Ikuo Hagino

Activation of cardiac progenitor cells through paracrine effects of mesenchymal stem cells

Mesenchymal stem cells (MSC) transplantation has been proved to be promising strategy to treat the failing heart. The effect of MSC transplantation is thought to be mediated mainly in a paracrine manner. Recent reports have suggested that cardiac progenitor cells (CPC) reside in the heart. In this study, we investigated whether MSC had paracrine effects on CPC in vitro. CPC were isolated from the neonatal rat heart using an explant method. MSC were isolated from the adult rat bone marrow. MSC-derived conditioned medium promoted proliferation of CPC and inhibited apoptosis of CPC induced by hypoxia and serum starvation. Chemotaxis chamber assay demonstrated that MSC-derived conditioned medium enhanced migration of CPC. Furthermore, MSC-derived conditioned medium upregulated expression of cardiomyocyte-related genes in CPC such as beta-myosin heavy chain (beta-MHC) and atrial natriuretic peptide (ANP). In conclusion, MSC-derived conditioned medium had protective effects on CPC and enhanced their migration and differentiation.

Ventricular Performance in Long-Term Survivors After Fontan Operation

BACKGROUND Ventricular function and arrhythmia in patients with Fontan circulation in long-term follow-up are still unknown. METHODS We retrospectively reviewed 48 patients who survived and were followed up for more than 15 years, among 110 patients who underwent Fontan operation in our institute from 1979 to 1992. Atriopulmonary connection was performed in 26 patients and total cavopulmonary connection in 22. The patients were categorized into right ventricle, left ventricle, and biventricle groups. Follow-up cardiac catheterization and exercise test were performed routinely every 5 years post surgery. Median age at Fontan operation was 5 years. RESULTS Mean follow-up was 18.5 years. Cardiac index in the total cavopulmonary connection group was higher than in the atriopulmonary connection group at 10 and 15 years post surgery (p<0.05). Ejection fraction in the left-ventricle group was higher than in the right-ventricle group. End-diastolic volume at 5, 10, and 15 years was significantly lower than at 1 year (p<0.05). End-diastolic pressure at 10 years was significantly higher than at 1 and 5 years (p<0.05). Beyond 15 years, 6 patients developed ventricular tachycardia. The only significant risk factors for the onset of ventricular tachycardia in a multivariate analysis were age at Fontan operation and absolute age (p<0.05). CONCLUSIONS Long-term follow-up of patients demonstrated that postoperative ventricular systolic performance seemed to become steady. Ventricular tachycardia was detected 15 years post surgery, especially in older patients with older age at Fontan operation, possibly revealing a risk factor in the long-term postoperative period, thereby meriting further consideration.

The effects of vasoactive intestinal peptide on monocrotaline induced pulmonary hypertensive rabbits following cardiopulmonary bypass: a comparative study with isoproteronol and nitroglycerine.

BACKGROUND Vasoactive intestinal peptide (VIP) has regulatory effects on myocardial and vasomotor functions usually demonstrated by in vitro or isolated heart studies. We studied in vivo effects in monocrotaline induced pulmonary hypertensive rabbits immediately after cardiopulmonary bypass (CPB) and tested them versus calcium channel and beta-blockers. METHODS The study consisted of six groups (N=30; five rabbits/group): (1) Control with no pretreatment, monocrotaline injected groups: (solutions were perfused following termination of CPB for 60 min); (2) Control for pulmonary hypertension (PHT); (3) isoproteronol; (4) VIP 10(-6) M; (5) VIP 10(-5) M; (6) nitroglycerine. Normothermic CPB was instituted in thirty rabbits at a flowrate of 100 ml/kg/min for 120 min. Heart rate, mean arterial pressure (MAP), central venous, left atrium (LAP), pulmonary artery (PAP) pressures, pulmonary resistance (Rp), blood gases and ions were measured before and 15, 30, 45 and 60 min after CPB. The VIP 10(-5) M group was subjected to an additional 1.7 x 10(-6) M propranol and 2 mM verapamil infusions for a further 15 min. RESULTS LAP, PAP, Qp, and Rp were significantly higher in the PHT control group (P<0.001). VIP 10(-5) M increased MAP and decreased PAP significantly with respect to isoproteronol and VIP 10(-6) M (P<0.05). VIP 10(-5) M also decreased Rp significantly in the early post CPB 15th minute (P<0.05), but did not show any superiority to other agents in the following minutes. Verapamil inhibited VIP 10(-5) M effects but propranol did not. CONCLUSION VIP has dose responsive, positive inotropic and pulmonary vasodilatory effects in whole body CPB model acting via calcium channels.

