Gen Shinohara

Prevention of ischemia/reperfusion-induced pulmonary dysfunction after cardiopulmonary bypass with terminal leukocyte-depleted lung reperfusion

OBJECTIVE Pulmonary ischemia and reperfusion during routine open heart surgery with cardiopulmonary bypass can lead to pulmonary dysfunction and vasoconstriction, resulting in a high morbidity and mortality. We investigated whether ischemia/reperfusion-induced pulmonary dysfunction after full-flow cardiopulmonary bypass could be prevented by the infusion of leukocyte-depleted hypoxemic blood during the early phase of reperfusion (terminal leukocyte-depleted lung reperfusion) and whether the benefits of this method were nullified by using hyperoxemic blood for reperfusion. METHODS Twenty-one neonatal piglets underwent 180 minutes of full-flow cardiopulmonary bypass with pulmonary artery occlusion, followed by reperfusion. The piglets were divided into 3 groups of 7 animals. In group I, uncontrolled reperfusion was achieved by unclamping the pulmonary artery. In contrast, pulmonary reperfusion was done with leukocyte-depleted hyperoxemic blood in group II or with leukocyte-depleted hypoxemic blood in group III for 15 minutes at a flow rate of 10 mL/min/kg before pulmonary artery unclamping. Then the animals were monitored for 120 minutes to evaluate post-cardiopulmonary bypass pulmonary function. RESULTS Group I developed pulmonary dysfunction that was characterized by an increased alveolar-arterial oxygen difference (204 + or - 57.7 mm Hg), pulmonary vasoconstriction, and decreased static lung compliance. Terminal leukocyte-depleted lung reperfusion attenuated post-cardiopulmonary bypass pulmonary dysfunction and vasoconstriction when hypoxemic blood was used for reperfusion (alveolar-arterial oxygen difference, 162 + or - 61.0 mm Hg). In contrast, no benefit of terminal leukocyte-depleted lung reperfusion was detected after reperfusion with hyperoxemic blood (alveolar-arterial oxygen difference, 207 + or - 60.8 mm Hg). CONCLUSION Reperfusion with leukocyte-depleted hypoxemic blood has a protective effect against ischemia/reperfusion-induced pulmonary dysfunction by reducing endothelial damage, cytokine release, and leukocyte activation.

Ischemic postconditioning promotes left ventricular functional recovery after cardioplegic arrest in an in vivo piglet model of global ischemia reperfusion injury on cardiopulmonary bypass

OBJECTIVE An in vivo study of piglets on cardiopulmonary bypass was performed to determine whether postconditioning has a cardioprotective effect after cardioplegic arrest in large animals. METHODS Eighteen piglets were subjected to 90 minutes of cardioplegic arrest followed by 30 minutes of reperfusion. In 6 animals (control), there was no intervention at reperfusion. In 6 other animals, 6 cycles of unclamping and reclamping for 10 seconds each were done before reperfusion (postconditioning 10), whereas 3 cycles of unclamping and reclamping for 30 seconds each were performed in another 6 piglets (postconditioning 30). RESULTS Recovery of left ventricular contractility and diastolic function (percent of preischemic value) was significantly better in both postconditioning groups (contractility: 89.2% and 118.2; diastolic function: 142.3% and 120.4; in the postconditioning 10 and 30 groups, respectively) compared with the control (contractility: 46.1%; diastolic function: 218.5%). Recovery of global cardiac function (ventricular function curve analysis) was improved only in the postconditioning 30 group. Troponin-T release during reperfusion was significantly reduced in the postconditioning 10 group compared with all groups (plasma troponin-T was 0.58 ng/mL in postconditioning 10, 1.85 in postconditioning 30, and 2.54 in control). The myocardial lipid peroxide was significantly higher in the control group than in both postconditioning groups after reperfusion (199% vs 112% and 131%). CONCLUSIONS Both postconditioning algorisms promoted functional recovery after cardioplegic arrest in a large animal model along with the limitation of lipid peroxidation with or without the reduction of troponin-T release.

Scimitar syndrome in an infant with right lung hypoplasia, ventricular septal defect, and severe pulmonary hypertension

A 5-month-old boy was presented for surgical repair of scimitar syndrome associated with right lung hyperplasia, severe pulmonary hypertension, ventricular septal defect (VSD), and atrial septal defect. The calculated shunt fraction (Qp/Qs) was 3.1:1.0, pulmonary vascular resistance was 4.6, and the perfusion lung scan showed a marked decrease (11%) in right pulmonary blood flow. Surgical repair was performed through the right fourth intercostal space with the patient supine. The anomalous vein was divided and interposed with a short azygos vein graft, followed by closure of the VSD. Finally, the interposed azygos vein was anastomosed to the left atrium. Although pulmonary artery pressure was normalized at the 2-year follow-up, cardiac catheterization 6 months after the operation demonstrated right pulmonary vein obstruction.

