Tohru Matsushita

Assessment of the intrapulmonary ventilation-perfusion distribution after the Fontan procedure for complex cardiac anomalies: Relation to pulmonary hemodynamics

In 12 patients who underwent the Fontan procedure for complex cardiac anomalies, lung scanning with xenon-133 was performed to assess the intrapulmonary ventilation-perfusion distribution, and comparison was made with a control group. All data were then analyzed in relation to either pre- or postoperative pulmonary hemodynamic data. In ventilation scans, the intrapulmonary distribution in the right lung was almost normal. In perfusion scans, an abnormal increased upper to lower lobe perfusion ratio greater than the normal value found in the control group was noted in seven patients (58.3%). There was a significant correlation (p less than 0.02) between the upper to lower lobe perfusion ratio and postoperative pulmonary vascular resistance. Furthermore, this perfusion ratio correlated inversely with the preoperative (p less than 0.005) and postoperative (p less than 0.02) right pulmonary artery area index, defined as the ratio of cross-sectional area to the normal value. Of five patients with less than 90% arterial oxygen saturation, four showed an abnormal distribution of pulmonary blood flow greater than the normal perfusion ratio. No patient had evidence of a pulmonary arteriovenous fistula by the echocardiographic contrast study. These results suggest that abnormal distribution of pulmonary blood flow to the upper lung segment may develop in patients after the Fontan procedure, and that insufficient size of the pulmonary artery before operation and the consequent postoperative elevation of pulmonary vascular resistance may be responsible for this perfusion abnormality.

Selectin on activated platelets enhances neutrophil endothelial adherence in myocardial reperfusion injury

OBJECTIVES The glycoprotein P-selectin is an adhesion molecule that is rapidly expressed on the surface of platelets and endothelium during the inflammatory process. P-selectin on endothelium has been reported to play an important role in reperfusion injury. However, little is known regarding P-selectin on platelets in contributing to the pathophysiology of myocardial reperfusion injury. In this study, we hypothesized that P-selectin on platelets may enhance neutrophil endothelial adherence and this may play a role in neutrophil-mediated reperfusion injury. METHODS Endothelial cells, cardiomyocytes, platelets and neutrophils were isolated from adult rats. Endothelial cells and cardiomyocytes were cultivated in a co-culture system. After exposure to hypoxia and reoxygenation, neutrophil adherence and migration were examined. RESULTS After exposure to 6 h of hypoxia, endothelial cells co-incubated with platelets showed significantly greater neutrophil adherence (63.1 +/- 4.0%) and migration (78.2 +/- 6.7%) than endothelial cells alone (adhesion: 44.2 +/- 2.8%, migration: 57.9 +/- 4.9%). These increases were significantly inhibited (adhesion: 42.1 +/- 3.5%, migration: 65.5 +/- 3.8%) by an anti-P-selectin monoclonal antibody. Moreover, the superoxide-anion production was significantly elevated when activated platelets were added to neutrophils. This enhanced production was also inhibited by anti-P-selectin antibody. CONCLUSION The presence of activated platelets enhanced neutrophil adhesion and migration process after hypoxia reoxygenation. This process may occur following platelet-neutrophil interactions via P-selectin and subsequent neutrophil activation.

Hypoxia induces alteration of bone morphogenetic protein receptor signaling in pulmonary artery endothelial cell.

Reduced expression of bone morphogenetic protein receptors (BMPR) has been implicated in the pathogenesis of pulmonary hypertension (PH), but changes in the intracellular signaling pathway of BMPR have not been fully understood. We hypothesized that BMPR signaling in pulmonary endothelial cells is altered during the development of PH, such as hypoxia-induced PH. We examined the expression of BMPR, BMP-regulated Smads and Id-1 in lung tissues of Sprague-Dawley rats exposed to 2 wk of hypoxia and in isolated lung vascular endothelial cells exposed to hypoxia. BMPRII was predominantly expressed in the endothelial cells (EC) of pulmonary vasculature. In hypoxic rats, reduced expression of BMPRII was observed in the EC of resistance pulmonary arteries. The expression of phosphorylated-Smad1/5/8 and Id-1 in EC was also reduced, whereas the expression of Smad1 as well as activin receptor-like kinase 1 (ALK1) was up-regulated during the development of PH. In in vitro exposure to hypoxia, the expression of mRNA transcripts for BMPRII, Smad8, and Id-1 in EC was reduced, whereas mRNA of Smad1 was not diminished. Our results suggest that hypoxia induces alteration of intracellular BMPR signaling in the EC of resistance pulmonary artery, which is involved in the pathogenesis of PH.

