Masataka Yoshida

Preischemic infusion of alpha-human atrial natriuretic peptide elicits myoprotective effects against ischemia reperfusion in isolated rat hearts.

Carperitide, a synthetic alpha-human atrial natriuretic peptide (ANP) is a newly developed drug for the treatment of heart failure. However, effects of carperitide on susceptibility to ischemia reperfusion injury are left to be determined. Isolated rat hearts were subjected to Langendorff perfusion. Six hearts received 0.1 μM of carperitide for 10 min, 6 hearts received 1 mM of a NO synthetase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) for 5 min before the infusion of carperitide, 6 hearts received 0.02 μM of a PKC synthetase inhibitor chelerythrine chloride for 5 min before the infusion of carperitide, 6 hearts received 100 μM of a selective mitochondrial ATP-sensitive potassium (KATP) channel blocker 5-dehydroxydecanoate (5HD) before the infusion of carperitide, 6 hearts received 10 μM of a soluble guanylate cyclase inhibitor methylene blue for 5 min before the infusion of carperitide, and 6 hearts served as a control with no drug infusion. All hearts were then subjected to 20 min of global ischemia followed by 120 min of reperfusion. Left ventricular pressures and coronary flow were measured throughout the experiment and infarct size was detected at the end of experiment. Both plasma and tissue cGMP levels were also determined. The results showed: (1) Carperitide significantly reduced infarct size compared to control (26.1 ± 2.8 vs. 42.7 ± 2.3%, carperitide vs. control, p < 0.05). This effect was reversed by L-NAME, chelerythrine and 5HD, but not methylene blue. (2) Plasma cGMP levels were increased in carperitide-treated group. This effect was reversed by L-NAME (0.16 ± 0.03 vs. 1.04 ± 0.09* vs. 0.28 ± 0.02 nmol/L, control vs. carperitide vs. L-NAME, *p < 0.01 vs. control). We conclude that preischemic infusion of carperitide exerts cardioprotective effects possibly through NO-PKC dependent pathway followed by mitochondrial KATP channel activation.

Intra-Arterial Bone Marrow Cell Transplantation Induces Angiogenesis in Rat Hindlimb Ischemia

Background: Bone marrow (BM) cells have been shown to augment local angiogenesis by differentiating vessels themselves and/or secreting paracrinally angiogenic growth factors. Herein, the angiogenic effects of intra-arterial BM mononuclear cell (BM-MNC) transplantation were evaluated in a rat ischemic hindlimb model. Methods: Unilateral hindlimb ischemia was created by excising the femoral artery and its branch in Lewis rats. BM-MNCs were isolated by centrifugation through a Histopaque density gradient. One week after excision of the unilateral femoral artery, BM-MNCs (5 × 106 cells, Group A, n = 6) or PBS (Group B, n = 7) were injected into the ischemic thigh skeletal muscles at the six points with a gauge needle. Another injection of BM-MNCs (3 × 107 cells, Group C, n = 6) or PBS (Group D, n = 7) was administered via the indwelling catheter in the right common iliac artery. Results: Four weeks after the BM-MNC transplantation, angiographic examination revealed the development of collateral vessels in both BM-MNC-transplanted groups. The difference in skin temperature between right and left hindlimbs was significantly reduced in both BM-MNC-transplanted groups (0.93 ± 0.15 vs. 2.84 ± 0.35 vs. 1.20 ± 0.26 vs. 2.61 ± 0.37°C, Group A vs. Group B vs. Group C vs. Group D, p < 0.05). Moreover, immunohistochemical analysis demonstrated that capillary endothelial cells were increased in both BM-MNC-transplanted groups. Conclusion: BM-MNC implantation was able to induce functional neovascularization in rat ischemic hindlimb. The intra-arterial administration offered similar levels of angiogenic activity as intramuscular injection.

