[Long-term result of arterial switch operation for corrected transposition of the great arteries or double inlet left ventricle].

The purpose of this study is to analyze the operative maneuver and long term outcome of the arterial switch operation (ASO) for congenitally corrected transposition of the great arteries (c-TGA) or double inlet left ventricle (DILV). Since October 1977, 221 patients had undergone ASO in National Cardiovascular Center, Japan. Of these, 8 patients underwent ASO as a part of double switch operation (DSO) for c-TGA, and 1 patient underwent ASO and ventricular septation for the DILV with a rudimentary right ventricle simultaneously. We retrospectively reviewed these 9 patients. Six patients had a past history of the pulmonary artery banding. Age at the time of ASO ranged from 6 months to 5 years (median 3 year). As a reconstruction of the pulmonary artery at the time of ASO, Lecompte maneuver was performed in 7 patients, and original Jatene procedure was performed in 2. Coronary transfer was done as usual in all patients. There was no early death, and 1 patient died 1 year after the operation due to chronic heart failure. Late complication related to the ASO was pulmonary artery stenosis (1 patient after DSO) and aortic regurgitation (1 patient after ventricular septation).

Chylothorax as a complication of innominate vein thrombosis induced by a peripherally inserted central catheter.

A 5-month-old boy with hypoplastic left heart syndrome developed chylothorax and oedema of the left upper arm more than 2 months after recovering from a Norwood stage II operation. Venography showed occlusion of the innominate vein with abundant collaterals crossing the midline to join the right internal jugular vein. The occlusion was caused by a peripherally inserted central catheter under systemic heparinisation. This case highlights the importance of a patent venous pathway, especially in patients with a cavopulmonary connection in the upper extremities.

Clinical application of vacuum-assisted cardiopulmonary bypass with a pressure relief valve.

OBJECTIVES: Hemodilution induced by cardiopulmonary bypass (CPB) often prevents open heart operations without blood transfusion because of a large CPB-priming volume. A vacuum-assisted venous drainage system appears to overcome this problem and our previous experimental study demonstrated the beneficial effect of a vacuum-assisted CPB with a pressure relief valve. In this study, we clinically applied this novel system, and evaluated its efficacy by comparing it with the results of a conventional siphon-dependent drainage system. METHODS: Sixty patients undergoing open heart operation were divided into Group V (vacuum-assisted system, n=30) and Group S (siphon-dependent system, n=30). The vacuum-assisted system contains a powerful vacuum generator and a pressure relief valve to keep the negative pressure in the reservoir constant when the blood suction is used. RESULTS: The CPB-priming volume was significantly smaller in Group V (V vs. S: 1071+/-88 vs. 1405+/-137 ml; P<0.01), resulting in the lower hemodilution in Group V evidenced by the minimum hemoglobin level (V vs. S: 6.83+/-1.06 vs. 5.78+/-0.79 mg/dl; P<0.01) and blood transfusion rate (V vs. S: 9 vs. 20%; P<0.01). There were no significant differences in the plasma free hemoglobin level and the reduction ratio of plasma haptoglobin between the groups. CONCLUSIONS: These data demonstrate that this vacuum-assisted CPB can provide simplification of the CPB circuit, resulting in a smaller CPB-priming volume and lower hemodilution. This vacuum-assisted CPB may attenuate the negative effect of CPB by minimizing hemodilution and appears to be a useful modification to accomplish no blood-requiring open heart operations.

Thymic carcinoma successfully resected with superior vena cava after chemoradiotherapy.

A 57-year-old woman hospitalized for thymic cancer invading the superior vena cava and left brachiocephalic vein evidenced both pleural and pericardial effusion. After chemotherapy with cisplatin and docetaxel and concurrent radiotherapy, the entire tumor was successfully resected along with the pericardium, superior vena cava, and left brachiocephalic vein, followed by vascular reconstruction. Pathologically, viable tumor cells were identified only in the center of the tumor as anaplastic cell carcinoma. Induction chemoradiotherapy thus appears useful in enabling complete resection of advanced thymic carcinoma.

Reduction in myocardial apoptosis associated with overexpression of heat shock protein 70.

