Clinical evaluation of oxidative stress and myocardial reperfusion injury in pediatric cardiac surgery.

BACKGROUND: To evaluate oxidative stress and myocardial damage after aortic crossclamping release (ACCR) during cardio pulmonary bypass (CPB) in children two parameters were investigated: total glutathione (GSH) and its oxidoreductive reactions (GSH/GSSG) as expression of oxidative stress, and plasmatic turnover of myocardial taurine (TAU) as expression of cell damage. METHODS: The study was divided in two periods: 1) first period: analysis of oxidative stress and myocardial damage in 18 children. 2) Second period: evaluation of myocardial cell protection by controlled anterograde low oxygen warm reperfusion (ALOWR) before declamping. Twenty-one children were divided in two groups: not receiving (Group 1, 9 patients) and receiving (Group 2, 12 patients) ALOWR. RESULTS: In the first period GSH values increased significantly after onset of mechanical ventilation (MV) in vein, after CPB start in artery and after ACCR in coronary sinus. Moreover TAU turnover in aortic and coronary sinus blood increased significantly after ACCR. In the second period, Group 2 showed a lower oxidative stress after ACCR, while no differences were observed in TAU turnover. CONCLUSIONS: 1) Assessment of TAU and GSH levels can be considered a good method to clinically evaluate myocardial injury during cardiac surgery. 2) MV and CPB can induce oxidative stress before aortic clamping and can decrease the physiologic scavengers. Therefore, to prevent that depletion, the strategy of these techniques must be adapted to the patient and to his cardiac disease. 3) Intramyocardial TAU turnover is not significantly modified by the reperfusion technique. 4) ALOWR can reduce myocardial oxidative stress and can improve heart recovery after the cardioplegic arrest.

[Circulation support in left thoracotomy for descending thoracic aorta diseases in pediatric patients]. / L'assistenza circolatoria in toracotomia sinistra nella patologia dell'aorta toracica discendente nel paziente pediatrico.

BACKGROUND: Complications of surgery of the descending thoracic aorta could include neurological problems such as paraparesis and paraplegia. Intestinal ischemia and acute renal failure could occur, too. During the cross-clamping time, the perfusion of the distal aorta by means of extracorporeal circulatory assistance can be useful to protect the spinal cord and the splanchnic organs and to reduce the incidence of these untoward events. The aim of this study was to verify the efficacy and suitability of this type of circulatory assistance in a pediatric age group. METHODS: From January 1996 to March 2000, in the Pediatric Cardiac Surgery Department of the Gaslini Institute (Genoa, Italy), 6 patients (mean age 39 months, mean weight 14.4 kg) were treated using extracorporeal circulatory assistance through the left thoracotomy. Indications for surgery included the removal of a migrated device previously inserted in order to close a patent ductus arteriosus in 1 patient, recurrent coarctation in 2 patients, and native coarctation with a poor collateral circulation in 3 patients. RESULTS: The early and late mortality rates as well as the morbidity rates (both neurological and splanchnic) were nil. CONCLUSIONS: Extracorporeal circulatory assistance can be helpful in pediatric patients and it can prevent neurological and renal injuries in cases of a) coarctation of the aorta with a poor collateral circulation and low distal pressure (< 40 mmHg during aortic occlusion); b) recoarctation with complex anatomy; c) other pathologies requiring prolonged descending thoracic aorta cross-clamping.

Quantitative and qualitative evaluation of blood salvaged after extracorporeal circulation (ECC) in paediatric heart surgery. Study of biochemical, morphological and structural variations of RBC after ECC and after salvaging of ECC circuit priming blood.

The salvaging of ECC circuit priming blood is essential for reducing the morbidity related to homologous blood transfusions and the importance of this technique is inversely proportionate to the age and weight of the child. In infants, the washing and centrifugation of blood not only drastically reduce the risk of contracting blood-transmitted diseases and cut management costs, but are also of considerable hemodynamic importance, producing a rapid normalization of the patient's hematocrit and hemoglobin and balancing the O2 consumption/demand ratio. The marketing of miniaturized salvagin devices with 55 ml bowls by Dideco has made possible the recovery of small quantities of blood, so as to normalise the hematic crisis and permit the application of total hemodilution in low-weight patients. The salvaged blood shows an average hematocrit of 52.7+/-9.7% (max 68.1%) and an average hemoglobin of 17.6 +/- 2.9 g/dl (max 20.7 g/dl), and maintains its structural components, osmotic resistance, concentration of intraerythrocytic hemoglobin and mean corpuscular hemoglobin all intact. Washing with isoosmotic and isoionic hydroelectrolytic solutions normalizes the ionic situation in the post-operative period and activated blood salvaging after Extracorporeal Circulation. The use of solutions without nutritional substances results however in a considerable fall in the number of enzymes in the intraerythrocytic metabolic glucide chain (G6PDH: -40.7 +/- 14.3% p<0.001), (PK: -23.8 +/- 20.5% p<0.03). This drop may be responsible for erythrocytic morphological alterations (echinocytic change) and probably for the release of hemoglobin from the red blood cells. Washing with isoionic, isoosmotic solutions containing G5% and adenine could, at least in theory, improve the quality of the salvaged blood, by normalizing the morphology and the volume of the RBC and by increasing the hematocrit.