Direct visualization of minimal cerebral capillary flow during retrograde cerebral perfusion : An intravital fluorescence microscopy study in pigs

BACKGROUND Retrograde cerebral perfusion (RCP) is used in some centers during aortic arch surgery for brain protection during hypothermic circulatory arrest. It is still unclear however whether RCP provides adequate microcirculatory blood flow at a capillary level. We used intravital microscopy to directly visualize the cerebral capillary blood flow in a piglet model of RCP. METHODS Twelve pigs (weight 9.7 +/- 0.9 kg) were divided into two groups (n = 6 each): deep hypothermic circulatory arrest (DHCA) and RCP. After the creation of a window over the parietal cerebral cortex, pigs underwent 10 minutes of normothermic bypass and 40 minutes of cooling to 15 degrees C on cardiopulmonary bypass ([CPB] pH-stat, hemocrit 30%, pump flow 100 mL x kg(-1) x min(-1)). This was followed by 45 minutes of DHCA and rewarming on CPB to 37 degrees C. In the RCP group the brain was retrogradely perfused (pump flow 30 mL x kg(-1) x min(-1)) during DHCA through the superior vena cava after inferior vena cava occlusion. Plasma was labeled with fluorescein-isothiocyanate-dextran for assessing microvascular diameter and functional capillary density (FCD), defined as total length of erythrocyte-perfused capillaries per observation area. Cerebral tissue oxygenation was determined by nicotinamide adenine dinucleotide hydrogen (NADH) autofluorescence, which increases during tissue ischemia. RESULTS During normothermic and hypothermic antegrade cerebral perfusion the FCD did not significantly change from base line (97% +/- 14% and 96% +/- 12%, respectively). During retrograde cerebral perfusion the FCD decreased highly significantly to 2% +/- 2% of base line values (p < 0.001). Thus there was no evidence of significant capillary blood flow during retrograde cerebral perfusion. The microvascular diameter of cerebral arterioles that were slowly perfused significantly decreased to 27% +/- 6% of base line levels during RCP. NADH fluorescence progressively and significantly increased during RCP, indicating poorer tissue oxygenation. At the end of retrograde cerebral perfusion there was macroscopic evidence of significant brain edema. CONCLUSIONS RCP does not provide adequate cerebral capillary blood flow and does not prevent cerebral ischemia. Prolonged RCP induces brain edema. However, there might be a role for a short period of RCP to remove air and debris from the cerebral circulation after DHCA because retrograde flow could be detected in cerebral arterioles.

Does the off-pump Fontan procedure ameliorate the volume and duration of pleural and peritoneal effusions?

OBJECTIVE We initiated an off-pump Fontan procedure by using temporary bypass from the inferior vena cava to the atrium and advanced the procedure in selected patients by simply cross-clamping the inferior vena cava. We aimed to investigate whether the off-pump Fontan procedure could ameliorate the volume and duration of pleural and peritoneal effusion. METHODS We retrospectively reviewed 74 patients (aged <4 years) who underwent Fontan completion between January 2001 and December 2006. The patients were classified into the following two groups: a cardiopulmonary bypass group in which cardiopulmonary bypass was required (n=27) and an off-pump group in which the procedure was completed without the use of cardiopulmonary bypass (n=47). A propensity score was used to control the treatment selection bias for the use of cardiopulmonary bypass. Fourteen patients from each group were successfully matched. Both bilateral pleural and peritoneal drainage tubes were placed in all the patients. The total volume of the effusion was measured at 6, 12, 24, 48, and 72h postoperatively and was corrected for body weight (kg) and intervals (h). RESULTS Significantly reduced effusion (ml/kg/h) was noted in the off-pump group compared to the cardiopulmonary bypass group at 12h (cardiopulmonary bypass group, 8.6 [4.8-11.5]; off-pump group, 2.5 [1.2-5.4]; p=0.006) and at 48h (cardiopulmonary bypass group, 6.1 [2.6-9.9]; off-pump group, 1.4 [0.9-3.1]; p=0.008). CONCLUSIONS The off-pump Fontan procedure may reduce the volume of postoperative pleural and peritoneal effusion.