It is reported that ischemia-reperfusion induces apoptotic cell death in myocardium. It is also demonstrated that heat shock protein 70 (HSP70) enhances myocardial tolerance. Therefore, it is hypothesized that HSP70 may play a role in the attenuation of myocardial apoptosis. To elucidate this goal, HSP70-overexpressing and control-transfected rat hearts were prepared using gene transfection by intra-coronary infusion of the hemagglutinating virus of Japan-liposome. In vivo experiment Hearts of both groups were subjected to global ischemia, followed by reperfusion in situ. Shorter recovery time to spontaneous beating (HSP70-transfected vs. control-transfected; 46.7+/-4.6 vs. 67.5+/-7.0 s, p = 0.033) and lower serum CPK levels (415+/-27 vs. 533+/-36 IU, p = 0.027) were observed in the HSP70-transfected group. The HSP70-transfected group also showed a lower percentage of cardiac myocytes positively stained by nick end labeling after ischemia-reperfusion (17.5+/-4.9 vs. 40.0+/-5.1%, p = 0.010). In vitro experiment Cardiac myocytes isolated from the hearts of both groups (prepared separately from the in vivo experiment) were subjected to hypoxia-reoxygenation. Flow cytometry was used to identify the cells that showed sub-G1 DNA content as apoptotic cells. Apoptotic cells as a percentage of viable cells increased more in the control-transfected group after hypoxia-reoxygenation (13.0+/-0.77 vs. 21.9+/-1.18%, p<0.0001). In conclusion, we demonstrated that apoptosis after ischemia-reperfusion was decreased in the HSP70-overexpressing heart in vivo and in vitro, leading to the suggestion that HSP70 could be associated with the reduction in myocardial apoptosis.

Role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.

OBJECTIVES: Nitric oxide is the most potent vasodilator among inflammation-mediated vasoactive substances. Tepid cardiopulmonary bypass has been known to maintain low vascular resistance and nitric oxide may also be involved. There has been no previous clinical study elucidating a role of nitric oxide in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass. METHODS: Thirty-one patients who underwent valvular surgery were randomly divided into two comparable groups; consisting of the hypothermic cardiopulmonary bypass (28 degrees C:14 patients) and the tepid cardiopulmonary bypass group (34 degrees C:17 patients). The serum levels of nitric oxide (NO(2)(-)+NO(3)(-)), prostaglandin E(2), bradykinin, 6-keto PGF1alpha, thromboxane B(2), endothelin-1, systemic vascular resistance index were measured before, 0, 12 and 24 h after cardiopulmonary bypass. RESULTS: The pattern of change in systemic vascular resistance index and nitric oxide during and after cardiopulmonary bypass were significantly different between the two groups (P=0.0008, P=0.02). The tepid group showed significantly lower levels of systemic vascular resistance index after cardiopulmonary bypass than the hypothermic group (0 h: 2278+/-735 vs. 4387+/-1289, 12 h: 1827+/-817 vs. 2817+/-1146 and 24 h: 1690+/-548 vs. 2761+/-641 dyne s cm(-5) m(2), P=0.0001, P=0.03, P=0. 0006). The nitric oxide levels were significantly higher at 0, 12 and 24 h after cardiopulmonary bypass in the tepid group than those in the hypothermic group (84.7+/-33.3 vs. 46.3+/-18.1, 69.8+/-31.1 vs. 40.1+/-17.5 and 80.1+/-38.5 vs. 39.1+/-15.6 micromol/l, P=0.008, P=0.03, P=0.01). The prostaglandin E(2) levels in the tepid group was significantly higher just after cardiopulmonary bypass than that in the hypothermic group (37.3+/-20.0 vs. 15.8+/-8.6 pg/ml, P=0.02). The bradykinin level in the hypothermic group was significantly higher just after cardiopulmonary bypass than that in the tepid group (2.40+/-0.32 vs. 1.85+/-0.21 log(10) (pg/ml), P=0.005). Only nitric oxide showed a significant negative correlation with the systemic vascular resistance index both during and after cardiopulmonary bypass (r=-0.60, P<0.0001) as compared with prostaglandin E(2) and bradykinin. CONCLUSIONS: These findings demonstrated that serum nitric oxide levels in tepid cardiopulmonary bypass were significantly higher than those in hypothermic cardiopulmonary bypass. Nitric oxide correlated with systemic vascular resistance. Thus, nitric oxide may play a pivotal role in a temperature dependent regulation of systemic vascular resistance in cardiopulmonary bypass.