Deletion of a 5-cM region at chromosome 8p23 is associated with a spectrum of congenital heart defects.

BACKGROUND: Cytogenetic evidence suggests that the haploinsufficiency of > or =1 gene located in 8p23 behaves as a dominant mutation, impairing heart differentiation and leading to a wide spectrum of congenital heart defects (CHDs), including conotruncal lesions, atrial septal defects, atrioventricular canal defects, and pulmonary valve stenosis. An 8p heart-defect-critical region was delineated, and the zinc finger transcription factor GATA4 was considered a likely candidate for these defects. We narrowed this region and excluded a major role of GATA4 in these CHDs. METHODS AND RESULTS: We studied 12 patients (7 had CHD and 5 did not) with distal 8p deletions from 9 families by defining their chromosome rearrangements at the molecular level by fluorescent in situ hybridization and short-tandem repeat analysis. Subjects with 8p deletions distal to D8S1706, at approximately 10 cM from the 8p telomere, did not have CHD, whereas subjects with a deletion that included the more proximal region suffered from the spectrum of heart defects reported in patients with 8p distal deletions. The 5-cM critical region is flanked distally by D8S1706 and WI-8327, both at approximately 10 cM, and proximally by D8S1825, at 15 cM. Neither GATA4 nor angiopoietin-2 (ANGPT2; a gene in 8p23 involved in blood vessel formation) were found to be deleted in some of the critical patients. We also found that CHDs are not related to the parental origin of deletion. CONCLUSIONS: Haploinsufficiency for a gene between WI-8327 and D8S1825 is critical for heart development. A causal relationship does not seem to exist between GATA4 and ANGPT2 haploinsufficiency and CHDs.

[Classification of congenital heart diseases and surgical interventions in pediatric cardiology for the standardization of hospitalization records]. / Classificazione delle cardiopatie congenite e degli interventi di cardiologia e cardiochirurgia pediatrica per una codifica standardizzata della documentazione di ricovero.

The utilization of DRGs for the evaluation of hospital activity requires the availability, on a current basis, of coded in-patient records (Hospital Discharge Form, SDO) with information concerning nosology of the patient and procedures performed. Consequently, the promotion of a standardized use of ICD.9 and ICD.9.CM code systems (International Classification of Diseases, 9th Revision, and International Classification of Diseases, 9th Revision, Clinical Modification) among clinicians is necessary. The National Research Council, Council Research Hospital for Cardiology and Cardiac Surgery (CREAS-IFC-CNR) has promoted the establishment of a permanent work group for the evaluation of the activity in the field of pediatric cardiology and cardiosurgery at a national level. In co-operation with two leading institution (AO "Bambino Gesù", Rome; AO "G. Gaslini", Genoa) an in-patient survey has been promoted including an overall revision of the ICD.9.CM code systems both for diagnosis and procedures in order to improve the standardization of data. Besides, the fitness of DRGs allocation by different codes has been judged. Some general and specific suggestions upon codes adequacy and DRGs identification have emerged from this study. The aim of this paper is to spread this preliminary standardization activity of the group as a contribution to the improvement of in-patient coded records quality.

[Differential types of pulmonary flow in bidirectional cavo-pulmonary anastomosis with an additional flow source]. / Differenti tipi di flusso polmonare nell'anastomosi cavo-polmonare bidirezionale con sorgente addizionale di flusso.

While Fontan operation is considered a palliative procedure for the treatment of complex congenital heart disease, its morbidity and mortality are certainly not negligible, especially in high-risk patients. In our opinion, a bidirectional cavo-pulmonary anastomosis with an additional source of blood flow to the lungs (Blalock-Taussig shunt, pulmonary artery banding, native pulmonary stenosis) represents a valuable surgical option in this subset of patients. From November 1992 to September 1994, sixteen patients with complex congenital heart disease underwent bidirectional cavo-pulmonary anastomosis, leaving an additional source of blood flow in place (modified Blalock-Taussig shunt in 9 cases, pulmonary artery banding in 6 cases, native pulmonary stenosis in 1 case). Eight of these patients (50%) were reinvestigated after a mean follow-up of 15.7 months (range 1-26 m). It has been possible to differentiate two types of pulmonary blood flow, according to the nature of the additional flow source; in the case of cavo-pulmonary anastomosis and pulmonary artery banding or pulmonary stenosis, pulmonary blood flow was pulsatile and evenly distributed to both lungs, while in the case of bidirectional cavo-pulmonary anastomosis and Blalock-Taussig shunt, pulmonary flow was non pulsatile and asymmetric (angiographic criteria). There were no hospital deaths. Late mortality was 12.5% (2 pts) due to worsening of atrioventricular valve regurgitation. In one of these two patients, prolonged pleural and pericardial effusion occurred. In conclusion, bidirectional cavo-pulmonary anastomosis with an additional flow source is a good alternative to classic or fenestrated Fontan operation in the treatment of complex congenital heart disease. The best results are obtained with an additional flow source represented by pulmonary artery banding or pulmonary stenosis, due to pulsatility and uniform distribution of blood flow in the pulmonary district. Morbility and mortality compare favorably with the rates observed in classic or fenestrated Fontan operation.

