[Transcatheter therapy of combined congenital heart diseases in children].

OBJECTIVE: To investigate the methods of interventional catheterization for combined congenital heart disease and to evaluate its efficacy in children. METHODS: From March 1994 to December 2003, 15 cases (6 boys, 9 girls) underwent transcatheter intervention for combined congenital heart diseases. The procedure of transcatheter intervention was as follows: for pulmonary stenosis (PS) and atrial septal defect (ASD) or patent ductus arteriosus (PDA), PBPV first, occlusion of ASD or PDA later; for coarctation of aorta (COA) and PDA, dilation of COA first, occlusion of PDA 4-15 months later; for aortic stenosis (AS) and PDA, PBAV first, occlusion of PDA later; for ventricular septal defect (VSD) and PDA, all occlusions with detachable coils. RESULT: Transcatheter intervention for combined congenital heart diseases was successful in all patients. There was no residual shunt after occlusion immediately apart from 2 cases of PDA which were little residual after occlusion immediately. Follow-up for (3.57 +/-2.61) years, the systolic pressure gradients across pulmonary valve and coarctation were normal by ultrasonic or transcatheter, except AS. There was 3 cases presented postoperative complications: 1 with mechanical haemolysis, 1 with fall off of coil and 1 with arterial embolism, respectively. CONCLUSION: Transcatheter intervention for combined congenital heart diseases could obtain satisfactory results with appropriate indications and procedure manipulations.

[Pathophysiology of bleomycin-induced pulmonary hypertension in immature rabbits].

OBJECTIVE: To investigate the evolution of pulmonary hypertension induced by intratracheal bleomycin (BLM) in immature rabbits. METHODS: Immature rabbits were divided into control and BLM groups. Two and four weeks after intratracheal normal saline or BLM, the systolic, diastolic and mean pulmonary artery pressure (PASP, PADP, MPAP) were measured by micro-catheter, the pathological changes and the expression of VEGFmRNA and eNOSmRNA of endothelial cells in pulmonary arteries were evaluated by HE and in situ hybridization. RESULTS: Pulmonary artery pressure was elevated 2 weeks and 4 weeks after intratracheal BLM. Two weeks after treatment PASP was (16.5 +/- 2.9 compared with 25.2 +/- 7.0) mmHg, PADP (8.8 +/- 4.2 compared with 13.1 +/- 3.8) mmHg, MPAP (12.1 +/-4.0 compared with 18.4 +/-4.7) mmHg in control and BLM groups, respectively; meanwhile 4 weeks after treatment, PASP was (16.7 +/-2.3 compared with 23.8 +/-7.1) mmHg, PADP (7.3 +/-1.5 compared with 13.8 +/-6.6) mmHg, MPAP (11.3 +/- 1.9 compared with 17.6 +/- 6.3) mmHg in control and BLM groups, respectively. The thickness of arterial wall increased and the cavity became narrow, and the thickness index (TI) and area index (AI) increased in middle and small pulmonary arteries 2 weeks and 4 weeks after intratracheal BLM. Two weeks after treatment TI was 0.52 +/- 0.16 compared with 0.65 +/- 0.16, AI 0.74+/- 0.17 compared with 0.84 +/- 0.14 in control and BLM groups, respectively; meanwhile 4 weeks after treatment TI was 0.52 +/- 0.11 compared with 0.64 +/- 0.15, AI 0.71 +/- 0.15 compared with 0.85 +/- 0.10 in control and BLM groups. The levels of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased 2 weeks and 4 weeks after intratracheal BLM. Two weeks after treatment VEGFmRNA was 0.83 +/- 0.09 compared with 0.45 +/- 0.11, eNOSmRNA 0.79 +/- 0.12 compared with 0.45 +/- 0.12 in control and BLM groups, respectively; meanwhile 4 weeks after VEGFmRNA was 0.81 +/- 0.19 compared with 0.46 +/- 0.15, eNOSmRNA 0.89 +/- 0.14 compared with 0.44 +/- 0.12 in control and BLM groups, respectively. CONCLUSION: Intratracheal bleomycin may induce the pathological changes of pulmonary arteries and decrease the expression of VEGFmRNA and eNOSmRNA in immature rabbits, which results in pulmonary hypertension.