Clinical evaluation of leukocyte-depleted blood cardioplegia for pediatric open heart operation.

BACKGROUND: Blood cardioplegia (BCP) is widely used for myocardial protection during open heart operation. However, BCP may have a chance to induce neutrophil-mediated myocardial injury during aortic cross-clamping. We clinically evaluated the myocardial protective effect of leukocyte-depleted blood cardioplegia (LDBCP) for initial and intermittent BCP administration in pediatric patients. METHODS: Fifty patients undergoing open heart operation for congenital heart disease between January 1997 and March 1999 were reviewed. Twenty-five were administered LDBCP for myocardial protection during ischemic periods (LDBCP group), and the remaining 25 were given BCP without leukocyte depletion (BCP group). RESULTS: The difference in plasma concentrations of malondialdehyde between coronary sinus effluent blood and arterial blood just after reperfusion in the LDBCP group (1.68 +/- 0.56 micromol/L) was significantly lower than that in the BCP group (2.35 +/- 0.62 micromol/L; p < 0.01). The LDBCP group showed significantly lower plasma concentrations of human heart fatty acid-binding protein at 50 minutes after reperfusion (LDBCP group, 103.5 +/- 38.7 IU/L; BCP group, 144.8 +/- 48.8 IU/L; p < 0.01) and the peak value of creatine kinase-MB during the first 24 postoperative hours (LDBCP group, 17.0 +/- 8.5 IU/L; BCP group, 26.0 +/- 11.6 IU/L; p < 0.01) than did the BCP group. The maximum dose of catecholamine was significantly smaller in the LDBCP group (LDBCP group, 3.20 +/- 2.18 microg x kg(-1) x min(-1); BCP group, 5.60 +/- 2.83 microg x kg(-1) x min(-1); p < 0.01). CONCLUSIONS: These results suggest the usefulness of LDBCP for protection from the myocardial injury that can be induced by BCP administration during aortic cross-clamping.

Biventricular repair for aortic atresia or hypoplasia and ventricular septal defect.

OBJECTIVE: Aortic valve atresia or hypoplasia can present with a ventricular septal defect and a normal mitral valve and left ventricle. These patients may be suitable for biventricular repair, although the optimal initial management strategy remains unknown. METHODS: From January 1991 through March 1999, 20 patients with aortic atresia or hypoplasia and ventricular septal defect underwent operation with the intent to achieve biventricular repair. Aortic atresia was present in 7 patients, and aortic valve hypoplasia was present in 13 patients. Among those patients with aortic hypoplasia, Z-scores of the aortic valve anulus ranged from -8.8 to -2.7. Associated anomalies included interrupted aortic arch (n = 12 patients), coarctation (n = 6 patients), aortopulmonary window (n = 1 patient), and heterotaxia (n = 1 patient). Nine patients were staged with an initial Norwood procedure followed by biventricular repair in 8 patients. One patient awaits biventricular repair after a Norwood procedure. The conditions of 11 patients were corrected with a single procedure. RESULTS: Among the 9 patients who underwent staged repair, there were no deaths after the Norwood procedure and 1 death after biventricular repair. For the 11 patients who underwent a primary biventricular repair, there was 1 early death and 2 late deaths from noncardiac causes. Follow-up ranged from 1 to 85 months (mean, 28 months). Actuarial survival for the entire group was 78% +/- 10% at 5 years and was not significantly different between staged repair (89%) and primary biventricular repair (73%). CONCLUSIONS: Both primary and staged biventricular repair for patients with aortic atresia or hypoplasia and ventricular septal defect may be performed with good late survival. Refinements in technique of conduit insertion and arch reconstruction have resulted in primary biventricular repair becoming our preferred approach.

The effects of a new ultra-short-acting beta-adrenergic blocker, ONO-1101, on cardiac function during and after cardiopulmonary bypass.