The clinical pathway for fast track recovery of school activities in children after minimally invasive cardiac surgery.

BACKGROUND Minimally invasive cardiac surgery is now becoming standard in the correction of simple congenital cardiac malfbrmations. We introduced a clinical pathway for fast track recovery of school activities in children after minimally invasive cardiac surgery, and assessed the function of the pathway in children with atrial or ventricular septal defects, comparing minimally invasive surgery to repair through a conventional full sternotomy. METHODS We studied 15 children of school age who underwent repair of an atrial or ventricular septal defect through a lower midline sternotomy, and 10 children undergoing repair through a full sternotomy. The clinical pathway was for extubation to take place in the operating room, echocardiographic evaluation on the 5th postoperative day, and discharge home on the 7th postoperative day, with return to school within 2 weeks, and resumption of all gymnastic activity within 6 weeks of the minimally invasive surgery. RESULTS In those having a lower midline sternotomy, postoperative hospital stay was 7.4 +/- 0.8 days, with return to school 8.0 +/- 2.4 days after discharge. They resumed gymnastics 41 +/- 11 days after the minimally invasive surgery. In those having a full sternotomy, in contrast, these parameters were 13.5 +/- 2.7, 23.1 +/- 8.4, and 95 +/- 43 days, respectively. Of the 15 children undergoing a minimally invasive approach, 12 (80%) fulfilled the criterions of our clinical pathway. CONCLUSIONS We conclude that minimally invasive cardiac surgery can safely be performed in children. In addition to its cosmetic role, the technique has added value in promoting early return to normal school life, including gymnastics.

Pulmonary blood flow distribution after the total cavopulmonary connection for complex cardiac anomalies.

SummaryIn total cavopulmonary connection (TCPC), the anastomotic portion of the caval veins to the pulmonary artery (PA) is decided empirically based on personal experience. To compare the pulmonary flow distribution from both caval veins in various types of cavopulmonary anastomosis, intrapulmonary ventilation-perfusion distribution after TCPC was studied using lung scanning. We studied 11 patients, 2 to 37 years old, at 30–84 months after TCPC. Lung scanning was performed by administering 185 MBq of xenon-133 saline solution from their upper extremities and, after xenon-133 was washed out, from their lower extremities. Radionuclide counts on both lungs were obtained and intrapulmonary ventilation-perfusion distribution was assessed. In 4 patients whose superior vena cava (SVC)-PA anastomosis was on the right side of the inferior vena cava (IVC)-PA anastomosis, the blood flow distribution of the right and left lungs was 57.4%: 42.6%. In 3 patients whose SVC-PA anastomosis was on the left side of the IVC-PA anastomosis, the blood flow distribution of the right and left lungs was equal in both lungs (right, 53.1%; left, 46.9%). Systemic arterial oxygen saturation increased after TCPC (before TCPC, 85.3% ± 2.7% and after TCPC, 89.8% ± 2.3% (P < 0.05) in group R; before TCPC, 86.1% ± 2.8% and after TCPC, 93.6% ± 0.6% (P < 0.02) in group L). After TCPC, the value in group L had a tendency to be greater than that in group R (P < 0.04), in spite of the same values of systemic arterial oxygen saturation before TCPC and cardiac index (group R, 2.9 ± 0.96; group L, 3.4 ± 0.37). Lung scanning with xenon-133 revealed the distribution of pulmonary blood flow in the patients after TCPC quantitatively, and in the patients whose SVC-PA anastomosis was on the left side of the IVC-PA anastomosis, the right and left balance of the pulmonary blood flow distribution appeared to be more balanced compared with patients whose connection was done the opposite way.

