival was significantly decreased in the atrial fibrillation group (5-year survival: 70 + or - 9.6% vs 87 + or - 1.8%; p=0.0018). Freedom from cerebral complications was also significantly decreased in the atrial fibrillation group (5-year survival: 85 + or - 8.3% vs 95 + or - 1.2%; p=0.0009), but there were no differences in cardiac death and major cardiac adverse events. On Cox proportional hazards regression analysis, preoperative atrial fibrillation was a significant adverse predictor for survival (hazard ratio=3.0, 95% confidence intervals (CIs) 1.3-6.9; p=0.009) and independent predictor of late cerebral infarction (hazard ratio=6.2, 95% CIs 2.0-19.3; p=0.0002). CONCLUSIONS Uncorrected preoperative atrial fibrillation is strongly associated with poor long-term survival and increased late cerebral complications after off-pump coronary artery bypass surgery. Concomitant atrial fibrillation surgery should be considered to improve the long-term results of surgical revascularisation.

Changes in T-Cell Receptor Subsets After Cardiac Surgery in Children

T cells are divided into two subsets, αβ and γδ, according to the T-cell receptor (TCR) expressed. Recent findings indicate that γδ T cells serve as the first defense against microbial pathogens, and represent a link between innate and acquired immunity. We conducted a study to investigate the changes in circulating TCR subsets after cardiac surgery in children. Blood samples from 24 children who underwent cardiac surgery with cardiopulmonary bypass (CPB) were collected serially to analyze TCR subsets by flow cytometry. The αβ T cells reached a nadir on postoperative day (POD) 1, but recovered to pre-CPB levels on POD 3. On the other hand, the γδ T cells decreased after CPB and did not recover to pre-CPB levels even after POD 7. The ααb/γδ T-cell ratio was increased after POD 3. In children, γδ T cells recover more slowly than αβ T cells after cardiac surgery. These changes in TCR subsets may contribute to postoperative immunosuppression.

Treatment of mediastinitis due to methicillin-resistant Staphylococcus aureus in a renal dysfunction patient undergoing adjustments to the linezolid dose.

This study is the first case report of the treatment of methicillin-resistant Staphylococcus aureus (MRSA) mediastinitis using therapeutic drug monitoring of the serum and wound exudate concentrations of linezolid in a renal dysfunction patient. In the present study, the serum trough concentration of linezolid was maintained between 2 and 7 μg/mL. Therapeutic drug monitoring dosage adjustments may be especially useful in patients with renal dysfunction and severe MRSA infection.

Effect of Exogenous Oct4 Overexpression on Cardiomyocyte Differentiation of Human Amniotic Mesenchymal Cells

Regenerative therapy is a new strategy for the end-stage heart failure; however, the ideal cell source has not yet been established for this therapy. We expected that the amnion might be an ideal cell source for cardiac regenerative therapy and that the differentiation potency of the human amnion mesenchymal cells (hAMCs) could be improved by overexpression of Oct4, a key factor that maintains the undifferentiated state. A plasmid vector was made by insertion of the Oct4 open reading frame (ORF) under control of a cytomegalovirus (CMV) promoter (pCMV-hOct4) and transfected into hAMCs by electroporation. The optimum induction time was investigated by comparing the quantity of stem cell-specific mRNAs, cardiac-specific mRNAs, and cardiac-specific proteins with time. hAMCs already expressed cardiac-specific proteins such as Nkx2.5 and Connexin43. After pCMV-hOct4 transfection, endogenous Oct4 mRNA and other stem cell markers showed a transient increase. With 5-azacytidine treatment, quantities of the cardiac-specific mRNAs, such as GATA4 and myosin light-chain-2v (Mlc-2v), were increased significantly. After Oct4 overexpression, the highest expression of cardiac-specific mRNAs and stem cell makers was seen at almost the same time. Furthermore, more mature myocardial contraction proteins were observed when hAMCs were induced at specific optimal times after gene transfection. In conclusion, hAMCs were activated to an undifferentiated state by overexpression of Oct4, and their cardiac differentiation potency was improved. Thus, the single-time transfection of the Oct4 expression vector may be a useful strategy for effective cell therapy. The use of cryopreserved hAMCs in cell therapy still requires more investigation.

Surgical Treatment of Complete Anterolateral Papillary Muscle Rupture Following Acute Myocardial Infarction

Papillary muscle rupture is a lethal complication of after acute myocardial infarction. We report the successful surgical management of complete anterolateral papillary muscle rupture associated with cardiogenic shock in an 80-year-old woman. The patient was admitted with the sudden onset of chest pain and dyspnea. After hemodynamics deteriorated rapidly, she was intubated and intra-aortic balloon pump was started immediately. Transthoracic echocardiography revealed severe mitral regurgitation due to complete anterolateral papillary muscle rupture associated with lateral myocardial infarction. Coronary angiography demonstrated complete occlusion of the first obtuse marginal artery. She underwent emergency mitral valve replacement and coronary artery bypass grafting. There were no complications of surgery and she was discharged on postoperative day 35. Rapid preoperative assessment and aggressive surgical management are important to improve the prognosis in this setting.

Management of pulmonary venous obstruction

Although improved surgical techniques have led to significantly better outcomes of surgery for total anomalous pulmonary venous connection, the risk of progressive pulmonary venous obstruction continues to be a clinical problem. Both obstructed total anomalous pulmonary venous connection and post-repair pulmonary venous obstruction are associated with a significant risk of recurrent obstruction or death, requiring reoperation for stenosis. In general, side to side anastomosis of the pulmonary venous confluence to the functional left atrium has been performed for supracardiac and infracardiac total anomalous pulmonary venous connection. Repair of total anomalous pulmonary venous connection to the coronary sinus invariably involved unroofing the coronary sinus, followed by pericardial patch closure of the atrial septal defect. Recently, sutureless technique has been adopted as the primary operation for the subgroups of patients that are thought to be at high risk for post-repair pulmonary venous obstruction, such as those with total anomalous pulmonary venous connection associated with right isomerism, infracardiac total anomalous pulmonary venous connection with small individual pulmonary veins, or mixed-type total anomalous pulmonary venous connection. Because the sutureless technique does not require direct anastomosis to the confluence, aggressive resection of the obstructed pulmonary venous tissue can be achieved, and surgically induced distortion of the suture line can be avoided, which may help to prevent subsequent pulmonary venous obstruction. Conventional management strategies for recurrent pulmonary venous obstruction have typically been associated with poor outcomes. Recent reports have supported the use of the sutureless technique to treat post-repair pulmonary venous obstruction.