The administration of an ultra-short-acting beta-adrenergic antagonist, esmolol, has been introduced as a novel method for beating-heart surgery. In the present study, a new ultra-short-acting beta-blocker, ONO-1101, was administered during cardiopulmonary bypass (CPB) to investigate its effects on cardiac function and hemodynamics. Nine adult mongrel dogs underwent 60 min of CPB during which they were given either ONO-1101 (ONO group; n = 4) or saline (control group; n = 5). In the ONO group, the hearts became flaccid enough for surgery to be performed without cardiac standstill within 10 min after the commencement of ONO-1101 with significant decreases in the heart rate, the preload recruitable stroke work (PRSW), and the slope of the end-systolic left ventricular pressure-volume relationship (Emax). The mean arterial pressure and systemic vascular resistance also decreased, but were maintained above 50 mmHg during CPB without catecholamine. These indices increased to the control group level 20 min after the discontinuation of ONO-1101. The serum concentration of ONO-1101 decreased from the maximum level of 121 +/- 15 microg/ml soon after infusion to 11 +/- 5 microg/ml within 30 min after discontinuation. These data suggest that ONO-1101 may be useful to enable beating-heart surgery to be performed without aortic cross-clamp as an ultra-short-acting beta-adrenergic blocker.

Nitric oxide gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal bypass circuits.

Heparin coated bypass circuits have been reported to improve the biocompatibility of extracorporeal circulation, although it is still insufficient and improvable. Nitric oxide (NO) is known to inhibit platelet activation and inflammatory reactions. In this study, the authors evaluated exogenous NO infusion in enhancing the effect of a heparin coated bypass circuit on the biocompatibility of an extracorporeal circuit, especially in view of the attenuation of the inflammatory response. A miniature closed bypass circuit, including an oxygenator (BioActive surface; Carmeda, Stockholm, Sweden) was primed with fresh human heparinized blood and perfused with a centrifugal pump. Either pure N2 gas (control group: n = 7) or NO gas (NO group [100 ppm in N2]: n = 7) was infused to the oxygenator. NO metabolites (nitrite and nitrate), platelet count, thrombin-antithrombin III complex (TAT), alpha2-plasmin-plasminogen inhibitor complex (PIC), beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), serotonin, complement 3 activation products (C3a), granulocyte elastase, and bradykinin were measured at 0, 30, 60, 120, and 180 min after starting perfusion. At every sampling point, platelet counts were significantly higher, and TAT, beta-TG, and bradykinin were lower in the NO group than in the control group. PF4, C3a, and granulocyte elastase were significantly lower in the NO group at 60, 120, and 180 min. These results suggest that NO gas infusion to the oxygenator enhances the biocompatibility of heparin coated extracorporeal circuits.

Interleukin-6 derived from hypoxic myocytes promotes neutrophil-mediated reperfusion injury in myocardium.

BACKGROUND: Reperfusion injury in the myocardium has recently been considered to be a type of inflammation, and close attention has been paid to the possible involvement of neutrophils, complement, and cytokines in the onset of this injury. Recently, it has been reported that serum levels of interleukin-6 are elevated significantly after myocardial infarction. The major site of interleukin-6 production and its exact roles are still unknown. In this study, we hypothesized that myocytes may produce interleukin-6 during hypoxia and this may play a role in neutrophil-mediated reperfusion injury. METHODS AND RESULTS: In the clinical study, 20 patients who underwent coronary artery bypass grafting were divided into 2 groups: group F, in which patients were treated with a serine protease inhibitor (FUT-175, 2 mg/kg per hour) during cardiopulmonary bypass, and group C (untreated patients). In group C, myocardial interleukin-6 production, as determined by the difference between the interleukin-6 level in the cardiopulmonary bypass circuit and its level in coronary venous blood, increased significantly after reperfusion (12+/-4 pg/mL) as compared with that before aortic crossclamping (2+/-2 pg/mL). In group F, the increase in the interleukin-6 level was suppressed significantly (before aortic crossclamping, 3+/-2 pg/mL; after reperfusion, 4+/-3 pg/mL). The interleukin-6 production differed significantly between group C and group F. In the in vitro experimental study, the supernatant from myocytes exposed to 2 hours of hypoxia (group 2H) showed significantly higher levels of interleukin-6 (455+/-260 pg/mL) than that from normoxic myocytes (group N) (47+/-15 pg/mL). This interleukin-6 production was suppressed by the addition of FUT-175 (123+/-24 pg/mL). The interleukin-6 production by endothelial cells of coronary vessels did not differ between group 2H (283+/-151 pg/mL) and group N (151+/-86 pg/mL). In a coincubation system with a monolayer of endothelial cells on collagen membrane and myocytes under collagen membrane in a modified Boyden chamber, 2 hours of coincubation showed a significantly higher percent of neutrophil transendothelial migration (group 2H vs N, 78%+/-13% vs 26%+/-11%), value of chemiluminescence (22+/-8 vs 5+/-2 x 10(3) counts/3 minutes), and percent of irreversibly damaged myocytes (48%+/-17% vs 12%+/-8%) than normoxic coincubation. In contrast, anti-interleukin-6 monoclonal antibody significantly attenuated neutrophil transendothelial migration (42%+/-19%) and irreversible damage of myocytes (26%+/-15%) in 2 hours of coincubation. CONCLUSIONS: Interleukin-6 is produced from myocardium during ischemia and reperfusion in patients undergoing coronary bypass grafting. This interleukin-6 may be derived from hypoxic myocytes and play a role in neutrophil-mediated reperfusion injury in myocardium.