[Effect of VEGF gene transfer on the bleomycin-induced pulmonary hypertension in immature rabbits].

OBJECTIVE: To investigate the effect of vascular endothelial growth factor (VEGF) gene transfer on the bleomycin(BLM)-induced pulmonary hypertension in immature rabbits. METHODS: Immature rabbits were divided into 4 groups; control, BLM, liposome and trans-gene groups. The systolic, diastolic and mean pulmonary artery pressure (PASP, PADP, MPAP) were measured by micro-catheter, the pathological changes and the expression of VEGFmRNA and eNOSmRNA of endothelial cells in pulmonary arteries were evaluated by HE stain and in situ hybridization. RESULT: (1) The PAP of BLM and liposome groups was higher than that of control and trans-gene groups. The PASP was 16.5+/-2.9, 25.2+/-7.0, 24.4+/-6.0 and 18.3+/-2.7 mmHg; the PADP was 8.8+/-4.2, 13.1+/-3.8, 13.7+/-4.6 and 10.2+/-2.6 mmHg; the MPAP was 12.1+/-4.0, 18.4+/-4.7, 18.4+/-5.1 and 14.1+/-2.5 mmHg in control, BLM, liposome and trans-gene groups respectively. (2) The thickness of wall increased and the cavity became narrow, and the thickness index (TI) and area index (AI) increased in middle and small pulmonary arteries of BLM and liposome groups. The TI was 0.52+/-0.16, 0.65+/-0.16, 0.63+/-0.11 and 0.55+/-0.13; and the AI was 0.74+/-0.17, 0.84+/-0.14, 0.85+/-0.08 and 0.79+/-0.12 in control, BLM, liposome and trans-gene groups,respectively. (3) The level of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased in BLM and liposome groups. The level of VEGFmRNA and eNOSmRNA expression in trans-gene group was higher than that in BLM and liposome groups, but lower than that in control group. VEGFmRNA was 0.83+/-0.09, 0.45+/-0.11, 0.45+/-0.13 and 0.65+/-0.18; eNOSmRNA was 0.79+/-0.12, 0.45+/-0.12, 0.50+/-0.14 and 0.56+/-0.08 in control, BLM, liposome and trans-gene groups, respectively. CONCLUSION: VEGF gene transfer in immature rabbits with BLM-induced pulmonary hypertension could attenuate the increasing of PAP and wall thickness in middle and small pulmonary arteries, and increase the level of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells.

Study on the effect of doxorubicin on expressions of genes encoding myocardial sarcoplasmic reticulum Ca2+ transport proteins and the effect of taurine on myocardial protection in rabbits.

To investigate the effect of doxorubicin(DOX) on gene expression of the myocardial sarcoplasmic reticulum (SR) Ca2+ transport proteins and the mechanism of taurine (Tau) protecting cardiac muscle cells, 9 rabbits were injected with DOX, 8 rabbits with DOX and Tau, and 9 rabbits with normal saline. Cardiac function, concentration of calcium in cardiomyocytes (Myo[Ca2+]i), activity of SR Ca(2+)-ATPase (SERCA2a), level of SERCA2a mRNA and Ca2+ released channels (RYR2) mRNA were detected. The left ventricle tissues were observed by electron microscopy. The results showed that cardiac index, left ventricular systolic pressure, activity of SR Ca(2+)-ATPase and level of SERCA2a mRNA decreased, while Myo[Ca2+]i increased in DOX-treated rabbits. DOX could not affect the level of RYR2 mRNA. Tau intervention could alleviate the increase of left ventricular diastolic pressure, Myo[Ca2+]i and the decrease of SERCA2a mRNA induced by doxorubicin. The results suggested that downregulation of SERCA2a gene expression was an important mechanism of DOX-induced cardiomyopathy and that Tau could partially improve the heart function by reducing calcium overload and alleviating downregulation of SERCA2a mRNA.

VEGFmRNA and eNOSmRNA expression in immature rabbits with bleomycin-induced pulmonary hypertension.

