Endogenous nitric oxide production and atrial natriuretic peptide biological activity in infants undergoing cardiac operations.

OBJECTIVES: To examine whether preoperative heart failure and cardiac surgery influence nitric oxide production and atrial natriuretic peptide (ANP) biological activity in infants and whether nitric oxide and ANP participate in the control of postoperative pulmonary vascular tone. DESIGN: Prospective, clinical study. SETTING: Tertiary pediatric cardiac intensive care unit in a referral cardiosurgical center. PATIENTS: Nineteen infants (median age 4 months) undergoing cardiac surgery: 13 infants with ventricular or atrioventricular septal defect associated with heart failure and pulmonary hypertension (group 1); and six infants with tetralogy of Fallot, without heart failure (group 2). INTERVENTIONS: Blood samples obtained from indwelling catheters or bypass circuit outlets. MEASUREMENTS AND MAIN RESULTS: Nitrite and nitrate blood concentrations (as a marker for nitric oxide synthesis) and the molar ratio of cyclic guanosine 3',5'-monophosphate (cGMP) to ANP (as a marker for ANP biological activity) were determined before, during, and up to 24 hrs after cardiopulmonary bypass (CPB). In group 1 patients, these biological parameters were related to postoperative pulmonary arterial pressure. Preoperative nitrite and nitrate concentrations were higher in group 1 patients than in group 2 patients (p < .02), and this difference persisted during CPB. Nitrite and nitrate concentrations 24 hrs postoperatively were lower than preoperative values in group 1 patients (p < .05) and were unchanged in group 2 patients. An inverse correlation was observed postoperatively between nitrite and nitrate concentrations and systolic pulmonary arterial pressure (r2 = 0.4, p < .05). Group 1 patients had a lower preoperative cGMP/ANP ratio than group 2 patients (p < .05), despite higher ANP levels (p < .005). The cGMP/ANP ratio decreased during CPB in both groups (p < .0001), and in group 2 patients, cGMP and ANP values remained below preoperative values < or = 24 hrs postoperatively. A correlation was observed between ANP levels and systolic pulmonary arterial pressure 2 and 4 hrs postoperatively (r2 = .4, p < .05, respectively), but no correlation was observed between ANP biological activity and postoperative pulmonary arterial pressure. CONCLUSIONS: Infants with heart failure and pulmonary hypertension have increased nitric oxide synthesis and decreased ANP biological activity; both phenomena may be involved in the pathophysiology of this clinical condition. CPB has no detectable effect on nitric oxide production but does decrease ANP biological activity. In patients with preoperative heart failure and pulmonary hypertension, endogenous nitric oxide appears to play a role in the control of postoperative pulmonary vascular tone.

Interleukin-10 release related to cardiopulmonary bypass in infants undergoing cardiac operations.