[Evaluation of cerebral circulation during cardiopulmonary bypass using near-infrared spectroscopy].

Cerebral oxygenation level during cardiopulmonary bypass (CPB) was measured using near-infrared spectroscopy as a monitor of cerebral circulation in 30 patients. Six adult cases with thoracic aortic aneurysm were operated on using selective cerebral perfusion (SCP). CPB was established under moderate hypothermic temperature in 9 adult cases (hypothermic group, lowest blood temperature during CPB; 25 degrees C) and under normothermic temperature in 9 adult cases (normothermic group, lowest blood temperature during CPB; 34 degrees C). In congenital cases (n = 6), CPB was established under moderate hypothermic temperature (congenital group, lowest blood temperature; 25 degrees C). The oxyhemoglobin (HbO2) level showed a significant positive correlation with cerebral blood flow during SCP (r = 0.715). There was no significant correlation between SjO2 and HbO2 in the SCP group. The HbO2 levels in the hypothermic group after 30 and 60 min, from the initiation of CPB and 30 min. before the weaning of CPB were significant lower than the control level (p < 0.05). HbO2 levels in the congenital group after 0, 30 and 60 min. from the initiation of CPB and 30 min. before the weaning of CPB were significantly lower than the control level (p < 0.01). The deoxyhemoglobin (HbR) level in the hypothermic group after 30 and 60 from the initiation of CPB and 30 min. before the wearing of CPB were significantly higher than the pre level (p < 0.05). The mixed venous saturation (SvO2) in the normothermic group showed significant lower levels than those in the hypothermic group (p < 0.01). However, there was no significant difference in HbO2 levels between the two groups. In conclusion, these results suggest that near-infrared spectroscopy may be a noninvasive and useful technique for the cerebral circulation monitoring during CPB.

[Decreasing sarcoplasmic reticular calcium gives rise to myocardial protection--the effect of thapsigargin for myocardial protection under conditions of normothermia].

Deceasing sarcoplasmic reticular (SR) calcium may contribute to the myocardiac protection against ischemia and reperfusion-induced injury. Therefore, using the isolated working rat heart model, we investigated the effect of Thapsigargin (TH)-induced SR calcium diminution on the myocardial protection when added either before onset of ischemia or at time of reperfusion under conditions of normothermic ischemia. Hearts (n = 6/group) from male Wistar rats were aerobically (37 degrees C) perfused (20 min) with bicarbonate buffer. In the experimental protocol A, this was followed by a 3 min infusion of St. Thomas' Hospital cardioplegic solution No. 2 (STS) containing various concentrations of TH. Hearts were then subjected to 34 min of normothermic (37 degrees C) global ischemia and 35 min of reperfusion (15 min Langendorff, 20 min working). Reperfusion cardiac functions at 20 min of working perfusion was measured and compared with the preischemia values. STS added to 0.1 and 0.25 mumol/L TH improved recovery of aortic flow after 20 min reperfusion from 47 +/- 3% in the TH free controls to 62 +/- 3, 63 +/- 2% (n = 6) (p < 0.05). There was no difference in creatine kinase (CK) leakage during Langendorff reperfusion between the TH treated groups and the control group. In the experimental protocol B, 3 min of cardioplegia without TH and 34 min of ischemia (37 degrees C) were followed by a 10 min Langendorff reperfusion with various concentrations of TH, then 10 min Langendroff reperfusion for washing out, and 20 min working reperfusion. When TH was added to reperfusate the recovery of aortic flow did not change, 0.5 mumol/L TH group had the detelious effect. Thus, TH, when added to the cardioplegia, enhanced myocardial protection. We conclude that lessened uptake of Ca2+ into sarcoplasmic reticulum by inhibitors of the Ca(2+)-ATPase pump can decrease ischemia and reperfusion-induced injury.

