Toru Shimaoka

University of Pennsylvania, Filadelfia, Pennsylvania, United States

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Publications (15)39.3 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We describe our initial experience with on-bypass and off-bypass (off-pump) mitral valve replacement with the modified version of our novel catheter-based sutureless mitral valve (SMV) technology, which was developed to atraumatically anchor and seal in the mitral position. The SMV is a self-expanding device consisting of a custom designed nitinol framework and a pericardial leaflet valve mechanism. For the current studies, our original device was modified (SMV2) to reduce the delivery profile and to allow for controlled deployment while still maintaining the key principles necessary for atraumatic anchoring and sealing in the mitral valve position. Ten Yorkshire pigs underwent successful SMV2 device implantation through a left atriotomy (on-pump, n = 6; off-pump, n = 4). Echocardiography and angiography revealed excellent left ventricular systolic function, no significant perivalvular leak, no mitral valve stenosis, no left ventricular outflow tract obstruction, and no aortic valve insufficiency. Postmortem examination demonstrated that the SMV2 devices were anchored securely. This study demonstrates the feasibility and short-term success of off-pump mitral valve replacement using a novel, catheter-based device in a porcine model. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.
    The Annals of thoracic surgery 04/2015; 99(4):1408-1412. DOI:10.1016/j.athoracsur.2014.12.045 · 3.65 Impact Factor
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    ABSTRACT: The present study was designed to investigate the effect of magnesium (Mg) depletion on the expression of voltage-gated calcium (Ca(2+)) channels and Ca(2+) currents in the heart and thereby on hypomagnesemic arrhythmogenesis in adult male rats. Male Wistar rats were fed an Mg-free diet or a normal diet for up to 16 weeks. Serum Mg concentrations were significantly reduced at week 4 or later with an Mg-free diet, which experimentally represents hypomagnesemia. Myocardial Mg contents were also reduced at week 16 accompanied by myocardial hypertrophy. Telemetric ECG recordings revealed a long-term changes of ECG parameters in hypomagnesemic rats; RR shortening, QT prolongation and appreciable PR prolongation. At the same time, hypomagnesemic rats demonstrate various bradycardiac arrhythmias including ventricular premature beats, atrioventricular blocks and sinus arrest, which were never recoded in rats fed by a normal diet. Electrophysiological studies elucidated that the L-type Ca(2+) channel current was decreased in Mg-deficient cardiomyocytes, and these findings were consistent with down-regulation of CaV1.2-mRNA but not in levels of CaV1.3, CaV3.1 or CaV3.2. These findings provide novel insights into hypomagnesemic electrophysiological disorders in the heart, and should be considered when assessing the design of effective antiarrhythmic treatments in patients with hypomagnesemia. Copyright © 2015 Elsevier B.V. All rights reserved.
    Pathophysiology 02/2015; 22(2). DOI:10.1016/j.pathophys.2015.01.002
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    ABSTRACT: Despite advances in design, modern ventricular assist device placement involves median sternotomy and cardiopulmonary bypass and is associated with infectious/embolic complications. In this study, we examine the feasibility and function of a novel minimally invasive, non-blood-contacting epicardial assist device in a porcine ischemic cardiomyopathy model. Feasibility was first tested in an ex vivo thoracoscopic trainer box with slaughterhouse hearts. Five male Yorkshire swine underwent selective ligation of the circumflex artery to create a posterolateral infarct Twelve weeks after infarct, all animals underwent left minithoracotomy. A custom inflatable bladder was positioned over the epicardial surface of the infarct and firmly secured to the surrounding border zone myocardium with polypropylene mesh and minimally invasive mesh tacks. An external gas pulsation system actively inflated and deflated the bladder in synchrony with the cardiac cycle. All animals then underwent cardiac magnetic resonance imaging to assess ventricular function. All subjects successfully underwent off-pump placement of the epicardial assist device via minithoracotomy. Ejection fraction significantly improved from 29.1% ± 4.8% to 39.6% ± 4.23% (P < 0.001) when compared with pretreatment. End-systolic volume decreased (76.6 ± 13.3 mL vs 62.4 ± 12.0 mL, P < 0.001) and stroke volume increased (28.6 ± 3.4 mL vs 37.9 ± 3.1 mL, P < 0.05) when assisted. No change was noted in end-diastolic volume (105.1 ± 11.4 vs 100.3 ± 12.7). On postmortem examination, mesh fixation and device position were excellent in all cases. No adverse events were encountered. Directed epicardial assistance improves ventricular function in a porcine ischemic cardiomyopathy model and may provide a safe alternative to currently available ventricular assist device therapies. Further, the technique used for device positioning and fixation suggests that an entirely thoracoscopic approach is possible.