OBJECTIVE: To investigate the evolution of pulmonary hypertension, the pathological changes of pulmonary arteries, and the expression of VEGFmRNA and eNOSmRNA of pulmonary arterial endothelial cells in immature rabbits treated with intratracheal bleomycin (BLM). METHODS: Immature rabbits were divided into control and BLM group. Two and four weeks after intratracheal normal saline or BLM injection, the systolic, diastolic and mean pulmonary artery pressure (PASP, PADP, MPAP) were measured by micro-catheter; the pathological changes and the expression of VEGFmRNA and eNOSmRNA of endothelial cells in pulmonary arteries were evaluated by HE and in situ hybridization. RESULTS: Two and four weeks after intratracheal injection of BLM, the PASP, PADP and MPAP increased 53%, 49%, 52% in 2 weeks, and 43%, 89%, 56% in 4 weeks; the wall thickness increased and the cavity in middle and small pulmonary arteries became narrow; the Thickness Index (TI) and Area Index (AI) increased 25%, 14% in 2 weeks, and 22%, 24% in 4 weeks; the level of VEGFmRNA and eNOSmRNA expression decreased 46%, 43% in 2 weeks, and 43%, 51% in 4 weeks. There was no significant difference between 2 weeks and 4 weeks BLM groups. CONCLUSION: The pulmonary artery pressure was elevated, the thickness of wall increased and the cavity became narrow in middle and small pulmonary arteries, and the level of VEGFmRNA and eNOSmRNA expression in pulmonary arterial endothelial cells decreased in immature rabbits after 2 weeks and 4 weeks of intratracheal 4 U/kg BLM injection.

[Effect of pinacidil on rat myocardial calcium regulation].

OBJECTIVE: To understand the effect of pinacidil on rat myocardial Ca(2+)regulation. METHODS: After baseline measurement and a period of equilibrium, myocytes were randomly allocated to one of 4 treatment groups: Control group (8 myocytes): incubation in Lactate Ringer's solution at 24 degrees C for 2 hours; K group (8 myocytes): incubation in Lactate Ringer's solution containing 16 mmol/L potassium at 24 degrees C for 2 hours; K+P group (8 myocytes): incubation in Lactate Ringer's solution containing potassium 16 mmol/L and pinacidil 50 micromol/L at 24 degrees C for 2 hours; K+P+G group (8 myocytes): incubation in Lactate Ringer's solution containing potassium 16 mmol/L, pinacidil 50 micromol/L and glibenclamide 10 micromol/L at 24 degrees C for 2 hours. After each incubation, myocytes were resuspended in cell culture media at the same temperature and intracellular [Ca(2+)](i) and SR Ca(2+) release were measured. RESULTS: The amplitude percent of [Ca(2+)](i) transient evoked by electrical stimulation in the K group was significantly decreased to 67.05% - 80.11% compared to 90.27% - 95.57% in the K+P group during reperfusion after ischemia (P<0.01). The percent amplitude of the [Ca(2+)](i) transient evoked by the rapid application of 10 mmol caffeine in the K group myocyte was approximately 112.00%+/-16.93% compared with that of the [Ca(2+)](i) transient evoked by electrical stimulation. However, in the K+P group myocyte the peak amplitude of the caffeine induced Ca(2+) release was 173.15%+/-26.01% compared with electrical stimulation (P<0.01). The duration of transient evoked by caffeine in K+P group (3.20+/-0.71 ms was significantly shorter than that in K group (3.93+/-0.46) ms (P<0.05). CONCLUSION: Cardioplegic arrest with simultaneous activation of KATP channels preserves rat myocardial Ca2+ by inducing sarcoplasmic reticulum Ca(2+) release and by alteration of Na(+)-Ca(2+) exchanger to better maintain [Ca(2+)](i) homeostasis.

[Postoperative hemodynamic parameter follow-up in children with severe pulmonary resistance hypertension due to ventricular septal detect].

OBJECTIVE: To study the relationship between the age at operation and prognosis in children with severe pulmonary hypertension (PH) due to ventricular septal defect (VSD). METHODS: Forty children with severe PH (increased total pulmonary circulation resistance)due to VSD were divided into two groups based on age at operation(Group I aged less than 2 years and group II more than 2 years). The hemodynamic parameter follow-up was measured by cardiac catheterization at presurgery, one week after surgery and 5-7 years postoperatively. RESULTS: The ratio of pulmonary arterial pressure and systemic arterial pressure (pp/ps),pulmonary resistance and systemic resistance (R(p)/R(s)), and pulmonary vascular resistance (PVR) and small pulmonary arterial resistance (PAR) were significantly different in two groups (P<0.01). During follow-up in the group less than 2 years, all the hemodynamic parameters were at normal level, while in the group more than 2 years, only p(p)/p(s) and R(p)/R(s) were close to normal level. The pulmonary arterial resistance was still abnormal. CONCLUSION: An early operation may be the only way to gain optimal long term result of surgery and decrease the incidence of pulmonary vascular disease in children with PH due to VSD.