Repetitive preischemic infusion of phosphodiesterase III inhibitor olprinone elicits cardioprotective effects in the failing heart after myocardial infarction

Beta-adrenergic (BA) signaling including cAMP-protein kinase A (PKA) pathway has been implicated in the mechanism of ischemic preconditioning (IPC). However, effect of IPC on the failing heart, in which BA signaling is supposed to be altered, is left to be determined. To assess a role of BA signaling in IPC, levels of beta2-adrenergic receptor (B2AR) mRNA were quantified by real time RT-PCR, and in vivo intracardiac function was evaluated in post-MI heart. The effect of IPC on post-MI heart was then determined with an isolated heart perfusion system. Finally, cardioprotective effect of repetitive preischemic infusion of phosphodiesterase III inhibitor olprinone (30 μM), which is known to increase myocardial cAMP levels, was evaluated with/without PKA inhibitor H-89 (2 μM). B2AR mRNA levels in post-MI heart were significantly reduced compared to non-MI heart. IPC was not effective in post-MI heart. Repetitive preischemic infusion of olprinone increased peak developed pressure (94.6 ± 6.3 vs. 62.8 ± 4.9%, OLP vs. control, p < 0.05) and decreased infect size (15.2 ± 0.4 vs. 33.5 ± 2.5%, OLP vs. control, p < 0.01). These effects were abolished by H-89. These results may indicate that repetitive preischemic infusion of olprinone mimics IPC through cAMP-PKA pathway in post-MI heart, and that BA signaling plays a crucial role in IPC response.

Primary hemangiopericytoma of the trachea

A 28-year-old man arrived at our hospital complaining of severe dyspnea. Bronchoscopic findings demonstrated that a tumor was located approximately 4 cm distant from the vocal cord, occupying most of the tracheal lumen. To urgently relieve the dyspnea, some parts of the tumor were cauterized with the neodymium:yttrium-aluminum garnet laser. Histopathologic examination of the cauterized specimen revealed malignant hemangiopericytoma. During the operation, the tumor was resected en bloc with a tracheal segment containing four tracheal cartilages. The patients postoperative course was uneventful with no evidence of recurrence 1 year after the operation.

Influence of Valsalva Sinus on Flow Field around the Aortic Valve and the Valve Characteristics (Quantitative Evaluation by Experiments in vitro Using a Realistic Model)

One of the well known cures for the annuloaortic ectasia is a vascular grafting surgery using a composite graft as an artificial ascending aorta and an artificial valve. Although, almost all conventional grafts do not have Valsalva sinus at the aortic root, the influence of omitting the Valsalva sinus have not yet been clarified. In order to understand the effect of the Valsalva sinuses at aortic root on the valve characteristics and flow field around the valve and furthermore the coronary blood flow, the authors have fabricated some realistic models of aortic valve using three-dimensional modeling machine, and have investigated the effect of the sinus existence by particle image velocimetry (PIV). As the result, the fluctuation of flow rate at coronary artery in the case of the straight wall model was larger than the Valsalva sinus model. The valve leaflets were pulled to the left ventricle, which could cause a diastolic regurgitant flow from the aorta into the left ventricle. The leaflet suction in the Valsalva sinus model was weaker than the straight wall model. Flow visualization results showed that vortex flow occurred in the Valsalva sinus due to jet flow through the valve leaflets during systole. At early diastole, flow into coronary artery around the Valsalva sinus was smoothly than the straight wall model. Consequently it was concluded from a standpoint of flow and valve characteristics that the Valsalva sinus had an important role for the aortic valve and the inlet of the coronary circulation.

Influence of Valsalva sinus on flow field around the aortic valve and the valve characteristics

One of the well known cures for the aortic regurgitateon is a vascular grafting surgery using a composite graft as an artificial ascending aorta and an artificial valve. Although, almost all conventional grafts do not have Valsalva sinus at the aortic root, the influence of omitting the sinus have not yet been clarified. In order to understand the effect of the sinuses at aortic root on the valve characteristics and flow field around the valve and furthermore the coronary blood flow, the authors have fabricated some realistic models of aortic valve using 3D modeling machine, and have investigated the effect of the sinus existence by PIV. As the result, flow into coronary artery around the Valsalva sinus was smoothly than the straight wall model at early diastole. Consequently it was concluded from a standpoint of flow and valve characteristics that the sinus had an important role for the aortic valve and the inlet of the coronary circulation.