Modified Norwood procedure with a handmade down-sizing valved right ventricle-to-pulmonary artery conduit.

First-stage palliation of hypoplastic left heart syndrome has been revolutionized by the recent introduction of a right ventricle-to-pulmonary artery (RV-PA) conduit as an alternative to a systemic-to-pulmonary shunt. However, most conduits are unvalved, and the use of valved xenografts was abandoned during the early era of this operation. We performed a successful modified Norwood operation in a 2-month-old infant with aortic atresia and ventricular and atrial septal defects using a hand-made down-sizing valved graft as an RV-PA conduit. The postoperative course was uneventful with well-balanced pulmonary and arterial perfusion. We believe that minimization of the regurgitant volume from an unvalved prosthetic conduit by utilizing this modification might be of benefit in this particular group of patients.

Intact Imaging of Human Heart Structure Using X-ray Phase-Contrast Tomography

Structural examination of human heart specimens at the microscopic level is a prerequisite for understanding congenital heart diseases. It is desirable not to destroy or alter the properties of such specimens because of their scarcity. However, many of the currently available imaging techniques either destroy the specimen through sectioning or alter the chemical and mechanical properties of the specimen through staining and contrast agent injection. As a result, subsequent studies may not be possible. X-ray phase-contrast tomography is an imaging modality for biological soft tissues that does not destroy or alter the properties of the specimen. The feasibility of X-ray phase-contrast tomography for the structural examination of heart specimens was tested using infantile and fetal heart specimens without congenital diseases. X-ray phase-contrast tomography was carried out at the SPring-8 synchrotron radiation facility using the Talbot grating interferometer at the bending magnet beamline BL20B2 to visualize the structure of five non-pretreated whole heart specimens obtained by autopsy. High-resolution, three-dimensional images were obtained for all specimens. The images clearly showed the myocardial structure, coronary vessels, and conduction bundle. X-ray phase-contrast tomography allows high-resolution, three-dimensional imaging of human heart specimens. Intact imaging using X-ray phase-contrast tomography can contribute to further structural investigation of heart specimens with congenital heart diseases.

Three Dimensional Visualization of Human Cardiac Conduction Tissue in Whole Heart Specimens by High-Resolution Phase-Contrast CT Imaging Using Synchrotron Radiation:

Background: The feasibility of synchrotron radiation-based phase-contrast computed tomography (PCCT) for visualization of the atrioventricular (AV) conduction axis in human whole heart specimens was tested using four postmortem structurally normal newborn hearts obtained at autopsy. Methods: A PCCT imaging system at the beamline BL20B2 in a SPring-8 synchrotron radiation facility was used. The PCCT imaging of the conduction system was performed with “virtual” slicing of the three-dimensional reconstructed images. For histological verification, specimens were cut into planes similar to the PCCT images, then cut into 5-μm serial sections and stained with Masson’s trichrome. Results: In PCCT images of all four of the whole hearts of newborns, the AV conduction axis was distinguished as a low-density structure, which was serially traceable from the compact node to the penetrating bundle within the central fibrous body, and to the branching bundle into the left and right bundle branches. This was verified by histological serial sectioning. Conclusion: This is the first demonstration that visualization of the AV conduction axis within human whole heart specimens is feasible with PCCT.

Reversal of oxidant-mediated biochemical injury and prompt functional recovery after prolonged single-dose crystalloid cardioplegic arrest in the infantile piglet heart by terminal warm-blood cardioplegia supplemented with phosphodiesterase III inhibitor

