Contributions of Respiration and Heartbeat to the Pulmonary Blood Flow in the Fontan Circulation.

BACKGROUND: In the Fontan circulation, driving forces with respiration, heartbeat, and lower limb muscle pump are relevant. However, the mechanics of these forces has not been proven, and their effects on the Fontan circulation remain unclear. METHODS: We performed catheter examinations and measured pressure and flow velocity simultaneously in the bilateral pulmonary arteries of 12 Fontan patients 1 year after the operation. The pulmonary pressure and flow velocity data were decomposed into respiratory and heartbeat components by discrete Fourier analysis. We then calculated respiratory and cardiac wave intensity (WI) based on the respiratory and heartbeat components of pressure and flow velocity data. RESULTS: Respiratory WI formed 2 negative peaks, a backward expansion wave during the inspiratory phase, and then a backward compression wave during the expiratory phase. In 2 phrenic nerve palsy cases and 1 case of a patient on a respirator, respiratory WI showed disturbed patterns and a negative pattern, respectively. Cardiac WI showed 2 or 4 negative peaks, the time phase of which matched that of the atrial contractions. CONCLUSIONS: WI analysis elucidated that inspiration acts as a sucking driving force and increases the pulmonary blood flow in the Fontan circulation. Respiratory complications compromise efficiency in the Fontan circulation. It was also revealed that the pulmonary blood flow was mutually dammed up and sucked in by increases and decreases in atrial pressure.

Timing of Haemophilus influenzae type b vaccination after cardiac surgery.

BACKGROUND: The best time for vaccination in infants with congenital heart disease (CHD) after cardiopulmonary bypass (CPB) surgery is unclear, but it is important to prevent Haemophilus influenzae type b (Hib) infection in infants with CHD after CPB surgery. To identify the best time for Hib vaccination in infants with CHD after CPB surgery, we investigated the immunological status, and the efficacy and safety of Hib vaccination after CPB surgery. METHODS: Sixteen subjects who underwent surgical correction of ventricular septal defect with CPB were investigated. Immunological status and cytokines were analyzed before surgery, 2 months after surgery, and before Hib booster vaccination. Hib-specific IgG was also measured to evaluate the effectiveness of vaccination. RESULTS: Immunological status before and 2 months after surgery (e.g. whole blood cells and lymphocyte subset profile) was within the normal range and no subjects had hypercytokinemia. Additionally, all subjects who received Hib vaccination at 2-3 months after CPB surgery had effective serum Hib-specific IgG level for protection against Hib infection without any side-effects. CONCLUSIONS: CPB surgery does not influence acquired immunity and Hib vaccination may be immunologically safe to perform at 2 months after CPB surgery. Hib vaccination at 2-3 months after CPB surgery was effective in achieving immunization for infants with simple left-right shunt-type CHD.

Quantitative evaluation of hemodynamics in the Fontan circulation: a cross-sectional study measuring energy loss in vivo.

Flow energy loss (EL) at the Fontan anastomosis has been thought to reflect flow efficiencies and to influence on hemodynamics in the Fontan circulation and has been often discussed in numerical studies. However, in vivo EL measurements have to date not been reported. We directly measured EL in the Fontan circulation and examined the relationship between the structural configuration and EL, as well as the influence of EL, on the hemodynamics in the Fontan circulation. We performed a catheterization study measuring simultaneous pressure and flow velocity to calculate EL in nine patients (mean age 2.3 ± 0.3 years) 1 year after the Fontan procedure. The measured EL was 9.66 ± 8.50 mW. One patient with left pulmonary artery stenosis recorded the highest EL (17.78 mW), and one patient with bilateral superior vena cava and left phrenic nerve palsy recorded the second highest EL (14.62 mW). EL significantly correlated with time constant tau and weakly with max-dp/dt during the isovolumic diastolic phase (r = 0.795 and -0.574, respectively). EL also correlated with max-dp/dt during the isovolumic systolic phase (r = 0.842) but not with ejection fraction or systemic blood flow (r = 0.384 and -0.034, respectively). In conclusion, inefficient structural configuration and phrenic nerve palsy seem to be related with increased in EL at the Fontan anastomosis. Although these preliminary findings also suggest that EL is associated with an impaired relaxation of the ventricle, a long-term study with a large population is warranted to reach such a definitive conclusion.

The lower limit of the pulmonary artery index for the extracardiac Fontan circulation.