Left ventricular regional systolic motion in patients with right ventricular pressure overload

Left ventricular regional systolic motion was investigated in patients with right ventricular pressure overload and 10 controls using tagged cine magnetic resonance imaging. The regional shortening fraction was determined in four segments (septal, lateral, inferior, and anterior) on the short-axis image. An asynchrony index, nonhomogeneity of regional shortening, was calculated. Septal shortening in these patients was depressed, and showed an inverse correlation with the right-to-left ventricular peak pressure ratio (r=-0.80, P<0.01). Lateral shortening was greater in the patients than in the controls (P<0.01). The asynchrony index was significantly greater in the patients than in the controls (P<0.01), and correlated with the right-to-left systolic pressure ratio (r=0.64, P=0.02) and the left ventricular end-diastolic pressure (r=0.79, P<0.01). The altered distribution of regional circumferential shortening results in an increased heterogeneity of regional systolic motion. These findings may have important implications for the assessment of ventricular function in patients with right ventricular pressure overload.

Changes in ANP responsiveness of normal and hypertensive porcine intrapulmonary arteries during maturation

Pulmonary vascular resistance falls rapidly after birth, but endothelium-dependent relaxation is relatively poor during the perinatal period. Atrial natriuretic peptide (ANP) is a potent vasodilator; however, its role in the process of perinatal adaptation is uncertain. Porcine intrapulmonary conduit arteries (IPA) from fetal, newborn (<5 min), 3-, 6-, and 17-d-old, and adult pigs, and from piglets made hypoxic from 0 to 3, 3 to 6, or 14 to 17 d, were isolated and mounted for isometric force recording. Rings were precontracted with prostaglandin-F2α (PGF2α, 10 μM) or KCl (40 mM). ANP was added cumulatively (10 pM to 100 nM). C-type natriuretic peptide (CNP) was added as a single concentration of 100 nM. Accumulation of cGMP under basal conditions and stimulated by ANP or CNP was measured by radioimmunoassay system. Frozen sections of lung tissue were incubated with 125I-labeled α-ANP, and binding site density was assessed on IPA with an image analysis system. ANP relaxed IPA in pigs at all ages, but the effect was significantly greater at 6 and 17 d of age. Hypoxia in animals from 14 to 17 d old impaired ANP-induced relaxation. CNP relaxed IPA poorly: <12% at all ages. ANP increased cGMP accumulation in both normal and hypoxic animals. CNP did not increase cGMP generation in IPA from normal animals but did so in IPA from 3-d-old hypoxic animals. ANP-specific binding sites were demonstrated on the pulmonary artery smooth muscle cells, with greater binding in the young animals. The increased relaxant responses to ANP during adaptation may be important in maintaining low pulmonary vascular resistance. In contrast, CNP was largely ineffective in relaxing pulmonary arteries.

Successful Mitral Valve Replacement for MELAS

Successful mitral valve replacement for severe mitral regurgitation in a patient with mitochondrial encephalomyopathy is reported. Renal failure due to low cardiac output improved dramatically after mitral valve replacement and he was discharged 10 weeks after surgery. The surgical indication and timing for valvular dysfunction in patients with mitochondrial cardiomyopathy are discussed.

Angiographic assessment of left ventricular volume, afterload and contractile state in normal children.

Left ventricular (LV) volume, mass and end-systolic stress were determined angiographically in 20 normal children aged 3 months to 16 years. LV contractile state was assessed by the analysis of the relation between end-systolic stress and ejection phase index or end-systolic volume. The LV volume and mass closely correlated with the body surface area. The LV mass/end-diastolic volume ratio (0.94 +/- 0.13 g/ml), ejection fraction (0.67 +/- 0.03) and circumferential end-systolic stress (163 +/- 21 kdynes/cm2, 165 +/- 21 g/cm2) remained constant despite the extensive increase in LV volume with physical growth. In all subjects significant inverse correlations were observed between end-systolic stress and ejection fraction or mean normalized systolic ejection rate. The ratio of the circumferential end-systolic stress to end-systolic volume index ranged from 5.00 to 12.57 (7.49 +/- 1.88). The ratio inversely correlated with age (r = -0.74, p less than 0.001), indicating that this ratio for estimating LV contractility is associated with ventricular size. These results suggested that the LV mass increased adequately in response to the extensive increase in LV cavity volume to maintain the end-systolic stress during growth in childhood and that physiologic cardiac growth was associated with appropriate hypertrophy with no significant change in LV contractile state.

Accelerated ventricular rhythm in the newborn

Accelerated ventricular rhythm was observed in two newborn infants. Neither of them had any causative clinical symptoms for the ventricular arrhythmia. The arrhythmia disappeared when the infants were 18 days and 45 days old, respectively. Arrhythmia was noted in the fetal period, especially in case 1.