| Objective: Left-to-right shunt congenital heart disease is the most commonly congenital cardiovascular anomaly, which accounts about 60%-70%. Left-to-right shunt leading to high pulmonary blood flow is the major feature of pathology and physiology in this disease. Pulmonary hypertension led by high pulmonary blood flow is the most common complication of the left-to-right shunt congenital heart disease, which degree will affect operating opportunity,achievement ratio and long-term living quality of patients after the operation. To this day, it is unclear about the mechanism of the pulmonary hypertension led by high pulmonary blood flow. The discovering of gaseous signal molecule provides a new channel for further identifying the mechanism of the pulmonary hypertension led by high pulmonary blood flow. For the past few years, gaseous signal molecules such as NO,CO and H2S have been thought very important in the generating and developing of pulmonary hypertension, and are becoming new hot spots[1,2] of study. Now, inhaled NO has been used to treat postoperative pulmonary hypertension in patients with congenital heart disease. Most of endogenous CO is produced by HO-1, HO-1/CO system is able to inhibit the generation of smooth muscle and relieve the reconstituted of pulmonary vascular structure. H2S is a new found gaseous signal molecule for the past few years which is a kind of vasoactive substance that can broaden blood vessel and inhibit the generation of smooth muscle. Animal experiment indicated: H2S donor─NaSH might prevent pulmonary hypertension and pulmonary artery structural remodeling induced by high pulmonary flow, and its mechanism might be associated with the changes in endogenous HO-1/CO system[3]. In recent years, there are many studys about effectiveness in pathology and physiology on animal experiments about the HO-1/CO system and H2S in the reconstituted of pulmonary vascular structure but few on pulmonary hypertension of patients with congenital heart disease in world. This dissertation, by measuring HO-1 activity in blood serum,HbCO percentage and H2S in the plasma levels of patients with left-to-right shunt congenital heart disease complicated with pulmonary hypertension researches on the effect and clinical significance of HO-1,CO and H2S on pulmonary hypertension.Method:Forty-eight patients with congenital heart disease who had left-to-right shunt were selected randomly from cardiac surgery in the Fourth Hospital of Hebei Medical University. Twenty-six were male, others were female. Their age ranged from four months to twenty-eight years(mean 5.37±3.84 years). There were 21 patients with VSD, 11 patients with ASD, 8 patients with PDA, 3 patients with VSD and ASD, 2 patients with VSD and PDA, 3 patients with ASD and PDA. Forty-eight patients were performed successfully on radical operation under complex intravenous anesthesia, 8 patients with PDA were operated without cardiopulmonary bypass(CPB), 40 patients with PDA were operated with cardiopulmonary bypass(CPB). Forty-eight patients were divided three groups according to pulmonary artery systolic pressure (PASP) by Doppler echocardiography before operation: group A was not pulmonary hypertension (PASP<30mmHg, n=15); group B was mild pulmonary hypertension (PASP3049mmHg, n=15); group C was heavy pulmonary hypertension(PASP≥50mmHg, n=18). The radial artery blood specimens were collected immediately before operation,1 and 24 hours after operation. HO-1 activity in blood serum was measured by Dual Wavelength Spectrophotometer at each period. HbCO percentage in plasma of blood was measured by Chalmers hemoglobin method at each period. H2S in plasma of blood was measured by optical absorbance method at 670nm at each period. The datum were analyzed by Repeated Measures, one-way-ANOVA, and analysis of linear correlation.Results:(1) The comparisons of HO-1 activity in the blood serum of different groups of congenital heart disease patients:The activity in blood serum of HO-1: group A, pre-operation 69.12±11.24nmol/L/h,1 hour post-operation 76.80±11.67 nmol/L/h,24 hours post-operation 73.73±12.76nmol/L/h;The activity in blood serum of HO-1: group