OBJECTIVE: In the era of the staged Fontan operation, small pulmonary artery index (<250 mm(2)/m(2)) has not affected the early or midterm results. The lower limit of pulmonary artery index, however, has not yet been determined. We created numeric models of the Fontan circulation to investigate the lower limit of the pulmonary artery size. METHODS: The extracardiac Fontan geometries with pulmonary artery index, ranging from 50 to 200 mm(2)/m(2) with every 10-mm(2)/m(2) increase, were created from the postoperative angiographic data of 17 patients. The superior and inferior vena caval flow rates at rest and on 2 exercise levels (0.5 and 1.0 W/kg) were given by magnetic resonance imaging flow studies. Respiration-driven transient flow analysis was performed with a finite element solver. Energy loss and mean inferior vena caval pressure were obtained from the results. RESULTS: Energy loss and mean inferior vena caval pressure were prominently increased in small pulmonary artery index models, especially during exercise. The pulmonary artery indices sufficient for mean inferior vena caval pressure less than 17 mm Hg were 80 mm(2)/m(2) at rest, 100 mm(2)/m(2) during 0.5-W/kg exercise, and 110 mm(2)/m(2) during 1.0-W/kg exercise. With the increase of pulmonary arterial resistance, mean inferior vena caval pressure increased, but the flow pattern did not change. CONCLUSIONS: A small pulmonary artery causes a high pressure gradient and a high energy loss. The lower limit of pulmonary artery index, considering the exercise tolerance, was 110 mm(2)/m(2).

Noninvasive assessment of pulmonary vascular resistance and pressure in patients with congenital heart disease: a new method using M-mode echocardiography.

BACKGROUND: The accurate evaluation of pulmonary vascular resistance (PVR) and mean pulmonary artery pressure is important to determine the optimal management and therapeutic strategy for patients with congenital heart disease (CHD). We evaluated the PVR and mean pulmonary artery pressure in 46 patients with several CHD types using the interventricular septum (IVS) motion determined by M-mode echocardiography. METHODS: We divided the patients into 2 groups according to the different IVS motions. We measured the maximum anterior displacement from the baseline during early systole (a) and the maximum posterior displacement from the baseline during early diastole (b). We defined type A to be a/b greater than or equal to 1.0, and type B to be a/b less than 1.0. RESULTS: The PVR and mean pulmonary artery pressure in type A patients were significantly higher than those in type B patients (p < 0.05). Type A IVS motion predicted patients with high PVR (>2.5 unit/m(2)) and high mean pulmonary artery pressure (>25 mmHg) (sensitivity 89%, specificity 89% and sensitivity 70%, specificity 91%, respectively). CONCLUSIONS: Our method can noninvasively separate high and low PVR among patients with CHD. This noninvasive method is therefore considered to be useful in the management of patients with CHD in a clinical setting.

Clinical score and transcript abundance patterns identify Kawasaki disease patients who may benefit from addition of methylprednisolone.

Intravenous immunoglobulin (IVIG) treatment-resistant patients are high risk of developing coronary artery lesions with Kawasaki disease. The IVIG-responsive (Group A; n = 6) and IVIG-resistant patients (Group B) were predicted before starting the initial treatment using the Egami scoring system and randomly allocated as a single-IVIG treatment group (group B1; n = 6) or as a IVIG-plus-methylprednisolone (IVMP) combined therapy group (group B2; n = 5). We investigated the transcript abundance in the leukocytes of those patients using a microarray analysis. Five patients in group A and one patient in group B1 responded to initial IVIG treatment. All group B2 patients responded to IVIG-plus-IVMP combined therapy. Before performing these treatments, those transcripts related to IVIG resistance and to the development of coronary artery lesions, such as IL1R, IL18R, oncostatin M, suppressor of cytokine signaling-3, S100A12 protein, carcinoembryonic antigen-related cell adhesion molecule-1, matrix metallopeptidase-9, and polycythemia rubra vera-1, were more abundant in group B patients in comparison with group A patients. Moreover, those transcripts in group B2 patients were more profoundly and broadly suppressed than group B1 patients after treatment. This study elucidated the molecular mechanism of the effectiveness of IVIG-plus-IVMP combined therapy.

Optimal conduit size of the extracardiac Fontan operation based on energy loss and flow stagnation.

BACKGROUND: In the extracardiac Fontan operation, larger conduits are used when considering the patients' growth rate. However, larger conduits may cause inefficient flow due to turbulence or stagnation, resulting in late problems such as thrombosis or stenosis. Our objective was to reveal the physiologic effects of respiration and exercise using numerical models, based on the energy loss and flow stagnation, and to determine optimal conduit size. METHODS: For the Fontan operation, a conduit from 14 to 22 mm was created based on angiographic data from 17 Fontan patients (mean age, 36.0 months; mean body surface area, 0.53 m(2)). Respiratory-driven flow of the superior and inferior vena cava was determined at rest and during exercise on two levels (0.5 and 1.0 W/kg) by magnetic resonance imaging flow studies. Flow stagnation was defined as the volume of the region where flow velocity was less than 0.01 m/second at both the expiratory and inspiratory phases. RESULTS: In larger conduits, backward flow at the expiratory phase was prominent. Energy loss was small even during exercise, but the change was slightly larger between 14 and 16 mm than other conduit sizes (14 mm, 5.759 mW; 16 mm, 4.881 mW; and 22 mm, 4.199 mW during 1.0 W/kg exercise). Stagnation volume at the expiratory phase increased with an increase of conduit size (14 mm, 9.20% vs 22 mm, 33.9% conduit volume at rest). CONCLUSIONS: Fontan circulation is a low-energy system even during exercise. Larger conduits were proven to have redundant spaces, thus 16 and 18 mm conduits were optimal.

