Takahiro Yamaguchi

Osaka City University, Ōsaka, Ōsaka, Japan

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Publications (7)13.53 Total impact

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    ABSTRACT: Therapeutic angiogenesis, induced by the direct injection of angiogenic growth factors or by transmyocardial laser revascularization (TMLR), has shown great potential as a new therapeutic strategy for end-stage coronary artery disease. However, no significant differences in angiogenic effects of TMLR and vascular endothelial growth factor (VEGF) have been reported. We compared the effects of the intramyocardial injection of hepatocyte growth factor (HGF), a novel angiogenic factor, with those of TMLR, by evaluating the improvement in regional blood flow and regional function in a canine heart model of chronic ischemia. To create a model of chronic ischemia, we ligated the left anterior descending artery (LAD) in 15 beagles. We divided the dogs into three groups according to the treatment given 1 month after ligation. Four dogs were given an intracardial injection of human recombinant HGF (H group), six dogs were given TMLR (T group), and five dogs were used as a control (C group). We compared the degree of improvement in regional blood flow and regional function 1 month after the treatment. The regional myocardial blood flow and function were significantly better in the H group than in the T or C groups (P < 0.05). Histologically, there were significantly more von Willebrand factor-positive cells in the LAD region in the H group than in the T or C groups. The intramural injection of recombinant human HGF resulted in therapeutic angiogenesis with an intrinsic contractile state, and it may have greater advantages than TMLR for the treatment of chronic ischemic heart disease.
    Surgery Today 09/2005; 35(10):855-60. · 1.21 Impact Factor
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    Ismayil Ahmet, Yoshiki Sawa, Takahiro Yamaguchi, Hikaru Matsuda
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    ABSTRACT: Hepatocyte growth factor (HGF) induces angiogenesis in myocardium. In the present study, its effects in chronic ischemic myocardium were tested. Four weeks after left anterior descending coronary artery ligation in canine hearts, HVJ-liposome containing either human HGF gene (160 microg; HGF group, n = 7) or nothing (control group, n = 6) was directly injected into ischemic myocardium. Four weeks after gene transfection, the thickness fraction (TF), an index of regional myocardial contractility (assessed by epicardial pulse-Doppler crystals), the myocardial perfusion flow (assessed by color microspheres), and the capillary density (assessed by immunostaining of vessels) were evaluated in ischemic myocardium. Thickness fraction (percent of nonischemic myocardium) was significantly improved in the HGF group (80 +/- 15 from 52 +/- 16 of pregene; p < 0.05) whereas it was not changed in the control group (52 +/- 10 from 50 +/- 8 of pregene). The perfusion flow (% of nonischemic myocardium) was significantly improved in the HGF group (98 +/- 17 from 51 +/- 14 of pregene; p < 0.05) while it was not changed in the Control group (58 +/- 13 from 62 +/- 18 of pregene). The capillary density was significantly higher in the HGF group (894 +/- 211/mm2; p < 0.05) than that in the control group (511 +/- 127/mm2). Gene transfection of HGF improved angiogenesis, thereby improved regional myocardial function and perfusion in chronic ischemic myocardium. It indicates a potent therapeutic value of HGF gene transfection for chronic ischemic heart diseases such as myocardial infarction.
    The Annals of Thoracic Surgery 04/2003; 75(4):1283-7. · 3.63 Impact Factor
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    ABSTRACT: Nitric oxide (NO) gas infusion to the oxygenator, as well as heparin-coated bypass circuits, have been reported to attenuate blood activation induced by the interaction with the artificial surfaces of an extracorporeal bypass circuit. Using a mock circulation model, we compared the effect of each and also evaluated the effect of their combination on attenuating bypass-induced blood activation. A miniature closed bypass circuit was primed with diluted fresh human blood and perfused for 180 minutes using a centrifugal pump. NO gas (0, 50, or 100 ppm) was infused to the oxygenator sweep gas of either a non-heparin-coated or a heparin-coated circuit. Platelet counts, beta-thromboglobulin, platelet factor 4, complement-3 activation products and granulocyte elastase were measured at 0, 30, 60, 120, and 180 minutes after starting the perfusion. One hundred ppm of NO was statistically equivalent to the heparin-coated circuit for attenuating bypass-induced blood activation, and a combination of the two significantly surpassed the results of either modification alone. Fifty ppm of NO alone provided only a slight attenuation of blood activation as compared with the non-heparin-coated circuit, though the difference was not significant. A combination of 50 ppm NO and the heparin-coated circuit did not significantly enhance the effects of the heparin-coated circuit alone. The combination of NO gas infusion and heparin-coated circuits appears to be a useful and promising modification for enhancing the attenuation of bypass-induced blood activation, though the optimal dose of NO infusion in terms of effectiveness and adverse effects to the whole body remains to be established.