    Innovations Technology and Techniques in Cardiothoracic and Vascular Surgery 02/2014; DOI:10.1097/IMI.0000000000000049
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    ABSTRACT: Transcatheter mitral valve replacement would represent a major advance in heart valve therapy. Such a device requires a specialized anchoring and sealing technology. This study was designed to test the feasibility of a novel mitral valve replacement device (the sutureless mitral valve [SMV]) designed to anchor and seal in the mitral position without need for sutures. The SMV is a self-expanding device consisting of a custom-designed nitinol framework and a pericardial leaflet valve mechanism. Ten sheep underwent successful surgical SMV device implantation. All animals underwent cardiac catheterization 6 hours postoperatively. Hemodynamic, angiographic, echocardiographic and necroscopic data were recorded. The mean aortic cross-clamp time was 9.5 ± 3.1 minutes. Echocardiography and angiography revealed excellent left ventricular systolic function, no significant perivalvular leak, no mitral valve stenosis, no left ventricular outflow tract obstruction, and no aortic valve insufficiency. Necropsy demonstrated that the SMV devices were anchored securely. This study demonstrates the feasibility and short-term success of sutureless mitral valve replacement using a novel SMV device.
    The Annals of thoracic surgery 08/2013; 96(2):670-4. DOI:10.1016/j.athoracsur.2013.02.065 · 3.65 Impact Factor
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    ABSTRACT: Heart failure after myocardial infarction (MI) is a result of increased myocardial workload, adverse left ventricular (LV) geometric remodeling, and less efficient LV fluid movement. In this study we utilize cardiac magnetic resonance imaging to evaluate ventricular function and flow after placement of a novel directed epicardial assist device. Five swine underwent posterolateral MI and were allowed to remodel for 12 weeks. An inflatable bladder was positioned centrally within the infarct and secured with mesh. The device was connected to an external gas exchange pump, which inflated and deflated in synchrony with the cardiac cycle. Animals then underwent cardiac magnetic resonance imaging during active epicardial assistance and with no assistance. Active epicardial assistance of the infarct showed immediate improvement in LV function and intraventricular flow. Ejection fraction significantly improved from 26.0% ± 4.9% to 37.3% ± 4.5% (p < 0.01). End-systolic volume (85.5 ± 12.7 mL versus 70.1 ± 11.9 mL, p < 0.01) and stroke volume (28.5 ± 4.4 mL versus 39.9 ± 3.1 mL, p = 0.03) were also improved with assistance. End-diastolic volume and regurgitant fraction did not change with treatment. Regional LV flow improved both qualitatively and quantitatively during assistance. Unassisted infarct regional flow showed highly discoordinate blood movement with very slow egress from the posterolateral wall. Large areas of stagnant flow were also identified. With assistance, posterolateral wall blood velocities improved significantly during both systole (26.4% ± 3.2% versus 12.6% ± 1.2% maximum velocity; p < 0.001) and diastole (54.3% ± 9.3% versus 24.2% ± 2.5% maximum velocity; p < 0.01). Directed epicardial assistance can improve LV function and flow in ischemic cardiomyopathy. This novel device may provide a valuable alternative to currently available heart failure therapies.
    The Annals of thoracic surgery 06/2013; DOI:10.1016/j.athoracsur.2013.04.012 · 3.65 Impact Factor
  • Journal of Cardiovascular Magnetic Resonance; 01/2013
  • Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) 01/2013; 74(10):2741-2744. DOI:10.3919/jjsa.74.2741
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    ABSTRACT: We report the case of an 80-year-old man who 11 years previously had undergone aortic valve replacement (St. Jude Medical mechanical heart valve 23 mm) because of aortic stenosis. At the current presentation, a 7-mm pedunculated tumor was discovered along the septal wall in the left ventricular outflow tract. In an attempt to perform a less invasive procedure because of the patient's advanced age, transaortic valve bronchoscopic resection was undertaken. A bronchoscope (Olympus BF P-200) was fed through a gap in the mechanical aortic valve. The entire tumor was removed using biopsy forceps, with histology revealing a papillary fibroelastoma. By using a bronchoscope, we avoided a second valve replacement.
    General Thoracic and Cardiovascular Surgery 08/2010; 58(8):411-4. DOI:10.1007/s11748-009-0547-5
  • 01/2010; 39(4):187-190. DOI:10.4326/jjcvs.39.187