[Effect of adriamycin on sarcoplasmic reticulum Ca2+ -ATPase activity in cardiomyocyte of rabbits]

OBJECTIVE: To evaluate influences of regular-dose of adriamycin (ADR) on heart function and sarcoplasmic reticulum (SR) Ca2+ -ATPase in cardiomyocyte of rabbits. METHODS: Nine rabbits received intraveneous injection of ADR (2mg/kg) once a week for 8 weeks, the rabbits injected with saline were used as control group. Cardiac output (CO), blood pressure (BP), mean artery pressure (MAP), left ventricular systolic pressure( LVSP), left ventricular end-diastolic pressure (LVEDP), calcium in cardiomyocyte (MyoCa2+) of rabbits and SR Ca2+ -ATPase activity were examinated 3 weeks after the final injection. RESULTS: CO, LVSP and SR Ca2+ -ATPase activity were significantly decreased in ADR treated group compared with the control group. Conversely, LVEDP and MyoCa2+ were significantly increased in ADR treated rabbits. CONCLUSION: Heart function can be decreased by regular-dose of ADR in injection. Calcium overload in cardiomyocyte and decrease of SR Ca2+ -ATPase activity is important physiopathologic mechanism in ADR-induced impairment of heart.

[Changes in CD69, CD25 and HLA-DR expressions in peripheral blood T cells in Kawasaki disease].

OBJECTIVE: The study was designed to investigate the changes in CD(69), CD(25) and HLA-DR expressions in peripheral blood T cell in Kawasaki disease (KD). METHODS: The authors detected CD(69), CD(25) and HLA-DR expressions in peripheral blood T cell by using flow cytometry. The patients who met the diagnostic criteria for KD comprised sixteen boys and fifteen girls (4 - 60 months of age; mean, 26 +/- 18 months). All received intravenous gammaglobulin at a dose of 1 g/(kg.d), for 2 days and oral aspirin at a dose of 30 - 50 mg/(kg.d). In case of persistent fever, a repeated dose of intravenous gammaglobulin or I.V. methylprednisolone at a dose of 20 mg/(kg.d) for three daily doses was attempted. The authors tested blood samples from 17 healthy controls consisting of nine boys and eight girls (3 - 84 months of age; mean, 25 +/- 18 months) and the samples from 31 patients. RESULTS: The percentage of peripheral blood CD(3)(+) T lymphocyte was (54.4 +/- 9.0)% in acute stage of KD and (65.0 +/- 7.0)% in healthy controls. There was a significant difference between the two groups (P < 0.001). The values of CD(69)(+) [(11.2 +/- 12.6)%, vs. (0.6 +/- 0.4)%], CD(25)(+) [(9.2 +/- 3.5)% vs. (3.9 +/- 1.8)%] and HLA-DR(+) [(8.3 +/- 5.0)% vs. (4.3 +/- 2.3)%] in KD patients were markedly increased compared to those of the healthy controls. After intravenous gammaglobulin treatment, the percentage of CD(3)(+)CD(69)(+) and CD(3)(+)CD(25)(+) significantly decreased [CD(3)(+)CD(69)(+): (14.0 +/- 13.0)% vs. (1.6 +/- 1.2)%, P < 0.05; CD(3)(+)CD(25)(+): (7.8 +/- 4.1)% vs. (2.0 +/- 0.6)%, P < 0.01]. However, the CD(3)(+) T lymphocytes increased [(50.8 +/- 5.0)% vs. (64.9 +/- 5.5)%, P < 0.01]. There was no significant difference in expression of CD(3)(+) T lymphocyte cell activating markers between coronary artery disease group and normal coronary artery group in KD cases (P > 0.05). CONCLUSION: CD(3)(+) T cell activation in the early and middle stages is involved in the mechanism responsible for cardiovascular injury.