To evaluate cytokine balance related to cardiopulmonary bypass, we prospectively investigated 11 infants undergoing cardiac operations for congenital heart disease. Proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-8) and the antiinflammatory cytokine interleukin-10 were measured at multiple time points before, during, and after bypass. Tumor necrosis factor-alpha and interleukin-8 values were within normal range before the operation. These values increased significantly during bypass, reaching their peaks after protamine administration (tumor necrosis factor-alpha, 133.6 +/- 124.9 pg/ml; mean +/- standard deviation; p<0.005) and 2 hours after termination of the procedure (interleukin-8, 92.1 +/- 44.1 pg/ml; p < 0.01). Tumor necrosis factor-alpha and interleukin-8 equaled normal prebypass values from the first postoperative day on. Interleukin-10 levels were within normal range before the operation and were already significantly increased 10 minutes after initiation of bypass (interleukin 10, 39.4 +/- 34.3 pg/ml; p<0.05). These levels remained elevated throughout the procedure but returned to normal after protamine administration. A second significant release of interleukin-10 occurred from the early postoperative period on, reaching its peak 24 hours after termination of cardiopulmonary bypass (interleukin-10, 351.6 +/- 304.0 pg/ml; p < 0.01). Interleukin-10 values were normal on the second postoperative day in all patients. Interleukin-10 kinetics showed an inverse pattern compared with tumor necrosis factor-alpha and interleukin-8. This difference suggests an interplay between proinflammatory and antiinflammatory cytokines released during and after cardiopulmonary bypass. Interleukin-10 levels measured 4 and 24 hours after bypass strongly correlated with the degree of hypothermia during bypass (Spearman's correlation coefficient, -0.77 [p < 0.01] and -0.89 [p < 0.0005], respectively); these levels did not correlate with duration of bypass and aortic crossclamping, however. This result suggests that besides immunologically mediated production of interleukin-10, hypothermia itself could modulate interleukin-10 production. In conclusion, this study demonstrates interleukin-10 production, in addition to interleukin-8 and tumor necrosis factor-alpha synthesis, in response to cardiopulmonary bypass in infants. Interleukin-10 could play a protective role by down-regulating proinflammatory cytokine release during and after cardiopulmonary bypass.

Obstructed total anomalous pulmonary venous return. Toward neutralization of a major risk factor.

Among 57 neonates undergoing repair of total anomalous pulmonary venous return with severe pulmonary venous obstruction from 1980 through 1989, date of operation (1980 to 1984), preoperative hemodynamic instability, and failure to monitor pulmonary artery pressure postoperatively were risk factors for death. Thus, among the 30 patients having repair between 1985 and 1989, the 55-month survival rate including hospital deaths was 83%.

[Obstruction of total anomalous pulmonary venous drainage. Factors influencing improvement in surgical results]. / Les retours veineux pulmonaires anormaux totaux bloqués. Facteurs influençant une amélioration des résultats chirurgicaux.

Of 107 patients operated for total anomalous pulmonary venous drainage (TAPVD) at Marie-Lannelongue Hospital between January 1980 and November 1989, 57 had severe pulmonary venous obstruction. The average age of the patients at operation was 13.6 days and their average body weight was 3.2 kg. Twenty eight patients had an infracardiac, 23 patients a supracardiac, 2 patients an intracardiac and 4 patients a mixed type of TAPVD. The diagnosis of pulmonary venous obstruction was made on the findings of low cardiac output and pulmonary hypertension exceeding the systemic blood pressure, and on the results of angiography and Doppler echocardiography. Seventy five per cent of patients were admitted in Class IV of the NYHA Classification. Since 1985, treatment has been directed towards prevention of pulmonary hypertension. Echocardiographic diagnosis is considered sufficient for posing the surgical indication. Surgery should be performed before degradation of the patient's clinical condition or after a short period of stabilisation. The prevention of hypertensive crises in the postoperative period depends on continuous monitoring of pulmonary pressures. This approach has considerably improved our surgical results as the mortality rate has fallen from 59 p. 100 (1980-1984) to 13.3 p. 100 (1985-1989) (p less than 0.005). In conclusion, obstruction of the pulmonary veins in TAPVD is no longer considered to be a poor prognostic factor, providing measures are taken to prevent pulmonary hypertension before, during and after surgery.

[Severe tracheo-bronchial compression caused by a circumflex aorta. Apropos of 3 cases treated by aortic uncrossing]. / Compression trachéo-bronchique sévère par une aorte circonflexe. A propos de trois cas traités par décroisement aortique.

The cases of three children with an encircling right aortic arch and left sided descending aorta illustrate the fact that this rare abnormality may cause severe compression of the tracheo-bronchial axis. A ventricular septal defect was associated to the abnormal vascular arch in all three cases. The compressive structure was the aorta and these children could only be extubated after surgical uncrossing . Before diagnosing tracheomalacia in a child operated for an abnormal vascular arch, residual compression must be excluded by tracheo-bronchial fibroscopy.