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    ABSTRACT: Lysophosphatidylcholine (LPC) accumulation in intracellular and/or interstitial space in cardiomyocytes may underlie as a mechanism for tachycardia and various arrhythmias during cardiac ischemia, which is usually accompanied by elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)). The present study was therefore designed to investigate possible mechanisms responsible for [Ca(2+)](i) elevation by LPC focusing on T-type Ca(2+) channel current (I(Ca.T)). LPC as well as phorbol 12-myristate 13-acetate (PMA) significantly accelerated the beating rates of neonatal rat cardiomyocytes. Augmentation of I(Ca.T) by LPC was dependent on the intracellular Ca(2+) concentration: an increase of I(Ca.T) was significantly larger in high [Ca(2+)](i) condition (pCa=7) than those in low [Ca(2+)](i) condition (pCa=11). In heterologous expression system by use of human cardiac Ca(V)3.1 and Ca(V)3.2 channels expressed in HEK293 cells, LPC augmented Ca(V)3.2 channel current (I(Cav3.2)) in a concentration-dependent manner but not Ca(V)3.1 channel current (I(Cav3.1)). Augmentation of I(Cav3.2) by LPC was highly [Ca(2+)](i) dependent: I(Cav3.2) was unchanged when pCa was 11 but was markedly increased when [Ca(2+)](i) was higher than 10(-10) M (pCa<or=10) by LPC application (10-50 microM). A specific inhibitor of protein kinase Calpha (Ro-32-0432) attenuated the increase of I(Cav3.2) by LPC. LPC stimulates I(Ca.T) in a [Ca(2+)](i)-dependent manner via PKCalpha activation, which may play a role in triggering arrhythmias in pathophysiological conditions of the heart.
    Journal of Molecular and Cellular Cardiology 09/2009; 48(1):131-9. DOI:10.1016/j.yjmcc.2009.08.032 · 5.22 Impact Factor
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    ABSTRACT: T-type Ca(2+) channel current (I(Ca,T)) plays an important role for spontaneous pacemaker activity and is involved in the progression of structural heart diseases. Estrogens are of importance for the regulation of growth and differentiation and function in a wide array of target tissues, including those in the cardiovascular system. The aim of this study was to elucidate the short-term and long-term effects of 17beta-estradiol (E(2)) on I(Ca,T) in cardiomyocytes. We employed in vivo and in vitro techniques to clarify E(2)-mediated modulation of heart rate (HR) in ovariectomized rats and I(Ca,T) in cardiomyocytes. Ovariectomy increased HR and E(2) supplement reduced HR in ovariectomized rats. Slowing of E(2)-induced HR was consistent with the deceleration of automaticity in E(2)-treated neonatal cardiomyocytes. Short-term application of E(2) did not have significant effects on I(Ca,T), whereas in cardiomyocytes treated with 10 nm E(2) for 24 h, estrogen receptor-independent down-regulation of peak I(Ca,T) and declination of Ca(V)3.2 mRNA were observed. Expression of a cardiac-specific transcription factor Csx/Nkx2.5 was also suppressed by E(2) treatment for 24 h. On the other hand, expression of Ca(V)3.1 mRNA was unaltered by E(2) treatment in this study. An ERK-1/2, 5 inhibitor, PD-98059, abolished the effects of E(2) on I(Ca,T) and Ca(V)3.2 mRNA as well as Csx/Nkx2.5 mRNA. These findings indicate that E(2) decreases Ca(V)3.2 I(Ca,T) through activation of ERK-1/2, 5, which is mediated by the suppression of Csx/Nkx2.5-dependent transcription, suggesting a genomic effect of E(2) as a negative chronotropic factor in the heart.
    Endocrinology 11/2008; 150(2):879-88. DOI:10.1210/en.2008-0645 · 4.64 Impact Factor
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    ABSTRACT: Pulmonary hypertension (PH) is a disease of unknown etiology that ultimately causes right ventricle heart failure with a lethal outcome. An increase in circulating endothelin (ET)-1 levels may contribute to disease progression. This study aimed to examine the possible effects of an orally active ET receptor antagonist, sulfisoxazole (SFX), for the rescue of PH, right ventricular hypertrophy, and eventual right ventricular failure. PH rats (single injection of monocrotaline [MCT]) were treated with an ET antagonist, SFX, an orally active sulfonamide antibody. Effects of SFX on PH rats were assessed in terms of survival rate, pulmonary artery blood pressure (PABP), autonomic nerve activity, and atrial natriuretic peptide (ANP) concentration in right ventricular myocytes and plasma. SFX did not change systemic blood pressure, however, it significantly suppressed the elevation of PABP. SFX maintained the derangement of autonomic nerve control, blunted an increase in ANP in myocytes and plasma, and significantly improved survival in right heart failure and/or related organs dysfunction in PH rats. The ET antagonistic action of the antimicrobial agent, SFX, was experimentally confirmed for treatment of PH in rats.
    Hypertension Research 10/2008; 31(9):1781-90. DOI:10.1291/hypres.31.1781 · 2.94 Impact Factor
  • Journal of Molecular and Cellular Cardiology 02/2008; 44(2):440-440. DOI:10.1016/j.yjmcc.2007.07.020 · 5.22 Impact Factor
  • Journal of Molecular and Cellular Cardiology 02/2008; 44(2):438-439. DOI:10.1016/j.yjmcc.2007.07.015 · 5.22 Impact Factor
  • Nihon Rinsho Geka Gakkai Zasshi (Journal of Japan Surgical Association) 01/2002; 63(4):862-865. DOI:10.3919/jjsa.63.862

Publication Stats

34 Citations
39.30 Total Impact Points

Institutions

  • 2015
    • University of Pennsylvania
      Filadelfia, Pennsylvania, United States
  • 2013
    • Philadelphia University
      Philadelphia, Pennsylvania, United States
    • The Children's Hospital of Philadelphia
      • Department of Pediatrics
      Philadelphia, Pennsylvania, United States
  • 2008
    • Oita University
      Ōita, Ōita, Japan