PurposeThe benefit of terminal blood cardioplegia (TWBCP) is insufficient after prolonged ischemia associated with inevitable oxidant-mediated injury by this modality alone. We tested the effects of TWBCP supplemented with high-dose olprinone, which is a phosphodiesterase III inhibitor, a clinically available compound with the potential to reduce oxidant stress and calcium overload. We evaluated the effects with respect to avoiding oxidant-mediated myocardial reperfusion injury and prompt functional recovery after prolonged single-dose crystalloid cardioplegic arrest in a infantile piglet cardiopulmonary bypass (CPB) model.MethodsFifteen piglets were subjected to 90 min of cardioplegic arrest on CPB, followed by 30 min of reperfusion. In group I, uncontrolled reperfusion was applied without receiving TWBCP; in group II, TWBCP was given; in group III, TWBCP was supplemented with olprinone (3 μg/ml). Myocardial performance was evaluated before and after CPB by a left ventricular (LV) function curve and pressure-volume loop analyses. Biochemical injury was determined by measurements of troponin-T and lipid peroxide (LPO) in coronary sinus blood.ResultsGroup III showed significant LV performance recovery (group I, 26.5% ± 5.1%; group II, 42.9% ± 10.8%; group III, 81.9% ± 24.5%, P < 0.01 vs. groups I and II), associated with significant reduction of troponin-T and LPO at the reperfusion phase. No piglets in group III needed electrical cardioversion.ConclusionWe concluded that TWBCP with olprinone reduces myocardial reperfusion injury by reducing oxidant-mediated lipid peroxidation, and it accelerates prompt and persistent LV functional recovery with suppression of reperfusion arrhythmia.

A Devised Option of Neonatal Palliation for Compromised Tetralogy of Fallot with Absent Pulmonary Valve Syndrome

Neonatal primary repair of tetralogy of Fallot (TOF) with absent pulmonary valve (APV) syndrome is associated with high mortality rates. Our plan involves a staged repair that avoids one-stage intracardiac repair (ICR), with a first palliation that closes the main pulmonary orifice using an expanded polytetrafluoroethylene (ePTFE) patch, pulmonary arterioplication, and an adjustable Blalock-Taussig (BT) shunt. This strategy was used for a neonatal case with TOF/APV syndrome with hypoplastic left ventricle (LV). There was evidence of subsequent progressive increase in the LV size, and bronchial compression was relieved and an ICR was performed successfully at 9 months of age.

Synergistic effects of remote perconditioning with terminal blood cardioplegia in an in vivo piglet model

OBJECTIVES This study tested the hypothesis that remote perconditioning offers effective and synergistic cardioprotection to terminal warm blood cardioplegia for prompt ventricular recovery after prolonged cardioplegic arrest in an in vivo piglet model. METHODS Twenty‐four piglets were subjected to 120 min of single‐dose cardioplegic arrest and were divided into 4 groups according to the mode of reperfusion: control (simple aortic unclamp), remote perconditioning, terminal warm blood cardioplegia or remote perconditioning + terminal warm blood cardioplegia; remote perconditioning (4 cycles of 5‐min ischaemia‐reperfusion of the lower limb) was applied prior to aortic unclamping. Left ventricular systolic and diastolic functions were assessed by pressure‐volume loop analysis at baseline and after 60 min of reperfusion. Biochemical injury was evaluated by plasma troponin T level. RESULTS The control group showed decreased end‐systolic elastance, preload recruitable stroke work and inverse of end‐diastolic pressure‐volume relationship of 51.3 ± 14.0%, 46.1 ± 22.5% and 34.8 ± 14.9%, respectively. Percentage recovery of end‐systolic elastance and preload recruitable stroke work were significantly better with terminal warm blood cardioplegia (with or without remote perconditioning) (end‐systolic elastance: 95% confidence interval, 38.6‐84.1; preload recruitable stroke work: 95% confidence interval, 0.4‐54.3). Percentage recovery of inverse of end‐diastolic pressure‐volume relationship was significantly better in the remote perconditioning groups (with or without terminal warm blood cardioplegia) (95% confidence interval, 1.6‐41.6). No synergistic effects of remote perconditioning and terminal warm blood cardioplegia on troponin T release were noted. CONCLUSIONS Remote perconditioning offers promising synergistic cardioprotection to terminal warm blood cardioplegia, implicating potential clinical benefit by contributing to prompt left ventricular functional recovery during paediatric open‐heart surgery.

An Infant with Bilateral Isolated Pulmonary Vein Stenosis

An Infant with Bilateral Isolated Pulmonary Vein Stenosis Yoshitaka Fujimoto1, 2), Kiyoshi Ogawa1), Fumie Kawachi1, 2), Kenji Sugamoto1), Takashi Hishitani1), Kenji Hoshino1, 2), Kouichi Muramatsu3), Gen Shinohara3), Kouji Nomura3), Hiroyuki Ida2) 1)Division of Cardiology, Saitama Children’s Medical Center, Saitama, Japan 2)Department of Pediatrics, Jikei University School of Medicine, Tokyo, Japan 3)Division of Cardiovascular Surgery, Saitama Children’s Medical Center, Saitama, Japan