B, pre-operation 59.90±4.93nmol/L/h,1 hour post-operation 73.73±9.05 nmol/L/h,24 hours post-operation 78.34±8.35nmol/L/h;The activity in blood serum of HO-1: group C, pre-operation 89.60±11.76nmol/L/h,1 hour post-operation 80.64±12.39 nmol/L/h,24 hours post-operation 61.44±8.54nmol/L/h. The comparisons of the HO-1 activity in blood serum of different groups at each period, it is no obvious difference on statistics(P>0.05);Compared with that of each group before operation, the HO-1 activity in blood serum of each group after operation is no obvious difference on statistics. (2) The comparisons of plasma levels of HbCO percentage of different groups of congenital heart disease patients:The plasma levels of HbCO percentage: group A, pre-operation 1.48±0.17,1 hour post-operation 1.43±0.19,24 hours post-operation 1.24±0.11;The plasma levels of HbCO percentage: group B, pre-operation 1.44±0.27,1 hour post-operation 1.47±0.25,24 hours post-operation 1.48±0.26 ; The plasma levels of HbCO percentage: group C, pre-operation 1.42±0.23,1 hour post-operation 1.40±0.21,24 hours post-operation 1.42±0.22;The comparisons of the plasma levels of HbCO percentage of different groups at each period, it is no obvious difference on statistics(P>0.05);Compared with that of each group before operation, the plasma levels of HbCO percentage of each group after operation is no obvious difference on statistics(P>0.05). (3) The comparisons of plasma levels of H2S of different groups of congenital heart disease patients:The plasma levels of H2S: group A, pre-operation 54.30±5.34μmol/L,1 hour post-operation 58.60±8.56μmol/L,24 hours post-operation 80.05±7.71μmol/L ; The plasma levels of H2S: group B, pre-operation 37.70±0.97μmol/L,1 hour post-operation 47.33±3.12μmol/L,24 hours post-operation 62.09±2.71μmol/L;The plasma levels of H2S: group C, pre-operation 27.44±2.85μmol/L,1 hour post-operation 30.17±2.59μmol/L,24 hours post-operation 37.28±2.71μmol/L; With increasing the degree of pulmonary hypertension, the plasma levels of H2S decrease. The plasma level of H2S in the group C was significantly lower than that of group B, the plasma level of H2S in the group B was significantly lower than that of group A before operation. Plasma level of H2S of each group after operation is higher than that of the same group before operation. Significant difference of the plasma level of H2S shows between 24 hours post-operation and pre-operation in the same group (P<0.05 or P<0.01). (4) There is no correlation between PASP and HO-1 activity in blood serum. (5)There is no correlation between PASP and the plasma level of HbCO percentage. (6) There is negative correlation between PASP and the plasma levels of H2S of the 3 groups at pre-operation,1 and 24 hours post-operation. (pre-operation r=-0.66, P<0.01; 1 hour post-operation r=-0.458, P<0.01; 24 hours post-operation r=-0.730, P<0.01). (7) There is positive correlation between the plasma level of HbCO percentage and the HO-1 activity in blood serum(r=0.873, P<0.01). Conclusions:(1) Following up the degree of pulmonary hypertension, the HO-1 activities in blood serum don't change obviously. There is no correlation between PASP and the HO-1 activities in blood serum, but HO-1 may be play an indirect action in the formation of pulmonary hypertension and restructure. (2) Following up the degree of pulmonary hypertension, the plasma levels of HbCO percentage don't change obviously. There is no correlation between PSAP and the plasma levels of HbCO percentage, but HbCO may be play an indirect action in the formation of pulmonary hypertension and restructure. (3)HO-1 results in most of endogenous CO in the body. (4) With increasing the degree of pulmonary hypertension, the plasma levels of H2S decrease. There is negative correlation between PASP and plasma level of H2S. H2S plays an important role in the formation of pulmonary hypertension and restructure. (5) Detecting the levels of H2S may be an experiment method to judge the degree of pulmonary hypertension. (6) There may be a new approach with treatment to pulmonary hypertension, by more studying HO-1,CO and H2S.
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