Bidirectional cavo-pulmonary anastomosis with an additional flow source to the lungs: clinical experience in 21 cases.

The Fontan operation is considered a palliative procedure for the treatment of complex congenital heart diseases with a morbidity and mortality that are not negligible, especially in high-risk patients. In these cases, a bidirectional cavopulmonary anastomosis with additional source of blood flow to the lungs can represent a valuable surgical option. Between November 1992 and December 1995, 21 patients with univentricular heart physiology were submitted to bidirectional cavopulmonary anastomosis with additional blood flow the additional flow consisted of an aortopulmonary shunt in 13 cases, pulmonary artery banding in seven cases, and pulmonary artery stenosis in one case. Mean age at operation was 35.5 months (range 4 months to 12 years) and mean body weight 10.9 (range 4-24.4) kg. Hospital mortality was zero. Morbidity (pleuropericardial effusions) was significant in one case. There were three late deaths (14%) caused by worsening atrioventricular valve regurgitation: two of these occurred in patients with right isomerism. Late haemodynamic evaluation documented a significant increase in cardiac output (P < 0.01) and oxygen saturation (P < 0.05) during pharmacological stress testing. Angiographic characterization of blood flow distribution to the lungs showed better results when the additional blood flow was represented by an anterograde source (pulmonary artery banding or native pulmonary artery stenosis). In conclusion, bidrectional cavopulmonary anastomosis with additional blood flow is a good alternative to classic or fenestrated Fontan technique in high-risk patients. Secondly, the diagnosis of isomerism could be a contraindication to this type of surgery, because the persistent volume overload could worsen atrioventricular valve regurgitation. Thirdly, the pharmacological stress testing shows a favourable behaviour of cardiac output and arterial oxygen saturation. Fourth, the type of additional blood flow seems to condition both pulsatility and distribution of pulmonary blood flow.

Surgical management of complete atrioventricular canal associated with tetralogy of Fallot.

Between 1984 and 1993, 12 children with an atrioventricular canal and tetralogy of Fallot underwent surgical repair. The mean(s.d.) age at operation was 58(18) months, and the mean(s.d.) body weight 15(4) kg. Nine patients underwent 11 palliative procedures. The ventricular septal defect was closed through a combined (right atrial and right ventricular) approach in nine cases, and through a right atrial approach in three, using a prosthetic patch with a wide anterior extension, secured with a running suture. The 'ostium primum' defect was closed with a separate prosthetic patch in 11 cases (double-patch technique). Right ventricular outflow obstruction was relieved by a composite infundibular patch (seven cases) or a transanular patch (five). There were four hospital deaths (33%). These were caused by low cardiac output in three cases and infection in one (three deaths occurred in patients with a transanular patch). One patient has so far died during follow-up. Assessment at 50(36) months by echo-Doppler showed moderate-to-severe 'mitral' regurgitation in three cases, and moderate 'tricuspid' regurgitation with right ventricular dysfunction in one case. Two patients have required further surgery.

Activation of the intracellular glutathione system by oxydative stress during cardiopulmonary bypass and myocardial perfusion.

The glutathione (GSH) system is the main defence of tissues against free radicals and red blood cells (RBC) are the most efficient sites for GSH redox cycle activation. Total GSH was assayed during cardiopulmonary bypass (CPB) in RBC and serum from the coronary sinus, peripheral arteries and veins in 18 children corrected of their cardiac defect. Our conclusions are: (1) RBC-GSH redox cycle is activated during heart ischaemia and reperfusion; (2) the activation of intracellular GSH system is preponderant compared with the extracellular one; (3) variations in intraerythrocytic total GSH during heart ischaemia and perfusion are detectable in peripheral veins and arteries, which can be the convenient sites for monitoring changes in the GSH cycle; and (4) increased total GSH levels are present in RBC before aortic crossclamping: at the beginning of mechanical ventilation in veins and, when CPB is started, also in arteries.