The strategy of immune globulin resistant Kawasaki disease: a comparative study of additional immune globulin and steroid pulse therapy.

BACKGROUND: We compared the clinical utility of additional intravenous immune globulin (IVIG) therapy with the clinical utility of steroid pulse therapy in patients with IVIG-resistant Kawasaki disease. METHODS: We enrolled 164 patients with Kawasaki disease who were treated with a single dose of IVIG (2 g/kg) and aspirin (30 mg/kg per day). Twenty-seven of these patients (16%) were resistant to the initial IVIG treatment. We compared the effectiveness of treatment strategies for the initial IVIG-resistant 27 patients, 14 of these patients were treated with additional IVIG therapy, and the other 13 patients were treated with steroid pulse therapy (methylprednisolone 30 mg/kg per day for 3 days). RESULTS: Three patients in the group receiving additional IVIG treatment had coronary artery aneurysms (21.4%), no patients had coronary artery aneurysm in the steroid pulse therapy group; the difference in the incidence of coronary artery aneurysm was not statistically significant. The duration of high fever after additional treatment in the steroid pulse therapy group (1 ± 1.3 days) was significantly shorter than that in the additional IVIG treatment group (3 ± 2.4 days; P < 0.05). The medical costs were significantly lower in the steroid pulse therapy group than in the additional IVIG treatment group. CONCLUSION: Steroid pulse therapy was useful to reduce the fever duration and medical costs for patients with Kawasaki disease. Steroid pulse therapy and additional IVIG treatment were not significantly different in terms of preventing the development of coronary artery aneurysm.

Visualization of interscapular brown adipose tissue using (99m)Tc-tetrofosmin in pediatric patients.

UNLABELLED: Brown adipose tissue (BAT) is a site of nonshivering thermogenesis in mammals. The mitochondria of BAT operate in an uncoupled mode and increase fatty acid oxidation to produce heat at birth. Thus, the BAT of human infants and children contains more active mitochondria than that of adults. We surmised that because (99m)Tc-tetrofosmin can be absorbed by functional mitochondria in the myocardium and in tumor cells, it could reveal mitochondrial function in BAT. METHODS: Between January 1999 and December 2002, we retrospectively analyzed 385 consecutive studies of (99m)Tc-tetrofosmin uptake in pediatric patients with cardiac disorders. All patients with symmetric (99m)Tc-tetrofosmin accumulation within the neck and shoulder region according to planar images were selected, and the features of the uptake were analyzed. RESULTS: Increased symmetric (99m)Tc-tetrofosmin uptake in the interscapular BAT was a typical profile of 65 of the 385 patients (17%). The frequency of (99m)Tc-tetrofosmin uptake was significantly higher in winter than in spring or summer (P < 0.05) and prominent in newborns. The frequency peaked between 0 and 2 y of age and then declined with age. CONCLUSION: Gamma-camera imaging with (99m)Tc-tetrofosmin can reveal interscapular BAT distribution in infants and children in terms of mitochondrial activity.

Transthoracic Doppler assessment of coronary flow velocity reserve in children with Kawasaki disease: comparison with coronary angiography and thallium-201 imaging.

OBJECTIVES: The purpose of this study was to determine the feasibility of coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) in children with Kawasaki disease (KD). BACKGROUND: Doppler-derived CFVR is a reliable marker predicting the presence of myocardial ischemia. METHODS: We studied 49 patients (median age 11 years) with KD. The CFVR was calculated as the ratio of hyperemic to basal peak (peak CFVR) and mean (mean CFVR) diastolic flow velocities in the posterior descending coronary artery (PD) and left anterior descending coronary artery (LAD). The CFVR measurements by TTDE were compared with the results of coronary angiography, thallium-201 (Tl-201) single-photon emission computed tomography (SPECT), and intracoronary Doppler study. RESULTS: The CFVR measurements by TTDE were obtained in 92 (94%) of 98 vessels of the PD and LAD in 49 study patients. Both peak and mean CFVRs for 21 stenotic vessels were significantly smaller than those for 35 normal vessels and for 20 vessels with aneurysmal lesions (p < 0.0001). Peak and mean CFVR <2.0 predicted significant coronary stenosis, as determined by coronary angiography, with sensitivities and specificities of 89% and 96% and 89% and 97%, respectively. Also, both peak and mean CFVRs were correlated with reversible perfusion defects on Tl-201 SPECT (agreement 80%; kappa 0.4). The correlation between peak and mean CFVRs determined by the TTDE and intracoronary Doppler studies in 36 vessels of 23 patients were 0.76 and 0.80, respectively. CONCLUSIONS: The CFVR measured by TTDE predicts the presence of significant coronary stenosis of either the right coronary artery or LAD, as well as myocardial ischemia of these territories in children with KD.