Yoshiharu Soga

Enhanced angiogenesis by gelatin hydrogels incorporating basic fibroblast growth factor in rabbit model of hind limb ischemia

Recently we have developed new sustained release system of basic fibroblast growth factor (bFGF) using gelatin hydrogel as a carrier. Using this system, we examined the effect of topical sustained release of bFGF on angiogenesis and tissue blood perfusion in a rabbit model of hind limb ischemia. Thirty-two rabbits underwent excision of right femoral artery under general anesthesia. Two weeks later the rabbits were randomized into four groups (n = 8 each): no treatment, intramuscular injection of gelatin hydrogel alone, and intramuscular injection of gelatin hydrogel incorporating 30 µg and 100 µg of bFGF. Four weeks after each treatment, selective angiography, tissue blood flowmetry using laser Doppler perfusion imaging, and histological examination of thigh muscle were performed. In groups treated with bFGF incorporating gelatin hydrogel, tissue blood flow, number of arterioles, and vascular density were significantly increased in a dose-dependent manner 4 weeks after the treatment. Serum concentrations of bFGF and vascular endothelial growth factor were not elevated 4 weeks after the treatment. In conclusion, sustained release of bFGF using gelatin hydrogel augmented angiogenesis and improved tissue blood flow after excision of the femoral artery.

Attenuation of adhesion formation after cardiac surgery with a chymase inhibitor in a hamster model

OBJECTIVE Chymase is one of the inflammatory mediators and is released from mast cells, which are closely associated with adhesion formation. Chymase also activates transforming growth factor beta1, which promotes tissue fibrosis. However, the role of chymase in cardiac adhesion formation has not yet been elucidated. We have assessed whether a specific chymase inhibitor, Suc-Val-Pro-Phe(p) (OPh)(2), prevents postoperative cardiac adhesions in hamsters. METHODS In 66 hamsters the epicardium was abraded, and then either chymase inhibitor or placebo was injected into the left thoracic cavity, leaving the pericardium open. Cardiac chymase activity, the level of transforming growth factor beta1 in the pleural fluid, and the density of epicardial mast cells were measured 3 days postoperatively. The degree of adhesion formation was evaluated macroscopically and histologically 2 weeks postoperatively by using a grading score ranging from 0 (no adhesions) to 4 (severe adhesions). RESULTS The cardiac chymase activity and level of transforming growth factor beta1 were lower in the chymase inhibitor-treated group compared with in the placebo-treated group (45.8 +/- 18.7 vs 79.7 +/- 13.7 microU/mg protein [P <.025] and 15.6 +/- 6.5 vs 33.2 +/- 9.8 microg/mL [P <.01], respectively). The density of mast cells was higher in the placebo-treated group, and there was suppression to 60% of this value in the chymase inhibitor-treated group. The adhesion scores were lower in the chymase inhibitor-treated group compared with in the placebo-treated group (1.3 +/- 1.3 vs 3.0 +/- 1.1, P <.01). CONCLUSION Use of a chymase inhibitor suppresses not only cardiac chymase activity but also the level of transforming growth factor beta1, and this results in a reduction in postoperative cardiac adhesion.

Attenuating Effects of Chymase Inhibitor on Pericardial Adhesion Following Cardiac Surgery