A novel technique for cardiopulmonary bypass using vacuum system for venous drainage with pressure relief valve: an experimental study.

To decrease the circuit priming volume, develop safety, and simplify the equipment, a cardiopulmonary bypass (CPB) circuit using a vacuum suction venous drainage system with a pressure relief valve was developed. The efficacy of this vacuum system was compared to that of a conventional siphon system. The system contains a powerful vacuum generator and a pressure relief valve to keep the negative pressure constant when blood suction is used. Using 8 mongrel dogs, the feasibility and the efficacy of this CPB system was tested. The changes in the negative pressure in the reservoir were within 5 mm Hg whether the suction lines were switched on or off. In all animals the amount of blood in the venous reservoir was stable throughout bypass. The decrease of priming volume was from 725 ml (siphon system) to 250 ml (vacuum system). At the end of CPB, the levels of hemoglobin in the vacuum system were significantly higher than those in the siphon system. These results demonstrated that this vacuum drainage system can provide simplification and a miniaturization of the cardiopulmonary bypass circuit resulting in low hemodilution during CPB.

Early detection of cardiac damage with heart fatty acid-binding protein after cardiac operations.

BACKGROUND: It is still difficult to evaluate myocardial damage in the acute phase of reperfusion in cardiac operations. We investigated the clinical significance of human heart fatty acid-binding protein (HH-FABP) for detecting myocardial damage after cardiac operations earlier than creatine kinase MB isoform or troponin-T. METHODS: Blood samples from 20 patients who underwent coronary artery bypass grafting were collected serially after reperfusion to measure serum levels of creatine kinase-MB, troponin-T, and HH-FABP. RESULTS: Serum HH-FABP levels peaked earliest after reperfusion. In addition, the maximum serum HH-FABP level was predictable immediately after reperfusion. The maximum serum HH-FABP level correlated with the maximum serum creatine kinase-MB or troponin-T level, as well as with the aortic cross-clamp time or the maximum dose of catecholamines administered after reperfusion. CONCLUSIONS: Measurements of HH-FABP allow for earlier evaluation of myocardial damage in the acute phase of reperfusion. Human heart fatty acid-binding protein may be a useful indicator of myocardial damage after cardiac operations.

A novel strategy for myocardial protection using in vivo transfection of cis element 'decoy' against NFkappaB binding site: evidence for a role of NFkappaB in ischemia-reperfusion injury.

BACKGROUND: NFkappaB, an important transcriptional factor, has been reported to play a significant role in the coordinated transcription of cytokine and adhesion molecule genes. Therefore, blocking the NFkappaB may attenuate ischemia reperfusion injury in the myocardium. For blocking transcriptional factors, gene therapy, such as cis element "decoy," appears to be an innovative and useful therapy. This study aimed to prove the efficacy of cis element decoy against NFkappaB binding site for myocardial protection. METHODS AND RESULTS: Rat hearts were transfected with fluorescence isothiocyanate-labeled cis element decoy against NFkappaB (NF)-binding site (NF group, n=6) and scrambled decoy (SD) group (n=6) by coronary infusion of hemagglutinating virus of Japan (HVJ)-liposome during cardioplegic arrest. Both the NF and SD groups showed marked FITC-staining in the nuclei of myocytes, demonstrating the efficacy of gene transfer into the nuclei of cardiac myocytes as compared with the control group transfected with empty liposomes. After 3 days of transfection, the NF group showed significantly higher percentages of recovery of left ventricular developed pressure (NF versus SD, 87+/-11 versus 54+/-12%) and coronary flow (97+/-16 versus 61+/-15%) than did the control hearts when exposed to ischemia (30 minutes, 37 degrees C) and reperfusion (30 minutes, 37 degrees C). The NF group showed a significantly lower percentage of neutrophil adherence to endothelial cells (38+/-6 versus 81+/-3%) and a lower tissue level of interleukin-8 (109+/-48 versus 210+/-55 ng/mg) than did the SD group. CONCLUSION: The hearts transfected with cis element decoy against NFkappaB binding site showed significant improvement in tolerance against ischemia-reperfusion injury in association with the inhibition of neutrophil adherence and tissue IL-8 production. This suggests that NFkappaB plays a significant role in ischemia-reperfusion injury. This method, using in vivo gene transfection of cis element decoy against NFkappaB binding site, appears to be a novel and future strategy for myocardial protection.