Neurodevelopment in 1-year-old Japanese infants after congenital heart surgery

Background:  The purpose of this study was to determine the prevalence of persistent neurodevelopmental sequelae in 1‐year‐old infants after open heart surgery for congenital heart disease, using the Bayley Scales of Infant Development second edition (BSID‐II). A secondary objective was to confirm the applicability and usefulness of the BSID‐II in Japanese infants.

Complete resection of cardiac leiomyosarcoma extending into the pulmonary trunk and right pulmonary artery

A cardiac leimyosarcoma is an extremely rare tumor. We report a case of complete resection of a cardiac leiomyosarcoma extending into the pulmonary trunk and the right pulmonary artery using the Freestyle bioprosthesis (Medtronic, Inc, Minneapolis, MN) and Xenomedica graft (Baxter Healthcare Corp, Horw, Switzerland). Extensive resection and reconstructive surgery with the addition of radiotherapy prolonged the patients life.

Successful Fontan Completion After Cardiac Resynchronization Therapy

This patient underwent a modified Norwood operation with a right ventricle–pulmonary artery shunt at the age of 7 days following the diagnosis of hypoplastic left heart syndrome with mitral and aortic atresia; this procedure was followed by bidirectional Glenn operation at the age of 5 months. The girl subsequently developed congestive heart failure despite the administration of angiotensin-converting enzyme inhibitors and β-blockers after the initial operation. At the age of 11 months, she required hospitalization and intravenous inotropic support. Coil embolization and surgical ligation of the aortopulmonary collaterals were performed at the age of 1 year but could not control the heart failure. The maximum plasma brain natriuretic peptide level after the second palliative operation was 3823 pg/mL. Cardiac catheterization performed at the age of 1 year and 4 months revealed ventricular dyssynchrony, ventricular ejection fraction of 36.2%, right atrial pressure of 7 mm Hg, superior vena cava pressure of 16 mm Hg, and grade 2 tricuspid regurgitation. QRS duration was 184 ms (Figure 1), and arterial oxygen saturation was 80%. To detect the most delayed and earliest …

Unroofing Aortic Intramural Left Coronary Artery Arising From Right Pulmonary Artery

We report an operative case of the anomalous origin of the left coronary artery from the right pulmonary artery with aortic intramural course. This particular anatomy was clearly identified with a preoperative angiogram. The restoration of the two-coronary system was accomplished by unroofing the intramural segment into the left sinus of Valsalva with encouraging midterm results. The details of this anatomical correction are described with a review of the literature.

Long-term results of total cavopulmonary connection with low ejection fraction

PurposeThe aim of this study was to investigate the surgical outcomes and change in cardiac performance after total cavopulmonary connection (TCPC) in patients with reduced ventricular ejection preoperatively.MethodsAmong the 195 patients undergoing TCPC between 1990 and 2001 were 52 who had a preoperative ejection fraction of ≤50% (30%–50%, mean 44%). A dominant ventricle was of the morphologically right type in 81% of patients.ResultsA total of 9 of the 52 patients died early. Two patients died in the intermediate term. Postoperative exercise testing showed maximum oxygen uptake of 26.4 ± 5.8 ml/kg/min (anaerobic threshold 18.3 ± 3.2 ml/kg/ min). The cardiac index was 3.1 ± 0.9 l/min/m2 at 1 year after TCPC, with no fundamental change at 5 years (3.1 ± 0.8 l/min/m2). The end-diastolic volume of the dominant ventricle was 130% ± 74% of the anticipated normal value at 1 year and 93% ± 27% at 5 years after TCPC, with ejection fractions of 48% ± 13% and 49% ± 9%, respectively. When these parameters were plotted for the individual patients, the ejection fraction increased during the first postoperative year, with the percent end-diastolic volume decreasing in 31 survivors; the trend appeared atypical in the remaining 12 survivors. Even in these patients, however, the parameters eventually changed toward favorable circumstances 5 years after TCPC.ConclusionChange in ventricular function was not necessarily pessimistic after TCPC in patients with reduced ventricular contraction preoperatively.