    Journal of Cardiac Surgery 11/2002; 17(6):477-84. · 0.89 Impact Factor
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    ABSTRACT: Background. We have reported a similar cardioprotective effect and mechanism of diadenosine tetraphosphate (AP4A) and ischemic preconditioning in rat hearts. In this study, the applicability of AP4A administration to cardiac surgery was tested by using a canine cardiopulmonary bypass model.Methods. Hearts underwent 60 minutes of cardioplegic arrest (34°C) by a single dose of cardioplegia. Cardioplegia contained either AP4A (40 μmol/L; n = 6) or saline (n = 6). Beagles were weaned from cardiopulmonary bypass 30 minutes after reperfusion, and left ventricular function was evaluated after another 30 minutes by using the cardiac loop analysis system.Results. Administration of AP4A significantly improved the postischemic recovery of cardiac function and reduced the leakage of serum creatine kinase compared with saline. Systemic vascular resistance, mean aortic blood pressure, and the electrocardiographic indices were not significantly altered by AP4A administration.Conclusions. Administration of AP4A was cardioprotective without apparent adverse effects. Because the cardioprotective mechanism may be similar to that of ischemic preconditioning, the addition of AP4A into cardioplegia may be a novel safe method for clinical application of preconditioning cardioprotection.
    The Annals of Thoracic Surgery 09/2000; · 3.63 Impact Factor
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    ABSTRACT: Cardiopulmonary bypass (CPB) is known to induce an inflammatory response in association with neutrophil mediated lung injury. P-Selectin has been reported to be involved in the initiation of this inflammatory response by promoting the adhesion of neutrophils to endothelial cells in postcapillary venules. However, the role of P-selectin in the inflammatory response induced by CPB has never been clarified. To elucidate its role, we evaluated the effect of an anti-rat specific P-selectin monoclonal antibody (ARP2-4; Sumitomo Pharmaceutical) on the response of inflammatory cytokines and lung injury in a rat-CPB model. Twenty Sprague-Dawley rats underwent CPB for 30 minutes (80 ml/kg per minute, 34 degrees C) under one of two conditions. In group P, ARP2-4 (3 mg/kg) was added to the priming solution of the bypass circuit (n = 10). Saline alone was given to group C (n = 10). Inflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin[IL]-1beta, IL-6, and IL-8) and respiratory index (RI) as a marker of pulmonary gas-exchange ability were measured 1) before the initiation of CPB, 2) at the termination of CPB, and 3) 2 hours after the termination of CPB. Neither TNF-alpha nor IL-1beta was detected during the experimental period in either group. The plasma levels of IL-6 and IL-8 increased after CPB in both groups, but they were significantly lower in group P than in group C. The RI value increased in a pattern similar to that of the inflammatory cytokines and was significantly lower in group P. These data demonstrate that the addition of an anti-rat specific monoclonal antibody inhibits the abnormal release of inflammatory cytokines and attenuates CPB induced lung injury in rats. Thus, P-selectin may play a role in the augmentation of CPB induced inflammatory response, and the use of its inhibitory monoclonal antibody seems to be a promising strategy for the treatment of CPB induced lung injury.
    ASAIO Journal 01/2000; 46(3):334-7. · 1.39 Impact Factor
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    ABSTRACT: Cardiopulmonary bypass (CPB) is known to result in the abnormal production of vasoactive substances contributing to the changes in hemodynamics such as systemic vascular resistance (SVR) during and after CPB. Nitric oxide (NO) is an inflammation-mediated vasoactive substance that plays a role in the whole-body inflammatory response induced by CPB. We evaluated the role of NO in the regulation of SVR during and after CPB. Fifteen patients underwent open-heart surgery for valvular heart disease. The perfusate blood temperature of CPB was set to 34°C. The plasma levels of NO metabolites (NO 2 − +NO 3 − ), prostaglandin E2 (PGE2), bradykinin (BK), and systemic vascular resistance index (SVRI) were measured before CPB and 0, 12, and 24 h after CPB. The plasma level of NO metabolites increased gradually after CPB (pre-CPB, 26.3 ±4.4; 0h, 33.7±6.5; 12 h, 49.8±11.1; 24 h, 43.1±7.5 μM). SVRI decreased gradually after CPB (pre-CPB, 2361±364; 0h, 2048±216; 12 h, 1590±308; 24 h, 1727±435 dyne·s·cm−5·m2). There was a significant inverse correlation between SVRI and the plasma level of NO metabolites as a whole (r=−0.674,P<0.0001). No significant correlations were observed between SVRI and the other vasoactive substances PGE2 and BK. These findings demonstrated that NO production increased gradually during and after CPB in association with the decrease in SVR.