Abstract  Objective: Chymase, a serine protease, is released from mast cells, which is closely associated with adhesion formation. Chymase activates transforming growth factor‐β1 (TGF‐β1), which promotes tissue fibrosis. Recently we have found that chymase may play an important role in adhesion formation in hamsters. Accordingly, this study was designed to confirm that a chymase inhibitor prevents postoperative cardiac adhesions in large animals. Methods: In 14 dogs, the epicardium was abraded 200 times with gauze and the mid‐portion of the left anterior descending coronary artery (LAD) was exposed with No. 15 blade. Either chymase inhibitor (CI group, n = 7) or placebo (P group, n = 7) was sprayed into the pericardial cavity, then the pericardium was closed. Cardiac chymase activity, the level of TGF‐β1 in the pericardial fluid, the density of epicardial mast cells, the adhesion area between the heart and the pericardium, and the presence of adhesion between the mid‐LAD and the pericardium were evaluated 1 and 2 months after surgery. Five nonsurgical dogs were used as a control for cardiac chymase activity. Results: Cardiac chymase activity and TGF‐β1 level were lower in CI group than in P group (53.7 ± 35.0 vs. 93.4 ± 20.4 μU/mg protein, p = 0.01, 3.2 ± 0.9 vs. 4.3 ± 1.1 μg/mL, p = 0.06, respectively). In CI group, the density of mast cells (19 ± 5 vs. 32 ± 8 cells/cm, p < 0.01), the adhesion area (2.2 ± 0.8 vs. 7.5 ± 1.5 cm2, p < 0.01), and adhesions between the heart and the mid‐LAD (0% vs. 57%) were all reduced. Conclusion: Chymase inhibitor suppresses cardiac chymase activity and reduces the TGF‐β1 level, resulting in a reduction of cardiac adhesion in a large animal.

Mitral valve nonbacterial thrombotic endocarditis: a rare multi-surgery-tolerant survivor of Trousseau’s syndrome

BackgroundFew previous reports have documented cases of nonbacterial thrombotic endocarditis associated with Trousseau’s syndrome for which surgery proved possible for both the primary tumor and the cardiac lesion. The effectiveness of direct oral anticoagulants in patients with Trousseau’s syndrome has also received scant attention.Case presentationA 69-year-old man with repeated episodes of cerebral infarction was diagnosed as having nonbacterial thrombotic endocarditis after mitral valve replacement surgery. Stroke recurred preoperatively under apixaban administration. A stomach biopsy also identified gastric adenocarcinoma, and gastric surgery was performed on the 40th postoperative day. The patient was discharged from the hospital and has been free of thromboembolism under a regime of subcutaneous heparin self-injection thereafter.ConclusionsWe have reported a rare multi-surgery-tolerant survivor of Trousseau’s syndrome in whom subcutaneous heparin injection was useful for preventing thromboembolic events over a long period.

Platypnea-orthodeoxia syndrome associated with aortic insufficiency and aortic elongation

An 81‐year‐old female developed dyspnea only upon assuming a sitting position. Trans‐esophageal echocardiography demonstrated left‐to‐right shunt flow across the atrial septum when the patient was sitting, and right‐to‐left shunt flow when she was supine, along with severe aortic insufficiency. She was diagnosed as having platypnea‐orthodeoxia syndrome and her symptoms were completely resolved following aortic valve replacement, closure of a patent foramen ovale, and shortening of an elongated ascending aorta.

Calcified Masses in the Inferior Vena Cava

Received October 12, 2017; revised manuscript received March 1, 2018; accepted March 27, 2018; released online June 6, 2018 Time for primary review: 68 days Department of Cardiovascular Surgery (Y.S., H.K., T.S., K.D.), Department of Radiology (M.W.), Nagahama City Hospital, Nagahama; Department of Cardiology, Hikone Municipal Hospital, Hikone (N.M., A.N., Y.H.), Japan Mailing address: Yoshiharu Soga, MD, PhD, Director, Department of Cardiovascular Surgery, Nagahama City Hospital, 313 Oh-inui-cho, Nagahama 526-8580, Japan. E-mail: sogakin@dd.iij4u.or.jp ISSN-1346-9843 All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jp Calcified Masses in the Inferior Vena Cava

Toward an Ideal Large Animal Model of Dilated Cardiomyopathy to Study Left Ventricular Volume Reduction Surgery

The Batista operation for dilated cardiomyopathy (DCM) has not, thus far, yielded satisfactory results. One of the explanations for disappointing results is the absence of a suitable animal model of dilated cardiomyopathy. Scientific research on volume reduction surgery needs to be carried out in an appropriate experimental model. This chapter reviews the few studies of volume reduction surgery using animal models of DCM published thus far, including our studies.