Portable cardiopulmonary support system as a bridge to left ventricular assist system implantation. A new strategy for the treatment of end stage cardiac disease.

The key to the successful implantation of a left ventricular assist system (LVAS) for patients with end stage cardiac disease is whether the functions of other vital organs are irreversibly damaged or not. The portable cardiopulmonary support system (PCPS) is not only as convenient as, but is more powerful than, the intra-aortic balloon pump (IABP) in resuscitating impaired end organ function. To investigate the efficacy of PCPS in end stage cardiac disease, end organ function before and after the application of PCPS was retrospectively analyzed for end stage cardiac disease. From 1992 to 1996, five cardiomyopathy patients with deterioration in end organ function, despite application of IABP, underwent PCPS support before implantation of LVAS. Urine volume and levels of liver enzymes (sAST and sALT) and serum creatinine were determined before and after institution of PCPS. After the start of PCPS, the urine output increased significantly (1,840 +/- 450-4,340 +/- 470 ml/day, p < 0.01), and levels of sAST, sALT, and serum creatinine decreased significantly (630 +/- 220-150 +/- 50 IU/L, 630 +/- 260-260 +/- 130 IU/L, and 2.9 +/- 0.5-1.2 +/- 0.1 mg/dl, respectively; p < 0.05). All five patients were successfully bridged to LVAS implantation, and none died of multiple organ failure caused by pre-existing cardiac failure. These results indicate that PCPS before LVAS implantation is useful in resuscitating impaired end organ function and improving the survival rate with LVAS implantation for end stage cardiac disease.

Biocompatibility of heparin-coated circuits in pediatric cardiopulmonary bypass.

In this study, we evaluated the biocompatibility of heparin-coated circuits in pediatric cardiopulmonary bypass (CPB). Eight patients were divided into 2 groups: the control group (Group C) and heparin-coated group (Group H). In Group H, CPB circuits, including the arterial pump, oxygenator, and cannulas were heparin-coated. Before, during, and after CPB, blood samples were obtained to assess the platelet counts (Plat), alpha 2-plasmin plasminogen inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), C3 activation products (C3a), interleukin (IL)-6, IL-8, and polymorphonuclear neutrophil leukocyte (PMN) elastase. There was no significant difference in Plat, PIC, or TAT between groups. Group H showed significantly low levels of C3a (during and after CPB), PMN elastase (during CPB), and IL-6 (after CPB). These data demonstrated that in pediatric CPB, heparin-coated CPB circuits reduced the activation of complements and the production of PMN elastase and IL-6, suggesting the superior biocompatibility of the heparin-coated circuits.

The contribution of Na+/H+ exchange to ischemia-reperfusion injury after hypothermic cardioplegic arrest.

BACKGROUND: Na+/H+ exchange has been reported to be one of the key mechanisms in myocardial ischemia-reperfusion injury. However, the effect of temperature on Na+/H+ exchange is not fully understood. METHODS: Sodium-propionate-induced cell swelling, an indicator of the function of the Na+/H+ exchanger, was measured in rat thymic lymphocytes. A Langendorff perfused rat heart model was also employed to investigate the effect of the pharmacologic inhibition of Na+/H+ exchange on the recovery of cardiac function after hypothermic ischemia. This was done using FR168888, an inhibitor of Na+/H+ exchange. RESULTS: In the in vitro study, rat lymphocytes were observed to swell at 17 degrees, 22 degrees, and 27 degrees C, indicating that the Na+/H+ exchanger remains functional even under hypothermic conditions. FR168888 was found to significantly inhibit Na+/H+ exchange-induced cell swelling, even at 17 degrees C. In the in vivo study, pretreatment with FR168888 was found to prevent the deterioration of ventricular function, even after 5 hours of hypothermic cardioplegic arrest. This was associated with a decrease in the reperfusion-induced elevation in resting tension. CONCLUSIONS: These results suggest that Na+/H+ exchange in the heart still occurs, even under hypothermic conditions, and contributes to reperfusion injury, even after hypothermic cardioplegic arrest.