    Journal of Artificial Organs 09/1999; 2(2):152-156. · 1.39 Impact Factor
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    ABSTRACT: Cerebral oxygenation level during cardiopulmonary bypass (CPB) was measured using near-infrared spectroscopy as a monitor of cerebral circulation in 30 patients. Six adult cases with thoracic aortic aneurysm were operated on using selective cerebral perfusion (SCP). CPB was established under moderate hypothermic temperature in 9 adult cases (hypothermic group, lowest blood temperature during CPB; 25 degrees C) and under normothermic temperature in 9 adult cases (normothermic group, lowest blood temperature during CPB; 34 degrees C). In congenital cases (n = 6), CPB was established under moderate hypothermic temperature (congenital group, lowest blood temperature; 25 degrees C). The oxyhemoglobin (HbO2) level showed a significant positive correlation with cerebral blood flow during SCP (r = 0.715). There was no significant correlation between SjO2 and HbO2 in the SCP group. The HbO2 levels in the hypothermic group after 30 and 60 min, from the initiation of CPB and 30 min. before the weaning of CPB were significant lower than the control level (p < 0.05). HbO2 levels in the congenital group after 0, 30 and 60 min. from the initiation of CPB and 30 min. before the weaning of CPB were significantly lower than the control level (p < 0.01). The deoxyhemoglobin (HbR) level in the hypothermic group after 30 and 60 from the initiation of CPB and 30 min. before the wearing of CPB were significantly higher than the pre level (p < 0.05). The mixed venous saturation (SvO2) in the normothermic group showed significant lower levels than those in the hypothermic group (p < 0.01). However, there was no significant difference in HbO2 levels between the two groups. In conclusion, these results suggest that near-infrared spectroscopy may be a noninvasive and useful technique for the cerebral circulation monitoring during CPB.
    The Japanese Journal of Thoracic and Cardiovascular Surgery 08/1998; 46(7):603-9.
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    ABSTRACT: To decrease the circuit priming volume, develop safety, and simplify the equipment, a cardiopulmonary bypass (CPB) circuit using a vacuum suction venous drainage system with a pressure relief valve was developed. The efficacy of this vacuum system was compared to that of a conventional siphon system. The system contains a powerful vacuum generator and a pressure relief valve to keep the negative pressure constant when blood suction is used. Using 8 mongrel dogs, the feasibility and the efficacy of this CPB system was tested. The changes in the negative pressure in the reservoir were within 5 mm Hg whether the suction lines were switched on or off. In all animals the amount of blood in the venous reservoir was stable throughout bypass. The decrease of priming volume was from 725 ml (siphon system) to 250 ml (vacuum system). At the end of CPB, the levels of hemoglobin in the vacuum system were significantly higher than those in the siphon system. These results demonstrated that this vacuum drainage system can provide simplification and a miniaturization of the cardiopulmonary bypass circuit resulting in low hemodilution during CPB.
    Artificial Organs 05/1998; 22(4):337-41. · 1.87 Impact Factor
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    ABSTRACT: The key to the successful implantation of a left ventricular assist system (LVAS) for patients with endstage cardiac disease is whether the functions of other vital organs are irreversibly damaged or not. The percutaneous cardiopulmonary support system (PCPS) is not only equal in convenience to the intra-aortic balloon pump (IABP), it is more powerful in resuscitating impaired end-organ function. To investigate the efficacy of PCPS for end-state cardiac disease, we retrospectively analyzed end-organ function before and after the application of PCPS. From 1992 to 1996, five cardiomyopathy patients with deteriorated end-organ function despite the application of IABP underwent PCPS support before implantation of LVAS. Urine volume and levels of liver enzymes (sAST and sALT) and serum creatinine were determined before and after the application of PCPS. After the application of PCPS, the urine output increased significantly (1840450 to 4340470 ml/day,P<0.01) and levels of sAST, sALT, and serum creatinine decreased significantly (630220 to 15050IU/l, 630260 to 260130IU/l, and 2.90.5 to 1.20.1 mg/dl, respectively) (P<0.05). All five patients were successfully bridged to LVAS implantation and none of them died of multiple organ failure caused by pre-existing cardiac failure although one out of five patients died on device ultimately. These results indicated that PCPS before LVAS implantation is useful to resuscitate impaired end-organ function and to improve the survival rate of LVAS implantation for end-stage cardiac disease.
    Journal of Artificial Organs 02/1998; 1(1):33-36. · 1.39 Impact Factor